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Biomedical subjects

G Gold

Publications and source records attributed to G Gold.

At least 19 recordsLinked to original sources
PubMed1995

A standardized patient program in a mandatory geriatrics clerkship for medical students.

This article describes the development and implementation of a new standardized patient program in a required geriatrics clinical clerkship for fourth-year medical students. A student survey was also conducted to provide evaluations of the program and to determine the frequency with which students' clinical skills are directly evaluated by faculty. Thirty-six percent reported never having been observed while obtaining a history and 24% having been observed only once; 26% had never been observed while completing a physical examination and 39% had been observed only once. The implementation of a standardized patient program provided students with direct feedback on their clinical skills and was rated positively, (good, very good, or outstanding) by 76% of the students.

Clinical Clerkship↗
PubMed1995

Hypertension: special concerns in managing the older patient.

In most populations, average diastolic BP increases with age until the sixth decade and then remains constant, whereas average systolic BP continues to rise. Many studies have shown an increase in cardiac and stroke risk with increasing BP, even in elderly populations. Antihypertensive therapy in the elderly has been shown to reduce the risk of nonfatal and fatal stroke, nonfatal and fatal coronary heart disease, and all-cause mortality. The right combination of diet and lifestyle changes can help to control hypertension and reduce cardiovascular risk. For optimal results, give the patient as much informed choice as possible in the selection of therapies and setting of goals. Proceed cautiously when it is necessary to add pharmacologic therapy, whatever agent is chosen.

Aged↗
PubMed1993

Education in geriatrics: a required curriculum for medical students.

The mandatory geriatrics and gerontology curriculum at The Mount Sinai School of Medicine in New York includes two modules for first- and second-year students and a four-week block experience for fourth-year students. The first-year curriculum emphasizes socioeconomic, psychosocial, biomedical, and attitudinal issues. The second-year experience serves as an introduction to clinical geriatrics. The fourth-year clerkship allows students to further develop their fund of geriatric knowledge, learn specific geriatric skills, and build on their internal medicine foundation, integrating new knowledge and skills and developing into comprehensive practitioners who can apply the team approach to address all the medical, functional, psychosocial, and ethical aspects of caring for the elderly.

Curriculum↗
PubMed1993

Health care for the homebound older adult: a medical model.

The medical home-care program is a logical and indispensable addition to the comprehensive, multilevel geriatric care offered by the Department of Geriatrics. The home-care program enables the frail and homebound elderly to remain in their home environment and continue to receive comprehensive primary medical care and supportive services. It also serves as a valuable teaching site for medical trainees. Program evaluation through assessment of patient and caregiver satisfaction, estimates of costs of care, and frequency of hospitalization and emergency room visits are ongoing.

Aged↗
PubMed1991

Human and rat amylin have no effects on insulin secretion in isolated rat pancreatic islets.

Amylin, an islet amyloid peptide secreted by the pancreatic beta cell, has been proposed as a humoral regulator of islet insulin secretion. Four separate preparations of amylin were tested for effects on hormone secretion in both freshly isolated and cultured rat islets and in HIT-T15, hamster insulinoma cells. With all three experimental models, exposure to human amylin acid and human and rat amylin at concentrations as high as 100 nM had no significant effect on rates of insulin or glucagon secretion. These observations suggest that amylin, even at concentrations appreciably higher than those measured in peripheral plasma, is not a significant humoral regulator of islet hormone secretion.

Amyloid↗
PubMed1988

Unregulated secretion of an exogenous glycotripeptide by rat islets and HIT cells.

Freshly isolated rat islets and cultured hamster insulinoma cells (HIT T15) were incubated with a membrane-permeable octanoyl tripeptide (N-octanoyl-ASN-TYR-THR-NH2), which contains an acceptor sequence for ASN-linked glycosylation. Labeled octanoyltripeptide (125[I]TYR) was glycosylated by both islets and HIT cells. The carbohydrate moiety of this glycotripeptide was removed by N-glycanase indicating that glycotripeptide was formed in the lumen of endoplasmic reticulum and, subsequently was secreted via the route for secretory protein. Secretion of glycotripeptide began more rapidly than that of insulin newly synthesized from 3[H]leucine. At 30 min glycotripeptide secretion was already significant but, over a 3-h period, it never represented more than 21% of glycotripeptide produced. Glycotripeptide secretion was not affected by compounds shown to regulate insulin secretion (glucose, forskolin, EGTA and streptozotocin). Thus in beta cells, it appears that glycotripeptide secretion is unregulated and that its cellular secretory pathway is different from that for insulin.

