Dieta Do Grupo Sanguíneo
Dra. Berenice Cunha Wilke

1. Eat Right For Your Type. Dr. Peter J. D’Adamo.
2. Live Right For Your Type. Dr. Peter J. D’Adamo.
3. Eat Right For Your Type. Complete Blood Type Encyclopedia. Dr. Peter J. D’Adamo. Riverhead Books. 2001.
4. Armas, Germes e Aço. Jared Diamond. Ed Record
5. You are your blood type. Nomi, T and A. Besher. Nova York: St Martin’s Press 1983.
6. What’s your type? Constantine, P. Nova York: Plume Books, 1997.
7. A Dieta do Tipo Sanguíneo. Dr. Peter J. Adamo. Editora Campus. Este livro é a tradução do 1º livro do Dr. D’Adamo, e embora seja muito interessante do ponto de vista histórico, a classificação dos alimentos foi profundamente por uma “errata” publicada após o lançamento do livro que corrige a classificação de cerca de 50 alimentos.
8. Viva melhor com A Dieta do Tipo Sanguíneo. Dr. Peter J. Adamo. Editora Campus (Prefira sempre o original – Live Right For Your Type. Dr. Peter J. D’Adamo – para evitar erros de tradução dos alimentos).
9. Armas, Germes e Aço. Jared Diamond. Ed Record
10. The lectinas proprierties. Functions e applicationsin biology and medicine. Irvin e. Liener. Academic Press1986,

Infecções:

Saliva-induced aggregation of oral streptococci and the influence of blood group reactive substances.
Ligtenberg AJ; Veerman EC; de Graaff J; Nieuw Amerongen AV
Arch Oral Biol; 35 Suppl:141S-143S, 1990.

Non-secretion of blood group antigens and susceptibility to infection by Candida species.
Thom SM; Blackwell CC; MacCallum CJ; Weir DM; Brettle RP; Kinane DF; Wray D
FEMS Microbiol Immunol; 1(6-7):401-5, 1989 Jun.

Secretor status and dental caries in Iceland.
Holbrook WP; Blackwell CC
FEMS Microbiol Immunol; 1(6-7):397-9, 1989 Jun.

Secretor status, candidal carriage and candidal infection in patients with diabetes mellitus.
Lamey PJ; Darwaza A; Fisher BM; Samaranayake LP; Macfarlane TW; Frier BM
J Oral Pathol; 17(7):354-7, 1988 Aug.

Oral carriage of Candida albicans, ABO blood group and secretor status in healthy subjects.
Burford-Mason AP; Weber JC; Willoughby JM
J Med Vet Mycol; 26(1):49-56, 1988 Feb

The ABO system and Lamblia infection. 2. The secretion of ABO system antigens and level of the specific humoral response in persons with Lamblia infection and the presence of group-specific antigens in Lamblia]
Osipova SO; Dekhkan-Khodzhaeva NA; Los'eva LR
Med Parazitol (Mosk); (6):16-9, 1985 Nov-Dec.

Non-secretion of ABO blood group antigens predisposing to infection by Haemophilus influenzae .
Blackwell CC; Jonsdottir K; Hanson MF; Weir DM
Lancet; 2(8508):687, 1986 Sep 20.

Doenças

Study of genetic markers of duodenal ulcer
Tsimmerman IaS; Onosova EA; Tsimmerman Iia
Klin Med (Mosk); 67(5):73-7, 1989 May.

The secretory type of persons who have survived a myocardial infarct
Slavchev S; Tsoneva M; Zakhariev Z
Vutr Boles; 28(2):31-4, 1989.

ABO blood group incompatibility and infertility in Nigerian couples .
Ogbimi AO; Oyeyinka GO; Omu AE
Immunol Lett; 14(4):299-301, 1987 Apr.

Frequency of non-secretor types among stomach cancer patients.
Csató E; Vass J
Haematologia (Budap); 19(2):147-50, 1986.

Blood group antigens and ABH secretor status in dystrophia myotonica (Curschmann-Steinert)
Mielke U; Gramer L; Schimrigk K
Klin Padiatr; 198(4):312-5, 1986 Jul-Aug.

Non-secretion of ABO blood group antigens predisposing to infection by Haemophilus influenzae .
Blackwell CC; Jonsdottir K; Hanson MF; Weir DM
Lancet; 2(8508):687, 1986 Sep 20 .

Examining the secretor status in the saliva of patients with oral pre-cancerous lesions.
Vidas I; Delajlija M; Temmer-Vuksan B; Stipetic-Mravak M; Cindric N; Maricíc D
J Oral Rehabil; 26(2):177-82, 1999 Feb.

Modulation of immune function by dietary lectins in rheumatoid arthritis.
Cordain L, Toohey L, Smith MJ, Hickey MS.
Br J Nutr 2000 Mar;83(3):207-17   

Do dietary lectins cause disease?
Editorials
David L J Freed , Allergist. 
BMJ 1999;318:1023-1024 ( 17 April )

Lectin s in the United States diet: a survey of lectins in commonly consumed foods and a review of the literature
MS Nachbar and JD Oppenheim
American Journal of Clinical Nutrition, Vol 33, 2338-2345

Dietary lectins can stimulate pancreatic growth in the rat.
Kelsall A; FitzGerald AJ; Howard CV; Evans RC; Singh R; Rhodes JM; Goodlad RA
Int J Exp Pathol; 83(4):203-8, 2002 Aug

Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulatedintestinal fluid-a comparative study.
Fu TJ; Abbott UR; Hatzos C
J Agric Food Chem; 50(24):7154-60, 2002 Nov 20.

Diet and colorectal cancer: an investigation of the lectin/galactose hypothesis.
Evans RC; Fear S; Ashby D; Hackett A; Williams E; Van Der Vliet M; Dunstan FD; Rhodes JM
Gastroenterology; 122(7):1784-92, 2002 Jun.

Dietary wheat germ agglutinin modulates ovalbumin-induced immune responses in Brown Norway rats.
Watzl B; Neudecker C; Hänsch GM; Rechkemmer G; Pool-Zobel BL
Br J Nutr; 85(4):483-90, 2001 Apr

Opposite effects on human colon cancer cell proliferation of two dietary Thomsen-Friedenreich antigen-binding lectins.
Yu LG; Milton JD; Fernig DG; Rhodes JM
J Cell Physiol; 186(2):282-7, 2001 Feb.

Decreased levels of heat shock proteins in gut epithelial cells after exposure to plant lectins.
Ovelgönne JH; Koninkx JF; Pusztai A; Bardocz S; Kok W; Ewen SW; Hendriks HG; van Dijk JE
Gut; 46(5):679-87, 2000 May.

Dietary soya beans and kidney beans stimulate secretion of cholecystokinin and pancreatic digestive enzymes in 400-day-old Hooded-Lister rats but only soya beans induce growth of the pancreas.
Grant G; Alonso R; Edwards JE; Murray S
Pancreas; 20(3):305-12, 2000 Apr.]

Immunological aspects of the potential role of dietary carbohydrates and lectins in human health
Kilpatrick DC
Eur J Nutr; 38(3):107-17, 1999 Jun.

Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils.
Haas H; Falcone FH; Schramm G; Haisch K; Gibbs BF; Klaucke J; Pöppelmann M; Becker WM; Gabius HJ; Schlaak M
Eur J Immunol; 29(3):918-27, 1999 Mar.

Modifications to physicochemical and nutritional properties of hard-To-cook beans (Phaseolus vulgaris L.) by extrusion cooking.
Martín-Cabrejas MA; Jaime L; Karanja C; Downie AJ; Parker ML; Lopez-Andreu FJ; Maina G; Esteban RM; Smith AC; Waldron KW
J Agric Food Chem; 47(3):1174-82, 1999 Mar.

Relative importance of phytohemagglutinin (lectin) and trypsin-chymotrypsin inhibitor on bean (Phaseolus vulgaris L) protein absorption and utilization by the rat.
Carvalho MR; Sgarbieri VC
J Nutr Sci Vitaminol (Tokyo); 44(5):685-96, 1998 Oct.

Cellular immune responses to beta casein: elevated in but not specific for individuals with Type I diabetes mellitus.
Ellis TM; Ottendorfer E; Jodoin E; Salisbury PJ; She JX; Schatz DA; Atkinson MA
Diabetologia; 41(6):731-5, 1998 Jun.

Peanut ingestion increases rectal proliferation in individuals with mucosal expression of peanut lectin receptor.
Ryder SD; Jacyna MR; Levi AJ; Rizzi PM; Rhodes JM
Gastroenterology; 114(1):44-9, 1998 Jan

Stimulation of proliferation in human colon cancer cells by human monoclonal antibodies against the TF antigen (galactose beta1-3 N-acetyl-galactosamine)
Yu LG; Jansson B; Fernig DG; Milton JD; Smith JA; Gerasimenko OV; Jones M; Rhodes JM
Int J Cancer; 73(3):424-31, 1997 Nov 4.

Stimulation of proliferation in human colon cancer cells by human monoclonal antibodies against the TF antigen (galactose beta1-3 N-acetyl-galactosamine)
Yu LG; Jansson B; Fernig DG; Milton JD; Smith JA; Gerasimenko OV; Jones M; Rhodes JM
Int J Cancer; 73(3):424-31, 1997 Nov 4.

In vitro influence of Phaseolus vulgaris, Griffonia simplicifolia, concanavalin A, wheat germ, and peanut agglutinins on HCT-15, LoVo, and SW837 human colorectal cancer cell growth.
Kiss R; Camby I; Duckworth C; De Decker R; Salmon I; Pasteels JL; Danguy A; Yeaton P
Gut; 40(2):253-61, 1997 Feb.

In vitro influence of Phaseolus vulgaris, Griffonia simplicifolia, concanavalin A, wheat germ, and peanut agglutinins on HCT-15, LoVo, and SW837 human colorectal cancer cell growth.
Kiss R; Camby I; Duckworth C; De Decker R; Salmon I; Pasteels JL; Danguy A; Yeaton P
Gut; 40(2):253-61, 1997 Feb.

Response of intestinal transglutaminase activity to dietary phytohaemagglutinin.
Sessa A; Tunici P; Rabellotti E; Bardocz S; Grant G; Pusztai A; Perin A
Biochim Biophys Acta; 1314(1-2):66-70, 1996 Nov 8.

Natural human antibodies to dietary lectins.
Tchernychev B; Wilchek M
FEBS Lett; 397(2-3):139-42, 1996 Nov 18.

Involvement of polyamines in pancreatic growth induced by dietary soyabean, lectin or trypsin inhibitors.
Grant G; Bardocz S; Brown DS; Watt WB; Stewart JC; Pusztai A
Biochem Soc Trans; 18(5):1009-10, 1990 Oct.

Effect of variable protein contents in diets containing Phaseolus vulgaris beans on performance, organ weights and blood variables in piglets, rats and chickens.
Huisman J; van der Poel AF; Mouwen JM; van Weerden EJ
Br J Nutr; 64(3):755-64, 1990 Nov.

Effects of a panel of dietary lectins on cholecystokinin release in rats.
Am J Physiol; 273(4 Pt 1):G946-50, 1997 Oct.

Dietary soya beans and kidney beans stimulate secretion of cholecystokinin and pancreatic digestive enzymes in 400-day-old Hooded-Lister rats but only soya beans induce growth of the pancreas.
Pancreas; 20(3):305-12, 2000 Apr.

Dietary lectins can stimulate pancreatic growth in the rat.
Int J Exp Pathol; 83(4):203-8, 2002 Aug

Natural human antibodies to dietary lectins.
FEBS Lett; 397(2-3):139-42, 1996 Nov 18.

Characteristics and consequences of interactions of lectins with the intestinal mucosa.
Arch Latinoam Nutr; 44(4 Suppl 1):10S-15S, 1996 Dec.

Identification of the dietary lectin, wheat germ agglutinin, in human intestinal contents.
Gastroenterology; 75(2):236-9, 1978 Aug.

