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Biomedical subjects

R M Smith

Publications and source records attributed to R M Smith.

At least 325 records · Page 18Linked to original sources
PubMed1986

Long term postnatal development of insulin secretion in early premature infants.

The postnatal development of insulin secretion was studied in a group of premature infants (26-30 weeks gestation at birth) for periods up to 110 days after birth and in a small group of full-term infants (38-42 weeks gestation) for up to 47 days after birth. Circulating insulin levels were measured before, and at 30 min after the commencement of a glucose infusion given either parenterally or enterally depending on conceptual age and the mode of nutrition of the infant. The insulin response was assessed as the ratio of the increase in plasma insulin concentration to the increase in blood glucose concentration at 30 min. There was a small insulin response to glucose on day 1 in the premature infants and this increased slowly over the remainder of the study period regardless of the route of administration of glucose or of the mode of nutrition. The full-term infants were more responsive over the seven postnatal weeks in which they were studied. It is concluded that early premature infants can take up to eighteen weeks to develop an ability to respond fully to hyperglycaemia with insulin secretion even though full oral nutrition had been established over the last twelve weeks.

Administration, Oral↗
PubMed1986

Circulating insulin-like growth factor I levels in newborn premature and full-term infants followed longitudinally.

Longitudinal circulating levels of insulin-like growth factor I (IGF-I) were measured by radioimmunoassay after acid/ethanol extraction of serum or plasma in 44 appropriate-for-gestational age (AGA) premature infants, 7 small-for-gestational age (SGA) premature infants and 9 AGA full-term infants. The subjects were divided into cohorts with gestational age at birth 26-29 weeks, 30-33 weeks, 34-37 weeks and 38-42 weeks (full-term). The premature infants in this study exhibited diminished growth as compared with normal intrauterine growth. In all but the earliest premature infant cohort there was an immediate fall from the mean fetal IGF-I level, as reflected by the cord value, to a basal postnatal circulating level of IGF-I. The basal level of circulating IGF-I in premature infants was related only to gestational age. It increased slowly from 25 weeks gestation until four weeks after full-term equivalent and was independent of time of birth. Full-term infants were distinguished from early premature infants by the occurrence of a prominent postnatal surge in circulating IGF-I levels that was characterised by a significant (P less than 0.02) increase between day 1 and days 10-15. The SGA and AGA infants in the 34-37 week cohort showed similar profiles of circulating IGF-I with no significant difference in cord values between the two groups.

Gestational Age↗
PubMed1986

A collaborative study to investigate the retention reproducibility of barbiturates in HPLC with a view to establishing retention databases for drug identification.

A collaborative study among 10 laboratories has been undertaken to investigate the interlaboratory reproducibility of retention measurements in a high performance liquid chromatographic (HPLC) system for separating barbiturates. The system involved an ODS-Hypersil column with an eluent of methanol:phosphate buffer (40:60, v/v) at pH 8.5; all laboratories used the same batch of packing material. The conventional methods of recording retention properties (retention times and capacity factors) gave poor interlaboratory reproducibility. Better results were obtained by expressing the retentions relative to a standard barbiturate (quinalbarbitone); relative adjusted retention times proved to be more effective than straightforward relative retention times. Retention indices based on the alkylarylketone scale were not as reproducible as the methods based on a single closely related compound. The best reproducibility was obtained using corrected capacity factors based on the retention of four barbiturates in a standard mixture. The results of the study are discussed with a view to selecting the best methods of recording retention in HPLC when considering the establishment of databases for drug identification.

Barbiturates↗
PubMed1986

Effects of short-term modification of dietary sodium intake on plasma catecholamines and blood pressure in prehypertensive children.

The influence of dietary sodium intake on plasma catecholamines was examined as part of a dietary intervention study in 21 prehypertensive school children. Diastolic blood pressure was significantly elevated in girls after 3 weeks on a high sodium diet compared with a low sodium diet. Plasma adrenaline levels were raised slightly by the high sodium intake but plasma noradrenaline was significantly reduced. Increases of plasma catecholamines in response to standing or cold stress were unaffected by changes in sodium intake. The results indicate that the pressor effect of dietary sodium in children is not attributable to increased sympathetic nerve activity.

Adolescent↗
PubMed1986

Effects of plasma norepinephrine elevation on the heart's adaptation to chronic aortic constriction in rats.

Chronically elevated plasma norepinephrine has the potential for supporting function of diseased hearts, yet may also initiate harmful biochemical and (or) structural changes in the myocardium. The present study investigated the dosage-related effects of chronic norepinephrine infusion on markers of myocardial damage and then tested the influence of a relatively low norepinephrine infusion rate (0.05 microgram X kg-1 X min-1) on the heart's adaptation to pressure overload in aortic constricted rats. Norepinephrine infusion at 0.50 microgram X kg-1 X min-1 led to significantly increased myocardial hydroxyproline concentration and significant mortality. A rate of 0.25 microgram X kg-1 X min-1 increased myocardial hydroxyproline concentration and mortality in aortic constricted rats but had no such effects on sham-operated rats. The lowest rate tested (0.05 microgram X kg-1 X min-1) significantly increased mean arterial pressure and lung weight of aortic constricted rats, without affecting the degree of left ventricular hypertrophy. This infusion rate and aortic constriction each increased plasma norepinephrine and impaired cardiac performance during rapid preloading, although their combination did not cause further impairment. Thus, it appears that even modest plasma norepinephrine elevation has a negative effect on the heart's adaptation to sustained pressure overload.

