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Biomedical subjects

C C Smith

Publications and source records attributed to C C Smith.

At least 127 records · Page 7Linked to original sources
PubMed1989

Platelet noradrenaline release in patients with familial hypercholesterolaemia.

We have examined resting and thrombin (0.3 units ml-1) induced release of noradrenaline by washed platelets from 15 normal subjects and eight patients with heterozygous familial hypercholesterolaemia. Platelets from both normal and hypercholesterolaemic subjects showed irreversible aggregation with 0.3 units ml-1 thrombin. Extents of aggregation were 76.3% and 90.8% respectively, platelets from hypercholesterolaemic patients being significantly more sensitive (P less than 0.002). Under resting conditions platelet noradrenaline release was 136% greater (P less than 0.02) in hypercholesterolaemic patients than in normal subjects. Thrombin-stimulated release of noradrenaline was also higher (73%, P less than 0.05) in hypercholesterolaemics than in normals. The differences between resting and thrombin-stimulated release were greater for hypercholesterolaemic patients than normal subjects (P less than 0.05). Under resting conditions total platelet noradrenaline levels (sum of supernatant and platelet pellet concentrations) were similar in preparations from the two groups. However, following thrombin stimulation total noradrenaline concentrations were substantially greater (86%) in platelets from hypercholesterolaemics than normals (P less than 0.02). In hypercholesterolaemic patients thrombin stimulation was associated with an 101% increase (over resting levels) in total platelet noradrenaline (P less than 0.01), no increases being observed with normal subjects. We suggest that platelet membranes may be more permeable in patients with familial hypercholesterolaemia leading to increased non-specific release of catecholamines. Platelets from patients with familial hypercholesterolaemia may also be more responsive to stimulation with respect to catecholamine release. The results obtained on calculation of total platelet noradrenaline levels may indicate that abnormalities of platelet dense granules occur in familial hypercholesterolaemia. In this context the relative proportions of free and conjugated catecholamine may be of relevance.

Adolescent↗
PubMed1989

Anxiety, type A personality and endocrine responses to surgery.

Twenty-seven patients underwent major abdominal surgery. Trait Anxiety and Type A personality were measured pre-operatively, and plasma cortisol, adrenaline and noradrenaline were measured pre-, per- and post-operatively. Anxiety correlated positively with noradrenaline but negatively with cortisol and adrenaline. Type A also showed opposite correlations with adrenaline and noradrenaline.

Adolescent↗
PubMed1989

Protein kinase activity associated with the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10).

The large subunit of the herpes simplex virus type 2 (HSV-2) ribonucleotide reductase (RR1) is demonstrated to possess serine/threonine-specific kinase activity. Computer-assisted sequence analysis identified regions within the amino terminus of ICP10 that are homologous to the catalytic domain of known protein kinases (PKs). An in vitro kinase assay confirmed the ability of ICP10, immunoprecipitated from either HSV-2-infected cells or from cells transfected with an ICP10 expression vector, to autophosphorylate and transphosphorylate exogenous substrates in the presence of ATP and Mg2+. The HSV-1 RR1 was shown to be negative for PK activity under these conditions. PK activity was localized to a 57-kDa amino-terminal region within ICP10 that lacked RR activity.

Algorithms↗
PubMed1989

Simultaneous Streptococcus pneumoniae, Giardia lamblia and Campylobacter pylori infection: an adult presentation of X-linked hypogammaglobulinaemia.

Primary X-linked (Bruton's) hypogammaglobulinaemia is uncommon. It usually presents clinically within the first two years of life--typically after the age of three months when maternal IgG is exhausted. Its diagnosis in middle life is exceptional. The presentation of the condition as a triple infection in a middle-aged man therefore seemed worthwhile reporting, as effective and safe prophylactic immunotherapy is now available.

Agammaglobulinemia↗
PubMed1988

Exercise-induced changes in platelet aggregation; a comparison of whole blood and platelet rich plasma techniques.

Studies have been performed to assess the effect of exercise on spontaneous platelet aggregation in shaken whole blood, and on agonist-induced platelet aggregation in whole blood and platelet rich plasma (PRP). Spontaneous platelet aggregation in shaken whole blood was increased following exercise compared to pre-exercise values. The increase in spontaneous aggregation after exercise correlated inversely with the increase in white cell count in whole blood. Platelet sensitivity in whole blood to adrenaline, collagen and adenosine diphosphate (ADP) was increased following exercise. Changes in platelet sensitivity to adrenaline following exercise correlated with increases in plasma noradrenaline levels but not with changes in blood cell counts. In PRP, platelet sensitivity to ADP and to collagen was increased following exercise when the pre and post-exercise PRP platelet counts were not corrected to allow for the increase in platelet count which occurred with exercise. When the PRP platelet counts were corrected, no changes in platelet sensitivity to any agonist after exercise were observed.