Lectin s in the United States diet: a survey of lectins in commonly consumed foods and a review of the literature.
American Journal of Clinical Nutrition, Vol 33, 2338-2345, 1980.

Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic and healthy children.
Diabetologia; 44(9):1140-7, 2001 Sep.

Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic and healthy children.
Diabetologia; 44(9):1140-7, 2001 Sep.

Impact of dietary protein and fat source on the development of insulin-dependent diabetes in the BB rat.
Diabetes Res; 20(1):33-41, 1992.

Detection of antibodies against wheat germ agglutinin bound glycoproteins on the islet-cell membrane.
Diabet Med; 5(2):139-44, 1988 Mar.

Wheat-germ agglutinin mimics metabolic effects of insulin without increasing receptor.
Cell Signal; 2(4):377-86, 1990.

Bound lectins that mimic insulin produce persistent insulin-like activities.
Endocrinology; 113(6):1921-6, 1983 Dec.

Insulin receptor antiserum and plant lectins mimic the direct effects of insulin on nuclear envelope phosphorylation.
Science; 221(4609):462-4, 1983 Jul 29.

Insulin receptor antiserum and plant lectins mimic the direct effects of insulin on nuclear envelope phosphorylation.
Science; 221(4609):462-4, 1983 Jul 29.

Stress, cortisol, interferon and "stress" diseases. I. Cortisol as the cause of "stress" diseases.
Med Hypotheses; 13(1):31-44, 1984 Jan.

Gastrointestinal hormones and cortisol in normal pregnant women and women with gestational diabetes.
Acta Endocrinol Suppl (Copenh); 277:24-6, 1986.

Early morning hyperglycaemia "dawn phenomenon" in non-insulin dependent diabetes mellitus (NIDDM): effects of cortisol suppression by metyrapone .
Diabetes Res; 14(4):181-5, 1990 Aug.

Maternal-child blood group incompatibility and other perinatal events increase the risk for early-onset type 1 (insulin-dependent) diabetes mellitus.
Diabetologia; 35(7):671-5, 1992 Jul.

An infectious aetiology of insulin-dependent diabetes mellitus? Role of the secretor status.
FEMS Microbiol Immunol; 1(6-7):411-6, 1989 Jun.

Total serum alkaline phosphatase (SAP) and serum cholesterol in relation to secretor status and blood groups in myocardial infarction patients.
Indian Heart J; 41(2):82-5, 1989 Mar-Apr.

Cholesterol modulates alkaline phosphatase activity of rat intestinal microvillus membranes.
J Biol Chem; 263(18):8592-7, 1988 Jun 25.

Cellular immune responses to beta casein: elevated in but not specific for individuals with Type I diabetes mellitus.
Ellis TM; Ottendorfer E; Jodoin E; Salisbury PJ; She JX; Schatz DA; Atkinson MA
Diabetologia; 41(6):731-5, 1998 Jun.

Impact of dietary protein and fat source on the development of insulin-dependent diabetes in the BB rat.
Hoorfar J; Buschard K; Brogren CH
Diabetes Res; 20(1):33-41, 1992.

1. Variations of lactose and oligosaccharides in milk from women of blood types secretor A or H, secretor Lewis, and secretor H/nonsecretor Lewis during the course of lactation.
Viverge D; Grimmonprez L; Cassanas G; Bardet L; Bonnet H; Sol ere M
Ann Nutr Metab; 29(1):1-11, 1985

Publicações:

Saliva-induced aggregation of oral streptococci and the influence of blood group reactive substances.
Ligtenberg AJ; Veerman EC; de Graaff J; Nieuw Amerongen AV
Arch Oral Biol; 35 Suppl:141S-143S, 1990.

Abstract: Aggregation of strains of Streptococcus rattus, Strep. mutans and Strep. salivarius by saliva from individuals of blood groups A, B and O was investigated. Blood group A salivas had a significantly higher aggregation activity with Strep. rattus than blood group B salivas (P less than 0.05). However, Strep. mutans and Strep. salivarius were better aggregated by blood group B saliva and this was significant for Strep. mutans (P less than 0.05). For all three strains, the variance within blood group O was too large to give significant differences with either blood group A or B. The blood group A-specific carbohydrate, N-acetyl-D-galactosamine, inhibited aggregation of Strep. rattus, but not of the other strains. The blood group B-specific carbohydrate, D-galactose, inhibited aggregation of Strep. mutans but not of Strep. rattus or Strep. salivarius. L-Fucose, specific for blood group O failed to inhibit aggregation of any of the three strains. These findings suggest that blood group-specific substances may be involved in bacterial aggregation.

Non-secretion of blood group antigens and susceptibility to infection by Candida species.
Thom SM; Blackwell CC; MacCallum CJ; Weir DM; Brettle RP; Kinane DF; Wray D
FEMS Microbiol Immunol; 1(6-7):401-5, 1989 Jun.

Abstract: One of the innate defences against superficial infections by Candida species appears to be the ability of an individual to secrete the water-soluble form of his ABO blood group antigens into body fluids. There was a significantly higher number of non-secretors (48.9%) among 174 patients with either oral or vaginal candida infections compared with the proportion of non-secretors in the local population (26.6%). The protective effect afforded by the secretor gene might be due to the ability of glycocompounds in the body fluids of secretors to inhibit adhesins on the surface of the yeast. In attachment studies, preincubation of blastospores with boiled secretor saliva significantly reduced their ability to bind to epithelial cells. Non-secretor saliva did not reduce the binding and often enhanced the numbers of attached yeasts. Possible host-parasite interactions underlying the susceptibility of non-secretors to candida and other infections are discussed.

Secretor status and dental caries in Iceland.
Holbrook WP; Blackwell CC
FEMS Microbiol Immunol; 1(6-7):397-9, 1989 Jun.

Abstract: The proportion of non-secretors of ABH blood-group substances among Icelanders is one of the highest recorded for European countries. Dental caries prevalence is also very high. In this study of dental caries in young adults mean number of decayed, missing and filled teeth for secretors were 17.4 and for non-secretors 19.9 (P less than 0.05). A majority of patients seeking free dental treatment in the Dental School were non-secretors (62.7%) significantly more than the proportion of non-secretors in the general population (36%; P less than 0.01). It is postulated that blood group substances may interfere with the adherence of Streptococcus mutans to teeth.

Secretor status, candidal carriage and candidal infection in patients with diabetes mellitus.
Lamey PJ; Darwaza A; Fisher BM; Samaranayake LP; Macfarlane TW; Frier BM
J Oral Pathol; 17(7):354-7, 1988 Aug.

Abstract: One hundred and nine patients with diabetes mellitus and 100 age-, sex- and denture-status-matched, non-diabetic individuals were investigated prospectively. Comparison was made of oral candidal carriage, clinical infection and inherited ability to secrete blood group antigens in saliva. Diabetic patients had a significantly higher prevalence of oral candidal carriage and infection (P less than 0.001) than non-diabetic individuals, but the candidal load between the 2 groups, was not significant. A comparable proportion of insulin-dependent, non-insulin dependent and control groups were secretors of blood group antigens, and there was no difference in the oral candidal carriage and infection rates between secretors and non-secretors.

Oral carriage of Candida albicans, ABO blood group and secretor status in healthy subjects.
Burford-Mason AP; Weber JC; Willoughby JM
J Med Vet Mycol; 26(1):49-56, 1988 Feb

Abstract: ABO blood group and secretor status were determined in healthy subjects in relation to oral carriage of Candida albicans, using a mouthwash technique to identify carriers and non-carriers. Of 100 subjects studied, 32% carried Candida, the main species isolated being C. albicans (94% isolates). Carriage of C. albicans was significantly associated with blood group O (p less than 0.001) and independently, with non-secretion of blood group antigens (p less than 0.001), with the trend towards carriage being greatest in group O non-secretors. This suggests that in healthy subjects, blood group O and non-secretion of blood group antigens are separate and cumulative risk factors for oral carriage of C. albicans.

The ABO system and Lamblia infection. 2. The secretion of ABO system antigens and level of the specific humoral response in persons with Lamblia infection and the presence of group-specific antigens in Lamblia]
Osipova SO; Dekhkan-Khodzhaeva NA; Los'eva LR
Med Parazitol (Mosk); (6):16-9, 1985 Nov-Dec.

Non-secretion of ABO blood group antigens predisposing to infection by Haemophilus influenzae .
Blackwell CC; Jonsdottir K; Hanson MF; Weir DM
Lancet; 2(8508):687, 1986 Sep 20.

Study of genetic markers of duodenal ulcer
Tsimmerman IaS; Onosova EA; Tsimmerman Iia
Klin Med (Mosk); 67(5):73-7, 1989 May.

Abstract: The results of determination of various hereditary predisposition markers in peptic ulcer are given: in the population, in patients with duodenal ulcer and in their siblings (risk group). Of importance for revealing subjects with hereditary predisposition to duodenal ulcer are the clinico-genealogical analysis, determination of the blood group, especially in simultaneous determination of a "secretory status" ("status of non-secretion" of the ABH blood system agglutinogen in the saliva), increase in the mass of parietal cells and, to some extent, of the distinguishing features of dermatoglyphics (in combination with the above markers). Determination of taste sensitivity to phenylthiocarbamide is non-informative.

The secretory type of persons who have survived a myocardial infarct
Slavchev S; Tsoneva M; Zakhariev Z
Vutr Boles; 28(2):31-4, 1989.

Abstract: 250 persons (117 men and 73 women) with past myocardial infarction, between 19 and 65 years of age, were examined for the secreting quality (or nonsecreting) of ABO(H) antigens in the saliva. The secreting persons were additionally examined for the antigens titer. 38.40% of the persons examined were found to be nonsecreting which is twice as many than are normally found among the Bulgarian population (18.69%). In the group of patients with past myocardial infarction the weak secreting persons were significantly more numerous while the moderate and strong secreting persons were significantly less. The data of the study allow the conclusion that the nonsecreting and the hyposecreting types are a risk factor for myocardial infarction.

ABO blood group incompatibility and infertility in Nigerian couples .
Ogbimi AO; Oyeyinka GO; Omu AE
Immunol Lett; 14(4):299-301, 1987 Apr.

Abstract: ABO blood group substances were determined in either the seminal plasma (male patients) or saliva of 100 infertile couples and 100 control subjects. Comprehensive infertility evaluation was performed in all patients. Results were analysed in groups of couples with respect to their ABO blood group and compared with fertile control subjects. Over 70% of fertile marriages were compatible. Comparison of infertile and fertile couples for either ABO compatibility or incompatibility did not reveal any statistically significant difference (P greater than 0.05). This suggests some measure of low zone tolerance to ABO antigens on spermatozoa, for only a small minority of sperm introduced during coitus gains access to the oviduct and ultimately to the peritoneal cavity.

Frequency of non-secretor types among stomach cancer patients.
Csató E; Vass J
Haematologia (Budap); 19(2):147-50, 1986.

Abstract: The secretor type and the ABO blood group characteristics were studied in 293 patients suffering from cancer of the stomach. The results were compared with the corresponding data of 760 healthy persons. The frequency of non-secretors was found to be 8.8% lower among the stomach cancer patients, and the incidence of A blood group substance 10% higher than in normal ones.

Blood group antigens and ABH secretor status in dystrophia myotonica (Curschmann-Steinert)
Mielke U; Gramer L; Schimrigk K
Klin Padiatr; 198(4):312-5, 1986 Jul-Aug.

Abstract: The linkage between the dominantly inherited Dystrophia myotonica and ABH-Secretor locus is well known. It has been used as a genetic marker for the early detection of heterozygous patients. Genetic counselling, however, requires exact knowledge of the gene combination. 25 persons from a special ambulance, patients and their advice seeking relatives, were examined for ABH, Lewis, Kidd, and Lutheran blood groups. Secretor test was performed from saliva. In 42% of the patients the combination of Dystrophia myotonica to the (Se) or (se) allele could not be exactly determined, nor in any of their relatives because the number of family members available for analysis was insufficient. Therefore this genetic marker is considered to be of limited practical importance for genetic counselling despite of its high theoretical value. The occurrence of lewis-b-antigen in the saliva of 3 nonsecretor patients cannot be explained yet.

