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Biomedical subjects

T Maki

Publications and source records attributed to T Maki.

At least 109 records · Page 6Linked to original sources
PubMed1992

Long-term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti-lymphocyte serum.

We investigated the therapeutic effect of anti-lymphocyte serum (ALS) on clinically overt diabetes by using a nonobese diabetic (NOD) mouse model of type I diabetes mellitus. ALS given within 14 days of disease onset gradually reversed hyperglycemia with a 76% cumulative incidence of remission. Combined use of anti-CD4 and anti-CD8 monoclonal antibodies, but not anti-CD4 or anti-CD8 antibody alone, was also effective with overall 64% remission. Diabetic NOD mice that failed to respond to ALS treatment accepted subsequent islet isografts for a prolonged period (mostly greater than 100 days), whereas islet isografts in diabetic NOD mice previously treated with normal rabbit serum were all destroyed as acutely as isografts in untreated diabetic NOD mice. These results suggest that persistence of diabetes was due to irreversible beta-cell destruction and that ALS has indeed abrogated autoimmunity. In addition, ALS treatment at the time of islet isografting achieved significant prolongation of graft survival with 8 of 13 mice maintaining euglycemia for greater than 100 days. Although ALS prolonged islet allograft survival in diabetic NOD mice, the degree of prolongation was much less for allografts than for isografts, suggesting that ALS is capable of suppressing autoimmunity more effectively than allograft responses.

Animals↗
PubMed1992

Age-related changes in the mechanisms of LHRH-stimulated LH release from pituitary cells in vitro.

In vitro release of LH in response to LHRH, phorbol myristate acetate (PMA), the ionophore A23187, and nifedipine was evaluated in primary cultures of anterior pituitary cells from intact mature (6 to 7 month) and old (23 to 24 month) male Wistar rats. LH release from pituitary cells is reduced approximately 30% and 60% after 4 and 48 h of 10(-7) M LHRH stimulation in cells of old rats, respectively. This impairment may be secondary to a loss of LHRH receptors. LHRH-stimulated LH release from cells of mature rats was inhibited 70% by the voltage-gated calcium channel blocker, nifedipine (10(-6) M), whereas LHRH-stimulated LH release from cells of old rats was too low to detect the effects of this drug. Age changes can be partially reversed by A23187 and PMA during 4 h, but not 48 hrs of stimulation. It therefore appears that short- and long-term (4 h and 48 h, respectively) stimulation of LH release may proceed through separate mechanisms that are differentially affected by aging.

Aging↗
PubMed1992

Long-term results of pylorus-preserving gastrectomy for gastric ulcer.

The postoperative results of pylorus-preserving gastrectomy (PPG) for gastric ulcer performed in 134 patients during the past 25 years (mean postoperative period, 16.6 years) were studied. The incidence of postoperative complications was low. Dumping syndrome occurred in only 4.4% and 0% of cases as assessed by questionnaire and interview, respectively. Four (5.4%) of 74 patients available for this study had ulcer recurrence. In one of these four patients concurrent gastroduodenal ulcer was suspected from preoperative gastric analysis. The site of recurrence was found in all cases to be the remnant antral gland area along the greater curvature between the proper gastric gland area and the duodenum. Basal and maximal acid outputs at the time of relapse were significantly higher in patients with recurrence than in patients without recurrence. The fasting and postprandial serum gastrin levels were high in one patient with recurrence, whose antrum was preserved as long as 3 cm proximal to the pyloric ring; this was longer than that described in our original method of PPG. In two other recurrent cases the serum gastrin levels were not different from those in nonrecurrent cases. Immunohistochemical examination of the residual antrum showed no increase in the G-cell density in patients either with or without recurrence. These results suggest that the long-term quality of life of patients treated with PPG remains favorable. Recurrence rate can be further reduced if PPG is strictly indicated for gastric ulcer only and carried out by meticulous surgical techniques. In the pathogenesis of the ulcer recurrence the role of gastrin release from the residual antral mucosa seems to be limited.

Adult↗
PubMed1992

Treatment of severely diabetic pancreatectomized dogs using a diffusion-based hybrid pancreas.

Long-term survival of dog islet allografts implanted in diabetic pancreatectomized dogs was achieved by islet encapsulation inside cylindrical chambers fabricated from permselective acrylic membranes (nominal M(r) exclusion of 50,000-80,000). Dog islets were isolated from the pancreases of outbred mongrel dogs by collagenase digestion. Chambers containing mean +/- SE 316 +/- 63K islet equivalents (mean islet volume, 558 +/- 111 mm3, purity 90-95%) were peritoneally implanted into six totally pancreatectomized dogs. The dogs were monitored for glycemic control by fasting and postprandial blood glucose determinations, and responses to both intravenous glucose (intravenous glucose tolerance test 0.5 g/kg) and oral glucose (oral glucose tolerance test 1 g/kg). All of the dogs required appreciably lower dosages of exogenous insulin therapy for control of fasting blood glucose levels, with the mean daily insulin dose dropping from 38 +/- 7 to 5 +/- 1 U/day during the 1st wk. Three recipients required no insulin for greater than 82, greater than 68, and 51 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 and 2 mo postimplantation were 2.7 +/- 0.4 and 2.0 +/- 0.5, respectively compared with 3.5 +/- 0.5 before pancreatectomy. The glucose values during oral glucose tolerance tests at 2 wk, although returning to less than 125 mg/dl (less than 7.0 mM) by 2 h, exceeded the normal range, with peak values of 174 to 202 mg/dl (9.7 to 11.3 mM). These preliminary results are encouraging, and represent an important step in determining the feasibility of using this type of diffusion-based hybrid artificial pancreas as treatment for diabetes mellitus in humans.