Adenoma, Islet Cell↗
PubMed1988

Biosynthetic regulation of endogenous hamster insulin and exogenous rat insulin II in transfected HIT cells.

To investigate mechanisms underlying biosynthetic regulation of an insulin gene, the rat insulin II gene was introduced into hamster beta-cells (HIT) by cotransfection with the neomycin phosphotransferase-selectable marker. The insulin gene fragment was 2.2 kilobases (kb) in length and contained all exons, introns, and approximately 700 base pairs (bp) of 5'-flanking DNA and 300 bp of 3'-flanking DNA. The HIT cell was known to have endogenous hamster insulin production under regulation by glucose and dexamethasone. In a pool of stably transfected cells (HIT M62pR2), rat insulin II and hamster insulin were produced at comparable rates. Glucose (20 mM) stimulated cellular [3H]leucine labeling of both hamster insulin and rat insulin II by approximately twofold. Addition of 10(-6) M dexamethasone to media containing 11.1 mM glucose inhibited biosynthesis of both hamster insulin and rat insulin II by greater than 90%. Thus, with both positive and negative biosynthetic regulation, changes in the cellular labeling of exogenous rat insulin II were qualitatively and quantitatively similar to those of the endogenous hamster insulin. These data suggest that the 2.2-kb rat insulin II gene fragment contained sufficient information for both expression and apparently "normal" biosynthetic regulation of exogenous rat insulin II (when compared with endogenous hamster insulin) in response to glucose and dexamethasone.

Animals↗
PubMed1988

Insulin biosynthesis in HIT cells. Effects of glucose, forskolin, IBMX, and dexamethasone.

Glucose, forskolin, 3-isobutyl-1-methylxanthine (IBMX), and dexamethasone were tested as regulators of proinsulin biosynthesis in HIT T-15 cells, which are glucose-responsive simian virus 40-transformed hamster beta-cells. Rate of [3H]leucine incorporation into proinsulin was increased as glucose concentrations were raised from 0 to 20 mM. Biosynthetic rate increases were significant after 48 but not at 4 or 24 h of glucose and were greater for proinsulin than for total extractable proteins. After 48 h, glucose-stimulated proinsulin biosynthesis was unaffected by 10(-6) M forskolin and/or 3 x 10(-5) M IBMX but was specifically and significantly inhibited by 10(-6) M dexamethasone. Four hours of exposure to dexamethasone had no effect. When cells were incubated for 24 h and then continuously labeled for an additional 24 h, cellular conversion of labeled proinsulin to insulin was increased by glucose, and this increase was reversed or inhibited by 10(-6) M dexamethasone. Therefore, proinsulin biosynthesis in transformed HIT T-15 cells is regulated in several ways by metabolites and hormones in a manner that compares with biosynthetic regulation in normal beta-cells.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Effects of tolbutamide pretreatment on the rate of conversion of newly synthesized proinsulin to insulin and the compartmental characteristics of insulin storage in isolated rat islets.