Examining the secretor status in the saliva of patients with oral pre-cancerous lesions.
Vidas I; Delajlija M; Temmer-Vuksan B; Stipetic-Mravak M; Cindric N; Maricíc D
J Oral Rehabil; 26(2):177-82, 1999 Feb.

Abstract: It has been demonstrated in a number of earlier studies on the aetiology and pathogenesis of certain diseases that the patients' secretor status (ABO (H) blood group antigens) may possibly be a factor influencing the development of systemic oral diseases. This likelihood has prompted the present study, to examine the differences in the saliva secretor status by comparing patients with oral pre-cancerous lesions on the one hand, and the healthy population on the other; (i) in relation to the intensity of the clinical manifestation of diseases and (ii) in relation to the intensity of epithelial dysplasia of patients with oral pre-cancerous lesions. In total 122 subjects were examined, half of whom suffered from oral pre-cancerous lesions (excluding Candida albicans in oral smears), while the other half were the healthy control group. All were subjected to clinical oral examinations and standard evaluation tests in order to establish the secretor status of their saliva. In the group of patients with oral pre-cancerous lesions (experimental group), a pathohistological examination of the oral mucosa was performed. The results have demonstrated that the large majority of the people examined in both groups were secretors and no significant difference between secretors and non-secretors was found in the comparison between the experimental group and the healthy control group. However, (i) we found a higher intensity of oral disease in the non-secretor group, and (ii) the occurrence of epithelial dysplasia was found exclusively in the non-secretor group.

Non-secretion of ABO blood group antigens predisposing to infection by Haemophilus influenzae .
Blackwell CC; Jonsdottir K; Hanson MF; Weir DM
Lancet; 2(8508):687, 1986 Sep 20 .

8. Modulation of immune function by dietary lectins in rheumatoid arthritis.
Cordain L, Toohey L, Smith MJ, Hickey MS.
Br J Nutr 2000 Mar;83(3):207-17  

Abstract: Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice versa, the nature of this relationship remains elusive. In the present review, we provide evidence for how the interaction of dietary lectins with enterocytes and lymphocytes may facilitate the translocation of both dietary and gut-derived pathogenic antigens to peripheral tissues, which in turn causes persistent peripheral antigenic stimulation. In genetically susceptible individuals, this antigenic stimulation may ultimately result in the expression of overt rheumatoid arthritis (RA) via molecular mimicry, a process whereby foreign peptides, similar in structure to endogenous peptides, may cause antibodies or T-lymphocytes to cross-react with both foreign and endogenous peptides and thereby break immunological tolerance. By eliminating dietary elements, particularly lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RA.

Do dietary lectins cause disease?
Editorials
David L J Freed , Allergist. 
BMJ 1999;318:1023-1024 ( 17 April )

Abstract: The evidence is suggestive and raises interesting possibilities for treatment 

In 1988 a hospital launched a "healthy eating day" in its staff canteen at lunchtime. One dish contained red kidney beans, and 31 portions were served. At 3 pm one of the customers, a surgical registrar, vomited in theatre. Over the next four hours 10 more customers suffered profuse vomiting, some with diarrhoea. All had recovered by next day. No pathogens were isolated from the food, but the beans contained an abnormally high concentration of the lectin phytohaemagglutinin. 1 Lectins are carbohydrate binding proteins present in most plants, especially seeds and tubers like cereals, potatoes, and beans. Until recently their main use was as histology and blood transfusion reagents, but in the past two decades we have realised that many lectins are (a) toxic, inflammatory, or both; (b) resistant to cooking and digestive enzymes; and (c) present in much of our food. 2 It is thus no surprise that they sometimes cause "food poisoning." But the really disturbing finding came with the discovery in 1989  that some food lectins get past the gut wall and deposit themselves in distant organs. 3 4 So do they cause real life diseases?

This is no academic question be cause diet is one part of the environment that is manipulable and be cause lectins have excellent anti dotes, at least in vitro. Be cause of their precise carbohydrate specificities, lectins can be blocked by simple sugars and oligosaccharides. Wheat lectin, for example, is blocked by the sugar N-acetyl glucosamine and its polymers. 5 These natural compounds are potentially exploitable as drugs should lectin induced diseases be identified.

Wheat gliadin, which causes coeliac disease, contains a lectin like substance that binds to human intestinal mucosa, 6 and this has been debated as the "coeliac disease toxin" for over 20 years. 7 But coeliac disease is already managed by gluten avoidance, so nothing would change were the lectin hypothesis proved. On the other hand, wheat lectin also binds to glomerular capillary walls, mesangial cells, and tubules of human kidney and (in rodents) binds IgA and induces IgA mesangial deposits. This suggests that in humans IgA nephropathy might be caused or aggravated by wheat lectin; indeed a trial of gluten avoidance in children with this disease reported reduced proteinuria and immune complex levels. 8

Of particular interest is the implication for autoimmune diseases. Lectins stimulate class II HLA antigens on cells that do not normally display them, such as pancreatic islet and thyroid cells. 9 The islet cell determinant to which cytotoxic autoantibodies bind in insulin dependent diabetes mellitus is the disaccharide N-acetyl lactosamine, 10 which must bind tomato lectin if present and probably also the lectins of wheat, potato, and peanuts. This would result in islet cells expressing both class II HLA antigens and foreign antigen together a sitting duck for autoimmune attack. Certain foods (wheat, soya) are indeed diabetogenic in genetically susceptible mice. 11 Insulin dependent diabetes therefore is another potential lectin disease and could possibly be prevented by prophylactic oligosaccharides.

Another suspect lectin disease is rheumatoid arthritis. The normal human IgG molecule possesses carbohydrate side chains, which terminate with galactose. In rheumatoid arthritis much of the galactose is missing, so that the subterminal sugar N-acetyl glucosamine is exposed instead. These deficient IgG molecules feature strongly in the circulating immune complexes that cause fever and symptoms. 12 In diet responsive rheumatoid arthritis one of the commonest trigger foods is wheat, and wheat lectin is specific for N-acetyl glucosamine the sugar that is normally hidden but exposed in rheumatoid arthritis. This suggests that N-acetyl glucosamine oligomers such as chitotetraose (derived from the chitin that forms crustacean shells) might be an effective treatment for diet associated rheumatoid arthritis. Interestingly, the health food trade has already siezed on N-acetyl glucosamine as an antiarthritic supplement. 13

Among the effects observed in the small intestine of lectin fed rodents is stripping away of the mucous coat to expose naked mucosa and overgrowth of the mucosa by abnormal bacteria and protozoa. 14 Lectins also cause discharge of histamine from gastric mast cells, 15 which stimulates acid secretion. So the three main pathogenic factors for peptic ulcer acid stimulation, failure of the mucous defence layer, and abnormal bacterial proliferation (Helicobacter pylori) are all theoretically linked to lectins. If true, blocking these effects by oligosaccharides would represent an attractive and more physiological treatment for peptic ulcer than suppressing stomach acid. The mucus stripping effect of lectins 16 also offers an explanation for the anec dotal finding of many allergists that a "stone age diet," which eliminates most starchy foods and therefore most lectins, protects against common upper respiratory viral infections: without lectins in the throat the nasopharyngeal mucus lining would be more effective as a barrier to viruses.

But if we all eat lectins, why don't we all get insulin dependent diabetes, rheumatoid arthritis, IgA nephropathy, and peptic ulcers? Partly be cause of biological variation in the glycoconjugates that coat our cells and partly be cause these are protected behind a fine screen of sialic acid molecules, attached to the glycoprotein tips. 10 We should be safe. But the sialic acid molecules can be stripped off by the enzyme neuraminidase, present in several micro-organisms such as influenzaviruses and streptococci. This may explain why diabetes and rheumatoid arthritis tend to occur as sequelae of infections. This facilitation of lectins by micro-organisms throws a new light on postinfectious diseases and makes the folklore cure of fasting during a fever seem sensible.

Alternative medicine popularisers are already publishing articles about dietary lectins, 17 often with more enthusiasm than caution, so patients are starting to ask about them and doctors need to be armed with facts. The same comment applies to entrepreneurs at the opposite end of the commercial spectrum. Many lectins are powerful allergens, and prohevein, the principal allergen of rubber latex, is one. It has been engineered into transgenic tomatoes for its fungistatic properties, 18 so we can expect an outbreak of tomato allergy in the near future among latex sensitive individuals. Dr Arpad Pusztai lost his job for publicising concerns of this type (20 February, p 483).

Lectin s in the United States diet: a survey of lectins in commonly consumed foods and a review of the literature
MS Nachbar and JD Oppenheim
American Journal of Clinical Nutrition, Vol 33, 2338-2345

Abstract: Plant lectins or phytohemagglutinins possess potent in vivo biological activities. Some, primarily of the family Leguminosae, have been shown to have deleterious nutritional effects. Little information exists, however, regarding the prevalence of lectins or the specific foods that contain lectins in the United States diet. In the present study the edible parts of 29 of 88 foods tested, including common salad ingredients, fresh fruits, roasted nuts, and processed cereals were found to possess significant lectin-like activity as assessed by hemagglutination and bacterial agglutination assays. Based on this survey and a review of the literature we conclude that dietary exposure to plant lectins is widespread. The spectrum of nutritional consequences of such exposure remains to be determined.

Abstract: To investigate the role of dietary components in immunoglobulin A mesangial nephropathy (IgAGN), this study focused on gliadin, based on the reported association between coeliac disease and IgAGN as well as the pilot observation that a gluten-free diet was able to reduce the levels of circulating IgA immune complexes (IgAIC). IgA mesangial deposits in mice were induced by oral immunization with gliadin and in rats by inducing alcoholic liver cirrhosis, which increased the levels of IgA against dietary antigens (Ag). Gliadin was able to bind to cultured mesangial cells by a lectinic bond, which was reversed by competitive sugars. Binding increased mesangial cell tumor necrosis factor synthesis and decreased prostaglandin E2 production. Several gluten lectinic fractions modulate leukocyte oxidative metabolism, cytotoxicity, and chemotaxis. In IgAGN patients, serum IgA to dietary Ag were sporadically positive and IgAIC containing IgA to dietary components were significantly increased. The affinity of serum IgA to various lectins was increased in some patients. Conversely, no substantial deposition in renal tissue of dietary Ags was observed by immunofluorescence. A gluten-free diet, given to IgAGN patients with high levels of circulating IgAIC and positive antigliadin IgA, was followed by a decrease in the mean levels of both IgAIC and IgA to various dietary Ag, parallel to a reduction in proteinuria. These data suggest that dietary components, such as Ag or lectins, may play a role in IgAGN by promoting IgAIC formation and perhaps favoring mesangial localization via lectinic interactions.

Dietary lectins can stimulate pancreatic growth in the rat.
Kelsall A; FitzGerald AJ; Howard CV; Evans RC; Singh R; Rhodes JM; Goodlad RA
Int J Exp Pathol; 83(4):203-8, 2002 Aug

Abstract: Lectins are proteins or glycoproteins of nonimmune origin, which bind specifically to carbohydrate structures. They are widespread in the human diet, and many are resistant to digestion. High doses of lectins have been shown to stimulate intestinal and pancreatic growth. The aim of the present study was to investigate the long-term actions of low doses of lectins on the rat intestine and pancreas. A long-term carcinogenesis study was performed using low levels (40 micro g/rat/day) of peanut (PNA) or mushroom lectin (ABA) which bind to O-linked (mucin-type) oligosaccharides in the gut. While this was primarily designed as a colon carcinogenesis study, the pancreas was also investigated. No significant changes in colon carcinogenesis were seen, however, the colons were slightly heavier in the lectin treated groups. The weight of the pancreas was significantly greater (by 18 and 23%) in both lectin treated groups (P < 0.03/0.001). The weights of the acini and septal tissue were also increased by 39-46% in PNA and ABA fed animals, respectively (P < 0.002); there was no significant change in the endocrine pancreas. In conclusion, long-term feeding of low doses of lectin can influence pancreatic growth, and this trophic action may have potential adverse implications for the development of pancreatic cancer in humans.

Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulatedintestinal fluid-a comparative study.
Fu TJ; Abbott UR; Hatzos C
J Agric Food Chem; 50(24):7154-60, 2002 Nov 20.

Abstract: Information on the comparative digestibility of food allergens and nonallergenic proteins is crucial when stability to digestion is to be used as a criterion to assess the allergenic potential of novel proteins. In this work, we compared the digestive stability of a number of food allergens and proteins of unproven allergenicity and examined whether allergens possess a higher stability than nonallergenic proteins of similar cellular functions, and whether there is a correlation between protein digestibility and allergenicity. The stability of groups of storage proteins, plant lectins, contractile proteins, and enzymes, both allergens and proteins with unproven allergenicity, in a standard simulated gastric fluid and a standard simulated intestinal fluid was measured. Food allergens were not necessarily more resistant to digestion than nonallergenic proteins. There was not a clear relationship between digestibility measured in vitro and protein allergenicity.

Diet and colorectal cancer: an investigation of the lectin/galactose hypothesis.
Evans RC; Fear S; Ashby D; Hackett A; Williams E; Van Der Vliet M; Dunstan FD; Rhodes JM
Gastroenterology; 122(7):1784-92, 2002 Jun.

Abstract: BACKGROUND & AIMS: Mucosal expression of terminal unsubstituted galactose is increased in colon cancer and precancer and allows interaction with mitogenic galactose-binding lectins of dietary or microbial origin. This study tests the hypothesis that galactose, which is variably plentiful in fruit and vegetable but not cereal fibers, might prevent cancer by binding and inhibiting such lectins. METHODS: Colorectal cancer cases (512) and controls (512) were matched for age, sex, primary care practitioner, and postal code. A 160-item food-frequency questionnaire was used to estimate their usual pre-illness (6 months previous) diet, aspirin intake, and exercise. RESULTS: Neither cereal fiber nor fruit and vegetable fiber were protective when assessed by univariate analysis, whereas dietary fiber galactose content showed a dose-related protective effect (odds ratio [OR] highest quartile/lowest quartile, 0.67; confidence interval [CI], 0.47-0.95) that remained protective when adjusted for energy, red meat, alcohol, calcium, protein and fat intake, regular aspirin usage, and exercise. Intake of nonlegume green vegetables, assessed because of the high lectin content of legumes, was also protective (OR, 0.54; CI, 0.35-0.81), but this was not independent of galactose. Protective effects of exercise and regular daily aspirin consumption and harmful effects of high energy consumption and high red meat intake were confirmed. CONCLUSIONS: The protective effect of fruit and vegetable fibers may be related to their galactose content. This provides further evidence that the association between diet and colon cancer is mediated via specific food components and may explain the discrepant results of studies addressing the protective effects of fiber.

Dietary wheat germ agglutinin modulates ovalbumin-induced immune responses in Brown Norway rats.
Watzl B; Neudecker C; Hänsch GM; Rechkemmer G; Pool-Zobel BL
Br J Nutr; 85(4):483-90, 2001 Apr

Abstract: The trend towards an increased consumption of minimally processed plant food results in a higher intake of non-nutritive compounds such as lectins. Lectins are typically globular proteins that are resistant to digestion in the gastrointestinal tract. They affect the integrity of the intestinal epithelium and the absorption of dietary antigens, and induce the release of allergic mediators from mast cells in vitro. Based on this information we have studied whether dietary wheat germ agglutinin (WGA) could be involved in triggering food allergies. Brown Norway rats were immunized intraperitoneally using ovalbumin (OVA; 10 microg/rat) and 10 d later treated for five consecutive days with WGA (10 mg/rat per d) administered intragastrically. Rats were then orally challenged with OVA (100 microg/rat) 1 h after the last WGA application, and blood was collected 4 h later. Immunological responses (anti-OVA immunoglobulins E and G, rat mast cell protease II, interferon-gamma and lymphocyte proliferation) were measured and lymphocyte subpopulations were determined. In immunized rats WGA treatment resulted in increased serum rat mast cell protease II concentrations (pre-challenge 0.26 (SE 0.08) microg/ml, post-challenge 0.49 (SE 0.09) microg/ml; P < 0.01) 4 h after the OVA challenge. After 5 d serum concentrations of anti-OVA immunoglobulin E were significantly increased only in the immunized controls (absorbance at 405 nm on days 14 and 19 was 0.09 (SE 0.008) and 0.24 (SE 0.046) respectively; P = 0.02), while in WGA-treated rats no significant increase was seen (0.08 (SE 0.004) and 0.15 (SE 0.037 respectively; P = 0.14). CD4+ : CD8+ T lymphocytes in the spleen was significantly increased at this time (OVA 1.1 (SD 0.2), 1.4 (sd 0.1), P < 0.05). The treatment did not impair the proliferation and interferon-gamma production of mesenteric lymphocytes. In conclusion, these data suggest that high dietary intake of lectins such as WGA may affect the allergic response towards oral antigens in the gut-associated lymphoid tissue.

Opposite effects on human colon cancer cell proliferation of two dietary Thomsen-Friedenreich antigen-binding lectins.
Yu LG; Milton JD; Fernig DG; Rhodes JM
J Cell Physiol; 186(2):282-7, 2001 Feb.

Abstract: Increased cell surface expression of the Thomsen-Friedenreich antigen (TF antigen, Galbeta1-3GalNAcalpha-) is a common feature in malignant and pre-malignant epithelia. Our previous studies have shown that dietary TF-binding lectins from peanut (Arachis hypogea) and edible mushroom (Agaricus bisporus) produce marked but different effects on human intestinal epithelial cell proliferation. This study investigates the proliferative effects of the other two known dietary TF-binding lectins: jacalin (Artocarpus integrifolia, JAC) and amaranth lectin (Amaranthus caudatus, ACA). JAC produced dose-dependent and non-cytotoxic inhibition of proliferation in HT29 human colon cancer cells with maximal effects of 46 +/- 4% at 20 microg/ml, whereas ACA produced dose-dependent stimulation of proliferation with maximal effects of 22 +/- 3% at 20 microg/ml when assessed both by incorporation of [3H]thymidine into DNA and by cell counting. The lectin-mediated effects were inhibitable by the presence of appropriate Galbeta1-3GalNAc-expressing glycoproteins but differences existed between JAC and ACA in their patterns of inhibition by such substances. Ligand binding equilibrium studies using iodinated lectins revealed different Kd of the two lectins for HT29 cell surface glycoproteins. Lectin blots of cell membrane extracts showed different binding patterns in all the four TF-binding lectins. These results provide further evidence that dietary TF-binding lectins can have marked effects on the proliferation of human malignant gastro-intestinal epithelial cells and hence may play a role in intestinal cancer development, and also show that the biological effects of dietary lectins cannot be predicted solely from their carbohydrate binding properties.

Abstract: Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice versa, the nature of this relationship remains elusive. In the present review, we provide evidence for how the interaction of dietary lectins with enterocytes and lymphocytes may facilitate the translocation of both dietary and gut-derived pathogenic antigens to peripheral tissues, which in turn causes persistent peripheral antigenic stimulation. In genetically susceptible individuals, this antigenic stimulation may ultimately result in the expression of overt rheumatoid arthritis (RA) via molecular mimicry, a process whereby foreign peptides, similar in structure to endogenous peptides, may cause antibodies or T-lymphocytes to cross-react with both foreign and endogenous peptides and thereby break immunological tolerance. By eliminating dietary elements, particularly lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RA.

Decreased levels of heat shock proteins in gut epithelial cells after exposure to plant lectins.
Ovelgönne JH; Koninkx JF; Pusztai A; Bardocz S; Kok W; Ewen SW; Hendriks HG; van Dijk JE
Gut; 46(5):679-87, 2000 May.

Abstract: BACKGROUND: The enterocytes of the intestinal epithelium are regularly exposed to potentially harmful substances of dietary origin, such as lectins. Expression of heat shock proteins (HSPs) by this epithelium may be part of a protective mechanism developed by intestinal epithelial cells to deal with noxious components in the intestinal lumen. AIM: To investigate if the lectins PHA, a lectin from kidney beans (Phaseolus vulgaris) and WGA, a lectin from wheat germ (Triticum aestivum) could modify the heat shock response in gut epithelial cells and to establish the extent of this effect. METHODS: Jejunal tissue sections from PHA and WGA fed rats were screened for expression of HSP70, HSP72, and HSP90 using monoclonal antibodies. Differentiated Caco-2 cells, the in vitro counterpart of villus enterocytes, were exposed to 100 microg/ml of PHA-E(4) or WGA for 48 hours and investigated for changes in DNA and protein synthesis by double labelling with [2-(14)C]thymidine and L-[methyl-(3)H]methionine. The relative concentrations of HSP60, HSP70, HSP72, and HSP90 and binding protein (BiP) in these cells exposed to lectins were analysed by polyacrylamide gel electrophoresis and immunoblotting. To establish if lectin exposed differentiated Caco-2 cells were still capable of producing a heat shock response, these cells received a heat shock (40 degrees C, 41 degrees C, and 42 degrees C) for one hour and were allowed to recover for six hours at 37 degrees C. During heat shock and recovery periods, lectin exposure was continued. RESULTS: Constitutive levels of HSPs were measured in the intestinal cells of lactalbumin fed (control) rats, as may be expected from the function of this tissue. However, in PHA and WGA fed rats a marked decline in the binding of antibodies against several HSPs to the intestinal epithelium was found. These results were confirmed by in vitro experiments using differentiated Caco-2 cells exposed to PHA-E(4) and WGA. However, after exposure to lectins, these cells were still capable of heat induced heat shock protein synthesis, and total protein synthesis was not impaired indicating specific inhibition of HSP synthesis in non-stressed cells. CONCLUSIONS: We conclude that PHA and WGA decrease levels of stress proteins in rat gut and enterocyte-like Caco-2 cells, leaving these cells less well protected against the potentially harmful content of the gut lumen.

Dietary soya beans and kidney beans stimulate secretion of cholecystokinin and pancreatic digestive enzymes in 400-day-old Hooded-Lister rats but only soya beans induce growth of the pancreas.
Grant G; Alonso R; Edwards JE; Murray S
Pancreas; 20(3):305-12, 2000 Apr.

Abstract: The effects of age on cholecystokinin (CCK) release, pancreatic enzyme secretion, and growth of the pancreas mediated by dietary kidney beans or soya beans were evaluated in trials with 30-, 90-, 250-, and 400-day-old rats. Soya beans increased blood CCK and caused hypersecretion of digestive enzymes and rapid pancreatic growth in all rats. Kidney beans also elevated circulating CCK and stimulated enzyme secretion. However, with 90-, 250-, and 400-day-old rats, the secretory responses were attenuated. Furthermore, kidney beans did not induce pancreatic growth in 250- and 400-day-old rats.

Immunological aspects of the potential role of dietary carbohydrates and lectins in human health .
Kilpatrick DC
Eur J Nutr; 38(3):107-17, 1999 Jun.

Abstract: BACKGROUND: Little is known regarding the immunobiology of dietary carbohydrate intake and its relevance to human health, although foodstuffs contain many simple and complex carbohydrates. SYNOPSIS: Lectins, immunoglobulins, viruses, bacteria and host cells interact with each other forming a delicate equilibrium within the alimentary canal which may be perturbed by saccharide intake. The ways in which these components may interact at different sites within the alimentary canal are discussed, as are the possible influences on mucosal immunity and the induction of oral tolerance. The possible systemic influences of absorbed saccharides at loci remote from the gut are considered in terms of inhibition of dietary and endogenous lectins, inhibition of bacterial attachment, and alteration of leukocyte homing behaviour. Finally, possible means by which dietary carbohydrates might modify various specific diseases are considered. CONCLUSIONS: It is probable that dietary carbohydrates can alter the equilibria between lectins, secretory IgA and micro-organisms in the alimentary canal, and this consideration could be exploited to promote health. The possible effects of dietary saccharides on allergy/oral tolerance or on recognition events at gut-remote sites warrant further investigation.

Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils.
Haas H; Falcone FH; Schramm G; Haisch K; Gibbs BF; Klaucke J; Pöppelmann M; Becker WM; Gabius HJ; Schlaak M
Eur J Immunol; 29(3):918-27, 1999 Mar.

Abstract: Dietary lectins, present in beans and other edible plant products, pose a potential threat to consumers due to their capacity to induce histamine release from basophils. In this study, we analyzed the capacity of 16 common, in particular dietary, lectins to induce human basophils to secrete IL-4 and IL-13, the key promoters of Th2 responses and IgE synthesis. Several of the lectins, especially concanavalin A, lentil lectin, phytohemagglutinin, Pisum sativum agglutinin and Sambucus nigra agglutinin, triggered basophils to release IL-4 at concentrations of up to 1 ng/10(6) basophils. Lectins with high IL-4-inducing capacity also stimulated the release of IL-13 and histamine. Lectin-induced IL-4 and IL-13 release reached a maximum after 4-6 h and more than 18 h, respectively. Affinoblotting revealed that lectins with the capacity to induce mediator release bind to IgE, suggesting IgE binding as initial step of signal generation. In conclusion, several dietary lectins can trigger human basophils to release IL-4 and IL-13. Since lectins can enter the circulation after oral uptake, they might play a role in inducing the so-called early IL-4 required to switch the immune response towards a Th2 response and type I allergy.

Modifications to physicochemical and nutritional properties of hard-To-cook beans (Phaseolus vulgaris L.) by extrusion cooking.
Martín-Cabrejas MA; Jaime L; Karanja C; Downie AJ; Parker ML; Lopez-Andreu FJ; Maina G; Esteban RM; Smith AC; Waldron KW
J Agric Food Chem; 47(3):1174-82, 1999 Mar.

Abstract: The objective of this work was to evaluate extrusion cooking as a means to improve the nutritional properties of Phaseolus vulgaris L. that had been stored either at 42 degrees C and 80% relative humidity for 6 weeks or for periods >1 year in cereal stores in tropical conditions. Storage under these conditions resulted in an increase in cooking time increased (7.7- and 12-fold, respectively) as a result of development of the hard-to-cook (HTC) defect. Single-screw extrusion of the milled beans was carried out at four barrel temperatures and two moisture contents. The extrudate bulk density and water solubility index decreased with increasing temperature, whereas the water absorption index increased due to the higher proportion of gelatinized starch in the extruded samples. Both fresh and HTC beans contained nutritionally significant amounts of lectins, trypsin, and alpha-amylase inhibitors, which were mostly inactivated by extrusion. Extrusion also caused a considerable redistribution of insoluble dietary fiber to soluble, although the total dietary fiber content was not affected. Changes in solubility involved pectic polysaccharides, arabinose and uronic acids being the main sugars involved. Stored beans subjected to extrusion cooking showed physical and chemical characteristics similar to those of extrudates from fresh beans.

Relative importance of phytohemagglutinin (lectin) and trypsin-chymotrypsin inhibitor on bean (Phaseolus vulgaris L) protein absorption and utilization by the rat.
Carvalho MR; Sgarbieri VC
J Nutr Sci Vitaminol (Tokyo); 44(5):685-96, 1998 Oct.

Abstract: The main objective of this work was to perform a comparative study of the antinutritional and/or toxic properties of phytohemagglutinin and trypsin-chymotrypsin inhibitor extracted from the seed of a commercial cultivar of edible bean used in Brazil. Bean proteins were extracted in acidic salt solution and fractionated by dialysis and centrifugation, then freeze-dried. The total freeze-dried bean extract and the globulin or albumin protein fraction were resuspended in distilled water and heated (100 degrees C, 30 min) for inactivation of hemagglutinin. Diets were prepared with unheated bean protein fractions and heated ones (100% trypsin inhibitor activity, but 0% phytohemagglutinin activity). As a result, the inhibition of growth and poor dietary protein utilization were observed in rats fed diets containing unheated bean protein fractions, but not in rats fed diets containing heated fractions. It was thus assumed that phytohemagglutinin is the main antinutritional and toxic factor that in dry bean (Phaseolus) protein and that trypsin inhibitor (Bowman-Birk type) did not interfere with rat growth.

Cellular immune responses to beta casein: elevated in but not specific for individuals with Type I diabetes mellitus.
Ellis TM; Ottendorfer E; Jodoin E; Salisbury PJ; She JX; Schatz DA; Atkinson MA
Diabetologia; 41(6):731-5, 1998 Jun.

Abstract: Elevated cellular immune responses against the cows' milk protein beta casein have been reported in individuals with Type I diabetes mellitus, a finding supportive of the concept that cows' milk consumption may be causative for the disease. We analysed cellular immune reactivities against beta casein in newly-diagnosed Type I diabetic patients, their immediate autoantibody negative relatives, and unrelated healthy individuals in order to further elucidate the role of anti-beta casein immunity in the pathogenesis of Type I diabetes mellitus. Peripheral blood mononuclear cells were stimulated in vitro with various concentrations of three different beta casein preparations, control antigens (tetanus toxoid, mumps extract) and a mitogen (phytohemagglutinin). The frequency and/or mean simulation index of cellular proliferation against two of the beta casein preparations at high antigen concentrations (i.e. 10 or 50 microg/ml) were significantly higher in newly-diagnosed Type I diabetic subjects compared with autoantibody negative healthy control subjects. However, reactivities against beta casein in the Type I diabetic probands and their autoantibody negative relatives, individuals with a very low-rate of disease development, were almost identical. Cellular immune reactivities to other antigens were similar between the subject groups. In addition to indicating the need for appropriately matched subject populations (e.g. human leukocyte antigen (HLA) matched relatives) when analysing cellular immune responses, these findings support our previous contention that individuals genetically prone to autoimmunity may be deficient in forming tolerance to dietary antigens. However, the significance of anti-beta casein immunity as a specific causative factor in the pathogenesis of Type I diabetes mellitus remains unclear.

Peanut ingestion increases rectal proliferation in individuals with mucosal expression of peanut lectin receptor.
Ryder SD; Jacyna MR; Levi AJ; Rizzi PM; Rhodes JM
Gastroenterology; 114(1):44-9, 1998 Jan

Abstract: The Thomsen-Friedenreich blood group antigen (galactose beta 1,3-N-acetyl galactosamine alpha-) acts as an oncofetal antigen in the colonic epithelium, with low expression in normal adult epithelia but increasing to fetal levels of expression in hyperplasia or malignancy. Peanut lectin is one of the commonest dietary lectins that binds this antigen. The aim of this study was to determine whether peanut ingestion can alter rectal epithelial proliferation. METHODS: Thirty-six patients with normal colonic mucosa consumed 100 g of peanuts each day for 5 days. Rectal mitotic index was measured before and after ingestion, and changes in proliferation were correlated with immunohistochemical detection of lectin receptor expression by colonocytes and fecal lectin activity as measured by hemagglutination assay. RESULTS: Peanut ingestion caused a 41% increase in rectal mucosal proliferation in individuals with macroscopically normal mucosa who express TF antigen in their rectal mucosae (10 of 36 patients studied). The proliferative response correlated with fecal hemagglutinating activity, and peanut lectin could be shown immunohistochemically within the rectal mucosa. CONCLUSIONS: The common expression of galactose beta 1,3-N-acetyl galactosamine alpha- by hyperplastic and neoplastic epithelia may therefore be functionally important because it allows interaction with mitogenic dietary lectins. This could be an important mechanism for the association between diet and colorectal cancer.

Stimulation of proliferation in human colon cancer cells by human monoclonal antibodies against the TF antigen (galactose beta1-3 N-acetyl-galactosamine)
Yu LG; Jansson B; Fernig DG; Milton JD; Smith JA; Gerasimenko OV; Jones M; Rhodes JM
Int J Cancer; 73(3):424-31, 1997 Nov 4.

Abstract: In many tissues, the TF (Thomsen-Friedenreich) blood group antigen (Galbeta1-3GalNAc alpha-) behaves as an onco-foetal carbohydrate antigen, showing increased expression in malignancy and hyperplasia. Dietary lectins which bind the TF antigen have marked effects on proliferation of epithelial cells without cytotoxicity. This led us to speculate that anti-TF antibodies, including those that naturally occur in humans, might have similar effects. Five anti-TF antibodies, TF2 (human), TF5 (human), 5A8 (mouse), 8D8 (mouse) and BM22 (mouse), but not TFI (human) or 49H.9 (mouse), showed marked dose-dependent stimulation (95-192%) of [3H]thymidine incorporation by HT29 human colon cancer cells. Similar stimulation of proliferation of HT29 cells by these monoclonal antibodies (MAbs) was found when cell count assessment was used. Antibody-stimulated proliferation was inhibited by co-incubation with glycoproteins expressing Galbeta1-3GalNAc alpha- (asialo glycophorin or [Galbeta1-3GalNAc alpha-O-p-aminophenyl]n-human serum albumin). A proliferative effect of these antibodies was also demonstrated on human colon cancer cell lines LS174T and HT29-MTX but not on Caco-2 cells. Although immunoblotting showed similar binding patterns of all the antibodies on HT29 cell membrane extracts, there was little correlation between cell surface binding assessed by immunofluorescence and proliferative response, and internalization of the biotinylated antibody TF5 was demonstrated by confocal microscopy. Our results provide further evidence that cell surface glycoproteins which express TF antigen may play an important role in the regulation of cell proliferation and also suggest that human anti-TF antibodies may have proliferative effects on cells which express TF antigen.

Effects of a panel of dietary lectins on cholecystokinin release in rats.
Jordinson M; Playford RJ; Calam J
Am J Physiol; 273(4 Pt 1):G946-50, 1997 Oct.

Abstract: We previously showed that soybean lectin (SBL) releases cholecystokinin (CCK) and have now asked whether other dietary lectins have this effect and if extracellular calcium is involved. Lectins and vehicle were first infused into the duodenum of anesthetized rats. The CCK response to vehicle was 3.1 +/- 0.6 pmol/l (P < 0.05 vs. basal). SBL and peanut lectin (PNL) (84 microg/ml) significantly increased plasma CCK concentrations from 2.0 +/- 0.4 pmol/l to a maximum of 8.4 +/- 0.5 pmol/l (P < 0.01 vs. vehicle, mean +/- SE) and from 1.9 +/- 0.5 to 7.0 +/- 0.6 pmol/l (P < 0.05 vs. vehicle, mean +/- SE), respectively. Wheat germ lectin (WGL) (840 microg) also increased plasma CCK levels from 1.5 +/- 0.3 pmol/l to a maximum of 9.7 +/- 1.3 pmol/l (P < 0.05 vs. vehicle, mean +/- SE). Corresponding increases in pancreatic protein output occurred. Broad bean lectin (BBL) had no effect on either parameter. Dose-dependent responses were seen with SBL, PNL, and WGL (1, 10, and 100 microg/ml) in perifused rat intestinal cells. These responses were abolished in calcium-free medium and in the presence of the competing sugars of the lectins. Therefore, SBL, PNL, and WGL, which bind to motifs including N-acetyl-D-galactosamine, galactose, and N-acetylglucosamine, respectively, released CCK, but BBL, which binds to mannose and glucose, did not. Ingestion of lectins may have major CCK-mediated effects on gastrointestinal function and growth.

In vitro influence of Phaseolus vulgaris, Griffonia simplicifolia, concanavalin A, wheat germ, and peanut agglutinins on HCT-15, LoVo, and SW837 human colorectal cancer cell growth.
Kiss R; Camby I; Duckworth C; De Decker R; Salmon I; Pasteels JL; Danguy A; Yeaton P
Gut; 40(2):253-61, 1997 Feb.

