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Biomedical subjects

T Maki

Publications and source records attributed to T Maki.

At least 55 records · Page 3Linked to original sources
PubMed1998

Suppressive effect of low amounts of safflower and perilla oils on diethylnitrosamine-induced hepatocarcinogenesis in male F344 rats.

We have investigated the modulating effects of low amounts of dietary oils rich in polyunsaturated fatty acids (PUFA) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male F344 rats. A total of 112 animals were divided into eight groups. Groups 1-4 were given drinking water containing 40 ppm DEN for five weeks. Groups 5-8 served as controls without DEN treatment. Groups 1 and 5 were fed a basal diet containing 5% beef tallow, Groups 2 and 6 were fed a 5% olive oil diet, Groups 3 and 7 were fed a 5% safflower oil diet, and Groups 4 and 8 were fed a 5% perilla oil diet for 21 weeks, starting 1 week before DEN exposure. Beef tallow, olive oil, safflower oil, and perilla oil are rich in saturated fatty acids, a monounsaturated fatty acid, n-6 PUFA, and n-3 PUFA, respectively. All rats were killed 20 weeks after the start of the experiment. Incidences of hepatocellular adenoma and carcinoma were 100% in DEN-treated groups, irrespective of dietary oils. Multiplicities of adenomas in Groups 3 and 4 were significantly (p < 0.05) lower than in Groups 1 and 2. Multiplicity of carcinoma in Group 3 was significantly (p < 0.05) lower than in Group 1. Mean volumes of placental glutathione S-transferase-positive foci per liver and the number of argyrophilic nucleolar organizer region proteins per nucleus in the liver tumors were significantly (p < 0.05) lower in Groups 3 and 4 than in Groups 1 and 2. ras mRNA expression in liver neoplasms was also suppressed significantly (p < 0.05) in Groups 3 and 4 compared with Groups 1 and 2. Significantly (p < 0.05) higher levels of n-6 and n-3 PUFA in the phospholipid fraction of the liver were found in Groups 3 and 4, respectively, than in the other groups. In contrast, a significantly (p < 0.05) decrease in monounsaturated fatty acid was observed in Groups 3 and 4 compared with Groups 1 and 2. These results suggest that safflower oil and perilla oil, rich in n-6 and n-3 PUFA, respectively, alter the membrane fatty acid composition of the liver and suppress the development of liver cell carcinoma in rats.

Animals↗
PubMed1998

[Compulsive manipulation of tools in the left hand following damage to the right medial frontal lobe].

In 1982, Mori and Yamadori first reported a woman who showed compulsive manipulation of tools (CMT) following an infarction in the left medial frontal lobe. When an object was shown, the patient's right hand reached, grasped and manipulated it properly against her will. Since then, there have been many similar case reports and CMT has been generally believed to occur in the right hand after damage to the left medial frontal lobe. However, there also have been a few case reports of CMT in the left hand of a patient with damage to the right medial frontal lobe. To clarify whether such a patient with CMT in the left hand is an exceptional case or not, we prospectively investigated CMT in the left hand of 10 patients with an infarction in the right medial hemisphere. All patients were examined within 6 weeks after stroke. Magnetic resonance images were used to determine the location and extension of a lesion. We found that 7 cases with a lesion involving the anterior cingulate gyrus (ACG) and the supplementary motor area (SMA) exhibited a grasp reflex and a visual grouping mainly in the left hand. Five of these 7 cases had a lesion extending into the middle and anterior parts of the ACG and displayed CMT in the left hand. Among those 5 patients, 2 with a lesion which was extensive enough into the ACG to involve almost entirely the anterior part of it adjoining the genu and anterior body of the corpus callosum showed a prominent CMT in the left hand. Two patients with a lesion principally confined to the SMA showed the grasp reflex and some subvarieties of the instinctive grasp reaction mainly in the left hand, but never showed visual grouping nor CMT. One patient with a lesion involving the posterior cingulate gyrus and medial parietal lobe but sparing both the SMA and ACG showed neither grasping responses nor CMT. From these observations, we conclude the following: (1) it is not an exceptional case that a right-handed patient with a right medial frontal lesion shows CMT in the left hand: and (2) extensive damage to the ACG involving its anterior part adjoining the genu and anterior body of the corpus callosum is most crucial for the development of CMT.

