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D H Mintz

Publications and source records attributed to D H Mintz.

At least 73 records · Page 4Linked to original sources
PubMed1982

Immunocytochemical localization of HLA-DR in human islets of Langerhans.

Previous reports of allogeneic transplantation studies in rodents have postulated that the primary carriers of Ia antigen in islets of Langerhans are passenger leukocytes. We sought to demonstrate directly the localization of the analogous human antigen, HLA-DR, in islet-enriched fractions (IEFs), utilizing a nonpolymorphic monoclonal anti-DR (alpha DR) antibody. The presence of DR in the IEFs was first demonstrated by radioimmunobinding assay. Light microscopic immunocytochemistry, in frozen sections of intact (unfixed) human pancreas, revealed a staining pattern suggestive of a vascular distribution of DR in islets. Ultrastructural localization of DR was then carried out by indirect immunoperoxidase labeling in the presence of NaN3 (to prevent internalization of bound alpha DR). The major site of DR expression in the islet was the endothelial cell surface. Endocrine cells were entirely devoid of alpha DR binding. Nonislet endothelium was also heavily labeled, but acinar and ductal cells were completely negative. Leukocytes bound alpha DR but were relatively rare in the IEFs. Human islets, therefore, clearly express HLA-DR, but predominantly on insular endothelial cells. Isolation of pure endocrine cell populations, specifically free of endothelium, would appear to be a rational approach to reducing immunogenicity in allogeneic transplantation.

Antibodies, Monoclonal↗
PubMed1981

Tumor-induced osteomalacia. Evidence of a surgically correctable alteration in vitamin D metabolism.

A 15-year-old boy was treated for nonfamilial hypophosphatemic rickets. Treatment with ergocalciferol, 100,000 units/day, and phosphorus, 2 to 4 g/day, failed to alleviate the rickets. Levels of 1 alpha, 25-dihydroxyvitamin D were low while levels of 25-hydroxyvitamin D were elevated. After removal of a benign fibroma, the level of 1 alpha, 25-dihydroxyvitamin D increased, the serum phosphorus level became normal, and the osteomalacia was cured. The alteration of vitamin D metabolism and associated hypophosphatemia in oncogenic osteomalacia is a potentially reversible cause of bone disease mediated by the tumor.

Adolescent↗
PubMed1980

Cyclic adenosine-3',5'-monophosphate stimulates islet B cell replication in neonatal rat pancreatic monolayer cultures.

A possible role for cyclic adenosine 3',5'-monophosphate (cAMP) in islet B cell replication was examined in neonatal rat pancreatic monolayer cultures. Islet cells deteriorated and insulin release decreased during 12 d of culture in medium with 5.6 mM glucose, whereas the cells survived and insulin release increased during culture in medium with 5.6 mM glucose plus the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 0.1 mM), or in medium with 16.7 mM glucose with or without IBMX. IBMX also increased the mitotic index and stimulated dose-dependent increases in [(3)H]thymidine incorporation in nuclei of islet B cells in aldehydethionine stained radioautographs; maximal stimulation of B cell replication occurred with addition of 0.1 mM IBMX to 5.6 mM glucose (+170%, P < 0.001), and this increase was similar to that observed with 16.7 mM glucose (+185%, P < 0.001). Also, 8-bromo-adenosine-3',5-monophosphate, but not 8-bromo-guanosine-3',5'-monophosphate produced dose-dependent increases in islet B cell replication in medium with 5.6 mM glucose. Measurement of cAMP levels in the cultures revealed dissociations between effects on B cell replication and insulin release. Thus, addition of 0.1 mM IBMX, or 0.1 nM cholera toxin, to 5.6 mM glucose produced slightly greater increases in cAMP levels and B cell replication than did 16.7 mM glucose, whereas insulin release was increased significantly more with 16.7 mM glucose. Also, addition of 0.1 mM IBMX, or 0.1 nM cholera toxin, to 16.7 mM glucose stimulated further increases in cAMP levels and insulin release in the cultures, but no further increases in B cell replication. We conclude that (a) cAMP stimulates islet B cell replication, (b) cAMP may mediate the effects of glucose on B cell replication, and (c) mechanisms regulating B cell replication may be more sensitive to cAMP and/or different from those regulating insulin secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Intercellular communication in pancreatic islet monolayer cultures: a microfluorometric study.