Abstract: Compared with normal colonic mucosa, lectin receptor expression is increased in hyperplastic and neoplastic tissues; some lectins have been shown to influence human colonic epithelial cell proliferation. The aim was to assess further the influence of five lectins (Phaseolus vulgaris (PNA), Griffonia simplicifolia (GSA), concanavalin A (Con A), wheat germ (WGA), and peanut (PHA-L) agglutinins) on cellular growth in three human colorectal cancer cell lines (LoVo, HCT-15 and SW837). METHODS: Cells were cultured in four lectin concentrations (0.1, 1.0, 10, and 100 micrograms/ml) and growth assessed at days 2, 3, 5, and 7. The experiments were performed in media supplemented with either 1% or 10% fetal calf serum (FCS). Growth was assessed using the MTT (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) colorimetric assay. RESULTS: Growth in each cell line was greatly affected by at least two of the lectins tested. There was some variation in the effect of a given lectin on different cell lines. Lectin effects showed a dose-response and the greatest effects generally resulted from the highest concentrations at the longest culture time. WGA and Con A induced large effects in all cell lines; the effects of Con A were partly blocked by the higher concentration of FCS. PNA had modest and uniform stimulatory effects overall. The effects of GSA and PHA-L varied between cell lines. CONCLUSIONS: The lectins studied all have the potential to affect colonic cancer growth in vitro. Many dietary lectins are resistant to digestion and may have important effects in vitro but the definition of their role in human colonic cancer biology must take into account the variability in lectin response.

Characteristics and consequences of interactions of lectins with the intestinal mucosa.
Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK.
Arch Latinoam Nutr; 44(4 Suppl 1):10S-15S, 1996 Dec.

Abstract: Lectins are essential and omnipresent plant (glyco)protein constituents and are ingested daily in appreciable amounts by both humans and animals. As they are biologically highly active, their consumption may have serious consequences for metabolism and health. Lectins, by virtue of their stability and specific recognition and binding by gut brush border epithelial cells, are potent exogenous metabolic growth signals for the gut and the body. As a result of their binding to surface glycans they may affect the turnover and loss of epithelial cells, damage the luminal membranes of the epithelium, interfere with their digestive/absorptive activities, stimulate shifts in the bacterial flora and modulate the immune state of the digestive tract. When eaten in relatively large quantities, these lectins have appreciable antinutritive effects for the consumers. In contrast, lectins which are not bound by the mucosa usually induce little or no harmful effects. From recent studies it is now realized that in addition to the major and sometimes dramatic effects of lectins on the gut which are mediated through their binding to pre-existing membrane glycosyl groups, lectins as metabolic signals, can also radically alter the state of glycosylation of the gut epithelium and thus further amplify their potent physiological effects. Accordingly, with the judicious use of dietary lectins it is now possible "to engineer' the digestive tract for improved physiological performance and bacterial ecology.

Response of intestinal transglutaminase activity to dietary phytohaemagglutinin.
Sessa A; Tunici P; Rabellotti E; Bardocz S; Grant G; Pusztai A; Perin A
Biochim Biophys Acta; 1314(1-2):66-70, 1996 Nov 8.

Abstract: The behaviour of the activity of tissue transglutaminase, a calcium-dependent enzyme, and the levels of polyamines which are physiological substrates for the enzyme, were studied in rat small intestine induced to grow by lectin phytohaemagglutinin. Transglutaminase activity greatly increased in the homogenates and the cytosolic fractions of the intestinal mucosa of lectin-treated rats compared to that of untreated animals. The measurement of enzyme activity in the presence of monodansylcadaverine, a competitive inhibitor of transglutaminase, testified that the assayed enzyme activity was authentic transglutaminase. As regards polyamines, the level of spermine did not change, whereas putrescine and spermidine contents were enhanced. The activation of transglutaminase, which was probably due to Ca2+ accumulation in enterocytes, could have a role in maintaining enterocyte adhesion and intestinal cell homeostasis, and/or repairing lectin-induced damages of microvilli of the gut epithelium.

Natural human antibodies to dietary lectins.
Tchernychev B; Wilchek M
FEBS Lett; 397(2-3):139-42, 1996 Nov 18.

Abstract: Natural antibodies to self and non-self proteins, including dietary proteins, are a significant part of the immune repertoire of humans. Antibodies to three structurally related legume lectins (Erythrina corallodendron lectin (ECorL), peanut agglutinin (PNA), and soybean agglutinin (SBA)) and to one cereal lectin (wheat germ agglutinin (WGA)) were purified by affinity chromatography from human sera and their binding specificity examined. The anti-SBA, anti-ECorL and anti-WGA antibodies exhibited high specificity, whereas the anti-PNA antibodies were polyreactive. Although the anti-WGA antibodies were highly specific for WGA, they also crossreacted slightly toward some other proteins. The anti-ECorL antibodies bound to native SBA, but the anti-SBA antibodies failed to bind to the native ECorL. Although the anti-SBA and anti-ECorL antibodies both exhibited specificity when interacting with native lectins, they bound to a wider range of denatured lectins, indicating a common or universal epitope which is recognized by many natural antibodies. Interestingly, the natural antibodies did not interfere with the agglutination properties of the lectins. These findings may provide a basis for studying the in vivo biological effects of anti-dietary protein antibodies, including those against carbohydrate-binding proteins.

Involvement of polyamines in pancreatic growth induced by dietary soyabean, lectin or trypsin inhibitors.
Grant G; Bardocz S; Brown DS; Watt WB; Stewart JC; Pusztai A
Biochem Soc Trans; 18(5):1009-10, 1990 Oct.

Effect of variable protein contents in diets containing Phaseolus vulgaris beans on performance, organ weights and blood variables in piglets, rats and chickens.
Huisman J; van der Poel AF; Mouwen JM; van Weerden EJ
Br J Nutr; 64(3):755-64, 1990 Nov.

Abstract: A comparison was made of the effects of antinutritional factors present in Phaseolus vulgaris on piglets, rats and chickens. Also the hypothesis of whether the negative effect on weight gain due to the inclusion of raw Phaseolus vulgaris in the diet can be attributed to an insufficient supply of amino acids was tested. Test diets containing 200 g raw Phaseolus beans/kg were balanced for digestible protein and amino acids; in one diet extra casein was incorporated. The main response criteria were live-weight gain and the weight of various organs including the intestine. Live-weight gain in piglets was markedly reduced during feeding 200 g raw Phaseolus vulgaris/kg in the diet, but not in rats and chickens. Addition of casein did not improve the weight gain of the piglets, indicating that a toxic factor was responsible for the reduced weight gain and not an insufficient supply of amino acids. The weights of the spleen and thymus were markedly reduced in the piglets when the diets with raw Phaseolus beans were given, but not in the rats and chickens. Additional supply of casein did not change this effect. Indications were found that when the supply of dietary protein is adequate there is no reduction in pancreas weight with raw Phaseolus beans as was observed in previous experiments. The weight of the intestine was increased in all three species due to feeding raw Phaseolus vulgaris.

Effects of a panel of dietary lectins on cholecystokinin release in rats.
Am J Physiol; 273(4 Pt 1):G946-50, 1997 Oct.

Abstract: We previously showed that soybean lectin (SBL) releases cholecystokinin (CCK) and have now asked whether other dietary lectins have this effect and if extracellular calcium is involved. Lectins and vehicle were first infused into the duodenum of anesthetized rats. The CCK response to vehicle was 3.1 +/- 0.6 pmol/l (P < 0.05 vs. basal). SBL and peanut lectin (PNL) (84 microg/ml) significantly increased plasma CCK concentrations from 2.0 +/- 0.4 pmol/l to a maximum of 8.4 +/- 0.5 pmol/l (P < 0.01 vs. vehicle, mean +/- SE) and from 1.9 +/- 0.5 to 7.0 +/- 0.6 pmol/l (P < 0.05 vs. vehicle, mean +/- SE), respectively. Wheat germ lectin (WGL) (840 microg) also increased plasma CCK levels from 1.5 +/- 0.3 pmol/l to a maximum of 9.7 +/- 1.3 pmol/l (P < 0.05 vs. vehicle, mean +/- SE). Corresponding increases in pancreatic protein output occurred. Broad bean lectin (BBL) had no effect on either parameter. Dose-dependent responses were seen with SBL, PNL, and WGL (1, 10, and 100 microg/ml) in perifused rat intestinal cells. These responses were abolished in calcium-free medium and in the presence of the competing sugars of the lectins. Therefore, SBL, PNL, and WGL, which bind to motifs including N-acetyl-D-galactosamine, galactose, and N-acetylglucosamine, respectively, released CCK, but BBL, which binds to mannose and glucose, did not. Ingestion of lectins may have major CCK-mediated effects on gastrointestinal function and growth.

Dietary soya beans and kidney beans stimulate secretion of cholecystokinin and pancreatic digestive enzymes in 400-day-old Hooded-Lister rats but only soya beans induce growth of the pancreas.
Pancreas; 20(3):305-12, 2000 Apr.

Abstract: The effects of age on cholecystokinin (CCK) release, pancreatic enzyme secretion, and growth of the pancreas mediated by dietary kidney beans or soya beans were evaluated in trials with 30-, 90-, 250-, and 400-day-old rats. Soya beans increased blood CCK and caused hypersecretion of digestive enzymes and rapid pancreatic growth in all rats. Kidney beans also elevated circulating CCK and stimulated enzyme secretion. However, with 90-, 250-, and 400-day-old rats, the secretory responses were attenuated. Furthermore, kidney beans did not induce pancreatic growth in 250- and 400-day-old rats.

Dietary lectins can stimulate pancreatic growth in the rat.
Int J Exp Pathol; 83(4):203-8, 2002 Aug

Abstract: Lectins are proteins or glycoproteins of nonimmune origin, which bind specifically to carbohydrate structures. They are widespread in the human diet, and many are resistant to digestion. High doses of lectins have been shown to stimulate intestinal and pancreatic growth. The aim of the present study was to investigate the long-term actions of low doses of lectins on the rat intestine and pancreas. A long-term carcinogenesis study was performed using low levels (40 micro g/rat/day) of peanut (PNA) or mushroom lectin (ABA) which bind to O-linked (mucin-type) oligosaccharides in the gut. While this was primarily designed as a colon carcinogenesis study, the pancreas was also investigated. No significant changes in colon carcinogenesis were seen, however, the colons were slightly heavier in the lectin treated groups. The weight of the pancreas was significantly greater (by 18 and 23%) in both lectin treated groups (P < 0.03/0.001). The weights of the acini and septal tissue were also increased by 39-46% in PNA and ABA fed animals, respectively (P < 0.002); there was no significant change in the endocrine pancreas. In conclusion, long-term feeding of low doses of lectin can influence pancreatic growth, and this trophic action may have potential adverse implications for the development of pancreatic cancer in humans.

Natural human antibodies to dietary lectins.
FEBS Lett; 397(2-3):139-42, 1996 Nov 18.

Abstract: Natural antibodies to self and non-self proteins, including dietary proteins, are a significant part of the immune repertoire of humans. Antibodies to three structurally related legume lectins (Erythrina corallodendron lectin (ECorL), peanut agglutinin (PNA), and soybean agglutinin (SBA)) and to one cereal lectin (wheat germ agglutinin (WGA)) were purified by affinity chromatography from human sera and their binding specificity examined. The anti-SBA, anti-ECorL and anti-WGA antibodies exhibited high specificity, whereas the anti-PNA antibodies were polyreactive. Although the anti-WGA antibodies were highly specific for WGA, they also crossreacted slightly toward some other proteins. The anti-ECorL antibodies bound to native SBA, but the anti-SBA antibodies failed to bind to the native ECorL. Although the anti-SBA and anti-ECorL antibodies both exhibited specificity when interacting with native lectins, they bound to a wider range of denatured lectins, indicating a common or universal epitope which is recognized by many natural antibodies. Interestingly, the natural antibodies did not interfere with the agglutination properties of the lectins. These findings may provide a basis for studying the in vivo biological effects of anti-dietary protein antibodies, including those against carbohydrate-binding proteins.

