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Biomedical subjects

C C Smith

Publications and source records attributed to C C Smith.

At least 73 records · Page 4Linked to original sources
PubMed1995

Accumulation of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in blood and organs of the Lewis rats.

3-(Phenylamino)alanine (PAA), a newly discovered impurity in case-associated L-tryptophan tablets, has been investigated as a possible contributing factor in the etiology of eosinophilia-myalgia syndrome (EMS). We have studied distribution and elimination of PAA in rats which were administered a single 5 mg/kg dose of PAA by gastric gavage. PAA concentrations in blood, brain, kidney and liver were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. The concentration of PAA in each tissue reached a maximum at 5 h, and then gradually declined. A high level of PAA still remained at 24 h, indicating gradual elimination. The concentration of PAA in brain at 5 h was 2139 ng/g tissue, demonstrating passage through the blood-brain barrier. Consecutive administration of PAA (5 mg/kg) for 4 days resulted in approximately double the concentration in all tissues. Chronic treatment using PAA incorporated into food pellets for 6 weeks resulted in similar accumulations in each tissue, and following 12 days on a PAA free diet, levels of this drug were still detectable in all tissues.

Alanine↗
PubMed1995

Plasma nitrate concentration and urinary nitrate excretion in patients with gastroenteritis.

The concentration of nitrate (the stable oxidation product of nitric oxide) in plasma and its excretion in urine was measured in 20 patients with a diagnosis of gastroenteritis. On day 1 of the illness plasma nitrate concentration was significantly elevated compared with a healthy control population (92.7 +/- 17.0 mumol/l vs. 33.1 +/- 1.6 mumol/l; P < 0.001) and continued to be elevated on days 2 and 3. Urinary nitrate excretion was also elevated. The plasma nitrate concentration correlated with disease severity as assessed by stool frequency and plasma urea concentration. Plasma nitrate concentration may be a sensitive and clinically useful indicator of severity of gastroenteritis.

Adult↗
PubMed1995

The potentiation of adrenaline-induced in vitro platelet aggregation by ADP, collagen and serotonin and its inhibition by naftopidil and doxazosin in normal human subjects.

1. Aggregation in platelet-rich plasma from normotensive men was induced by adrenaline (0.25-16 microM), ADP (0.25-16 microM), collagen (0.25-8 micrograms ml-1) or serotonin (10 microM) alone, or by previously sub-threshold concentrations of adrenaline (0.03-1 microM) in combination with sub-threshold concentrations of serotonin (2.5 microM), ADP (0.5 microM) or collagen (0.125 micrograms ml-1). The effects of the alpha 1-adrenoceptor blockers naftopidil and doxazosin on platelet aggregation were investigated. 2. The dose-response curves for collagen and ADP were unaffected by either drug. However, naftopidil (40 microM) inhibited serotonin-induced platelet aggregation (23.9%, 95% confidence interval (CI) 10.7 to 37.1%; P < 0.01) and caused a slight shift to the right of the adrenaline dose-response curve with a mean increase in the EC50 value of 0.5 microM (95% CI 0.07 to 0.93 microM; P < 0.05). Doxazosin had no effect on serotonin or adrenaline-induced aggregation. 3. A marked potentiation of the aggregation induced by subthreshold concentrations of adrenaline resulted from the prior addition of low concentrations of ADP, collagen or serotonin. 4. These potentiated responses were inhibited in a dose-dependent manner by naftopidil and to a lesser extent doxazosin. The maximum inhibitions (%) produced by naftopidil (40 microM) on the responses of adrenaline potentiated by ADP were 58.3% (95% CI 36.8 to 79.8%; P < 0.001), serotonin 58.9% (95% CI 40.0 to 77.8%; P < 0.001), and collagen 70.9% (95% CI 52.5 to 89.3%; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1995

Ecstasy induced hepatitis mimicking viral hepatitis.

Three cases of jaundice after ingestion of 3,4-methylenedioxymetamphetamine (MDMA), known as 'ecstasy', are reported and the complications associated with the misuse of this drug, which was initially misrepresented as 'safer than alcohol' are described. Ingestion of 'ecstasy' should be considered when investigating unexplained jaundice in younger patients.