Single islet cells in monolayer cultures of neonatal rat pancreas were microinjected with fluorescein and scanned topographically by microfluorometry. Fluorescein spread from an injected islet cell directly into neighboring islet cells, and, in the presence of 16.7 millimolar glucose, significantly more islet cells communicated with the injected cell than in glucose-free medium. Islet cells were also microinjected with glycolytic substrates and activators that produced transient changes in cellular levels of reduced pyridine nucleotides-nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate [NAD(P)H]. Changes in NAD(P)H fluorescence were observed in islet cells incubated first for 18 hours in very low glucose concentrations and then in a glucose-free medium and injected with glycolytic substrates and activators; however, little change of fluorescence occurred in adjacent islet cells. In contrast, after adding 16.7 millimolar glucose to the medium, injection of glycolytic substrates and activators produced transient changes in NAD(P)H fluorescence in the injected cell and in neighboring cells.

Animals↗
PubMed1979

Establishment of rat pancreatic endocrine cell lines by infection with simian virus 40.

The feasibility of infection and transformation by SV40 (simian virus 40) of primary cell cultures derived from newborn-rat pancreas was investigated. As judged by the presence of intranuclear SV40 T-antigen, exposure to the virus resulted specifically in infection and transformation of epithelioid (predominantly endocrine) cells. The transformed cells were subcultured (more than 64 passages) and cloned. Culture medium and acid/ethanol extracts of the cells did not contain detectable amounts of immunoreactive insulin after the third subculture. However, inoculation of such SV40-transformed pancreatic cells into immunodeficient rats results in tumours in which insulin production was partially restored through the passage in vivo, since the tumour cells contained and synthesized small amounts of immunoreactive insulin which co-migrated with an insulin marker on gel chromatography. Interestingly, the transformed cells maintained under tissue-culture conditions produced a protein immunologically related to insulin, soluble in aqueous buffer but insoluble in acid/ethanol. This 3000-dalton protein is too large to be a translation product of the rat preproinsulin 9S mRNA. SV40-transformed pancreatic cells might prove useful in the investigation of the factors controlling and maintaining insulin biosynthesis.

Animals↗
PubMed1979

Factors from fibroblasts promote pancreatic islet B cell survival in tissue culture.

A possible role for fibroblasts in promoting the survival and function of islet B cells in tissue culture was examined by the addition of fibroblasts from a mouse embryo cell line (3T3-L2) to islet cell monolayer cultures prepared from newborn rat pancreases. Co-culture of islet cells with fibroblasts significantly increased the recovery of insulin in medium and cells after 7 days of culture in medium supplemented with 10% serum, and prevented the deterioration of islet cells cultured in serum-free medium. Similarly- serum-free medium, conditioned by cultures of either 3T3-L2 fibroblasts or fibroblasts freshly isolated from newborn rat pancreases, maintained the release and content of insulin in islet cell monolayer cultures at levels four- to eightfold higher than in control serum-free medium. Serum-free, fibroblast-conditioned medium also enhanced the survival of intact islets maintained in free-floating culture for 28 days. The active factor(s) in fibroblast-conditioned medium has a high molecular weight and is heat-stable. We conclude that fibroblastic cells produce a macromolecular factor(s) capable of enhancing the survival of functional islet B cells in tissue culture.

Animals↗
PubMed1978

Acute renal failure in insulin-dependent diabetics: episodes secondary to intravenous pyelography.

Diabetic patients with chronic renal failure are known to be at risk for exacerbation of renal failure if they undergo intravenous pyelography (IVP). The present report demonstrates that diabetic patients with normal serum creatinine levels can sustain irreversible renal failure following an IVP. The experiences with this case suggest that, if the creatinine clearance is decreased in an insulin-dependent patient irrespective of the serum creatinine value, one must be aware of the possible hazard of acute renal failure and irreversible renal damage following the IVP. This would appear to be especially true if the diabetic patient has proteinuria in combination with the decreased creatinine clearance.

Acute Kidney Injury↗
PubMed1977

Fetal pancreatic glucagon responses in glucose-intolerant nonhuman primate pregnancy.

Rhesus monkey pancreatic alpha-cell function in streptozotoc-induced glucose-intolerant pregnancy is similar to that in normal primate pregnancy. Specifically, basal maternal and fetal plasma glucagon levels equate, and the fetal alpha cell does not respond to the glucagonogenic stimulus of either intravenous alanine or insulin-induced hypoglycemia. This contrasts with the accelerated maturation of the fetal beta cell in glucose-intolerant pregnancy, and does not support the concept of functional coupling of the pancreatic islet by a common glucose-based process. Fetal plasma glucagon levels do increase after L-dopa injection to the fetus. These data indicate that alpha cell unresponsiveness is a function of the glucagon-releasing mechanism rather than inadequate hormonal synthesis.