Tolbutamide (1 g/kg body wt) was administered to male rats for 3 days to determine the effects of this pretreatment on subsequent insulin biosynthesis and compartmental storage characteristics of freshly isolated islets. Islets were isolated 16 h after the last tolbutamide administration, at a time when fed plasma glucose concentrations were normal. Islet glucagon was unchanged but insulin content was significantly reduced (38 +/- 1.2 ng IRI/islet from seven untreated rats versus 7.9 +/- 1.2 ng IRI/islet from eight treated rats). After tolbutamide pretreatment, the rate of incorporation of 3H-leucine into islet proinsulin was unchanged, but the t1/2 of labeled proinsulin-to-insulin conversion was significantly (P less than 0.001) decreased from 36 to 20 min. After treatment, actual rates of glucose-stimulated insulin secretion were 50% lower, however, because due to the proportionately greater depletion of islet insulin content, the fractional rate of secretion was increased two-fold. After treatment, there was evidence of compartmental, heterogeneous insulin storage, and glucose still marked newly synthesized insulin for preferential release; however, the differential release of new and old insulin converged rapidly with time. Mathematical integration of the data suggested dilution of the newly synthesized insulin compartment with unlabeled insulin during the chase period, but additionally indicated more rapid mixing of newly synthesized with previously stored, unlabeled insulin. Thus, tolbutamide-treated rats partially compensated for acute insulin depletion by increasing the rate of proinsulin-to-insulin conversion, but not increasing the rate of proinsulin biosynthesis; doubling the glucose-stimulated fractional secretory rate of the depleted cellular insulin storage compartment; and retaining compartmental storage characteristics but mixing newly synthesized insulin more rapidly with the compartment of previously stored, unlabeled insulin.

Animals↗
PubMed1984

Effects of monensin on conversion of proinsulin to insulin and secretion of newly synthesized insulin in isolated rat islets.

When isolated rat islets were incubated with 10(-10) - 10(-6) M monensin, a sodium and proton ionophore, glucose-stimulated insulin release was inhibited in a concentration- and time-dependent manner. After removal of monensin, inhibition of insulin secretion persisted during stimulation with a variety of secretagogues, including 5 mM glucose plus 15 mM arginine, 20 mM glucose, and 20 mM glucose plus 1 mM 3-isobutyl-1-methylxanthine. Within the same low range of monensin concentrations, proteolytic conversion of newly synthesized proinsulin to insulin was also blocked. At each concentration, prohormone-to-hormone conversion was inhibited to almost the same extent as inhibition of insulin secretion. Therefore, both processes may have equal or common dependency on a subcellular ionic gradient. Although monensin decreased total insulin secretion, the glucose-regulated marking process was unaffected. Regardless of the monensin concentration or the overall rate of insulin secretion, the percentage of secreted newly synthesized versus older insulin remained the same, and the threefold differences in the fractional secretory rates of newly synthesized versus total insulin also remained the same. Thus, rather than specifically blocking protein traffic through the Golgi apparatus of the beta cell, monensin probably first inhibited insulin secretion by disrupting proton gradients in secretory vesicles and, thereby, also inhibited other processes occurring within this organelle.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Contrasting patterns of insulin biosynthesis, compartmental storage, and secretion. Rat tumor versus islet cells.

A series of 3H-leucine pulse-labeling experiments was carried out with dispersed cells freshly isolated from transplanted rat insulinomas. After secreted fractions were separated, insulin was purified and specific activities were determined for both secreted and average cellular insulins. Labeling patterns in this line of tumor cells were compared with those previously established for isolated rat islets. With both tumors and islets, conversion of labeled proinsulin to insulin occurred to the same extent by 2.5 h, suggesting similar onset and half-time of proteolysis in these cells. However, total cellular insulin in tumors attained a threefold higher specific activity than in islets. Because total B-cell mass in these tumors was unknown, either a more rapid proinsulin biosynthesis or diminished cellular storage (or both) could lead to this faster fractional replacement of total stored insulin. Insulin secretion in these tumor cells was insensitive to high glucose but responded, albeit poorly, to leucine plus 3-isobutyl-1-methylxanthine (IBMX). Under all secretory conditions tested, tumor cells continuously secreted insulin at elevated fractional rates, which were slightly higher than fractional insulin secretory rates in maximally glucose-stimulated islets. In contrast with normal islets, newly synthesized insulin was stored homogeneously in tumor cells, and compartmental storage characteristics were not generated by incubation with either 20 mM glucose or leucine plus IBMX in the marking period. Thus, preferential secretion of insulin was never observed in tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1982

Evidence that glucose "marks" beta cells resulting in preferential release of newly synthesized insulin.