Characteristics and consequences of interactions of lectins with the intestinal mucosa.
Arch Latinoam Nutr; 44(4 Suppl 1):10S-15S, 1996 Dec.

Abstract: Lectins are essential and omnipresent plant (glyco)protein constituents and are ingested daily in appreciable amounts by both humans and animals. As they are biologically highly active, their consumption may have serious consequences for metabolism and health. Lectins, by virtue of their stability and specific recognition and binding by gut brush border epithelial cells, are potent exogenous metabolic growth signals for the gut and the body. As a result of their binding to surface glycans they may affect the turnover and loss of epithelial cells, damage the luminal membranes of the epithelium, interfere with their digestive/absorptive activities, stimulate shifts in the bacterial flora and modulate the immune state of the digestive tract. When eaten in relatively large quantities, these lectins have appreciable antinutritive effects for the consumers. In contrast, lectins which are not bound by the mucosa usually induce little or no harmful effects. From recent studies it is now realized that in addition to the major and sometimes dramatic effects of lectins on the gut which are mediated through their binding to pre-existing membrane glycosyl groups, lectins as metabolic signals, can also radically alter the state of glycosylation of the gut epithelium and thus further amplify their potent physiological effects. Accordingly, with the judicious use of dietary lectins it is now possible "to engineer' the digestive tract for improved physiological performance and bacterial ecology.

Identification of the dietary lectin, wheat germ agglutinin, in human intestinal contents.
Gastroenterology; 75(2):236-9, 1978 Aug.

Abstract: Plant lectins are known to have potent biological actions of normal and malignant cells. High concentrations of these lectins are present in many types of high residue diets. The specific binding of wheat germ agglutinin, a dietary plant lectin, to N-acetylglucosamine was used as the basis for purification of this lectin by biospecific chitin affinity chromatography. Subsequently, methods were developed for the extraction, purification, and identification of wheat germ agglutinin from fecal samples. Biologically intact wheat germ agglutinin was detected in ileostomy effluent and fecal collections from human subjects consuming a diet containing wheat germ. These studies demonstrate that wheat germ agglutinin can traverse the human small intestine intact. It is feasible that orally ingested wheat germ agglutinin and other plant lectins which interact with a wide variety of cell membranes may alter intestinal epithelial or bacterial cell function in the human bowel.

Lectin s in the United States diet: a survey of lectins in commonly consumed foods and a review of the literature.
American Journal of Clinical Nutrition, Vol 33, 2338-2345, 1980.

Plant lectins or phytohemagglutinins possess potent in vivo biological activities. Some, primarily of the family Leguminosae, have been shown to have deleterious nutritional effects. Little information exists, however, regarding the prevalence of lectins or the specific foods that contain lectins in the United States diet. In the present study the edible parts of 29 of 88 foods tested, including common salad ingredients, fresh fruits, roasted nuts, and processed cereals were found to possess significant lectin-like activity as assessed by hemagglutination and bacterial agglutination assays. Based on this survey and a review of the literature we conclude that dietary exposure to plant lectins is widespread. The spectrum of nutritional consequences of such exposure remains to be determined.

Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic and healthy children.
Diabetologia; 44(9):1140-7, 2001 Sep.

Abstract: AIMS/HYPOTHESIS: Cows' milk proteins have been proposed to play a part in the pathogenesis of Type I (insulin-dependent) diabetes mellitus but both epidemiological and immunological studies have given conflicting results. Thus we aimed to study the immunological response to cows' milk proteins among diabetic and healthy children, focusing on the balance of Th1- and Th2-like lymphocytes. METHODS: Peripheral blood mononuclear cells from 30 Type I diabetic children (4 to 18 years old) were examined and compared with peripheral blood mononuclear cells from 18 healthy age-matched control children (7 to 15 years old). Expression of IFN-gamma and IL-4 mRNA were detected by realtime RT-PCR and as protein by ELISA after stimulation with BSA, the ABBOS-peptide (a. a. 152-169) and beta-lactoglobulin (betaLG) from cows' milk and ovalbumin from hens' egg. Phytohaemagglutinin and keyhole limpet haemocyanin were used as positive and negative controls, respectively. RESULTS: Bovine serum albumin caused a weak Th2-like response in Type I diabetic children, whereas BSA antibodies decreased with age only among healthy children. Otherwise, cows' milk proteins (BSA, ABBOS and betaLG) caused increased expression for IFN-gamma and IL-4 mRNA in diabetic and healthy children. BetaLG caused the strongest immunological response, which decreased with age only among diabetic children. However, ovalbumin from egg caused a similar activation of the immune system and the immune response was similar in both diabetic and healthy children. CONCLUSION/INTERPRETATION: Proteins from cows' milk caused an equal Th1- and Th2-like immune response in diabetic and healthy children. Thus, our results do not support the hypothesis that cows' milk antigens are important for the immune process associated with Type I diabetes.

Cellular immune responses to beta casein: elevated in but not specific for individuals with Type I diabetes mellitus.
Diabetologia; 41(6):731-5, 1998 Jun.

Abstract: Elevated cellular immune responses against the cows' milk protein beta casein have been reported in individuals with Type I diabetes mellitus, a finding supportive of the concept that cows' milk consumption may be causative for the disease. We analysed cellular immune reactivities against beta casein in newly-diagnosed Type I diabetic patients, their immediate autoantibody negative relatives, and unrelated healthy individuals in order to further elucidate the role of anti-beta casein immunity in the pathogenesis of Type I diabetes mellitus. Peripheral blood mononuclear cells were stimulated in vitro with various concentrations of three different beta casein preparations, control antigens (tetanus toxoid, mumps extract) and a mitogen (phytohemagglutinin). The frequency and/or mean simulation index of cellular proliferation against two of the beta casein preparations at high antigen concentrations (i.e. 10 or 50 microg/ml) were significantly higher in newly-diagnosed Type I diabetic subjects compared with autoantibody negative healthy control subjects. However, reactivities against beta casein in the Type I diabetic probands and their autoantibody negative relatives, individuals with a very low-rate of disease development, were almost identical. Cellular immune reactivities to other antigens were similar between the subject groups. In addition to indicating the need for appropriately matched subject populations (e.g. human leukocyte antigen (HLA) matched relatives) when analysing cellular immune responses, these findings support our previous contention that individuals genetically prone to autoimmunity may be deficient in forming tolerance to dietary antigens. However, the significance of anti-beta casein immunity as a specific causative factor in the pathogenesis of Type I diabetes mellitus remains unclear.

Impact of dietary protein and fat source on the development of insulin-dependent diabetes in the BB rat.
Diabetes Res; 20(1):33-41, 1992.

Abstract: Epidemiological studies show a remarkable geographical difference in the prevalence of IDDM, suggesting a role for environmental factors such as diet, infection, or stress in the etiology of the disease. Dietary modification has already been shown to be effective in the prevention of autoimmune diabetes in the BB rat and NOD mouse. We studied the effect of protein and fat source in the prophylaxis of diabetes in the BB rat. Natural ingredient rat chow was consistently associated with a high expression of the disease, whereas a casein-based, defined diet significantly inhibited the development of diabetes. Substitution of casein with raw red lentils resulted in a markedly higher incidence. This is the first highly diabetogenic defined diet in the BB rat. Neither fish oil nor soy oil enhanced diabetes expression in the BB rat. Increased amounts of soy oil also did not influence the disease process. These results suggest a central role for dietary protein source in the pathogenesis of BB rat diabetes. We speculate that plant proteins containing anti-nutrients such as chemicals, lectins, enzyme inhibitors, and nonphysiologic amino acids may initiate or hasten the pathogenesis process via beta cell stress or immune response activation.

Detection of antibodies against wheat germ agglutinin bound glycoproteins on the islet-cell membrane.
Diabet Med; 5(2):139-44, 1988 Mar.

Abstract: An attempt was made to detect islet cell surface antibodies (ICSAb) using solubilized islet-cell glycoproteins as antigens. Isolated rat islets were labelled with 125I-wheat germ agglutinin (WGA) and solubilized by Nonidet P-40 with sonication. 125I-WGA-bound islet-cell proteins were incubated with test sera, and bound antibodies were precipitated with anti-human IgG or IgM immunobeads. Serum which had a bound percent beyond the mean plus 2SD of control sera was defined as antibody-positive. Results obtained by this method correlated well with those by the immunofluorescence method of detecting ICSAb. Prevalences of antibodies were 21/114 (18%) for IgG antibodies and 9/114 (8%) for IgM antibodies in patients with insulin-dependent diabetes mellitus (IDDM). The prevalence was highest for both IgG and IgM antibodies in patients within a year of the onset of disease (38 and 25%, respectively), and decreased thereafter. The prevalence of IgM antibodies was lower than that of IgG antibodies at all stages. In NIDDM patients, the prevalence of antibodies was 5/72 (7%) for both IgG and IgM antibodies. If these preliminary results are confirmed, this radioassay may be developed to detect antibodies against islet cell membrane proteins on a large scale.

Wheat-germ agglutinin mimics metabolic effects of insulin without increasing receptor.
Cell Signal; 2(4):377-86, 1990.

Abstract: Expression of insulin metabolic effects can be obtained by anti-receptor antibodies without activation of the tyrosine kinase activity [O'Brien R. M., Soos M. A. and Siddle K. (1987) EMBO J. 6, 4003-4010; Forsayeth J. R., Caro J. F., Sinha M. K., Maddux B. A. and Goldfine I. D. (1987) Proc. natn. Acad. Sci. U.S.A. 84, 34,448-34,514; Ponzio G., Contreres J. O., Debant A., Baron V., Gautier N., Dolais-Kitabgi J. and Rossi B. (1988) EMBO J. 7, 4111-4117; Hawley D. M., Maddux B. A., Patel R. G., Wong K. Y., Mamula P. W., Firestone G. L., Brunetti A., Verspohl E. and Goldfine I. D. (1989) J. biol. Chem. 264, 2438-2444; Soos M. A., O'Brien R. M., Brindle N. P. J., Stigter J. M., Okamoto A. K., Whittaker J. and Siddle K. (1989) Proc. natn. Acad. Sci. U.S.A. 86, 5217-5221.]. Recently, we have proposed that receptor cross-linking is sufficient in itself to stimulate glycogen synthesis, even if aggregation was performed on receptors mutated on Tyr 1162 and Tyr 1163 and thus devoid of tyrosine kinase activity [Debant A., Ponzio G., Clauser E., Contreres J. O. and Rossi B. (1989) Biochemistry 28, 14-17]. The aim of this study was to gain information on the involvement of receptor clustering in the expression of the different insulin biological effects. To this end, we studied the mimetic effects of wheat-germ agglutinin, which is likely to induce receptor aggregation without interacting with the receptor protein moiety. Wheat-germ agglutinin failed to promote DNA synthesis, whereas the lectin behaved as a potent mimicker of insulin on tyrosine aminotransferase activity and amino-acid transport. However, this stimulatory effect did not parallel the activation of receptor autophosphorylation. Our data reinforce the idea that the expression of the metabolic effects of insulin are not strictly dependent on a general tyrosine kinase activation.

Bound lectins that mimic insulin produce persistent insulin-like activities.
Endocrinology; 113(6):1921-6, 1983 Dec.

Abstract: Short preincubation of rat adipocytes with wheat germ agglutinin, followed by removal of unbound lectin, resulted in persistent activation of lipogenesis, which lasted at least 3 h. The bound lectin also inhibited lipolysis initiated by isoproterenol 1 or 2 h after the removal of the free lectin. This property was also shared by other insulinomimetic lectins, such as Concanavalin A and wax bean agglutinin. Persistent bioactivation is the consequence of lectin adsorbed to external cell surface determinants in a permanent fashion. This fraction is not internalized, processed, or appreciably dissociated from the cells, since the addition of N-acetyl-D-glucosamine at any time after the onset of wheat germ agglutinin-induced persistent lipogenesis leads to termination. The property of producing persistent bioactivation is not shared by insulin itself, since removal of the unbound hormone results in termination of bioactivation. This study indicates the existence of externally located fat cell surface determinants, which, upon being occupied continuously, produce persistent insulin-like activities. The study also strongly supports the notion that the initial perturbation is sufficient to activate the insulin machinery system, and that internalization and processing of hormone-receptor complexes are the sole pathway for termination.