Adult↗
PubMed1997

Use of CTLA4-Ig in combination with conventional immunosuppressive agents to prolong allograft survival.

BACKGROUND: The objective of our study was to determine the effectiveness of CTLA4-Ig, a novel immunosuppressive agent, in augmenting allograft survival when combined with either cyclosporine, sirolimus, donor-specific bone marrow alone (BM), or bone marrow in conjunction with antilymphocyte serum (ALS). METHODS: Full-thickness skin allografts were used in C3H to B6AF1 (class I mismatch) and AKR to C57BL/6 (complete mismatch) models. Groups of mice (n=6-14) were treated with various combinations of the following treatment protocols: murine CTLA4-Ig, L-6 control Ig, sirolimus, cyclosporine, ALS, or ALS/BM. RESULTS: In the class I mismatch model, L-6 control Ig had no effect whereas use of CTLA4-Ig alone resulted in a doubling of the median graft survival compared with controls. The addition of either sirolimus or cyclosporine to CTLA4-Ig increased graft survival over that achieved with CTLA4-Ig alone. CTLA4-Ig demonstrated no efficacy when used in combination with BM, ALS, or ALS/BM. CTLA4-Ig was clearly less effective in the complete mismatch model. CONCLUSION: These data suggest that CTLA4-Ig may be effective clinically in combination with cyclosporine or sirolimus but offers no additional effectiveness in combination with antilymphocyte serum with or without donor-specific bone marrow.

Abatacept↗
PubMed1997

Expansion of intermediate T cell receptor cells expressing interleukin-2 receptor alpha- beta+, CD8alpha+ beta+, and lymphocyte function-associated antigen-1+ in the liver in association with intrahepatic islet xenograft rejection from rat to mouse: prevention of rejection with anti-interleukin-2 receptor beta monoclonal antibody treatment.

BACKGROUND: The precise mechanisms involved in islet xenograft rejection remain unknown. The purpose of the present study was to determine cellular mechanisms responsible for islet xenograft rejection in the liver to facilitate finding a procedure for prevention of immune rejection. METHODS: Hepatic mononuclear cells (MNC) as well as splenocytes, peripheral blood MNC, and thymocytes from streptozotocin-induced diabetic mice (BALB/c) rejecting the intrahepatic rat (Lewis) islet xenografts were isolated and examined by two-color FACS analysis. RESULTS: The characteristic finding of the hepatic MNC from the mice rejecting islet xenografts compared with mice receiving isografts was a significant increase in the yield as well as in the percentage of the cells expressing CD3+ interleukin-2 receptor (IL-2R) alpha- beta+, CD3+ CD8alpha+ beta+, and T cell receptor (TCR) alphabeta+ lymphocyte function-associated antigen-1+. The expression of CD3 and TCR alphabeta of these T cells was found to be of intermediate intensity (TCR(int) cells). The expansion of these TCR(int) cells occurred predominantly in the liver. There was no significant difference in the cells expressing CD3+ IL-2R alpha+, CD3+ CD4+, CD3+ TCRgammadelta+, CD3- IL-2Rbeta+ (natural killer cells), and B220+ (B cells). In vivo administration of anti-IL-2Rbeta monoclonal antibody directed to the expanded cells produced a prevention of rejection. CONCLUSIONS: These findings suggest that islet xenograft rejection in the liver from rat to mouse is an event for which the TCR(int) cells are responsible.

Animals↗
PubMed1997

Superiority of sirolimus (rapamycin) over cyclosporine in augmenting allograft and xenograft survival in mice treated with antilymphocyte serum and donor-specific bone marrow.

