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Biomedical subjects

D M Smith

Publications and source records attributed to D M Smith.

At least 235 records · Page 13Linked to original sources
PubMed1993

Influence of islet amyloid polypeptide and the 8-37 fragment of islet amyloid polypeptide on insulin release from perifused rat islets.

IAPP, or amylin, is a 37-amino acid peptide that is co-secreted with insulin from the pancreatic beta-cells. We have determined the effects of IAPP and the antagonist 8-37 fragment of IAPP on the secretion of insulin from isolated rat islets studied in a perifusion system. Insulin secretion was stimulated by 8 mM glucose and 0.2 microM carbachol. IAPP at 10(-7) M reduced insulin release by 32% from 7.1 (95% Cl 5.8-8.6) to 4.8 (3.0-7.5) fmol.min-1 x islet-1 (P = 0.046, n = 7). IAPP at 1.5 x 10(-6) M reduced insulin release by 62% from 6.5 (3.4-12.3) to 2.5 (1.4-4.4) fmol.min-1 x islet-1 (P = 0.001, n = 6). IAPP at 10(-5) M decreased insulin release by 70% (P < 0.001, n = 6). When IAPP (8-37) at 10(-5) M was added to IAPP at 1.5 x 10(-6) M, there was only a 22% reduction of insulin release (P = 0.06, n = 6) compared with control chambers with no peptide added. This reduction was less (P = 0.002) than observed with IAPP (1.5 x 10(-6) M) alone. IAPP (8-37) at 4 x 10(-5) M in the absence of exogenously added IAPP increased insulin secretion by 48% (P = 0.01, n = 6), but IAPP (8-37) at 10(-5) M did not alter insulin secretion. These findings demonstrate that IAPP decreases insulin secretion from islet beta-cells, an effect that can be antagonized by the 8-37 fragment of IAPP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1993

Findings in pinnipeds stranded along the central and northern California coast, 1984-1990.

Personnel at The Marine Mammal Center (The Center) treated 1,446 stranded marine mammals recovered from the central and northern California (USA) coast from 1984 through 1990, including California sea lions (Zalophus californianus), northern elephant seals (Mirounga angustirostris), Pacific harbor seals (Phoca vitulina richardsi), northern fur seals (Callorhinus ursinus), Steller sea lions (Eumetopias jubatus), and Guadalupe fur seals (Arctocephalus townsendi). The primary disease findings in stranded California sea lions were renal disease, renal disease complicated by severe verminous pneumonia, verminous pneumonia, seizures of unknown etiology, and renal disease complicated by severe pneumonia of unknown etiology. Stranded elephant seals included pups, yearlings with dermatological problems, and neonates. Most harbor seals admitted to The Center were underweight and premature pups. Stranded northern fur seals included animals with seizures of unknown etiology and emaciated pups. Stranded Steller sea lions included underweight pups and aged adult females with pneumonia. Two Guadalupe fur seals had hemorrhagic gastroenteritis. Incidental findings at the time of stranding among the six species included verminous pneumonia and pneumonia of unknown etiology, renal disease, internal parasitism, ophthalmologic problems, gastrointestinal disorders, otitis externa, and external wounds.

Animals↗
PubMed1993

Association of fluoxetine and return of sexual potency in three elderly men.

BACKGROUND: Fluoxetine, a highly specific serotonin reuptake inhibitor, has been reported to cause sexual dysfunction in a minority of patients. Although priapism has been associated with other serotonergic antidepressants, no published reports have correlated restoration of sexual potency with use of fluoxetine. METHOD: The case histories of three geriatric patients treated with fluoxetine for depression or obsessive compulsive disorder are presented. RESULTS: Three patients with histories of impotence experienced a return of sexual potency after treatment with fluoxetine. In two of the cases, the patients had documented histories of vascular disease, which their internists had identified as the cause of their impotence. The improvement in sexual response was seemingly unrelated to abatement of depression or obsessive compulsive disorder, and there was no description of priapism by any of the patients. CONCLUSION: Sexual side effects of fluoxetine may be more variable than previously thought. Animal models showing paradoxical or opposing responses to serotonin-enhancing agents may apply to human sexual functioning as well.