Adenosine Diphosphate↗
PubMed1988

The opiate receptor: a single 110 kDa recognition molecule appears to be conserved in Tetrahymena, leech, and rat.

We compared the molecular nature of the rat brain opiate receptor with that of the invertebrate leech, Haemopis marmorata, and the protozoan, Tetrahymena, in order to examine the issue of apparent receptor heterogeneity with respect to biochemical structure. A binding study with rat brain membrane verified that [125I]beta-endorphin [( 125I]beta E), a broad specificity ligand, is displaced by the antagonist (-)-naloxone, but not the inactive stereoisomer (+)-naloxone; agonists considered prototypes for mu, delta, and kappa opiate receptors all displayed stereospecific binding displacement. For SDS-PAGE analysis of the opiate receptor [125I]beta-endorphin was covalently affixed to its recognition molecule with the cross-linking reagent DSS. Primary reaction products occur at 110, 58/55, and 29 kDa. Cross-linking products of all 3 molecular weights are effectively reversed by opiate ligands, regardless of their mu, delta, or kappa specificities. Peptide mapping studies in SDS gels, using limited proteolysis, showed that the 110 kDa band can be digested into 58 and 29 kDa fragments and the 58 kDa band into a 29 kDa fragment. Additional smaller molecular weight fragments were generated from the 110, 58/55, and 29 kDa bands which shared their molecular weights. Two possible explanations for the extensive sequence homology between the three major cross-linking products are: (1) the 110 kDa species is the opiate receptor, and the 58 and 29 kDa species are proteolytic fragments; and (2) one of the lower molecular weight species is the opiate receptor, and adjacent receptors are aggregated into the 110 kDa complex through cross-linking.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Identification and characterization of the opiate receptor in the ciliated protozoan, Tetrahymena.

Tetrahymena, a ciliated protozoan, is a highly specialized, differentiated eukaryotic organism. It is known to possess many informational substances, including beta-endorphin (beta E). We wished to investigate the possibility that this organism possesses a functional opiate receptor which might be similar to the well-characterized opiate receptor in the rat brain. Binding assays using both living cells and membrane preparations, verified stereospecific, saturable, reversible 125I-beta E binding. This binding was displaceable by various opiates chosen to represent each of the putative opiate subtypes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of a disuccinimidyl suberate cross-linked 125I-beta E-receptor complex revealed a pattern of bands which consistently included bands at 110, 58-55, and 29 kDa. These bands, which were all displaceable by the classical antagonist, naloxone, as well as by other opiates, are thought to be prototypic for various opiate receptor subtypes. Limited proteolysis in SDS-PAGE showed that the 110 kDa band could be fragmented into 58-55 and 29 kDa bands and that the 58 kDa band could generate a 29 kDa fragment. The limited digest fragments of the 110, 58-55 doublet and 29 kDa bands were remarkably similar to those generated from the rat brain receptor. Analytical isoelectric focusing of digitonin solubilized 125I-beta E-receptor complexes showed the isoelectric points (pI) from both the rat and Tetrahymena were identical (pI 4.6). Chemotactic experiments with the intact Tetrahymena, demonstrated that these unicellular animals migrated toward a 10(-9) M beta E gradient. Chemotaxis was blocked by (-)-naloxone but not (+)-naloxone, suggesting a stereospecific opiate receptor-mediated response. We conclude that Tetrahymena possesses a functional opiate receptor (recognition molecule) very similar to the opiate receptor of the rat brain.

Animals↗
PubMed1988

AIDS and its dementia as a neuropeptide disorder: role of VIP receptor blockade by human immunodeficiency virus envelope.

The CD4 molecule was originally described as a marker for a subset of lymphocytes; however, recent work has shown that a similar, if not identical, molecule is present on human brain. We have realized that this cell-surface recognition molecule is normally modulated by vasoactive intestinal peptide (VIP), one of the 50 or more neuropeptides that compose a shared intercellular network joining the brain, glands, and immune system. Human immunodeficiency virus (HIV), the etiological agent of acquired immunodeficiency syndrome (AIDS), has been found to mimic VIP binding via peptide T (4-8), a pentapeptide sequence present in approximately the same region of all 20 HIV isolates whose sequences are currently known. AIDS dementia results from interference of gp120, present on the HIV envelope protein, with normal VIP-ergic neurotrophic effects, and effects on cerebral blood flow.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The relationship of preoperative distress to endocrine and subjective responses to surgery: support for Janis' theory.

