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Biomedical subjects

R M Smith

Publications and source records attributed to R M Smith.

At least 361 records · Page 20Linked to original sources
PubMed1982

Hereditary thrombotic thrombocytopenic purpura: microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency occurring in consecutive generations.

Microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency occurred in a mother an daughter when each was in her third decade. The mother had prominent neurological findings, fever, and expired from renal insufficiency. Her daughter's only major symptom was renal insufficiency. The similarity of the mother's illness to thrombotic thrombocytopenic purpura and of the daughter's to adult hemolytic uremic syndrome suggests that these diseases are variants of a single clinical disorder, while their occurrence in direct descendents strengthens the postulate that in selected instances a genetic predisposition to these disorders may be important.

Adult↗
PubMed1982

A simplified method of producing biologically active monomeric ferritin-insulin for use as a high resolution ultrastructural marker for occupied insulin receptors.

A new, simplified, and highly reproducible method for preparing biologically active monomeric ferritin-insulin that can be used as a high-resolution ultrastructural marker for occupied insulin receptors is described. The ferritin-insulin conjugate was stable, and contained negligible free insulin and low levels of free ferritin. The hormone conjugate behaved identically to native insulin in both binding assays and biological activity (glucose oxidation) assays. The immunological and biological activities of the insulin in the conjugate were equal. Biogel 1.5 column purification was used to yield a product monomeric in ferritin.

Adipose Tissue↗
PubMed1981

Computer assisted analysis of ferritin-insulin receptor sites on adipocytes and the effects of cytochalasin B on groups of insulin receptor sites.

A computerized quantitative technique was used to analyze the distribution of ferritininsulin receptor sites on rat adipocytes and the effects of cytochalasin B on groups of receptor sites. Computer analysis of separation distances between receptor sites established that insulin receptor sites on adipocytes did not have a random distribution but have a distinct tendency to exist in groups with a maximum separation distance between particles of 400 A. A peak in the distribution of separation distances occurred at 100-200 A. Cytochalasin B, but not cytochalasin D, treatment of adipocytes resulted in a decrease in the number of large groups of receptor sites and a corresponding increase in single and paired receptor sites without affecting the separation distance between the remaining grouped receptors. This suggested that when cytochalasin B disrupted the bond holding receptor sites together, it caused complete disruption. These observations provided additional information on the ultrastructural characteristics of the insulin receptor. Further application of these techniques to the analysis of insulin receptors may provide the necessary structural correlates to the biochemically observed differences in insulin action in other tissues and diseased states.

Adipose Tissue↗
PubMed1981

An analysis of 200 patients with negative small bowel enemas.

Clinical, operative and pathological findings were used to assess the ability of the small bowel enema to exclude organic disease in the small intestine. On the basis of 200 patients with negative small bowel enemas it is concluded that there was a very low incidence of false negative results on clinical grounds and in 36 patients coming to surgery or autopsy, 25 (69%) had no evidence of intrinsic or extrinsic small bowel disease while 11 (31%) had various lesions which are discussed. Review of the radiology in these patients indicated a number of technical problems.

Barium Sulfate↗
PubMed1981

Effects on breathing of putative neurotransmitters in the rostral hypothalamus of the rat.

The putative neurotransmitters norepinephrine (NE) and thyrotropin releasing hormone (TRH) are normally present in the rostral hypothalamic region (RHT) of the rat, and our aim was to evaluate possible effects of these agents on ventilatory regulations associated with this region. Using haloperidol-tranquilized Sprague-Dawley rats, microinfusions of both NE and TRH into the RHT resulted in an increase in rate, but not depth, of breathing. Control infusions and control infusion sites, mainly in the posterior hypothalamus, yielded no significant effect on breathing rate. Since NE and TRH can inhibit the discharge of some cells in the RHT, it was possible that the observed effects on breathing were due to depression of an inhibitory neural pathway. This idea was further tested by performing microinfusions using lidocaine. Evidence suggests that lidocaine can inhibit discharge in the central nervous system and that inhibitory pathways may be preferentially affected. Lidocaine produced effects on breathing comparable to NE and TRH, thereby supporting the proposition that inhibition of neural pathways in the RHT can stimulate breathing.

Animals↗
PubMed1981

Zinc, copper and environmental factors in the aboriginal peoples of the North West.