Age Factors↗
PubMed1992

Mechanisms regulating cardiac fuel selection in hyperthyroidism.

Starvation (48 h) decreases fructose 2,6-bisphosphate (Fru-2,6-P2) concentrations and the ratio of free to acylated carnitine in hearts of euthyroid rats. These decreases, which are indicative of increased lipid fuel oxidation, are accompanied by decreased rates of glucose uptake and phosphorylation, assessed by using radioactive 2-deoxyglucose. Cardiac concentrations of acylated carnitines were increased at the expense of free carnitine even in the fed state in response to experimental hyperthyroidism, but neither Fru-2,6-P2 concentrations nor rates of glucose utilization were suppressed. Starvation (48 h) did not further increase the proportion of acylated carnitine in the heart in hyperthyroidism, and suppression of Fru-2,6-P2 concentrations and glucose utilization rates by starvation was attenuated. Although glucose utilization rates were decreased, starvation did not decrease immunoreactive GLUT 4 protein concentrations. Furthermore, although hyperthyroidism was associated with a statistically significant (30-40%) increase in relative abundance of GLUT 4 mRNA, the amount of GLUT 4 protein was not increased by hyperthyroidism in either the fed or the starved state. The results demonstrate a significant effect of hyperthyroidism to enhance cardiac glucose utilization in starvation by a mechanism which does not involve changes in GLUT 4 expression but may be secondary to changes in glucose-lipid interactions at the tissue level.

Animals↗
PubMed1992

Investigation of the interaction of VIP binding sites with VIP and PACAP in human brain.

We have compared the binding of [125I]vasoactive intestinal polypeptide (VIP) to human brain membranes with that of [125I]PACAP27. [125I]VIP was displaced by PACAP27, VIP and two synthetic peptides, peptide-1 (N-terminal PACAP27/C-terminal VIP) and peptide-2 (N-terminal VIP/C-terminal PACAP27), but the IC50 of PACAP27 and peptide-1 were 10-20 times lower than those of VIP and peptide-2. [125I]PACAP27 was readily displaced by PACAP27 and peptide-1, with an IC50 of less than 1 nM, but poorly by VIP and peptide-2. Chemical cross-linking revealed that both labels were bound to polypeptides of Mr 66,000 and Mr 50,000. The results indicate that in human brain membranes both binding sites have a higher affinity to the N-terminal sequence of PACAP27, and VIP binding sites prefer PACAP27 to VIP itself.

Adenylyl Cyclases↗
PubMed1992

Glucose transporter expression and glucose utilization in skeletal muscle and brown adipose tissue during starvation and re-feeding.

Starvation (48 h) decreased the concentration of mRNA of the insulin-responsive glucose transporter isoform (GLUT 4) in interscapular brown adipose tissue (IBAT) (56%) and tibialis anterior (10%). Despite dramatic [7-fold (tibialis anterior) and 40-fold (IBAT)] increases in glucose utilization after 2 and 4 h of chow re-feeding, no significant changes in GLUT 4 mRNA concentration were observed in these tissues over this re-feeding period. The results exclude changes in GLUT 4 mRNA concentration in mediating the responses of glucose transport in these tissues to acute re-feeding after prolonged starvation.

Adipose Tissue, Brown↗
PubMed1992

Collection of blood mononuclear cells by leukapheresis for transplantation in a Yucatan miniature swine model.

A large animal model is needed to evaluate new apheresis technologies. These technologies include novel methods of harvesting the blood mononuclear cell population which contains the hematopoietic stem cells needed to restore hematopoiesis in recipients of hematopoietically lethal therapy and the use of cytokines to provide a safe and predictable method of manipulating these circulating hematopoietic stem cells. We describe the methods used to collect mononuclear cells by leukapheresis from Yucatan miniature swine. These animals are of sufficient size to tolerate the procedures and have many physiologic and hematologic similarities to man. They are of good temperament and are easily trained. Long-term venous access was obtained using single lumen silicone rubber catheters placed in the inferior vena cava. The animals were apheresed while fully awake using a Haemonetics Model V50 machine and a modified lymphocyte collection protocol. The procedure was highly efficient for the collection of mononuclear cells and a 10 pass procedure yielded a product which contained 19.7 x 10(9) mononuclear cells, 10.7 x 10(9) granulocytes, and 17 ml of erythrocytes in a volume of approximately 100 ml. This product can be cryopreserved and used for subsequent transplantation. The content of four apheresis procedures provides hematopoietic reconstitution of lethally irradiated swine on a time scale equivalent to transplantation of optimal numbers of bone marrow cells.