To test Janis' theory that preoperative worry can improve postoperative recovery, endocrine and subjective responses were measured in 27 patients undergoing major abdominal surgery which entailed threat to their health or longevity. Questionnaires to assess emotional and somatic state were completed preoperatively and for 7 days postoperatively. Plasma cortisol, noradrenaline, adrenaline, and glucose were measured pre-, per-, and postoperatively. Preoperatively, noradrenaline correlated positively with pain and distress, and adrenaline negatively. Postoperatively, endocrine levels and distress were not clearly related. Nevertheless, preoperative pain negatively correlated with postoperative adrenaline and cortisol levels. This, and the negative correlation between preoperative distress and postoperative pain are consistent with Janis' theory. In addition, we found that the longer patients waited on the day of surgery, the greater were the cortisol, noradrenaline, and glucose responses.

Adolescent↗
PubMed1988

Tissue zinc and copper levels in diabetic C57BL/KsJ (db/db) mice fed a zinc-deficient diet: lack of evidence for specific depletion of tissue zinc stores.

We investigated whether the decreased femur zinc concentrations reported in genetically obese diabetic db/db C57BL/KsJ mice reflected an increased propensity to zinc deficiency by determining zinc concentrations in tissues from 18-19-wk-old db/db and control mice following ad libitum feeding of a zinc-deficient diet (2 mg/kg) or restricted or ad libitum feeding of a zinc-adequate diet (20 mg/kg) for 12 wk. Although hepatic and renal zinc concentrations of db/db mice fed the zinc-deficient diet tended to be lower than in any other experimental group when expressed on a dry weight basis, zinc concentrations in these tissues were either not different from or greater than those of their nondiabetic controls when expressed on an ash weight basis, i.e., relative to all mineral constituents of these organs. Hepatic and renal copper concentrations of the diabetic db/db mice were either not different from or greater than those of their controls on an ash weight basis. Femur zinc concentrations of diabetic db/db mice fed zinc-adequate diets were lower than those of their controls on a dry weight basis but were not different from their controls on an ash weight basis. We found proportionately lower dry zinc, calcium and magnesium concentrations in femurs of the db/db mice fed a nonpurified diet than in femurs of their db/m and m/m controls. These findings suggest that the low femur zinc concentration reported in the diabetic db/db mouse probably reflects a generalized decrease in bone mineral content rather than a specific depletion of tissue zinc stores.

Animals↗
PubMed1988

Antigen-specific immune-suppressor factor in herpes simplex virus type 2 infections of UV B-irradiated mice.

UV B-irradiation (280 to 320 nm) of mice at the site of cutaneous infection with herpes simplex virus type 2 (HSV-2) induced suppressor T-cell circuits that decreased HSV-2-induced proliferative responses of HSV-2-immune lymph node cells. Adoptive transfer experiments indicated that splenocytes from UV B-irradiated HSV-2-infected animals contain L3T4+ cells that suppress proliferative responses in vivo, consistent with suppressor inducer cells. However, following in vitro culture of the splenocytes with HSV-2 antigen, the proliferation of immune lymph node cells was inhibited by Lyt2+ suppressor T cells, consistent with antigen-induced suppressor effector cells. Antigen-specific and nonspecific suppressor factors were fractionated from supernatants of HSV-2-stimulated spleen cells by molecular-sieve chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the Sephadex fraction that contained the antigen-specific suppressor factor, in the presence or absence of 2-mercaptoethanol, defined a 115-kilodalton protein consisting of two disulfide-bound components with molecular sizes of 70 and 52 kilodaltons. The implications of these results with respect to the regulation of HSV-induced cell-mediated immunity following UV B-irradiation are discussed.

Animals↗
PubMed1988

Raised concentrations of glucose and adrenaline and increased in vivo platelet activation after myocardial infarction.

Plasma concentration of beta thromboglobulin was used as an index of in vivo platelet activation in 36 patients after acute myocardial infarction. Twelve patients had diabetes, seven had pulmonary oedema or cardiogenic shock (pump failure) or both, and 17 had uncomplicated infarcts. On the first day of admission, concentrations of beta thromboglobulin were higher in the patients with diabetes and those with pump failure than in those with uncomplicated infarcts. Concentrations of beta thromboglobulin in the non-diabetic patients were studied by multiple regression analysis and were significantly associated with plasma concentrations of adrenaline, pump failure, and glucose but not with noradrenaline or infarct size. When all subjects were considered together, glucose, adrenaline, and pump failure were associated with the beta thromboglobulin concentration but diabetes was without significant effect. Hyperglycaemia and raised plasma adrenaline concentration after myocardial infarction may activate platelets, and this could contribute to poor outcome in such patients.