BACKGROUND: Sirolimus is a potent immunosuppressive agent with great therapeutic potential. The objective of our study was to evaluate the efficacy of sirolimus versus cyclosporine in augmenting the unresponsiveness induced by an antilymphocyte serum (ALS)/donor-specific bone marrow (BM)-based regimen across three levels of histoincompatibility: class I and II disparate (DBA/2 to B6AF1), complete mismatch (AKR to C57BL/6), and xenograft (ACI rat to B6AF1). METHODS: Full-thickness skin grafts were taken from donors and placed on recipients in standard fashion. Seven groups of recipient mice (n=10-28) received various combinations of the following treatment protocols: sirolimus, 1.5 mg/kg (3.0 mg/kg for xenografts) every other day from day 0 to day 12; cyclosporine, 50 mg/kg every other day from day 10 through 22; ALS, 0.5 ml on days -1 and 2 for allografts and days -1, 2, and 4 for xenografts; and BM, 25 million donor-specific cells IV on day 7. RESULTS: The administration of ALS or ALS/BM resulted in modest but significant prolongation of skin graft survival in all combinations tested. Cyclosporine combined with ALS or ALS/BM significantly extended allograft survival compared with ALS or ALS/BM alone (P<0.05) but had no effect on xenograft survival. In contrast, the combination of sirolimus with ALS or ALS/BM resulted in a two- to threefold increase in allograft survival and over a fourfold increase in xenograft survival when compared with the comparable cyclosporine-based regimen. Additionally, lymphocytes isolated from class I and II incompatible mice with skin grafts surviving >100 days demonstrated markedly reduced interleukin 2 and interferon-gamma secretion in response to irradiated donor-specific lymphocytes in culture. CONCLUSIONS: In the regimens tested, sirolimus was superior to cyclosporine in augmenting donor BM-induced skin graft prolongation in ALS-treated mice across all levels of histoincompatibility.

Adjuvants, Immunologic↗
PubMed1997

Regulation of autoimmune diabetes by interleukin 3-dependent bone marrow-derived cells in NOD mice.

Interleukin-3 (IL-3), a multilineage colony stimulating factor, has been shown to augment alloreactive bone marrow-derived suppressor cell activity in vivo and in vitro. The present study examined the effect of IL-3 on autoimmune-mediated diabetes in NOD mice. Administration of IL-3 twice weekly starting at 2-4 weeks of age delayed the onset and reduced the overall incidence of diabetes. Bone marrow cells obtained from IL-3-treated NOD mice protected NOD mice from cyclophosphamide-induced diabetes but failed to prevent adoptively transferred diabetes. In vitro culture of bone marrow cells in medium containing IL-3 produced a Thy-1+CD3epsilonloCD4-CD8-CD25- immature T cell clone which prevented cyclophosphamide-induced diabetes. The cloned cells also effectively delayed the development of diabetes induced by transfer of T cells in adult thymectomized, irradiated, bone marrow-reconstituted NOD mice. These results suggest that IL-3 is capable of regulating extrathymic T cell development from the bone marrow and that these cells mediate strong immunoregulatory function.

Adoptive Transfer↗
PubMed1997

Development of degenerative muscle weakness by chronic administration of beta,beta'-iminodipropionitrile in the drinking water to rats: a model for motorneuropathy.

Progressive muscle weakness accompanied by progressive muscle atrophy was investigated in rats administered beta,beta'-iminodipropionitrile (IDPN) chronically in the drinking water. Spontaneous running wheel activity declined slowly and reached a constant low level before postural muscle weakness was apparent. The rats being offered IDPN in the drinking water showed definite postural muscle weakness about 25 weeks after first being given IDPN, and muscle strength declined gradually throughout the remainder of the experiment (to 66 weeks). Flaccid paralysis became apparent in the hind limbs in the later stages of the experiment. Neurogenic muscle atrophy, measured by group atrophy of the muscle fibers, also progressed slowly, almost in parallel with the loss of muscle strength. At the end of the experiment, muscle weight of the gastrocnemius had decreased to about 20% that of control [F(2, 12) = 40.4, p < 0.05]. Plasma creatinine in the rats given IDPN in the drinking water for 66 weeks was significantly elevated over that of controls [F(2, 12) = 20.1, p < 0.05]. On the other hand, in rats given IDPN intraperitoneally, postural muscle weakness and muscle atrophy were less apparent, and plasma creatinine was normal. However, in these animals, abnormal behaviors, such as hyperexcitement, circling, and choreic movement (ECC syndrome), were apparent. These results suggest that the present model, which administers IDPN chronically in the drinking water ad lib and does not show involuntary movements and ECC syndrome, is of potential importance for investigation of chronic diseases of progressive muscle weakness with progressive muscle atrophy, and for assessing the efficacy of drugs and therapies for treating chronic neuromuscular diseases.