Animals↗
PubMed1986

Insulin processing by cultured hepatocytes.

The chloroquine-sensitive and chloroquine-insensitive steps in insulin degradation by cultured hepatocytes have been explored by employing low temperature to retard processing. Under standard conditions (90 min association and 60 min dissociation) chloroquine inhibited insulin degradation at 15 degrees C but not at 37 degrees C. However, if the association and dissociation periods were short so that only early degradation was examined, marked inhibition of insulin degradation by chloroquine could also be observed at 37 degrees C. This inhibitory effect was observed only during the first 15 min, being masked by increased insulin degradation subsequently. An increase in slowly dissociable insulin, as well as a twofold increase in volume density of multivesicular bodies (MVB), occurred in the presence of chloroquine at both 37 and 15 degrees C. Rapid insulin processing from the slowly dissociable compartment at 37 degrees C masked chloroquine's effect on insulin processing under usual conditions at that temperature. At physiological temperature the chloroquine-sensitive step is not obligatory for insulin degradation by hepatocytes.

Animals↗
PubMed1986

Cell type-specific variability of bacitracin's effects on insulin binding and intracellular accumulation.

Bacitracin is known to inhibit proteolytic degradation of insulin and several other peptide hormones. Previous work with isolated rat adipocytes showed that bacitracin blocked insulin degradation by the plasma membrane and, even in the absence of detectable insulin degradation, bacitracin increased insulin binding by decreasing the rate of insulin dissociation. The present study examined the effects of bacitracin on insulin binding and degradation and on levels of intracellular insulin in a variety of cell types. Bacitracin inhibited insulin degradation in all cell types. Maximal inhibition varied from 70% (H4IIEC3 hepatoma cells) to 95% (rat adipocytes); concentrations giving half-maximal inhibition varied from 25 microM (3T3-A31 fibroblasts) to 250 microM (H4IIEC3). Dose-response curves showed three distinctive effects on insulin binding: dose-dependent stimulation (rat adipocytes), a biphasic curve with slight stimulation at low doses and inhibition at concentrations greater than 50 microM (human fibroblasts, H4IIEC3, and 3T3-L1 adipocytes), or dose-dependent inhibition of binding (3T3-L1 preadipocytes and 3T3-A31 fibroblasts). The intracellular accumulation of insulin rat adipocytes was not affected by bacitracin but was decreased in all other cell types. These data illustrated type-specific variability in the effects of bacitracin on insulin processing resulting from cellular heterogeneity either in processing insulin or in response to bacitracin, or both, and suggest that insulin binding studies performed in the presence of bacitracin can be biased.

Adipose Tissue↗
PubMed1986

Heterogeneous effects of inhibitors of receptor processing on insulin binding and intracellular accumulation in various cell types.

This study utilized uniform incubation conditions and demonstrated heterogeneity in the effects of various agents on 125-insulin binding and intracellular accumulation in five cell types. The cells used in this study included rat adipocytes, H4IIEC3 cultured hepatoma cells, normal human fibroblasts, and 3T3-L1 preadipocytes and adipocytes. Bacitracin increased insulin binding to rat adipocytes but inhibited binding to all other cells. Chloroquine increased total cell-associated insulin in all cells except H4IIEC3 hepatoma cells. Methylamine and dansylcadaverine increased or decreased binding depending on cell type. Similar heterogeneity was found in the intracellular accumulation of insulin. Under control conditions, intracellular insulin at steady state varied from 16 to 52% of the total cell-associated insulin. Bacitracin decreased intracellular accumulation of insulin in 3T3-L1 adipocytes, preadipocytes, and human fibroblasts but increased accumulation in rat adipocytes. Chloroquine increased insulin accumulation in all cell types except H411EC3 hepatoma cells. Both methylamine and dansylcadaverine increased intracellular insulin in rat adipocytes and decreased accumulation in human fibroblasts. These results provide additional evidence of heterogeneity in insulin and/or insulin receptor processing among different cell types.

Adipose Tissue↗
PubMed1985

Ultrastructural analysis of the organization and distribution of insulin receptors on the surface of 3T3-L1 adipocytes: rapid microaggregation and migration of occupied receptors.

