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Biomedical subjects

R M Smith

Publications and source records attributed to R M Smith.

At least 343 records · Page 19Linked to original sources
PubMed1984

Growth hormone releasing factor immunoreactivity in rat hypothalamus.

Neurones immunoreactive to antibodies against human pancreatic growth hormone releasing factor1-40 (hpGRF) were identified in the hypothalamus of the rat after pretreatment with colchicine. Reactive perikarya were concentrated in the arcuate nucleus and were also present around the anterior commissure. hpGRF immunoreactive fibres were observed in the median eminence and preoptic area where they tended to complement the distribution of somatostatin immunoreactive fibres. The distribution of GRF-immunoreactive perikarya in the rat hypothalamus is similar to that reported in monkey, and is consistent with other studies which suggest that neural mechanisms stimulatory for growth hormone secretion in the rat are situated in the medial basal hypothalamus.

Animals↗
PubMed1984

Effect of edema and hemodynamic changes on extravascular thermal volume of the lung.

The extravascular thermal volume of the lung (ETV) has been measured in dogs as the difference between mean transit time (t) volumes for heat and indocyanine green dye across the pulmonary circulation, calculated as the product of thermal dilution cardiac output (CO) and the difference in t for aortic indicator-dilution curves generated by right and left atrial injections. ETV measurements were compared with the extravascular lung mass (ELM): in 21 normal dogs, ETV/ELM = 1.11 +/- 0.14 (SD); in 17 dogs with hydrostatic pulmonary edema (up to 21 g/kg), ETV/ELM = 0.90 +/- 0.11; and in 27 dogs with alloxan pulmonary edema (up to 51 g/kg); ETV/ELM = 0.93 +/- 0.13. For all 65 dogs the mean ETVELM was 0.98 +/- 0.15, and the liner regression was ETV (ml/kg) = 0.90 ELM (g/kg) + 0.86 +/- 2.25 (SEE; r = 0.96). Calculations based on measurements of lung specific heat predict that ETV/ELM should equal 0.984. With acute changes in pulmonary hemodynamics, ETV was reduced by reductions in pulmonary arterial pressure (Ppa) sufficient to produce zone 1 conditions at the top of the lung. However, ETV was not affected by increases in CO (mean = 50%) produced by nitroprusside or by increases in Ppa and pulmonary blood volume (mean = 27%) produced by partial mitral valve obstruction. Distortion of the thermal dilution curve due to position of the arterial thermistor appears to be the greatest source of variability and overestimation. Simultaneous measurements from pairs of thermistors differed by 14% (range 0.4-50%).

Animals↗
PubMed1984

Endotoxin protection of rats from O2 toxicity: chemiluminescence of lung neutrophils.

Endotoxin (1 mg/kg body weight, I.P.) greatly reduces pulmonary permeability edema in rats breathing greater than 99% O2. Polymorphonuclear leukocytes (PMN's) have the potential to damage tissue by releasing free radicals or proteolytic enzymes and are needed to produce permeability edema in some models. This study evaluates the possibility that endotoxin protects rats from the pulmonary edema of O2 toxicity by inhibiting free radical release by lung PMN's. The potential of lavaged phagocytes to generate free radicals was determined using zymosan stimulated chemiluminescence (Cl). Values were then expressed as peak C1/10(6) PMN's. We found that PMN peak C1 fell progressively with time of O2 exposure. Peak C1 by PMN's from saline pretreated rats breathing O2 for 3 days was 80% lower than peak C1 by PMN's from paired rats pretreated with endotoxin. Assuming that peak C1 (measured in vitro) inversely reflects the level of free radical release by PMN's prior to lavage, the data suggest that endotoxin protects rats from O2 toxicity by inhibiting in vivo free radical release by lung PMN's.

Animals↗
PubMed1983

A biochemical and immunohistochemical study of central serotonin nerves in rats with chronic thiamine deficiency.

An immunohistochemical and neurochemical investigation of central serotonin (5-HT) nerves was made in rats deprived of dietary thiamine at various stages of development. The classical symptoms of severe thiamine deficiency were produced in adult rats which had been maintained on a synthetic thiamine-free diet for 5-8 weeks and in young rats reared from birth to weaning by thiamine-deficient mothers. Offspring of rats which had been thiamine-deficient throughout pregnancy were also studied; there were no visible symptoms of thiamine deficiency in these rats after weaning. The number and distribution of 5-HT nerve cell bodies in the brainstem were compared in control and thiamine-deficient rats after visualizing the cells by immunofluorescence of endogenous 5-HT. 5-HT nerve terminals and axons were also compared in normal and deficient rats by immunofluorescence after loading with 5,7-dihydroxytryptamine. The immunohistochemical examination showed that central 5-HT nerves were not affected in any of the groups of thiamine-deficient rats studied. This was confirmed by measurements of tryptophan hydroxylase activity and 5-HT concentration in several brain regions. These results do not support earlier reports of a selective impairment of central 5-HT nerves in chronic diet-induced thiamine deficiency.