Three-hundred Aboriginal people five to 70 yr have been studied at three missions in the north west of Australia-Beagle Bay, Lombadina and One Arm Point. The prevalence of hypozincaemia and hypercupraemia (a departure of more than 2 S.D. from the expected normal) has been assessed. Plasma iron concentration was determined. Half of the individuals had hypozincaemia and for some age groups the prevalence was greater (almost 100% for 15 to 20-year-old females at Lombadina). Hypercupraemia was prevalent and ranged from 70 to 100% for most age groups. Hypoferraemia was detected frequently. By the use of anthropometric methods the children were found to be growth retarded and to have reduced weight for height. These people are known to be infected with intestinal parasites which cause bleeding into the bowel or malabsorption which can cause losses of zinc or failure of adsorption. They prefer unleavened bread which contains phytic acid which inhibits zinc absorption. The soil is zinc deficient and the climate conducive to large losses of zinc in sweat. Geophagia is practiced and pica is found to occur in children. Preliminary evidence of elevated copper status is available. We speculate that growth failure may be related to zinc deficiency or copper toxicity.

Adolescent↗
PubMed1980

Insulin receptors: differences in structural organization on adipocyte and liver plasma membranes.

Comparison was made of the distribution of the insulin receptor sites on adipocyte and liver plasma membranes by using ferritin-insulin. Two-thirds of the occupied insulin receptors on adipocytes occurred in groups of two or more whereas up to two-thirds of the receptors on liver occurred as single receptors. Ferritin-insulin did not cause aggregation of the receptor sites in either tissue. The naturally occurring groups of receptors on adipocyte membranes may play a role in the greater sensitivity of adipocytes to insulin.

Adipose Tissue↗
PubMed1980

Effects of thyroid state on brain development: beta-adrenergic receptors and 5'-nucleotidase activity.

The effect of thyroid status on beta-adrenergic receptor binding and 5'-nucleotidase activity was studied in the forebrain and the cerebellum of the rat during the first 5 postnatal weeks. The developmental increase in beta-adrenergic receptor binding was significantly depressed in thyroid deficiency in both the forebrain and the cerebellum. The effect was more pronounced in the cerebellum, where at day 35 the concentration and the total number of beta-adrenergic receptor sites were reduced by 35% and 50% respectively. In contrast, hyperthyroidism had no significant effect on the development of beta-adrenergic receptors in the brain. On the other hand, hyperthyroidism led to a sustained increase in the forebrain in the activity of 5'-nucleotidase, an enzyme which is also associated with plasma membranes and has been proposed to play some role in neurotransmission. In thyroid deficiency the enzyme activity was markedly depressed. The effect was significant from day 12 in the cerebellum and from day 21 in the forebrain, the maximal depression, at day 21, being 55% and 45% respectively. In comparison with these plasma membrane markers, the accretion of membranous proteins was less affected: although this was retarded in hypothyroidism and advanced in hyperthyroidism there was no residual effect at 35 days except those attributable to changes in organ size. The results indicated, therefore, that the biochemical specialization of cells, as reflected in certain plasma membrane constituents, are chatacteristically influenced in the developing brain by thyroid disorders.

Aging↗
PubMed1980

Effects of thyroid state on brain development: muscarinic acetylcholine and GABA receptors.

A study was made of the effects of age, neonatal hypothyroidism and hyperthyroidism on the development in rat brain of muscarinic cholinergic and GABA receptors. The former receptors were estimated by the binding of [3H]quinuclidinylbenzilate and the latter by binding of [3H]muscimol to crude membrane preparations from the forebrain and the cerebellum. In the normal forebrain, the density of muscarinic cholinergic receptors (in terms of unit membrane proteins) doubled during the period 6-35 days after birth. Thyroid state had relatively little effect on this development. In contrast, in the normal cerebellum the peak of the density of the receptors was attained in the early neonatal period followed by a progressive decline reaching about half of the maximum at day 35. Furthermore, in the cerebellum this development was significantly influenced by thyroid disorders: the rate of decrease in receptor density was accelerated by hyperthyroidism and retarded in thyroid deficiency. In comparison with euthyroid rats, the density of muscarinic receptors in the cerebellum was 30% lower in the hyperthyroidism (at day 21) and 40% higher in thyroid deficiency (at day 35). The increase in the density of GABA receptors with age was very small in the normal forebrain relative to the marked rise in the cerebellum. In the forebrain, thyroid state had no significant effect on this development. In contrast, in the cerebellum the ontogenesis of GABA receptors was advanced by thyroid hormone treatment and retarded in thyroid deficiency. However, by day 35 receptor density was normal in both conditions. Thyroid state had no significant influence on the affinity of either [3H]muscimol or the [3H]quinuclidinylbenzilate binding. The results suggest that thyroid hormone disorders during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems.

Acetylcholine↗
PubMed1980

High-performance liquid chromatographic determination of protoporphyrin and zinc protoporphyrin in blood.

Zinc protoporphyrin and protoporphyrin free acid in blood were determined by high-performance liquid chromatography on a C18 column. Results for 63 human blood samples obtained through a lead poisoning detection program compared favorably with the widely-used ethyl acetate--acetic acid extraction determination. Blood from 16 rats which had been maintained on water heavily spiked with chloroform or bromodichloromethane and blood from a lead-poisoned cow were examined by this procedure.