Studies of isolated islets labeled with radioactive leucine show that glucose at a critical time "marks" islets in such a way as to cause preferential release of newly synthesized insulin. The preferential release of insulin from marked islets is relatively independent of subsequent secretagogues or rates of insulin secretion. Previous kinetic studies have indicated that the critical time at which marking occurs is after proinsulin biosynthesis but before the secretory event. Thus, secretory cells may regulate the diversion of newly synthesized material for immediate release as it is approaching or transiting the Golgi apparatus.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Heterogeneity and compartmental properties of insulin storage and secretion in rat islets.

To investigate compartmental properties of insulin storage and secretion, isolated rat islets were used for pulse-labeling experiments, after which proinsulin and insulin were purified rigorously. Processing of proinsulin to insulin neared completion by 3 h without additional loss of either radioactive peptide by cellular or extracellular proteolysis. The amount of labeled hormone rapidly diminished in islets; it was secreted at a higher fractional rate than immunoreactive insulin, resulting in secreted insulin's having a higher specific activity than the average cellular insulin. Newly synthesized insulin, therefore, was secreted preferentially. Changes in the specific activity of secreted and cellular insulin with time were consistent with changes predicted for islets containing 33% of their total insulin in a glucose-labile compartment. Predictions were based on steady-state analysis of a simple storage-limited representation of B cell function. Islets from either the dorsal or ventral part of the pancreas also contained 33% of their total insulin in a glucose-labile compartment. The same compartment was mobilized by 20 mM glucose, 50 mM potassium + 2 mM glucose, or 20 MM glucose + 1 mM 3-isobutylmethylxanthine as indicated by the specific activity ratio of secreted vs. cellular insulin, even though average secretion rates with these stimuli differed by more than threefold. In the absence of calcium, the effectiveness of 20 mM glucose as a secretagogue declined markedly, and the older stored insulin was preferentially mobilized because secreted insulin had a lower rather than a higher specific activity than cellular insulin. Results provide insight into the mechanisms of nonrandom mobilization and secretion of insulin form the B cell.

Animals↗
PubMed1981

Effect of variations in islet size and shape on glucose-stimulated insulin secretion.

The present study considers the effects of differences islet size and shape on in vitro glucose-stimulated insulin secretion. Islets were obtained from young rats and rapidly sorted into different size categories before incubation with 16.7 mM glucose. Subsequently, the diameters of each islet were measured and estimates of surface area and volume, assuming various spheroidal or ellipsoidal shapes, were obtained for each islet. These various figures were correlated with the amount of insulin secreted from the same islets and a regression curve was generated for each different islet shape. The results indicate that insulin secretion rates increased directly as a function of islet size (volume or surface area), regardless of islet shape (r = 0.78, p less than .01); thus, islet size is of major importance in predicting insulin secretion and studies utilizing isolated islets should be normalized for this factor. Measurements of islet diameter provide an easy solution to this problem.

Animals↗
PubMed1981

Diabetes induced with multiple subdiabetogenic doses of streptozotocin: lack of protection by exogenous superoxide dismutase.

The addition of exogenous superoxide dismutase (SOD) was examined as a possible means of protecting B-cells of mice against either the immediate or delayed toxicity caused by multiple injections of low doses of streptozotocin (Sz). Three different routes of SOD administration (i.p. and i.v. injection and continuous s.c. infusion) and several different doses and schedules were tried. In addition, a long-acting derivative of SOD was synthesized and tested. Despite the observation of a modest delay in the onset of diabetes in one experiment, no protective effect of SOD on the progressive elevation of blood glucose concentrations was evident in the majority of studies. Moreover, a loss in pancreatic insulin content and a tripling of pancreatic glucagon content occurred in all mice treated with low dosages of Sz, irrespective of whether or not either SOD or a long-acting derivative of SOD was administered. Finally, in parallel experiments in vitro, this enzyme was ineffective in protecting isolated rat islets from the acute toxicity of exposure to Sz on glucose-stimulated insulin release.

Animals↗