Animals↗
PubMed1997

Effect of dietary supplementation with branched-chain amino acids on spontaneous motor activity and muscle function in beta,beta'-iminodipropionitrile-treated rats: a model for motorneuropathy.

Beta,beta'-iminodipropionitrile (IDPN)-induced muscle weakness in rats is a model for motorneuropathy diseases. The effects of oral administration of branched-chain amino acids on the progression of muscle weakness and muscle atrophy induced by the administration of IDPN in the drinking water, were investigated in this study. The spontaneous motor activity of the animals, as measured with a running wheel, slowly declined after IDPN administration, reaching a steady and low level at approximately week 15. Progressive muscle weakness and muscle atrophy were observed beginning at approximately 15 weeks after the initiation of administration of IDPN. Administration of branched-chain amino acids (BCAA) as a dietary supplement did not improve the lowered spontaneous motor activity seen in IDPN animals, but it did significantly improve measures of postural weakness and muscle strength [range of F values (2, 24) = 4.1-9.5, p < 0.05]. Plasma creatinine of the IDPN-treated rats was markedly elevated, and BCAA administration also significantly suppressed this elevation [F(2, 24) = 41.2, p < 0.05]. Moreover, although BCAA in plasma were elevated in the rats administered BCAA [range of F values (2, 21) = 25.7-29.7, p < 0.05], skeletal muscle showed no differences (at the p < 0.05 level) in the amounts of BCAA, whether or not BCAA were administered. These data suggest that the BCAA taken up in the skeletal muscle were utilized in the muscle of motorneuropathic rats and improved muscle function, such as energy metabolism, and that the BCAA treatment is one important therapeutic approach for retarding the progression of muscle weakness seen in certain neuromuscular disorders.

Amino Acids, Branched-Chain↗
PubMed1997

T-lymphocytes regulate genetically determined airway hyperresponsiveness in mice.

Airway hyperresponsiveness (AHR) is a hallmark of asthma and a heritable polygenic trait in the mouse. In the mouse, candidate gene products of hematopoietic origin implicated in asthma mapped to the regions of the previously defined quantitative trait loci. Since hematopoietic cells have been implicated in the pathogenesis of asthma, we evaluated the role of hematopoietic cells in general and T cells specifically in the genetic modulation of native airway responsiveness in mice. Here, with the use of bone marrow transplantation, anti-T-cell monoclonal antibody treatment and T-cell transfer, we demonstrate that intrinsic non-atopic AHR is mediated by T lymphocytes. Our data support the novel concept that, in the absence of identified environmental influences, T cells enhance genetically determined airway responsiveness.

Adoptive Transfer↗
PubMed1997

Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166).

1. (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166), a novel oral hypoglycaemic agent is a non-sulphonylurea insulin secretagogue. 2. We investigated the insulin-releasing action and hypoglycaemic effect of A-4166 compared to sulphonylureas in vitro and in vivo. 3. A-4166 stimulated insulin secretion from rat freshly isolated pancreatic islets at concentrations from 3 x 10(-6) M to 3 x 10(-4) M in the presence of 2.8 mM glucose. There was no obvious difference in glucose dependency between the insulinotropic effect of A-4166 and that of glibenclamide, and no additive or synergistic effect was observed between these two drugs. 4. A-4166 displaced [3H]-glibenclamide bound to intact HIT-T15 cells in a concentration-dependent manner. The Ki value was 4.34 +/- 0.04 x 10(7) M, and the displacement potency of A-4166 was between that of glibenclamide and tolbutamide, being similar to that of gliclazide. 5. Inf fasted beagle dogs, A-4166 showed a dose-dependent hypoglycaemic effect after oral administration over the range 1 to 10 mg kg-1. The hypoglycaemic action of A-4166 showed an earlier onset and a shorter duration than that of sulphonylureas. 6. Simultaneous measurement of plasma insulin levels revealed that the hypoglycaemic effect of A-4166 was caused by a rapid-onset and brief burst of insulin secretion. 7. The pharmacokinetic profile of A-4166 was consistent with the changes of the blood glucose and plasma insulin levels. 8. Although the in vitro insulin-releasing effect of A-4166 was similar to that of sulphonylureas, its hypoglycaemic effect was more rapid and shorter-lasting, associated with rapid absorption and clearance. Thus, A-4166 may be useful in suppressing postprandial hyperglycaemia in patients with non-insulin-dependent diabetes mellitus.