Animals↗
PubMed1980

Intravascular mucinosis with mucin emboli and thrombosis accompanying adenocarcinomas.

Three cases of adenocarcinoma that were complicated by nonbacterial thrombotic endocarditis and disseminated intravascular coagulation are described. In two of these cases mucin was demonstrable within vascular channels as well as within the thrombotic vegetations of the cardiac valves. This intravascular mucin was also responsible for vascular occlusion with resultant infarction in such organs as heart and brain. Intravascular mucin of this magnitude has not been previously recorded and mucinous accumulations behaving as thromboemboli with infarcts have not been heretofore described.

Adenocarcinoma↗
PubMed1980

Differences in organizational structure of insulin receptor on rat adipocyte and liver plasma membranes: role of disulfide bonds.

Binding of 125I-labeled insulin to rat liver and adipocyte plasma membranes has been investigated after treatment of the membranes with agents that modify disulfide bonds or sulfhydryl groups. Dithiothreitol, a disulfide-reducing agent, produced a bimodal response in adipocyte plasma membranes with dose-dependent increases in binding occurring over the range of 0-1 mM dithiothreitol; 5 mM dithiothreitol produced decreased binding. Insulin binding reached its maximal increase at 1 mM and was 3 times control values. Scatchard analysis of the 1 mM dithiothreitol effect revealed a straight line plot indicative of one class of sites with a Ka of 1.0 x 10(8) M-1 which is intermediate between the two Kas obtained from the curvilinear Scatchard plot of control membranes. There was a 20-fold increase in the number of intermediate-affinity receptors compared to high-affinity receptors. The increased 125I-labeled insulin binding after dithiothreitol treatment was reversed by oxidized glutathione in a dose-dependent manner. Interposition of treatment with N-ethylmaleimide, an alkylating agent, prevented oxidized glutathione from reversing the dithiothreitol effect. Reduced glutathione produced the same effect as dithiothreitol. Liver plasma membranes treated with up to 1 mM dithiothreitol exhibited a maximum increase in insulin binding of 20% compared to control. Dithiothreitol at 5 mM decreased insulin binding below that of control membranes. The results indicate that the dithiothreitol effect on insulin binding to adipocyte plasma membranes is due to disruption of disulfide bonds, and that the structural organization of the insulin receptor on the plasma membranes is different for liver and for adipose tissue. The data imply that the insulin receptors on the plasma membrane of adipocytes possess at least two functionally distinct subclasses of disulfide bond but liver insulin receptors do not.

Adipose Tissue↗
PubMed1980

Surface structure changes of rat adipocytes during lipolysis stimulated by various lipolytic agents. A scanning electron microscopic study.

A qualitative and quantitative electron microscopic study was performed on rat adipocytes during stimulation of lipolysis by various agents. Scanning electron microscopy of control cells revealed a spherical cell with a textured glycocalyx surface exhibiting small irregular projections. Globular surface evaginations or protrusions measuring 8-18 muM in diameter were seen on cell hemispheres, and there was an average of one protrusion for every two hemispheres examined. Distribution analysis showed that 60 percent of the hemispheres had no protrusions, and 25, 10, and 5 percent of the hemispheres had one, two or three protrusions, respectively. Thin-section and freeze- fracture electron microscopy of the protrusions showed a small triglyceride droplet surrounded by a thin cytoplasmic rim that was continuous with the main cytoplasmic matrix. The glycocalyx coating and plasma membrane extended from the cell surface onto, and over, the protrusion. Scanning microscopy of cells stimulated by lipolytic agents, including epinephrine, adrenocorticotropic hormone, theophylline, and dibutyryl cyclic AMP, revealed a dose-dependent increase in the number of protrusions per cell hemisphere. Maximal concentrations of lipolytic hormones cuase an average 2.5-fold increase in the number of protrusions per hemisphere without changing the average size of the protrusions. Only 40 percent of the stimulated cell hemispheres exhibited no protrusions; over 15 percent of the cells contained three or more; and a number of the protrusions were multilobulate. Insulin prevented the increase in the number of protrusions and the change in distribution caused by the lipolytic hormones but did not prevent the increase caused by theophylline and dibutryl cyclic AMP. The data suggest that the protrusions are a structural feature of the cell and may be related to the lypolytic pathway. These observations may help explain some of the discrepant biochemical data relating to hormonal stimulation of lipolysis.

Adipose Tissue↗
PubMed1980

A simple office spirometer for the pediatrician.

A comparative study of a new, simple, pneumatic, direct-recording office spirometer versus a long-accepted, water-sealed, water-filled spirometer was performed on 103 patients ranging from four to 20 years of age. Good correlation between the two spirometers was seen through a wide range of values for forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced expiratory flow during 25% to 75% of forced vital capacity and FEV1/FVC.

Adolescent↗