Adult↗
PubMed1994

The transmembrane domain of the large subunit of HSV-2 ribonucleotide reductase (ICP10) is required for protein kinase activity and transformation-related signaling pathways that result in ras activation.

The large subunit of Herpes simplex virus type 2 ribonucleotide reductase (ICP10) is a chimera consisting of a Ser/Thr protein kinase (PK) with features of a transmembrane (TM) helical segment localized at the amino terminus, and the RR1 domain localized at the carboxy terminus. To elucidate the role of the TM segment in ICP10-mediated transformation we established cell lines that constitutively express ICP10 (JHLa1) or its TM deleted mutant p139TM (JHL15). ICP10 was associated with purified JHLa1 plasma membranes. Membrane immunofluorescence and FACS analysis with antibodies to synthetic peptides located upstream and downstream of the TM indicated that ICP10 is a membrane-spanning protein. p139TM was not associated with JHL15 plasma membranes. ICP10 kinase activity was detected in JHLa1 but not JHL15 cells as determined by immunocomplex kinase assays and metabolic labeling. JHLa1 cells displayed anchorage-independent growth whereas JHL15 cells and JHL9 cells that express a mutant deleted in the PK catalytic domain were negative. ras-GTPase activating protein (ras-GAP) was phosphorylated in JHLa1 but not JHL15 cells and GTPase activity was lower in JHLa1 than JHL15 cells. Furthermore, ICP10 but not p139TM bound the guanine nucleotide releasing factor son of sevenless 1 (Sos1) and ras-GTP (activated ras) was higher in JHLa1 than JHL15 cells. The data suggest that ICP10 constitutively increases ras activity, and its TM segment plays a critical role in transformation-related signaling pathways.

Base Sequence↗
PubMed1994

Cutaneous ultraviolet radiation inhibits herpes simplex virus-induced lymphoproliferation in latently infected subjects.

Exposure of herpes simplex virus (HSV) latently infected subjects to ultraviolet irradiation (UVR) (1 minimum erythema dose, 90% body surface) caused a significant inhibition of HSV and phytohemagglutinin-induced lymphoproliferation. The inhibition was observed on Day 3 post-UVR and lasted at least 9 days. UVR-induced downregulation of HSV-specific lymphoproliferation was associated with increased levels of activated transforming growth factor beta. However, the relationship between UVR-induced immune downregulation and the development of recurrent HSV lesions was incomplete.

Adult↗
PubMed1994

An analysis of 900 consecutive admissions to a regional infection unit.

A total of 900 consecutive admissions to the Regional Infection Unit at the City Hospital Aberdeen in 1991 have been analysed and the results compared with a similar study during 1980 and 1981. The annual number of admissions increased from 605 to 900, of which 72% in 1991 had proven infections compared with 60% a decade earlier. More patients were admitted with gastroenteritis, tonsillitis and soft tissue infection in 1991 and fewer with non-infectious jaundice. HIV-related conditions contributed 4% of the admissions and 29% of the mortality. Brucellosis disappeared as a reason for requesting hospital admission in North East Scotland.

AIDS-Related Opportunistic Infections↗
PubMed1994

Platelet function in patients with hypercholesterolaemia.

Platelets and plasma lipoproteins, particularly low density lipoprotein, have important roles in atherogenesis. Evidence from several sources suggests that important interactions occur between these individual components of the atherogeneic process. Here we review work from our own laboratory on platelet function in normal individuals and patients heterozygous for familial hypercholesterolaemia (FH). Data is presented on the role of platelet noradrenaline and also on altered cellular signalling in platelets from FH individuals who have plasma low density lipoprotein concentrations which are approximately double those seen in normal subjects.

Blood Platelets↗
PubMed1994

Synergistic antiviral activities of oligonucleoside methylphosphonates complementary to herpes simplex virus type 1 immediate-early mRNAs 4, 5, and 1.