Aging↗
PubMed1983

Quantitative ultrastructural analysis of receptor-mediated insulin uptake into adipocytes.

Monomeric ferritin-insulin was used as an ultrastructural marker to determine by quantitative electron microscopy the time course and route of insulin uptake in rat adipocytes. To approximate steady state membrane binding conditions prior to any internalization, adipocytes were prefixed with glutaraldehyde and incubated for 30 min with 70 nM monomeric ferritin-insulin. Electron micrographs of these cells showed that the ferritin-insulin particles were predominantly in small groups of receptor sites on the plasma membrane and in pinocytotic-like invaginations of the plasma membrane. Significant amounts of ferritin-insulin were observed in cytoplasmic vesicles of unfixed cells as early as 2 min and in multivesicular bodies and lysosome-like structures within 5 to 10 min after the addition of the ligand. Ferritin-insulin accumulation reached steady state levels in the cytoplasmic vesicles in 5 to 10 min and in the lysosome-like structures in 15 min. Little ferritin-insulin was bound to coated pits, and the relative paucity of coated pits found in adipocytes suggested that these specialized endocytotic structures have a relatively insignificant role in insulin uptake in fat cells. Quantitative analysis of the uptake process suggested that a proportion of the insulin internalized by the cell may not be transported to lysosomes, but may be recycled along with the insulin receptor to the plasma membrane.

Adipose Tissue↗
PubMed1983

Regional effects of hypothyroidism on 5'-nucleotidase and cyclic nucleotide phosphohydrolase activities in developing rat brain.

The activities of 5'-nucleotidase (EC 3.1.3.5) and of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) (EC 3.1.4.37) were measured in crude membrane preparations from 6 brain regions of hypothyroid rats 31 days and 42 days after conception (8-9 days and 19-20 days after birth respectively) and from normal rats 31, 36 and 42 days after conception. At 42 days the activities of both enzymes were markedly and significantly lower than in controls in all hypothyroid brain regions. The pattern of increase in CNP activity in the brain regions of normal animals reflected the caudo-rostral progress of myelination. At 42 days postconception in the more caudal regions of hypothyroid brain, myelination, as assessed by CNP activity, was delayed by 5-7 days. In the more rostral regions where normal activity had not yet developed, the delay due to hypothyroidism was not clearly defined. The lowered activity of 5'-nucleotidase observed using crude membrane preparations from hypothyroid animals was shown not to be due to a redistribution of enzyme between cytosol and membranes or to losses into the supernatant fraction during preparation of the particulate fraction used for assays. In addition the lowered activity of 5'-nucleotidase could not be accounted for in terms of the delayed myelination and consequent absence of myelin-associated enzyme. In contrast to the results with CNP, the effects of hypothyroidism on 5'-nucleotidase in the 6 regions showed no caudo-rostral pattern. Although it was clear that the lowered activity of 5'-nucleotidase in hypothyroid brain at 20 postnatal days was not directly attributable to the state of delayed myelination, no identification of the structures or cell types affected could be made.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1983

Partial disruption of naturally occurring groups of insulin receptors on adipocyte plasma membranes by dithiothreitol and N-ethylmaleimide: the role of disulfide bonds.

In this ultrastructural study, monomeric ferritin-insulin was used to further elucidate the role of disulfide bonds in maintaining the natural groups of insulin receptors on adipocyte plasma membranes. Dithiothreitol (1 mM) caused partial disruption of the occupied receptor groups with an increase in single receptors to greater than 50% of total occupied receptors. N-Ethylmaleimide (1 mM) disrupted the groups to the same extent as dithiothreitol and the effect was partly additive with the dithiothreitol effect. The magnitude of the disruption caused by dithiothreitol or N-ethylmaleimide was similar to that caused by cytochalasin B. Dithiothreitol, a reducing agent, caused a marked increase in binding of insulin to the plasma membranes while N-ethylmaleimide and cytochalasin B, both thiol reagents, had little if any effect on insulin binding. These data suggest that two different sets of disulfide bonds are involved. One set was susceptible to both reducing and thiol reagents and responsible for holding the receptor groups together, and the other set was susceptible to reducing agents only and related to the increased insulin binding caused by dithiothreitol. A proposed model is discussed.

Adipose Tissue↗
PubMed1983

Change in white cell count during treatment of advanced cancer of the prostate with estramustine phosphate and with stilboestrol.

Patients with locally advanced (category T3-4 of the TNM system) and metastatic prostatic cancer, not previously treated, seen by one of the authors (P.H.S.) have been entered into EORTC Protocol 30762 which has compared the therapeutic effects of estramustine phosphate (Estracyt) and of diethyl-stilboestrol (DES) as primary treatment. A gradual and as yet unexplained rise in the total leucocyte count was seen in patients treated with estramustine phosphate. This was always apparent within 2 months of starting treatment and did not change significantly thereafter unless treatment was stopped, when the raised values soon returned to normal. In four patients in whom the white cell count rose to levels above the normal range a neutrophil leucocytosis was always reported. The cause of this is not yet understood.