Monomeric ferritin-insulin and high-resolution electron microscopic analysis were used to study the organization, distribution, and movement of insulin receptors on differentiated 3T3-L1 adipocytes. Analysis of the binding to prefixed cells showed that insulin initially occupied single and paired receptors preferentially located on microvilli. The majority of receptors (60%) were found as single molecules and 30% were pairs. In 1 min at 37% C, 50% of the receptors on nonfixed cells were found on the intervillous plasma membrane and more than 70% of the total receptors had microaggregated. By 30 min only 7% of the receptors were single or paired molecules on microvilli. The majority were on the intervillous membrane, with 95% of those receptors in groups. The receptor groups on the intervillous plasma membrane could be found in both noncoated invaginations and coated pits. The concentration of occupied receptors in the noncoated invaginations and the coated pits was similar; however, ten times more noncoated invaginations than coated pits contained occupied insulin receptors. The observations in this study contrast with those reported on rat adipocytes using identical techniques (Jarett and Smith, 1977). Insulin receptors on adipocytes were initially grouped and randomly distributed over the entire cell surface and did not microaggregate into larger groups. Insulin receptors on rat adipocytes were found in noncoated invaginations but were excluded from the coated pits. The differences in the organization and behavior of the insulin receptor between rat and 3T3-L1 adipocytes suggest that the mechanisms regulating the initial organization of insulin receptors and the aggregation of occupied receptors may be controlled by tissue-specific processes. Since both of these cell types are equally insulin sensitive, the differences in the initial organization and distribution of the insulin receptors on the cell surface may not be related to the sensitivity or biological responsiveness of these cells to insulin but may affect other processes such as receptor regulation and internalization. On the other hand, the microaggregates of occupied receptors on both cell types may relate to biological responsiveness.

Adipose Tissue↗
PubMed1985

Nonoperative management of extradural hematoma.

Extradural hematomas (EDHs) do not always require surgical evacuation. We report a subgroup of conscious patients harboring EDHs who were referred for computed tomographic (CT) scanning several days after head injury with neurological signs that were static or improving. Twelve patients with EDHs 12 to 38 ml in volume were offered nonsurgical management and were followed by serial CT scanning. All patients made a complete neurological recovery and showed resolution of the hematoma on CT scanning over a period of 3 to 15 weeks. The features that may make an extradural hematoma suitable for conservative treatment are discussed.

Adolescent↗
PubMed1985

Chemical and biological investigations of a transformer accident at Binghamton, NY.

A transformer fire occurred in a state office building in Binghamton, NY on February 5, 1981. Particulates from inside surfaces of ceiling panels on 16 of the 17 floors had concentrations of polychlorinated dibenzofurans (PCDFs) ranging from less than 1 part per million (ppm) to 1200 ppm while polychlorinated biphenyl (PCB) concentrations varied from 28 ppm to 23,000 ppm. In spite of the wide variations in contaminant concentrations, complete analytical data from 11 floors showed that there was a consistent PCDF/PCB ratio (0.067 +/- 0.026) and also consistent PCDF isomer group distributions (tetra-CDFs, 33 +/- 5%; penta-CDFs, 40 +/- 3%; hexa-CDFs, 18 +/- 7%; hepta-CDFs, 6 +/- 3%). It was found that the particulate samples could be successfully ranked in order of their degree of chemical contamination by an in vitro bioassay. The bioassay was based on induction of keratinization or changes in morphology in mouse epithelial cells. Animal toxicology experiments were carried out with a soot sample containing a PCDF concentration which approximated the mean value found on the ceiling particulates. The single dose oral LD values of the soot and its benzene extract equivalent, each administered to female guinea pigs in 0.75% methyl cellulose, were 410 and 327 mg/kg, respectively. These results demonstrated that the soot matrix had virtually no effect on the toxicity of the chemical contaminants in the soot. Morphological alterations in liver tissues from animals receiving the soot were found after examination by electron and light microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational↗
PubMed1985

Endotoxin protection of rats from pulmonary oxygen toxicity: lack of complement involvement.

Endotoxin (1 mg/kg, I.P.) greatly reduces lung damage and pleural edema in rats exposed to greater than 99% oxygen. Endotoxin also activates and depletes complement in vitro. Prior in vivo complement depletion has been shown to protect rats from lung edema in some experimental models. This study was designed to evaluate the possibility that endotoxin may protect rats from oxygen toxicity by activating and thereby depleting complement. We found no significant changes in complement hemolytic activity in serum from endotoxin pretreated rats breathing greater than 99% oxygen at sea level for 60 hours. We also found that complement depletion prior to oxygen exposure failed to protect rats from the lung damage of oxygen toxicity. These results indicate that the mechanism of endotoxin protection from pulmonary oxygen toxicity does not involve complement.

Animals↗
PubMed1984

Lowering of blood pressure in chronic aortic coarctate hypertensive rats with anti-digoxin antiserum.

A marked lowering of arterial blood pressure was observed in chronic aortic coarctate (CAC) hypertensive rats after intravenous administration of anti-digoxin antiserum. The hypotensive effect lasted for about 30 min after dosing. In contrast to the pronounced changes observed following treatment with anti-digoxin antiserum in CAC rats, only a transient pressor effect was observed in both water- and saline-drinking CAC rats following injection of normal goat serum. In addition, a transient depressor effect was observed in normotensive rats after injection of anti-digoxin antiserum. The results of this study provide additional evidence indicating that an endogenous digoxin-like substance may play an important role in the maintenance of chronic low-renin hypertension induced by aortic coarctation.

Animals↗