An oligonucleoside methylphosphonate (ONMP) complementary to the splice acceptor site of immediate-early (IE) pre-mRNAs 4 and 5 (IE4,5SA) inhibits herpes simplex virus type 1 (HSV-1) growth in vitro and in infected animals. The antiviral effect appears to be due to inhibition of IE pre-mRNA 4 and 5 splicing and/or IE4 gene expression (M. Kulka, M. Wachsman, S. Miura, R. Fishelevich, P. S. Miller, P. O. P. Ts'o, and L. Aurelian, Antiviral Res. 20:115-130, 1993). We describe the potentiation of antiviral activity when we targeted two IE genes with different ONMPs. A psoralen derivative of an ONMP complementary to the IE mRNA 1 (IE1) translation initiation site (IE1TI) covalently bound a 2.8-kb transcript that hybridized with a 20-base oligonucleotide complementary to the 5' leader sequence of IE1 but not a 20-base oligonucleotide complementary to the first intron of IE1. IE1TI inhibited IE1 gene expression and virus replication in cells infected with HSV-1 in vitro. Inhibition was specific because it was not observed with oligomers mutated in two (IE1TImu1) or four (IE1TImu2) central residues or in cells infected with an IE1 deletion mutant (HSV-1 dl1403). IE1TI potentiated the antiviral activity of IE4,5SA (synergistic effect), while potentiation was not observed when IE4,5SA was mixed with IE1TImu1. A similar synergistic effect was seen when IE1TI was mixed with an ONMP complementary to the translation initiation site of IE mRNA 4 but not with an ONMP complementary to the translation initiation site of IE mRNA 5. These findings suggest that synergistic antiviral activity is mediated by targeting at least two IE genes (IE1 and IE4).

Animals↗
PubMed1994

Differential mineralocorticoid (type 1) and glucocorticoid (type 2) receptor expression in Lewis and Fischer rats.

Lewis (LEW/N) and Fischer (F344/N) rats represent two extremes of the spectrum of corticosterone responses to stressful stimuli, from the chronical hyporesponsiveness of LEW/N to the chronical hyperresponsiveness of F344/N. It might be expected that the amount of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) binding, and the levels of their corresponding mRNAs in various tissues in LEW/N and F344/N rats might reflect the overall integrated levels of corticosterone to which these receptors have been exposed. We have found that while the binding affinity (Kd) of MR and GR varies between tissues, there was no strain difference in any tissue. Receptor binding number (Bmax), however, varied not only between tissues, but also between strains. MR Bmax in the hippocampus and pituitary was lower in LEW/N than in F344/N, whereas the GR Bmax in the LEW/N thymus was greater than that found in F344/N rats. The hippocampal levels of MR mRNAs in Adx LEW/N and F344/N rats were in good agreement with, and paralleled, the functional levels of these receptors as determined by binding assays. On the other hand, the number of hippocampal GR binding sites and the level of GR nRNA while similar were not identical in the two strains: the hippocampal GR Bmax did not differ between strains, while the hippocampal GR mRNA level was slightly, but significantly, lower in Adx LEW/N compared to F344/N rats.

Aldosterone↗
PubMed1994

Factors influencing general practitioners' referral to hospital of adults with presumed infective diarrhoea.

BACKGROUND: Acute infective diarrhoea is one of the commonest reasons for admission to hospital with an infectious disease. AIM: This study set out to describe the clinical features of infective diarrhoea at the time of presentation in adults managed in the community or admitted to hospital in 1990-91, in order to try to understand the decision-making process which led to referral to hospital. METHOD: Data were collected from general practitioners by computer assisted telephone interview for 114 patients with presumed infective diarrhoea referred to the infection unit at the City Hospital, Aberdeen from all practices in the Grampian region and for 121 non-referred patients managed within seven practices. RESULTS: General practitioners appeared to use examination, investigation and referral selectively in patients presenting with diarrhoeal illness. A comparison of referred and non-referred patients identified differences in patients' reasons for consultation and the general practitioners' clinical findings, suggesting these were important in the decision to refer the patient for hospital admission. General practitioners were more likely to refer adult patients with infective diarrhoea if the patients were older, were seen at home and were more acutely unwell with fever, dehydration and abdominal tenderness. CONCLUSION: The identification of these criteria may help general practitioners to decide when to refer a patient with infective diarrhoea to hospital.

