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Biomedical subjects

C C Smith

Publications and source records attributed to C C Smith.

At least 145 records · Page 8Linked to original sources

Platelet catecholamines and platelet function in normal human subjects.

We have used high-performance liquid chromatography with electrochemical detection to measure plasma and platelet catecholamines in 24 normal subjects. In the same subjects platelet function was assessed by measuring platelet aggregation in response to adenosine 5'-pyrophosphate, thrombin, adrenaline and collagen. Platelet sensitivity to prostacyclin was also examined. Platelet noradrenaline showed a positive correlation with extent of aggregation induced by 'low-dose' collagen (1 microgram/ml). No correlation was seen at the higher collagen concentration. Platelet noradrenaline content also correlated with sensitivity of platelets to prostacyclin. High platelet noradrenaline concentrations appeared to result in decreased sensitivity to prostacyclin. No other correlations were observed. These data suggest that platelet noradrenaline rather than plasma levels may be involved in modifying platelet function in vivo. Local release of platelet catecholamines may affect the platelet/vessel wall interaction, the primary physiological step in platelet activation.

Adult↗

Protection of guinea pigs from primary and recurrent herpes simplex virus (HSV) type 2 cutaneous disease with vaccinia virus recombinants expressing HSV glycoprotein D.

Vaccinia virus recombinants containing herpes simplex virus (HSV) type 1 (VP176) or type 2 (VP221) glycoprotein D (gD) genes were studied for their protective potential in the guinea pig model of recurrent HSV type 2 disease. Cells infected with these recombinants synthesized at least one protein (precursor, mature form, or both) that was precipitated with monoclonal antibody to HSV type-common determinants on gD. These determinants were detected on the surface of cells infected with the recombinants at 2 hr after infection. VP176 immunization protected against primary (P much less than .001) and recurrent (P much less than .001) cutaneous HSV type 2 lesions and ganglionic latency (62% protection). VP221 immunization protected against recurrent disease (P less than .05), although HSV type 2 ganglionic infection was established. Protection, first observed at two weeks after immunization, apparently did not involve HSV-specific neutralizing antibody because seroconversion was detected at 35-45 days after immunization. Protection was correlated with HSV-specific lymphoproliferation and the elaboration of lymphokines that enhance natural killer cell cytolysis.

Animals↗

A program for improving energy conservation behaviors in adults with rheumatoid arthritis.

This paper presents the design and evaluation of an occupational therapy program developed at the National Institutes of Health for teaching energy conservation and joint protection to adults with rheumatoid arthritis. An existing model for educational diagnosis in health education was used to identify program, behavioral, and educational objectives for the new program. The use of this model resulted in measurable objectives, which were used as outcome measures in the randomized research evaluation of the new program. The dependent variables measured were activity-of-daily-living status, psychosocial adjustment to illness, knowledge, disease activity, pain, and fatigue. None were significantly different after the intervention. The independent variables measured included components of balancing rest and physical activity. After 3 months, a greater percentage of the subjects receiving the workbook-based occupational therapy program than those receiving traditional occupational therapy demonstrated an application of the behaviors the intervention was designed to change.

Arthritis, Rheumatoid↗

Monoclonal antibody to HSV2 protein as an immunodiagnostic marker in cervical cancer.

The present study was designed to evaluate the possible use of monoclonal antibodies (mAbs) as diagnostic adjuncts to exfoliative cytology and tissue sections in intraepithelial (CIN) and invasive cervical cancer. Specimens were collected from 42 patients with various degrees of CIN, 15 patients with invasive cancer and two patients with condylomatous changes only. mAb H17, that recognizes a herpes simplex virus protein (ICP) representing a component of the viral ribonucleotide reductase, stained atypical exfoliated cells from 55% of patients with mild dysplasia and 100% of those with more severe lesions. The mean percentage of positive atypical cells increased as a function of the grading of CIN (32.6 +/- 6.3%, 63.5 +/- 2.7%, 67.9 +/- 8.1%, 81.4 +/- 10.1%, and 85.6 +/- 2.0% for mild, moderate, and marked dysplasia, CIS, and invasive cancer, respectively). Only a very small proportion of atypical cells from only two patients stained with a mAb to another herpes simplex virus protein (gA/B). Normal squamous, metaplastic, inflammatory, or koilocytotic cells did not stain with the mAbs. Of the 15 cases examined by cryostatic fresh sections with immunohistochemical techniques, only one case of invasive cancer did not stain with mAb anti-ICP, and all controls were negative. The high specificity and sensitivity of MAbH17 suggests that it may be a useful diagnostic/prognostic marker in CIN.

Animals↗

Determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction.