Animals↗
PubMed1991

Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression.

Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, greater than 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for greater than 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in less than 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P less than 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs.

Analysis of Variance↗
PubMed1991

Biohybrid artificial pancreas: long-term implantation studies in diabetic, pancreatectomized dogs.

Diabetic complications such as neuropathy, retinopathy, and renal and cardiovascular disease continue to pose major health risks for diabetic patients. Consequently, much effort has focused on approaches that could replace conventional insulin therapy and provide more precise regulation of blood glucose levels. The biohybrid perfused artificial pancreas was designed to incorporate islet tissue and a selectively permeable membrane that isolates this tissue from the immune system of the recipient. Biohybrid pancreas devices containing canine islet allografts were implanted in ten pancreatectomized dogs requiring 18 to 32 units of injected insulin daily. These implants resulted in good control of fasting glucose levels in six of these animals without further exogenous insulin for periods of up to 5 months.

Animals↗
PubMed1991

Serum hepatitis C virus sequences in posttransfusion non-A, non-B hepatitis.

We investigated 17 patients (12 males and 5 females, ages 2 to 57 years old) with posttransfusion non-A, non-B hepatitis to determine relationships between clinical courses and hepatitis C virus (HCV) markers. The patients were grouped according to time course of abnormal serum alanine aminotransferase (ALT) levels into three categories (chronic biochemical disease, biochemically resolved chronic disease, and acute disease). Latest serum samples (1.3 to 10.8 years after blood transfusion) were used to detect antibodies against C100-3 antigen (anti-HCV) by enzyme-linked immunosorbent assay and HCV sequences by polymerase chain reaction (PCR) assay. Of the 17 patients, 13 patients (76.5%) were anti-HCV positive and 8 patients (47.1%), including one anti-HCV negative case, were positive for HCV RNA. In total, 14 patients (82.4%) were positive for either HCV markers. With respect to clinical course, HCV RNA was detected in six of eight patients (75%) with chronic biochemical disease, and in two of five patients (40%) with biochemically resolved chronic disease. HCV RNA was not detectable in convalescent sera from four patients with acute disease. These results show that there is a relationship between clinical status and HCV viremia, but that normal liver function tests do not always represent the clearance of the virus. Viremia in two patients with normal ALT level suggests that hepatitis is not only caused by viral cytopathic effects, but also by immunologic reactions against virus-infected cells. Thus, PCR is useful in determining the persistence of HCV infection as well as to diagnose anti-HCV negative HCV infection.

Adolescent↗
PubMed1991

Transplantation of islet allografts and xenografts in totally pancreatectomized diabetic dogs using the hybrid artificial pancreas.

Previously the authors reported on a Hybrid Artificial Pancreas device that maintained patent vascular anastomoses in normal dogs and, when seeded with allogeneic canine islets, maintained normal fasting blood sugars (FBS) in diabetic pancreatectomized dogs. Eventual failure of these devices was believed to be related to loss of islet viability and/or insufficient islet mass. The current study evaluates the effect of increased islet mass produced by implantation of two islet-seeded devices in pancreatectomized dogs and compares the results with those from dogs that received a single device. Twelve of fifteen dogs receiving single devices showed initial function as determined by elimination or reduction of exogenous insulin requirement; four showed initial function and seven showed extended function (100 to 284 days). Excessive weight loss (more than 20%), despite normal FBS and insulin dependence, required that four animals in this latter group be killed. Devices seeded with xenogeneic islets have met with limited success. One dog that received two bovine islet-seeded devices achieved function for more than 100 days; the remaining bovine-seeded devices (n = 8) functioned for only 3 to 16 days. Porcine islet-seeded devices were assessed by intravenous glucose tolerance tests (IVGTT). Recipients of two devices seeded with allogeneic islets demonstrated improved IVGTT results when compared to those from pancreatectomized dogs and recipients of single devices but were abnormal when compared to intact animals. Histologic examination of device and autopsy material from all failed experiments was performed and showed no mononuclear cell infiltration of the islet chamber or vascular graft material, only a few incidence of device thrombosis, and varying degrees of islet viability as judged by morphologic and immunohistochemical evaluation. The authors believe they have demonstrated progress toward the development and clinical applicability of the Hybrid Artificial Pancreas.

Animals↗