Clinical Trials as Topic↗
PubMed1983

The patient with bleeding problems.

A brief discussion of the patient with bleeding problems inevitably attempts to make a complex subject simple. Obviously this is not possible, yet there is a remarkable degree of consistency today in the way such patients are managed. The research and technology in progress offers continued hope for more knowledge and technical capability. The dentist who must deliver a health service predicated upon the surgical approach to treatment must continue to keep abreast of new developments. He must be comprehensive in the evaluation and management of his patients. This requires a sense of responsibility and the willingness to share responsibility with those physicians best able to deal with the problem.

Blood Coagulation Disorders↗
PubMed1982

Inhibition by bacitracin of rat adipocyte plasma membrane degradation of 125I-insulin is associated with an increase in plasma membrane bound insulin and a potentiation of glucose oxidation by adipocytes.

The present study demonstrated that at physiological concentrations of insulin bacitracin inhibited the degradation of specifically bound insulin by enzymes located in the rat adipocyte plasma membrane. Bacitracin increased the amount of intact insulin specifically bound to the plasma membrane and potentiated the stimulation of adipocyte glucose oxidation by submaximal concentrations of the hormone. In contrast to agents such as chloroquine, which inhibit lysosomal degradation of internalized insulin, bacitracin was shown by two approaches to inhibit a degradative process localized to the adipocyte plasma membrane. Cyanide and 2,4-dinitrophenol, agents which inhibit energy requiring endocytosis, had no effect on the bacitracin inhibition of cellular degradation of 125I-insulin. Bacitracin directly inhibited 125I-insulin degradation by isolated plasma membranes at similar concentrations and to a similar extent as found with cells. The degradative process inhibited by bacitracin accounted for the majority of cellular degradation of the hormone. The increased 125I-insulin bound to adipocytes was shown to be intact by gel chromatographic analysis and was localized to the plasma membrane by direct and indirect approaches. Bacitracin increased 125I-insulin specifically bound to isolated plasma membranes as early as 2 min. The 125I-insulin bound to adipocytes in the presence of bacitracin was completely dissociable by the addition of 8 microM unlabeled insulin whereas a significant portion of 125I-insulin bound to chloroquine-treated cells could not be dissociated. Bacitracin slowed dissociation of 125I-insulin from the cells. Bacitracin increased the 125I-insulin binding to cells in the presence and absence of cyanide and 2,4-dinitrophenol. Bacitracin potentiated the stimulation of adipocyte glucose oxidation at submaximal concentrations of insulin.

Adipose Tissue↗
PubMed1982

Ultrastructural basis for chloroquine-induced increase in intracellular insulin in adipocytes: alteration of lysosomal function.

A quantitative morphological analysis of insulin uptake into adipocytes was undertaken to determine the structural basis for chloroquine-induced increases in intracellular insulin. Adipocytes were incubated with ferritin-labeled insulin in the presence or absence of 50 microM chloroquine at 37 degrees C for 2-90 min and the uptake of the hormone conjugate was determined quantitatively. Quantitative morphometry of cellular organelles also was performed. Chloroquine treatment of adipocytes incubated with 70 nM ferritin-labeled insulin resulted in: (i) a 120% increase in the number of lysosomes in the cytoplasm; (ii) a 75% increase in the average concentration of ferritin-labeled insulin in a lysosome; and (iii) a 25% increase in the percentage of lysosomes containing ferritin-labeled insulin. The cumulative result of these effects was a substantial increase in the amount of intact intracellular hormone within the lysosomes. These morphological data are consistent with biochemical data concerning chloroquine-induced accumulation of 125I-labeled insulin in adipocytes.

Adipose Tissue↗
PubMed1982

Canine thoracic electrical impedance with changes in pulmonary gas and blood volumes.

The purpose of this study was to evaluate transthoracic impedance (Z) as an index of total lung liquid content at constant lung gas volume (LGV). To this end we produced rapid changes in pulmonary blood volume (PBV) in anesthetized, paralyzed, closed-chest dogs with the airway occluded at functional residual capacity. Changes in PBV produced by inflation of balloons on catheters positioned in the left atrium (LA) or inferior vena cava (IVC) were estimated from the changes in chest wall recoil pressure, using the chest wall as a plethysmograph after calibration with changes in LGV. Whereas Z increased linearly with decreases in PBV (1-6 ml/kg) produced by the IVC balloon (% delta Z/delta PBV = -0.43 ml/kg, r = -0.81), Z did not change significantly with increases in PBV (1-6 ml/kg) produced by the LA balloon. These observations indicate that changes in PBV are not the primary determinant of changes in Z and raise the possibility that other hemodynamic events are more important. Whereas aortic pressure decreased with both IVC and LA balloon inflations, right atrial pressure (Pra) increased with mitral valve obstruction and decreased with IVC obstruction. Changes in chest wall blood volume in response to changes in Pra could explain the changes in thoracic impedance. Thus, even at constant LGV, events in the systemic circulation appear to invalidate Z as an indicator of lung liquid content.

Animals↗