Insulin receptor antiserum and plant lectins mimic the direct effects of insulin on nuclear envelope phosphorylation.
Science; 221(4609):462-4, 1983 Jul 29.

Abstract: Insulin directly inhibits protein phosphorylation in isolated rat liver nuclear envelopes. In the present studies, an antiserum to insulin receptor as well as the plant lectins concanavalin A and phytohemagglutinin mimicked insulin action in isolated nuclear envelopes. These studies suggest that insulin and agents that mimic it may directly regulate nuclear functions.

Lectins mimic insulin in the induction of tyrosine aminotransferase.
Science; 214(4522):799-800, 1981 Nov 13.

Abstract: Various lectins were found to induce tyrosine aminotransferase in H-35 rat hepatoma cells grown in monolayer culture. Wheat germ agglutinin gave a maximal induction of tyrosine aminotransferase 6 hours after its addition. The induction time course was similar to that elicited by insulin. Fourteen micrograms of wheat germ agglutinin per milliliter gave half-maximal enzyme induction and 50 micrograms per milliliter gave the maximal response. The induction of tyrosine aminotransferase by wheat germ agglutinin was additive with the induction by either dexamethasone or dibutyryl adenosine 3',5'-monophosphate, but was not additive with the tyrosine amino transferase induction by insulin. Wheat germ agglutinin also mimicked insulin in the inhibition of cellular protein degradation in the absence of serum. The insulin-like effects of lectins should be considered in lectin-mediated manipulations such as agglutination.

Stress, cortisol, interferon and "stress" diseases. I. Cortisol as the cause of "stress" diseases.
Med Hypotheses; 13(1):31-44, 1984 Jan.

Abstract: An attempt is made to define a biochemical formula for stress, as an overproduction of cortisol +/- impaired interferon response. The behavior Type A individual under stress, would exhibit elevated levels of cortisol with normal interferon response, whereas the Type C individual, would exhibit elevated levels of cortisol and impaired interferon responses. Evidence is presented that elevated levels of cortisol manufactured chronically under the affect of stress, and regardless of the type of individual affected, are a cause or the cause of chronic diseases, and not the result of same. This evidence would show that: Elevated levels of cortisol precede certain diseases, and do not follow them, when cortisol is checked out for this purpose in pre-disease conditions. When elevations of cortisol levels are induced through long-term corticosteroids therapy, in patients suffering of diseases requiring this type of treatment, conditions mimicking chronic diseases, would appear. When corticosteroids therapy would be discontinued, the "chronic diseases" mentioned above would disappear. When pharmaceuticals with potential cortisol antagonistic capabilities, were used in diseases totally unrelated, but having in common, elevated levels of cortisol, alleviation of symptoms and/or diseases would occur.

Gastrointestinal hormones and cortisol in normal pregnant women and women with gestational diabetes.
Acta Endocrinol Suppl (Copenh); 277:24-6, 1986.

Abstract: In pregnancy the secretion of a number of gastro-enteropancreatic hormones is considerably altered. These changes might be involved in the gestational modification of gastrointestinal physiology. The enteral stimulation of insulin secretion (the incretin effect) is diminished in pregnancy--both when determined indirectly and when the gastric inhibitory polypeptide (GIP) response to glucose ingestion is considered. Whether this is important for the deterioration of glucose tolerance in pregnancy is uncertain. In gestational diabetics similar findings as in normal pregnant women were obtained except that the GIP response to glucose ingestion was smaller and the GIP response to lipid ingestion greater than in normal women. It is, however, unlikely that these differences are responsible for the development of gestational diabetes. Significant positive correlations were found between the increase of plasma cortisol levels during normal pregnancy and the concomitant decrease in glucose tolerance indicating that the increased cortisol levels might be involved in the development of the insulin resistance found in normal pregnancy.

Early morning hyperglycaemia "dawn phenomenon" in non-insulin dependent diabetes mellitus (NIDDM): effects of cortisol suppression by metyrapone .
Diabetes Res; 14(4):181-5, 1990 Aug.

Abstract: To assess the effect of metyrapone on the early morning plasma glucose (PG) rise, seven NIDDM patients were studied from 2400 to 0900 h on two separate occasions one week apart. During the control study nights, patients received conventional therapy only (diet plus sulphonylurea) whereas on treatment nights, patients received in addition 30 mg/kg metyrapone orally at 2400 h. The plasma glucose (PG) levels from 0530 to 0900 h were significantly higher during the control night than the corresponding values following metyrapone. The control mean PG concentrations increased continuously from a nadir 8.4 +/- 1.1 mmol/l at 0400 h to a maximum of 9.4 +/- 1.1 mmol/l at 0800 h (p less than 0.01). In contrast following metyrapone administration a continuous decline in the PG concentration was noted from 2400 to 0800 h. The plasma glucose levels fell from 9.0 +/- 1.2 at 0400 h to 7.7 +/- 1.0 mmol/l at 0800 h (p less than 0.05). The mean overnight cortisol levels were 167.2 +/- 13.2 and 55.9 +/- 6.4 nmol/l (p less than 0.001) during the control and treatment studies, respectively. The cortisol levels were significantly higher during the control study at all time points from 0400 to 0900 h. No significant changes in insulin, C-peptide, glucagon, GH or catecholamine levels were observed between the two study periods. We conclude that the physiologic early morning rise in plasma cortisol possibly contributes to the pathogenesis of the dawn phenomenon in NIDDM patients.

Maternal-child blood group incompatibility and other perinatal events increase the risk for early-onset type 1 (insulin-dependent) diabetes mellitus.
Diabetologia; 35(7):671-5, 1992 Jul.

Abstract: The nationwide Swedish Childhood Diabetes Registry, which ascertains 99% of recent-onset Type 1 (insulin-dependent) diabetic children (0-14 years) in Sweden, was linked with the Swedish Medical Birth Registry. A matched case-control study was carried out analysing about 20 perinatal variables concerning mother and child. A total of 2757 infants who became diabetic during the period 1978-1988 were analysed. For each case infant three control children were randomly selected from among all infants born in the same year and at the same delivery unit as the case infant. The following statistically significant risk factors were identified for Type 1 diabetes with an onset before 15 years of age: maternal diabetes (OR = 3.90), maternal age above 35 (OR = 1.36), maternal non-smoking (OR = 1.54), pre-eclamptic toxaemia (OR = 1.19), caesarian section (OR = 1.32), and maternal-child blood group incompatibility (OR = 1.61). When the analysis was restricted to Type 1 diabetes with an onset before the age of 5 years, most odds ratios were increased - for blood group incompatibility OR = 3.86 (95% confidence interval 1.54-9.65). Icterus without blood group incompatibility was not a significant risk factor. When each risk factor was analysed after standardization for all other risk factors, the odds ratios remained significantly increased. Scrutiny of medical records for cases and control children with a diagnosis of blood group incompatibility verified the diagnosis in close to 90% of children. The more severe cases needing phototherapy and/or blood transfusion were found to have a greater risk than milder cases.(ABSTRACT TRUNCATED AT 250 WORDS)

An infectious aetiology of insulin-dependent diabetes mellitus? Role of the secretor status.
FEMS Microbiol Immunol; 1(6-7):411-6, 1989 Jun.

Abstract: Studies of patients with insulin-dependent diabetes and their families have shown increased incidences of HLA markers B8, B15, DR3 and DR4. While these genetic predispositions are obviously important, additional factors such as environmental influences are presumed to trigger the events leading to the development of diabetes. Infectious triggers, in particular several viruses, have been suggested. The evidence from epidemiological and in vitro studies for a viral aetiology is summarized here. The significance of the recent finding of an increased proportion of non-secretors among patients with insulin-dependent diabetes is discussed in the context of other 'autoimmune' diseases for which infectious aetiologies have been proposed.

Persistent insulin secretion, assessed by plasma C-peptide estimation in long-term juvenile diabetics with a low insulin requirement.
Diabetologia; 15(3):169-72, 1978 Sep.

Abstract: In order to investigate whether patients with long-standing juvenile diabetes mellitus (onset of diabetes before the age of 30) and a low daily insulin requirement (less than 0.50 units/kg body weight) still have functioning B-cells, plasma C-peptide was determined after stimulation (OGTT and glucagon/tolbutamide) in 64 patients with diabetes of more than 18 years' duration (mean 31 years). Measurable endogenous insulin production was found in 24% of the patients. The prevalence of severe retinopathy was lower in the secretors than in the non-secretor group. There was no difference in insulin antibody concentration between the two groups. Furthermore, the insulin requirement in the secretor group was relatively constant during the course of diabetes. Metabolic control was similar in both groups. It is concluded that a persisting but low activity of endogenous insulin production can be found in many long-term juvenile diabetics with a low insulin requirement, while others without any residual beta-cell function develop a low insulin requirement for unknown reasons.

Total serum alkaline phosphatase (SAP) and serum cholesterol in relation to secretor status and blood groups in myocardial infarction patients.
Indian Heart J; 41(2):82-5, 1989 Mar-Apr.

The relation of total serum alkaline phosphatase and serum cholesterol in convalescing patients of myocardial infarction with secretor status and blood groups have been studied. Serum cholesterol and alkaline phosphatase levels showed significant difference in secretors (98) and nonsecretors (56) in myocardial groups. Total cholesterol and total serum alkaline phosphatase levels showed significant difference in secretors when blood groups A and O are compared. While in nonsecretors, significant values obtained in A/O, A/B for cholesterol and A/B, A/AB for alkaline phosphatase levels.

Cholesterol modulates alkaline phosphatase activity of rat intestinal microvillus membranes.
J Biol Chem; 263(18):8592-7, 1988 Jun 25.

Abstract: Experiments were conducted, using a nonspecific lipid transfer protein, to vary the cholesterol/phospholipid molar ratio of rat proximal small intestinal microvillus membranes in order to assess the possible role of cholesterol in modulating enzymatic activities of this plasma membrane. Cholesterol/phospholipid molar ratios from 0.71 to 1.30 were produced from a normal value of 1.05 by incubation with the transfer protein and an excess of either phosphatidylcholine or cholesterol/phosphatidylcholine liposomes for 60 min at 37 degrees C. Cholesterol loading or depletion of the membranes was accompanied by a decrease or increase, respectively, in their lipid fluidity, as assessed by steady-state fluorescence polarization techniques using the lipid-soluble fluorophore 1,6-diphenyl-1,3,5-hexatriene. Increasing the cholesterol/phospholipid molar ratio also decreased alkaline phosphatase specific activity by approximately 20-30%, whereas decreasing this ratio increased this enzymatic activity by 20-30%. Sucrase, maltase, and lactase specific activities were not affected in these same preparations. Since the changes in alkaline phosphatase activity could be secondary to alterations in fluidity, cholesterol, or both, additional experiments were performed using benzyl alcohol, a known fluidizer. Benzyl alcohol (25 mM) restored the fluidity of cholesterol-enriched preparations to control levels, did not change the cholesterol/phospholipid molar ratio, and failed to alter alkaline phosphatase activity. These findings, therefore, indicate that alterations in the cholesterol content and cholesterol/phospholipid molar ratio of microvillus membranes can modulate alkaline phosphatase but not sucrase, maltase, or lactase activities. Moreover, membrane fluidity does not appear to be an important physiological regulator of these enzymatic activities.

An increased risk of ischemic heart disease in men with the Lewis blood group phenotype Le(a-b-) has been reported. It has been suggested that the Le(a-b-) phenotype is a genetic marker of the insulin resistance syndrome. To examine whether Le(a-b-) confers the insulin resistance syndrome, we studied a random sample of unrelated healthy young white men and women living in Copenhagen (n = 380, 18 to 32 years). All individuals had their insulin sensitivity estimated using Bergman's min