Aged↗
PubMed1988

Ex vivo platelet studies following oral nisoldipine in normotensive insulin-dependent diabetics and non-diabetic controls.

The effect of 24 hours and 7 days treatment with nisoldipine (10 mg, twice daily) on platelet function was studied in 12 normotensive volunteers of whom six were insulin-dependent diabetics without clinical evidence of vascular complications. Platelet aggregation was assessed by platelet rich plasma (PRP) and whole blood (WB) techniques. In addition, the effect of nisoldipine on platelet hyperaggregability following exercise was assessed. After taking nisoldipine for 24 hours, in vitro platelet hypersensitivity to adenosine diphosphate was observed in PRP (p less than 0.01) and WB (p less than 0.01), to adrenaline in WB (p less than 0.03), and to collagen in PRP (p less than 0.02). After seven days treatment, platelet sensitivities to all agonists at rest in both PRP and WB showed no differences from pre-treatment values. Exercise-induced platelet hypersensitivity in WB to all three agonists was unchanged after nisoldipine treatment. Plasma noradrenaline and adrenaline concentrations increased after 24 hours treatment, although changes in agonist EC50s at 24 hours were not related to changes in plasma catecholamine levels. No effects of nisoldipine were observed on platelet thromboxane B2 release in PRP, or on plasma beta-thromboglobulin levels. No differences in the effects of nisoldipine were observed between diabetic and non-diabetic subjects. Nisoldipine treatment for seven days is not associated with altered platelet function, but platelet hypersensitivity is observed after treatment for 24 hours in both insulin-dependent diabetics and controls.

Adenosine Diphosphate↗
PubMed1988

Imipenem versus standard therapy in the treatment of serious soft tissue infection.

Thirty-five patients with 36 episodes of serious soft tissue infection were entered in a prospective randomised trial to receive treatment with either intravenous imipenem or standard therapy, most commonly i.v. cloxacillin and benzylpenicillin. Eighteen patients received imipenem (Group 1) and eighteen standard therapy (Group 2). In Group 1, fourteen patients were cured, one improved and three failed therapy. The three failures comprised two where imipenem had to be stopped because of side-effects and one changed to standard therapy after 48 h because of lack of response. In Group 2, fourteen patients were cured, three improved and one failed therapy. This last case was due to lack of clinical response. Tolerance of both drugs was good, although eight patients in Group 1 versus none in Group 2 developed infusion phlebitis. All significant bacterial isolates were sensitive to imipenem, although several were resistant to cloxacillin and/or benzylpenicillin. No development of bacterial resistance was noted in isolated pathogens. There was no significant difference in rapidity of response or length of treatment between Groups 1 and 2. Imipenem is a safe and effective alternative to standard regimens in the treatment of serious soft tissue infection, although its side-effects and broad spectrum make it difficult to justify its use for uncomplicated cellulitis.

Abscess↗
PubMed1988

Catecholamine content of human erythrocytes.

We used high-performance liquid chromatography with electrochemical detection to measure the catecholamine content of human erythrocytes. The ratio of free norepinephrine to epinephrine was three to four times lower than that in plasma and four to seven times lower than that in platelets. This suggests differences in uptake, degradation, or conjugation of norepinephrine and epinephrine by erythrocytes, as compared with plasma and platelets. Erythrocyte free norepinephrine was significantly greater (P less than 0.01) in women than in men.

Adult↗
PubMed1987

Reactivation of herpes simplex virus is associated with production of a low molecular weight factor that inhibits lymphokine activity in vitro.

Peripheral blood mononuclear cells obtained during recrudescent Herpes simplex virus (HSV) infection and stimulated with UV-inactivated viral antigen (UV-HSV) for 24 hr produced a low molecular weight (dialyzable) factor that inhibited lymphokine activity. This factor prevented the expression of leukocyte inhibitory factor (LIF) activity, but not its production. It was not made in UV-HSV-stimulated cultures grown in presence of 2 X 10(-6) M indomethacin nor in cultures of peripheral blood mononuclear cells obtained during convalescence or quiescence (greater than 4 days from onset of clinical symptoms) or from seropositive controls without a history of recurrent HSV disease. Dialyzable inhibitory factor production required OKM1+, OKT8+, and OKIa+ cells as determined by complement-mediated lysis with monoclonal antibody. Dialyzable inhibitory factor activity was associated with a trypsin-sensitive 8.2 K fraction as determined by Sephadex chromatography followed by sodium dodecyl sulfate-acrylamide gel electrophoresis.

Antigens, Viral↗