Animals↗
PubMed1997

Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down-regulating adipocyte differentiation.

We examined the effect of dietary oils with different fatty acid compositions on the growth of visceral adipose tissue in rats. Rats were fed for 4 mo starting at weaning a basal diet containing (12 g/100 g diet) perilla oil rich in (n-3) polyunsaturated fatty acids (PUFA), safflower oil rich in (n-6) PUFA, olive oil rich in monounsaturated fatty acid, or beef tallow rich in saturated fatty acids. The amount of food consumed and body weight gain did not differ among the four dietary groups. The weight of the epididymal fat pad and the serum triglyceride concentration in perilla oil-fed rats were significantly lower (P < 0.05) than those of olive oil- and beef tallow-fed groups. The product of [(volume of individual adipocytes) x (number of adipocytes in epididymal fat pad)], which presumably represents total adipocyte volume in the fat pad, was significantly lower (P < 0.05) in perilla oil-fed rats than in beef tallow- and olive oil-fed groups. Expression of the late genes of adipocyte differentiation, peroxisome proliferator-activated receptor alpha, adipocyte P2 and adipsin, was significantly (P < 0. 05) down-regulated in epididymal fat tissue of rats that had been fed perilla oil rather than beef tallow or olive oil, whereas expression of the early gene, lipoprotein lipase, was not significantly affected. Greater levels (P < 0.05) of (n-3) PUFA in the membrane phospholipid fraction of the fat tissue were observed in perilla oil-fed rats than in the other dietary groups. These results suggest that perilla oil or (n-3) PUFA prevents excessive growth of adipose tissue in rats at least in part by suppressing the late phase of adipocyte differentiation.

Adipocytes↗
PubMed1997

Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population.

Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components, and several candidate genes have been reported to be linked to atopy in Caucasian populations. We conducted a study of linkage between asthma and markers on chromosomes 5q31-q33 and 11q13 in 68 Japanese families (306 members) by affected sib-pair analysis. Families for the linkage study were ascertained through asthmatic children visiting the allergy clinic. The results provide supportive evidence for linkage between asthma and gene markers in or near the interleukin-4 (IL-4) gene, the IL-9 gene, and D5S393 on chromosome 5q31-q33 (p = 0.0013, p = 0.018, and p = 0.0077, respectively). Linkage between atopic phenotype and these genetic markers was also suggested (p = 0.006, p = 0.01, and p < 0.0001 for atopy, respectively). However, we failed to find evidence for linkage of asthma or atopy to the IgE high-affinity receptor gene on 11q13 (p > 0.1). These findings indicate that beyond ethnicity, there are specific loci that contribute to susceptibility to atopy on chromosome 5q31-q33. In addition, our findings suggest that loci on chromosome 5q31-q33 are linked to the development of asthma in childhood.

Adolescent↗
PubMed1997

Effect of a new hypoglycemic agent, A-4166 [(-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclamide.

(-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166) is a new nonsulfonylurea hypoglycemic agent that lowers blood glucose by stimulating insulin release. In the present study, we examined the effects of A-4166, voglibose (an alpha-glucosidase inhibitor), and glibenclamide (a sulfonylurea) on the postprandial glycemic increase in rats with or without diabetes mellitus. Oral administration of A-4166 (25-100 mg/kg) dose-dependently decreased blood glucose with a rapid onset and short duration in normal rats. On the other hand, glibenclamide (1-4 mg/kg) showed a slower onset of its hypoglycemic action, and voglibose (0.2 mg/kg) had no effect. In the case of postprandial glucose excursion, the carbohydrate-induced increase in blood glucose was reduced by oral administration of either A-4166 or voglibose without causing sustained hypoglycemia in both normal and neonatal streptozotocin-induced diabetic rats. However, the efficacy of voglibose varied with the type of carbohydrate load. Glibenclamide produced a prolonged decrease in blood glucose without any appreciable effect on the initial glucose excursion. After sucrose loading, plasma insulin levels during the initial 1 h were significantly higher in A-4166-treated rats than in control rats, while voglibose completely inhibited the insulin response to sucrose. In glibenclamide-treated rats, an augmented insulin response was not seen. In conclusion, unlike other hypoglycemic agents, A-4166 suppresses postprandial glucose excursions by stimulating the early phase of insulin secretion.