Diarrhea↗
PubMed1993

The influence of aspirin on plasma and platelet catecholamine levels, and platelet function in normal man.

The aim of the study was to determine whether aspirin influences sympathoadrenal output in normal human subjects. Plasma and platelet adrenaline and noradrenaline levels were measured before and after chronic administration of oral aspirin (300 mg per day for 7 days). Catecholamine concentrations measured immediately following aspirin did not differ from control (pre-treatment) values. Platelet noradrenaline and plasma adrenaline levels were, however, significantly increased 2 weeks after cessation of treatment. Platelet TxB2 generation was significantly reduced following aspirin treatment indicating that platelet cyclooxygenase had been inhibited. Catecholamine concentrations did not correlate with TxB2 generation. In vitro platelet aggregation induced by ADP, adrenaline and collagen was reduced after aspirin providing additional confirmation of cyclooxygenase inhibition. However, the in vivo markers of platelet function, beta-TG and PF4 were unaffected. These data do not provide convincing evidence for an action of aspirin on sympathoadrenal outflow, either directly or via a prostaglandin (thromboxane) mediated effect, although this does not exclude a later, delayed effect. There was no evidence for interactions between thromboxane, catecholamine levels in plasma and platelets, and platelet function.

Adenosine Diphosphate↗
PubMed1993

The effect of ephedrine isomers and their oxazolidines on locomotor activity in rats.

1. The four stereoisomeric ephedrines and four oxazolidines formed by reaction of each ephedrine isomer with salicylaldehyde were tested for their ability to increase locomotor activity in rats. 2. All ephedrine isomers except (-)pseudoephedrine increased locomotor activity; the order of potency was (-)ephedrine > (+) pseudoephedrine > (+) ephedrine. 3. All oxazolidine derivatives increased locomotor activity except (-)pseudoephedrine oxazolidine. 4. The oxazolidines derived from (-) and (+) ephedrine were slightly more active than their parent drugs. (+) Pseudoephedrine oxazolidine was less active than its parent. 5. Half-lives of hydrolysis were measured for the oxazolidines in aqueous buffer, ephedrine oxazolidines hydrolyze faster than pseudoephedrine oxazolidines.

Animals↗
PubMed1993

Interaction between the effects of 5-hydroxytryptamine and adrenaline on the growth of platelet thrombi in the coronary artery of the anaesthetized dog.

1. The interaction between adrenaline and 5-hydroxytryptamine (5-HT) has been quantitated on the rate of thrombus formation, in the stenosed coronary artery with damaged endothelium of the anaesthetized dog. 2. Changes in the plasma concentration of adrenaline were produced by varying the rate of an intravenous infusion of adrenaline and in the effects of 5-HT, by intravenous injections of the selective 5-HT2 receptor antagonist, ICI 170809. 3. Increases in the plasma concentration of adrenaline, which did not cause significant changes in blood pressure and heart rate, increased the rate of thrombus formation. 4. Antagonism of the 5-HT2 receptor by ICI 170809, in the absence of an infusion of adrenaline, abolished thrombus formation (mean ED50 0.41 microgram kg-1, i.v.). 5. The effects of adrenaline were non-competitively antagonized by ICI 170809; maximum effects were obtained in the dose-range 50-200 micrograms kg-1, i.v., when the mean dose-ratio increase in adrenaline required to restore equivalent rates of thrombus formation was 39 fold. 6. These results are consistent with a synergism between adrenaline and 5-HT and emphasize the importance of both on thrombus formation.

Anesthesia↗
PubMed1993

Gas-forming infections.

A 89 year old woman was admitted with increasing confusion and difficulty in walking. Her left thigh was swollen, erythematous and had associated crepitus.

Aged↗
PubMed1992

Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.

We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [3H]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (Bmax) than F344/N rats, but there were no differences in benzodiazepine binding affinities (Kd) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine Bmax to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hypothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary-adrenal axis function through differential sensitivity to GABA-mediated feedback.

Adrenalectomy↗