Search PubMed⌕ Search

Biomedical subjects

D H Mintz

Publications and source records attributed to D H Mintz.

At least 37 records · Page 2Linked to original sources
PubMed1993

Primary structure of the canine CD4 antigen.

After PCR amplification two overlapping cDNA clones encoding the dog homologue of the human CD4 glycoprotein were identified. This internal fragment of the mature protein including the complete extracellular domains, consists of 1297 bp with a deduced amino acid sequence of 432 residues. The dog CD4 molecule differs from the corresponding protein of other species including human in the second domain. We found nine extra residues in the beginning of that domain, a cysteine at position 138, usually involved in a disulfide bridge, is substituted by tryptophan, and three new glycosylation sites are present.

Amino Acid Sequence↗
PubMed1992

Effect of FK506 on insulin secretion in normal dogs.

In this report, we describe the effect of FK506 on glucose-mediated insulin release in normal dogs. Dogs were placed into one of two groups, group 1 dogs received FK506 (1 mg/kg/d orally) for 2 weeks, and group 2 dogs received FK506 at the same dose, but for 4 weeks. Following the treatment period, both groups of dogs were allowed a recovery period during which time no FK506 was administered. Intravenous glucose tolerance tests (IVGTT) were performed (0.5 mg/kg IV) before FK506 treatment, after 2 or 4 weeks of treatment, and following the recovery periods. Complete blood cell counts (CBC) and serum chemistries were also obtained at these times. Following FK506 treatment for either 2 or 4 weeks, the dogs experienced a delay in glucose disappearance in response to IV glucose injection. Insulin secretion during IVGTT was unchanged in dogs treated for only 2 weeks, but was significantly decreased in dogs treated for 4 weeks. Following the recovery period, glucose disappearance during IVGTT returned to normal in dogs that were treated for 2 weeks, and was more rapid than normal in dogs that had been treated for 4 weeks. Insulin secretion after the recovery period remained unchanged in group 1 dogs, but continued to be significantly reduced in group 2 dogs that had received FK506 for 4 weeks. No significant change was detected in the CBCs or serum chemistries.

Animals↗
PubMed1992

Detection of intrahepatic human islets following combined liver-islet allotransplantation.

This article describes the localization of intact insulin-containing intrahepatic islets after combined liver-islet allotransplantation. The patient was a 36-year-old woman who underwent upper abdominal exenteration for neuroendocrine carcinoma; 289,000 islets were transplanted via portal vein infusion immediately after complete revascularization of the liver. Immunosuppression was with low-dose FK-506. OKT3 and steroids were used to treat one rejection episode 2 weeks after transplantation, but the patient subsequently developed multiple infections and died 109 days after transplantation. At autopsy, the transplanted liver did not show any sign of rejection and well-preserved islets were present in portal triads sampled from the anterior inferior edge of the right lobe. Immunohistochemical labeling confirmed the presence of insulin-containing cells. This finding indicated that human islets can survive after intrahepatic allotransplantation, despite positive cross-match with no HLA antigen match, suggesting that upper abdominal exenteration and liver transplantation may constitute a protective factor for the survival of allogeneic human islets.

Adult↗
PubMed1992

Human islet isolation and allotransplantation in 22 consecutive cases.

This report provides our initial experience in islet isolation and intrahepatic allotransplantation in 21 patients. In group 1, 10 patients underwent combined liver-islet allotransplantation following upper-abdominal exenteration for cancer. In group 2, 4 patients received a combined liver-islet allograft for cirrhosis and diabetes. One patients had plasma C-peptide greater than 3 pM and was therefore excluded from analysis. In group 3, 7 patients received 8 combined cadaveric kidney-islet grafts (one retransplant) for end-stage renal disease secondary to type 1 diabetes mellitus. The islets were separated by a modification of the automated method for human islet isolation and the preparation were infused into the portal vein. Immunosuppression was with FK506 (group 1) plus steroids (groups 2 and 3). Six patients in group 1 did not require insulin treatment for 5 to greater than 16 months. In groups 2 and 3 none of the patients became insulin-independent, although decreased insulin requirement and stabilization of diabetes were observed. Our results indicate that rejection is still a major factor limiting the clinical application of islet transplantation in patients with type 1 diabetes mellitus, although other factors such as steroid treatment may contribute to deteriorate islet engraftment and/or function.

Adolescent↗
PubMed1991

Influence of portal delivery of insulin on intracellular glucose and lipid metabolism.