Animals↗
PubMed1992

Phosphatidylinositol hydrolysis by phospholipase A2 and C activities in human peripheral blood neutrophils.

We describe here and partially characterize a Ca(2+)-independent phospholipase A2 that acts on phosphatidylinositol in normal human peripheral blood neutrophils. Neutrophils incubated with myo-[3H]inositol to form [3H]phosphatidylinositol and then stimulated with the calcium ionophore A23187 produced [3H]lysophosphatidylinositol. This deacylation was further characterized in cell sonicates by the specific release of [3H]arachidonic acid from exogenous [1-14C]stearoyl-2-[3H]arachidonyl-phosphatidylinositol. This phospholipase A2 is Ca2+ independent, retaining full activity in the presence of 10 mM EDTA, and is optimally active at alkaline pH (pH 9). A phosphatidylinositol-hydrolyzing phospholipase C activity was characterized by the production of [3H]-/[14C]-diglycerides. This phospholipase C activity is dependent on the presence of exogenous Ca2+ and is optimally active at neutral pH (pH 7.5). The lipoxygenase/cyclooxygenase inhibitors eicosatetraenoic acid and nordihydroguaiaretic acid and the calmodulin antagonist trifluoperazine were the only compounds tested that showed significant inhibition of phospholipase A2 activity. However, none of these phosphatidylinositol-hydrolyzing phospholipase A2 inhibitory compounds resulted in the accumulation of any radiolabeled diglyceride, monoglyceride, or phosphatidic acid intermediates. Following subcellular fractionation on sucrose density gradients, it was found that the plasma membrane-enriched fractions contained the highest specific activity for phospholipase A2; however, the cytosolic fraction contained a large part of the total phospholipase A2 activity. Furthermore, when neutrophils were first exposed to several agents, including lipopolysaccharide, phorbol myristate acetate, or N-formyl-methionyl-leucyl- phenylalanine, and then subfractionated, there was a significant translocation of the enzyme activity from the cytosolic fraction to the membrane-enriched fractions. These data suggest that this Ca(2+)-independent, phosphatidylinositol-hydrolyzing phospholipase A2 may play an important role in early cell activation, providing free arachidonic acid for subsequent metabolism into biologically active eicosanoids.

Arachidonic Acid↗
PubMed1992

Amniotic fluid and umbilical artery levels of sex hormones and prostaglandins in human cocaine users.

Biochemical evaluation of amniotic fluid contents is often used to monitor fetal secretory and excretory functions. To determine whether cocaine use during pregnancy affects fetal endocrine secretions, amniotic fluid and umbilical artery samples were collected at term, and selected gonadal hormones and prostaglandins were assayed. Gestational age, birth weights, and placental weights were recorded. The data showed that birth weights were significantly decreased (P less than 0.001) in cocaine users, but gestational age and placental weights were unaffected. Amniotic fluid levels of androstenedione and testosterone were decreased (P less than 0.05) in males born to cocaine users; females were not affected. Prostaglandins (PGF2 alpha and PGE2) were significantly increased (P less than 0.01) in cocaine users. In the umbilical artery, follicle-stimulating hormone was increased (P less than 0.01) in males and females, while luteinizing hormone was increased (P less than 0.01) only in males. We conclude that cocaine passes through the placenta and affects the fetal testes-hypophyseal endocrine system.

Adult↗
PubMed1992

Predicting post-hospital discharge health care costs.

