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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 361 records · Page 20Linked to original sources
PubMed1984

Release of hydrolases and acetylcholine sensitivity in rat skeletal muscle.

Cytosol prepared from the hind-limb muscles of the rat contained factors which increased the acetylcholine (ACh) contractures in intact normally innervated muscles in vitro. Muscles which had been denervated 4-6 days previously and normally innervated muscles released a factor upon incubation which increased the ACh responses of normal muscles. The normal muscles, however, also released an inhibitor of this effect. The medium obtained after incubation of the muscles contained a variety of hydrolytic enzymes including phospholipase C, acid protease and calcium-activated neutral protease. The amounts of phospholipase C released by normal and denervated muscles were similar, but approximately four times more of the two proteases was released from the denervated muscles than from normal muscles. The possibility that these hydrolases could be the factors which increased the ACh sensitivity in normal muscles is discussed.

Acetylcholine↗
PubMed1984

Structural requirements and species specificity of the inhibition by beta-endorphin of heavy acetylcholinesterase from vertebrate skeletal muscle.

The molecular forms of acetylcholinesterase in extracts of gastrocnemius muscle from four vertebrate species and in electric eel (Electrophorus) electric organ were separated and identified by low-salt precipitation and velocity sedimentation. The activity of the heavy insoluble (A12) form of human muscle acetylcholinesterase was inhibited by synthetic human beta-endorphin (500 mM). The homologous form in rat muscle extracts was poorly inhibited by human beta-endorphin at the same concentration, but was more effectively inhibited by camel beta-endorphin. The activities of heavy forms of pseudocholinesterase, present in small amounts in both species, were not reduced by beta-endorphin. Selective inhibition of homologous heavy forms of acetylcholinesterase activity by camel and human beta-endorphin was also seen in skeletal muscle extracts from frog and pigeon, but with decreased effectiveness. No inhibition was detectable in the heavy acetylcholinesterase form from extracts of electric organ tissue of the electric eel. The inhibition of heavy acetylcholinesterase activity in human muscle by human beta-endorphin was dependent on the presence of its NH2-terminal pentapeptide sequence. Maximal inhibitory potency depended on the presence of the entire amino acid sequence, since potency was considerably reduced in synthetic peptide analogues lacking either middle or COOH-terminal segments of beta-endorphin. The relative potency of beta-endorphin from various species as inhibitors of rat heavy acetylcholinesterase activity was also investigated. beta-Endorphin sequences most closely resembling that of the rat peptide (camel, equine) were most potent, whereas those with sequence differences of more than one amino-acid were less potent (turkey, human) or had no inhibitory activity (ostrich). The selective inhibition of heavy acetylcholinesterase by beta-endorphin thus exhibits species specificity, even among mammals, in which homologues of this molecular form of the enzyme are otherwise indistinguishable.

Acetylcholinesterase↗
PubMed1983

Myelin protein metabolism in demyelination and remyelination in the sciatic nerve.

Lysophosphatidylcholine (LPC) was injected intraneurally into the right sciatic nerve of a series of rats, leaving the left nerve as a control. At various time points up to 30 days after LPC treatment, the injected and control nerves were removed and incubated with [3H]amino acids, then purified myelin was prepared from the nerves. At all time points investigated the uptake of labeled amino acids was much higher in myelin proteins from the LPC-treated nerve than in those from the intact control nerve. [3H]Fucose uptake was also slightly increased. In the first week after LPC injection the increased amino acid incorporation was much greater in the myelin proteins of molecular weight higher than P0. From 10 days on, the smaller myelin proteins including P0, 19K, P1 and P2 showed the largest increase. From comparison of the morphology and biochemistry at 3 and 7 days after LPC injection, we propose that in the first 7 days, while myelin is degenerating, those proteins associated with Schwann cell or myelin reaction, interaction, and recognition functions are most stimulated metabolically, while after ten days the structural myelin proteins are actively resynthesized and the axon is remyelinated.

Animals↗
PubMed1983

Immunocytochemical staining for glial fibrillary acidic protein and the metabolism of cytoskeletal proteins in experimental allergic encephalomyelitis.