We have investigated whether portal delivery of insulin as a result of intrahepatic islet cell autografts would prevent the development of metabolic alterations. Seven pancreatectomized dogs received islet autografts transplanted into the liver through the portal vein (PD). One year after transplantation, their intravenous glucose tolerance and insulin responses were similar to age-matched control (C) dogs (n = 5). Also, normal triglyceride content in arterial smooth muscle and striated muscle was observed in the dogs with portal insulin delivery in contrast to the substantial increases we observed in pancreatectomized dogs (n = 7) with pancreatic autografts that drained into the systemic circulation (SD). In these dogs, the tissue samples were taken at the age of 3 to 4 years. Triglyceride content (mean +/- SEM) in the aorta was 4.9 +/- 1.2 versus 2.6 +/- 0.6 versus 20.7 +/- 8.0 mumol/g (P less than .01) in C, PD, and SD models, respectively. The corresponding values for triglyceride content in striated muscles were 29.1 +/- 1.2, 25.9 +/- 1.5, and 171.4 +/- 46.6 mumol/g (P less than .01). Glucose-6-phosphate dehydrogenase (G-6-PDH) and malic enzyme, key enzymes for lipid synthesis, were also normal in the PD model, in contrast to the fivefold increased activity of these enzymes in the SD model (P less than .01). The glycolytic enzymes, hexokinase (HK) and phosphofructokinase (PFK), were normal compared with the decreased values in the SD. These data indicate that it is possible to normalize glucose and lipid metabolism in arterial walls by portal delivery of insulin, following intrahepatic islet cell transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

In vivo effect of FK506 on human pancreatic islets.

The purpose of this study was to evaluate the in vivo effect of FK506 on human pancreatic islets. Twenty-five nude mice were made diabetic by one intravenous injection of streptozotocin. Approximately 600 islets were administered in the renal subcapsular space 3-5 days following streptozotocin administration. One week after transplantation, the mice were divided in four groups. In group 1, the animals received 1 injection of 0.5 ml of diluent i.p. daily for one week. In groups 2, 3, and 4 the treatments were daily i.p. injection of 0.3, 1, and 3 mg/kg FK506, respectively. After treatment, the functional integrity of the transplanted human islets was tested by measuring the plasma glucose and human C-peptide response to intraperitoneal glucose injection in groups 1 and 4. IPGTT alone was assessed in groups 2 and 3. The results indicate that i.p. administration of FK506 for one week at a dose 0.3 mg/kg/day did not result in any significant alteration of glucose disappearance and C-peptide response to IPGTT. Higher doses of FK506 produced a significant delay in glucose disappearance in groups 3 and 4, and a significant inhibition of glucose-mediated C-peptide response in group 4.

Anti-Bacterial Agents↗
PubMed1990

Pancreatic islet transplantation after upper abdominal exenteration and liver replacement.

Nine patients who became diabetic after upper-abdominal exenteration and liver transplantation were given pancreatic islet-cell grafts obtained from the liver donor (eight cases), a third-party donor (one), or both (four). Two patients were diabetic when they died of infections after 48 and 109 days, as was a third patient who died of tumour recurrence after 178 days. The other 6 are alive 101-186 days postoperatively, and five are insulin-free or on insulin only during night-time parenteral alimentation. C-peptide increased 1.7 to 3.3 fold in response to intravenous glucose in these five patients who have had glycosylated haemoglobin in the high normal range. However, the kinetics of the C-peptide responses to intravenous glucose in all eight patients tested revealed an absent first-phase release and a delayed peak response consistent with transplantation and/or engraftment of a suboptimal islet cell mass. The longest survivor, who requires neither parenteral alimentation nor insulin, is the first unequivocal example of successful clinical islet-cell transplantation.

Abdomen↗
PubMed1990

Isolation of pancreatic islets from dogs. Semiautomated purification on albumin gradients.

We describe a procedure for the isolation of large numbers of canine pancreatic islets with a high level of purity. The method utilizes enzymatic and mechanical disruption of the pancreas, followed by islet purification on discontinuous density gradients of bovine serum albumin. Purification has been semiautomated through use of the Cobe 2991 cell processor. Islet preparations have a purity of 86.5% and contain 36.8 microliters of endocrine tissue. Islets isolated by this procedure are functionally intact, and restore fasting euglycemia following autotransplantation.

Animals↗