Alanine↗
PubMed1976

Gastrin in the perinatal rat pancreas and gastric antrum: immunofluorescence localization of pancreatic gastrin cells and gastrin secretion in monolayer cell cultures.

The presence and development of immunoreactive gastrin (IRGa) in the fetal and neonatal pancreas and pyloric antrum of the rat were studied. IRGa appeared in both organs at least as early as the 16th day of fetal life. Antral IRGa increased rapidly and continuously in the neonatal period, while pancreatic IRGa concentration increased and was maintained at a relatively constant level from days 5 to 35. Monolayer cell cultures of the neonatal rat pancreas were used to evaluate the role of cyclic AMP mediated release of gastrin. The addition of N6,O2'-dibutyryl cyclic AMP (4 mM) or theophylline (4 mM) to the culture medium induced significant release of gastrin. The stimulation of adenylate cyclase with cholera toxin (10 ng/ml) also resulted in significant gastrin release. Long-term cultures (18-24 days) were shown to release gastrin continuously at a relatively constant rate. The cellular localization of pancreatic gastrin in 7-day-old cultures was performed by immunological techniques, using fluorescein-labeled antibodies to gastrin. The gastrin-containing cells were located at the periphery of most of the endocrine cell clusters. Immunofluorescence techniques for insulin and glucagon also showed that the alpha cells had a similar peripheral distribution, although they were more frequent in number. In contrast, insulin-containing cells were numerous and were present in all areas of the endocrine cell clusters. The studies support the following conclusions: a) Gastrin is present in the rat pancreas, even as early as late fetal life; b) Gastrin-producing cells are present and functionally competent in monolayer cell cultures of the neonatal rat pancreas for prolonged periods of time (24 days); c) Gastrin is released from these cells when intracellular levels of cyclic AMP are increased; d) By immunofluorescence methods, the gastrin-producing cells in pancreatic cell cultures are found to be located at the periphery of the endocrine cell clusters.

Animals↗
PubMed1975

Maternal-fetal plasma glucose relationships in late monkey pregnancy.

Maternal hyperglycemia was induced in six late gestation monkey pregnancies with intravenous glucose injection plus infusion. The maximum measured plasma glucose levels of the mother varied from 380 to 1,020 Gm. per cent. A significant linear relationship evolved between maternal and fetal plasma glucose peak concentrations. A saturation limit to placental transfer of glucose across the placenta is not apparent from these data.

Animals↗
PubMed1975

Purification of monolayer cell cultures of the endocrine pancreas.

Experimental use of primary cultures of endocrine pancreas is constrained by early, vigorous proliferation of fibroblastoid cells. The addition of heavy metals, sodium ethylmercurithiosalicylate, phenyl mercuric acetate, phenyl mercuric nitrate and sodium aurothiomalate to the culture media selectively destroys these fibroblastoid cells yielding highly enriched, morphologically intact, functionally competent endocrine cells that are capable of cell replication. This action of heavy metals appears to be due to reversible inhibition of sulfhydryl enzymes since glutathione and thioglycolate were demonstrated to completely inhibit the cytotoxic effects of the mercury and gold containing agents, respectively. Certain variables in the application of the mercurial agents to pancreatic endocrine cell cultures were defined, most notably the enhanced sensitivity of fetal vs. neonatal tissue, and in inverse relationship of cell density to effective toxicity. After removal of the heavy metal agent from the culture media, many pancreatic islets send out cytoplasmic projections, containing large numbers of oriented microtubules which serve as bridging units to adjacent endocrine cells. The sustained availability of virtually pure pancreatic endocrine cell cultures, which results from the application of mercury to the culture media will undoubtedly permit many aspects of the cell biology of the endocrine pancreas to be directly and sequentially assailed.

Animals↗
PubMed1975

Perinatal primate parathyroid hormone metabolism.

Near-term fetal and neonatal parathyroid gland function has been studied in the Rhesus monkey. Fetal serum ionized calcium (Ca++) levels are significantly greater than simultaneously obtained maternal levels. Fetal serum parathyroid hormone (PTH) was undetectable both in the basal state and in association with EDTA-induced fetal hypocalcemia. Induced maternal hypocalcemia was associated with increased maternal serum PTH levels and no change in fetal basal serum Ca++ or PTH levels. Only a minimal decrease in simian neonatal serum Ca++ occurred over the first 48 h of life. Normal adult levels of serum PTH were present as early as 6 h of neonatal life. Induced hypocalcemia at 12 h of age resulted in a significant increase in serum PTH levels.

Animals↗