Spinal cord sections from Lewis rats with acute experimental allergic encephalomyelitis (EAE) showed greatly increased staining of astrocytes when stained immunocytochemically for glial fibrillary acidic protein (GFAP). Fibrous processes in white matter were heavily stained early in the course of the disease when paralysis was first evident (10-12 days after injection of guinea pig spinal cord myelin), then protoplasmic astrocytes were stained in the gray matter and became more heavily stained at 20 days post-injection. The stained astrocytes were evenly distributed throughout the tissue, and did not correspond to the sites of the lesions. Spinal cord slices of control and EAE rats were incubated with [3H]amino acids, then cytoskeletal proteins were prepared in an enriched fraction, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and the protein bands counted for radioactivity. In the EAE rat all cytoskeletal proteins, including the neurofilaments, vimentin, microtubules, GFAP and actin, showed increased uptake of radioactive amino acids. Immunoprecipitation of GFAP with specific antiserum showed increased radioactivity in the complex beginning at day 10 when cellular infiltration was beginning in the EAE animals. As the disease became acute, the radioactivity in the immunoprecipitated GFAP increased, in some cases to very high levels, then by day 18 when recovery was underway, the radioactivity had fallen to normal levels. Possible agents causing metabolic activation of protein synthesis in EAE animals include stimulating substances elaborated by infiltrating lymphoid cells, and the generalized edema accompanying the demyelinative condition. The activation of GFAP protein staining and metabolism in EAE might serve as a model for the activated growth of astrocyte processes which cause the severe gliosis seen in multiple sclerosis.

Animals↗
PubMed1983

The migration of lymphocytes across specialized vascular endothelium. VI. The migratory behaviour of thoracic duct lymphocytes retransferred from the lymph nodes, spleen, blood, or lymph of a primary recipient.

Thoracic duct lymphocytes labelled with 51Cr were injected into a primary recipient and then were transferred for a second time from the lymph nodes (cervical and/or mesenteric), spleen, lymph, or blood into a series of final recipients. Measurement of the organ distribution of labelled lymphocytes in the final recipients enabled three main conclusions to be drawn. (1) Lymphocytes that had localized in the spleen, mesenteric lymph nodes (LN), or cervical LN of the first recipient showed no tendency to return in increased numbers to the same organ in the final recipient. (2) Lymphocytes that had recently entered the spleen or LN were temporarily impaired in their ability to reenter LN. This capacity was recharged when the cells returned to the lymph and the blood. (3) Lymphocytes that had been passaged from blood to lymph and collected for up to 4 hr at room temperature entered the LN of a recipient much faster than did nonpassaged thoracic duct lymphocytes collected overnight at 0 degree C. Supplementary experiments indicated that the different migratory behavior of thoracic duct lymphocytes under these two circumstances was mainly a consequence of their handling in vitro during the collecting and the labelling procedures. This functional impairment was not associated with a diminished ability to enter the spleen and bone marrow or to survive in recipients for up to 24 hr.

Animals↗
PubMed1983

Reliability of computerized versus manual death searches in a study of the health of Eldorado uranium workers.

An epidemiological follow-up study of 16,000 uranium mine and refinery employees has made use of computerized techniques for searching a national death file. The accuracy of this computerized matching has been compared with that of corresponding manual searches based on one-eighth of the worker file. The national death file--Canadian Mortality Data Base--at Statistics Canada includes coded causes of death for all deaths back to 1950. The machine search was carried out using a generalized record linkage system based upon a probabilistic approach. The machine was more successful than the manual searchers and was also less likely to yield false linkages with death records not related to the study population. In both approaches accuracy was strongly dependent on the amount of personal identifying information available on the records being linked.

Canada↗
PubMed1983

Benign cystic nevus of the conjunctiva.

A 51-year-old white man presented with a large, cystic conjunctival mass along the inferotemporal limbus which was obscuring his vision. Differential diagnosis included benign cystic nevus of the conjunctiva, lymphangioma, lymphangiectasia, and multiple conjunctival inclusion cysts. Biopsy revealed a large cystic nevus of the conjunctiva.

Conjunctiva↗
PubMed1983

The migration of lymphocytes across specialized vascular endothelium VII. The migration of T and B lymphocytes from the blood of the athymic, nude rat.

The primary migration of lymphocytes from the blood was compared in nude rats and in euthymic rats. The flatter endothelium in the post-capillary venules (PCV) in the lymph nodes of nude rats was as efficient as the high endothelium of PCV in euthymic rats at capturing both T and B lymphocytes from the blood, although lymphocytes took a longer time to cross the PCV wall in nude recipients. The organ distribution of both lymphocytes and lymphoblasts ([125I]UdR-labelled cells) was broadly similar in nude and euthymic recipients. A second aim was to compare B and T lymphocytes with respect to the rate and sites at which they leave the blood after intravenous injection. As judged by sampling venous blood, B lymphocytes left the blood faster, but this was partly attributable to a larger intravascular pool of B lymphocytes in small blood vessels, especially in the lung. Thoracic duct lymphocytes from nude rats collected under standard conditions (16 h, O degrees C) entered the cervical lymph nodes very poorly, but when lymphocyte transfer was performed under more physiological conditions entry of B lymphocytes into lymph nodes was about half that of T lymphocytes. B lymphocytes did show a slight preference for entry into Peyer's patches compared with lymph nodes.

Animals↗
PubMed1983

The recirculation of T and B lymphocytes in the athymic, nude rat.