Animals↗
PubMed1997

[A case of probable Creutzfeldt-Jakob disease with a point mutation of prion protein gene codon 180 and atypical MRI findings].

A case of probable Creutzfeldt-Jakob disease (CJD) is reported. A 70-year-old Japanese woman was admitted with a complaint of amnesia. She initially developed Klüver-Bucy syndrome, hypergraphia, and later showed myoclonus and startle response. She developed akinetic mutism within nine months from the onset. Prion protein gene codon 180 point mutation (Met/Ile) was detected and we diagnosed her as CJD. Serial MRI studies revealed abnormal T2 elongation and thickening limited to the cerebral cortices, which started at bilateral temporal lobes and later extended to frontal, parietal, and occipital lobes with relative sparing of hippocampi and central gyri. Serial EEG did not show periodic synchronous discharge (PSD). Three cases of CJD with a point mutation of codon 180 were reported in the past. There are several common features in the past cases and the present case, i.e. 1) negative familial history, 2) late onset, 3) T2 high intensity at cerebral cortices on MRI, and 4) negative PSD. These may be characteristic features of CJD with a point mutation of codon 180.

Aged↗
PubMed1997

Porcine islet xenotransplantation utilizing a vascularized bioartificial pancreas.

Successful pancreas/islet transplantation restores normal glucose metabolism in patients with insulin dependent diabetes mellitus (IDDM) but requires chronic immunosuppression which is associated with morbidity and mortality. Immune exclusion devices containing pancreatic islets (bioartificial pancreas) are designed to provide glycemic control without immunosuppression. The immune exclusion is achieved by separating islets from the host by semipermeable membranes. Small molecules such as glucose, insulin and nutrients pass through, whereas immune lymphocytes and immunoglobulins are excluded by the membrane and unable to cause destruction of the islets. Use of xenogeneic islets (i.e., porcine islets) in the device also circumvents the shortage of human donor organs. This report provides a brief summary of our experience with vascularized bioartificial pancreas (VBAP) containing allogeneic and xenogeneic islets for treatment of experimental diabetes in dogs and describes our plans for a clinical trial of the VBAP in patients with IDDM.

Animals↗
PubMed1996

Liquid chromatographic analysis of penem antibiotic FCE22101 in biological fluids with a liquid-liquid extraction procedure.

A sensitive high-performance liquid chromatographic method has been developed for the determination of penem antibiotic FCE22101 in plasma and urine. FCE22101 was extracted from plasma and urine with ethyl acetate. After evaporating, the sample solutions were analyzed by a reversed-phase high-performance liquid chromatographic system using a two-sided bracketing injection technique. The determination limit of FCE22101 was 5 ng/ml in plasma. Analysis of the spiked plasma samples demonstrated the good accuracy and precision of the method. The proposed method improved from five- to ten-fold on the analytical sensitivity in comparison with the most commonly ultrafiltration method.

Acetates↗
PubMed1996

Protection of nonobese diabetic mice from autoimmune diabetes by reduction of islet mass before insulitis.

Nonobese diabetic mice spontaneously develop diabetes that is caused by autoimmune cell-mediated destruction of pancreatic beta cells. Here we report that surgical removal of 90% of pancreatic tissue before onset of insulitis induced a long-term diabetes-free condition in nonobese diabetic mice. Pancreatectomy after development of moderate insulitis had no effect on the course of diabetes. The effect of pancreatectomy was abrogated with subsequent development of diabetes by infusion of islet-cell-specific T lymphocytes and by transplantation of pancreatic islets. Lymphocytes from pancreatectomized diabetes-free mice exhibited low response to islet cells but responded normally to alloantigens. These results suggest that the islet cell mass plays a critical role in development of autoimmune diabetes.

Adoptive Transfer↗