Patients in this study represented an important group for health services research; their postdischarge costs were high, resulted from readmissions (especially for nonelective reasons), and were incurred by a minority of patients. Moreover, intensive interventions delivered by ambulatory care providers has the potential to reduce overall costs if patients at highest risk for readmission could be identified prospectively (Smith et al., 1988; Weinberger et al., 1988). We developed a model to predict post-hospital discharge costs in these patients using strategies to maximize their predictive capability. Although the model appeared to account for more variance in costs than currently available models in the derivation set, its performance in the validation set, albeit statistically significant, was disappointing. Because we considered a broad array of predictors, expanding the number of patient-oriented variables may not be fruitful. Instead, future research may need to consider more homogenous subgroups of patients in whom specific laboratory tests would have clinical significance; variance in providers' behaviors; and studies in health maintenance organizations, where control over resource utilization may make costs more predictable. Finally, empirically derived models must be tested in an independent sample. Without validating predictive models, the models' ability to predict health care costs may be overestimated.

Ambulatory Care↗
PubMed1992

Investigation and characterization of binding sites for islet amyloid polypeptide in rat membranes.

Islet amyloid polypeptide (IAPP) is a 37-amino acid peptide shown to be cosecreted with insulin from the pancreatic beta-cells. We have investigated the existence and characteristics of IAPP binding sites in the rat. Specific binding sites for [125I]IAPP were found to be highest in the lung followed by the stomach fundus, spleen, brain stem, hypothalamus, and the liver, respectively. The interaction of [125I]IAPP with its binding site was rapid and temperature dependent, displaying optimum binding at 4 C. This may be explained by the rapid degradation of the label observed at 22 C and 37 C, as determined by fast protein liquid chromatography analysis, and also degradation of the receptor at 37 C. Binding of [125I]IAPP was rapidly dissociated by the addition of 200 nM unlabeled peptide. The presence of nonmetabolizable GTP-gamma-S (0.5 microM) reduced binding, thus suggesting the coupling of the binding site to a G protein. Rat IAPP displaced [125I]IAPP displaying an IC50 of 5.75 x 10(-9) M (mean, n = 4). Displacement was also seen with human IAPP (IC50 = 5.53 x 10(-8) M), human alpha-calcitonin gene-related peptide (CGRP) (IC50 = 3.8 x 10(-8) M), rat alpha-CGRP (IC50 = 9.0 x 10(-7) M), and rat beta-CGRP (IC50 = 5.53 x 10(-8) M); suggesting an IAPP-specific binding site. Scatchard plots for rat IAPP binding in the lung gave a dissociation constant of 10.4 +/- 2.63 nM (mean +/- SE, n = 4) and maximal binding of 3.1 +/- 0.97 pmol/mg (mean +/- SE, n = 4), displaying a single class of binding site. Chemical cross-linking analysis showed binding of IAPP to sites of Mr 67,000, 64,000, and 38,000. These findings suggest that specific IAPP binding sites exist which differ from the CGRP receptors in rat tissues. This indicates a possible novel autocrine/paracrine role for IAPP.

Adenosine Triphosphate↗
PubMed1992

Immunosuppressive effects of blood transfusion.

Various in vitro studies, animal models, and retrospective investigations suggest that blood transfusion modulates the immune system. Not all studies, however, support this trend. This article provides a balanced presentation of the issues surrounding the concept of the immunosuppressive effects of blood transfusion.

Animals↗
PubMed1992

Chronic catheterization of the inferior vena cava in Yucatan miniature swine.

Long-term venous access for leukapheresis, repeated blood sampling, and administration of drugs and fluids can be accomplished nonsurgically in Yucatan miniature swine. The catheter is placed under fluoroscopic guidance into the inferior vena cava using a needle and guidewire. This procedure has the advantage that it avoids a surgical incision, allows high flow rates, exists conveniently on the lower back, and can be replaced easily in the event of mechanical failure or thrombosis. Actuarial analysis of the duration of patency disclosed that of 41 catheters placed in 30 animals, the probability of function at 28, 42, and 54 days was 75%, 50%, and 25%, respectively. Eleven nonfunctioning catheters were replaced and nine of these continued to function until the completion of the experiment. No catheters were removed due to infection. Chronic catheterization of the inferior vena cava is a convenient method for long-term venous access in swine.

Animals↗