The recirculation of lymphocytes through the tissues and their return to the blood were compared in nude and euthymic rats. Three approaches were used: the organ distribution of 15Cr-labelled lymphocytes from nude or euthymic donors at 24 h after injection; the compartmental distribution of B and T lymphocytes as assessed by autoradiography of the spleen, lymph nodes, and Peyer's patches; and the tempo of recirculation from blood to thoracic duct lymph as estimated by counting timed fractions of lymph from a recipient of labelled lymphocytes. The following conclusions were drawn: (1) The distribution of lymphocytes between organs and within organs is very similar in nude and euthymic recipients. In particular, B lymphocytes proceed normally to the follicular areas in the absence of T cells. (2) The recirculation from blood to lymph is delayed in nude rats. (3) For equal numbers of B and T cells injected intravenously about half as many B cells as T cells enter mesenteric and cervical lymph nodes, but approximately equal numbers of B and T cells enter the spleen and Peyer's patches.

Animals↗
PubMed1983

Inhibition of prostaglandin biosynthesis in human adipose tissue by glucocorticosteroids.

Cultured stromal cells derived from human sc adipose tissue synthesized and secreted into the medium prostaglandin E2 (PGE2), PGF2 alpha, and 6-keto-PGF1 alpha, a metabolite of prostacyclin. PGE2 was quantitatively the major PG formed by these cells. Dexamethasone inhibited PG biosynthesis in a concentration- and time-dependent manner; dexamethasone (2.5 X 10(-10) M) caused greater than 50% inhibition of PGE2 synthesis after 24 h of incubation and 90% inhibition after 48 h. The effect of dexamethasone to inhibit PGE2 synthesis was blocked by simultaneous incubation of cells with cortisol-21-mesylate, an antagonist of the binding of glucocorticosteroids to cytosolic receptors. (Bu)2cAMP (1 mM), forskolin (10 microM), and 1-methyl-3-isobutylxanthine (0.1 mM) markedly stimulated PGE2 biosynthesis in cultured adipose stromal cells. The inhibitory effect of dexamethasone on PGE2 synthesis was attenuated by simultaneous incubation of cells with (Bu)2cAMP. The results of this study suggest that glucocorticosteroids inhibit PG biosynthesis in adipose tissue stromal cells, whereas cAMP and certain analogs thereof stimulate PG biosynthesis and overcome the inhibitory action of glucocorticosteroids.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

The recirculating lymphocyte pool of the rat: a systematic description of the migratory behaviour of recirculating lymphocytes.

A comprehensive study of lymphocyte traffic in AO rats was performed under conditions as near to the physiological state as was practicable. In the light of previous results on the effect of environmental factors on the migratory behaviour of lymphocytes, thoracic duct cells were passed from blood to lymph in an intermediate rat before injection into a series of recipients for examination at time intervals from 1 min to 24 hr. At 1, 2 and 5 min after injection most of the labelled cells were in the blood, lungs and liver. The concentrations in these compartments fell over the next 25 min as the cells entered the spleen, lymph nodes (LN) and Peyer's patches according to a regular pattern. The peak localization in these latter organs occurred between 1 hr and 18 hr. Each organ had a characteristic time pattern of lymphocyte localization. Entry into mesenteric LN lagged behind other LN until 2.5 hr after injection following which mesenteric LN localization easily outstripped that in other LN to reach a delayed peak at 18 hr. Intravenously injected lymphocytes began to reappear in thoracic duct lymph in large numbers earlier than in previous studies so that the time taken for most T lymphocytes to cross LN from blood to lymph fell within the broad time band of 4-18 hr. Lymphocytes took on average 5-10 min to cross high endothelial venules when entering LN from the blood.

Animals↗
PubMed1982

Prostaglandin infusion and endotoxin-induced lung injury.

The use of prostaglandins is currently undergoing clinical trials in respiratory failure accompanying sepsis. The effect of prostaglandin E1 (PGE1) and prostacyclin (PGI2) infusion on endotoxin-induced lung injury, with attention to interstitial fluid flux (QL), pulmonary vascular pressure (Ppa), leukocytes, platelets, and release of the lysosomal enzyme beta-glucuronidase, was investigated. A chronic lung lymph fistula model in sheep was used. Seven sheep alternately received Escherichia coli endotoxin and endotoxin plus PGE at a dosage of 1 microgram/kg/min. Six sheep received PGI2 (0.2 microgram/kg/min) instead of PGE1. Both PGE1 and PGI2 decreased the pulmonary hypertension and the interstitial edema produced by endotoxin primarily through their vasodilatory properties. Prostacyclin seemed to have an additional membrane-stabilizing effect. A rebound increase in QL, Ppa, and platelets occurred when PGE1 or PGI2 infusion was discontinued.

Alprostadil↗