Determinants of plasma glucose concentrations were studied in patients on admission to hospital with confirmed acute myocardial infarction but without previous glucose intolerance as evidenced by raised concentrations of glycosylated haemoglobin (HbAlc). Mortality in hospital increased significantly with increasing plasma concentrations of glucose in patients with both normal (p less than 0.0001, n = 311) and borderline (p less than 0.02, n = 70) concentrations of HbAlc. There was a weak relation between plasma glucose concentrations and infarct size as estimated by peak aspartate transaminase activity in both HbAlc groups (rs = 0.26, n = 101 and rs = 0.41, n = 35 respectively). A correlation was found between adrenaline and plasma glucose concentrations (r = 0.47, n = 27) and cortisol and plasma glucose concentrations (r = 0.75, n = 19), but the relation of plasma noradrenaline and plasma glucose suggested a threshold effect. Concentrations of adrenaline, but not those of noradrenaline or cortisol, correlated with infarct size as measured both by peak aspartate transaminase activity and cumulative release of creatine kinase MB isoenzyme. Multiple regression analysis showed that concentrations of cortisol, adrenaline, and noradrenaline (but not the concentration of HbAlc, infarct size, or age) are the main determinants of plasma glucose concentration measured in non-diabetic patients when admitted to hospital after acute myocardial infarction.

Aged↗

Stimulus-induced release of endogenous catecholamines from human washed platelets.

Using high-performance liquid chromatography with electrochemical detection, we have studied the release of endogenous catecholamines from washed platelets induced to aggregate by ADP and thrombin. Washed platelets exhibit irreversible aggregation with 10 mumol/l ADP and 0.3 unit of thrombin/ml, extents of aggregation being 27% and 76% respectively. ADP (10 mumol/l) increased noradrenaline release to the medium by 20% and adrenaline by 28%. As observed with aggregation, 0.3 unit of thrombin/ml produced a more marked effect on release than ADP, noradrenaline and adrenaline being increased by 570% and 169% respectively. Values for platelet noradrenaline content were found to mirror those for the release from platelets induced by thrombin. A correlation was observed between catecholamine release and the concentration of thrombin present in incubations. These data reflect the changes observed with platelet aggregation. This is the first study to determine catecholamine release from platelets by direct measurement. Local catecholamine release after platelet aggregation in vivo may have important consequences for tissue perfusion.

Adenosine Diphosphate↗

Antiviral effect of an oligo(nucleoside methylphosphonate) complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5.

Selective inhibition of regulatory immediate early (IE) genes of herpes simplex virus type 1 (HSV-1) should inhibit virus growth. Treatment of HSV-1-infected cells with the oligo(nucleoside methylphosphonate) d(TpCCTCCTG) (deoxynucleoside methylphosphonate residues in italic), which is complementary to the acceptor splice junction of HSV-1 IE pre-mRNA 4 and 5, before (1-24 hr) or at the time of infection caused a dose-dependent inhibition in virus replication. Virus titers were decreased 50% and 90% in cells treated with 25 microM and 75 microM oligomer, respectively; at 300 microM, a 99% reduction in virus production was observed. Viral DNA synthesis was reduced 70-75% and there was a 90% reduction in synthesis of viral proteins, including other IE species and viral functional (130-kDa major DNA-binding) and structural (glycoprotein gB) proteins. In the same concentration range, d(TpCCTCCTG) caused a minimal reduction (0-30%) in protein synthesis and growth rates (less than 40%) of uninfected cells. The data suggest that oligo(nucleoside methylphosphonate)s may be effective in antiviral chemotherapy.

Animals↗

Effects of genetic diabetes and zinc nutriture on in vivo cell-mediated immunity in the mouse.

To examine whether an abnormal zinc status contributes significantly to the impaired in vivo cell-mediated immunity of the genetically diabetic C57BL/KsJ db/db mouse, we measured specific cytotoxicity of spleen cells from db/db and heterozygous (db/m) and homozygous (m/m) control mice fed either zinc-deficient (2 mg/kg) or zinc-adequate (20 mg/kg) semipurified diets. Low serum and femur zinc concentrations were seen after 4 wk in all mice fed the zinc-deficient diet, but impaired cytotoxicity was not seen until later in control mice fed that diet. In contrast, db/db mice fed zinc-adequate diets had diminished spleen weights and markedly impaired cytotoxicity by 4 wk. These mice had normal serum and only mildly decreased femur zinc concentrations. We, therefore, found no evidence to suggest that the mildly altered zinc status of db/db mice fed zinc-adequate diets is a major factor contributing to their markedly impaired in vivo cell-mediated immunity.

Animals↗

Intracellular localization and serological identification of a HSV-2 protein in cervical cancer.

Exfoliated atypical cells from US and Italian patients with cervical intraepithelial neoplasia or invasive cancer stained in indirect immunofluorescence with a monoclonal antibody to a high MW HSV-2 protein (ICP10). The proportion of staining cells increased as a function of the severity of the cervical anaplasia. In the majority of cases with mild or moderate dysplasia staining was restricted to the cytoplasm while atypical cells from 6 of 7 cases with marked dysplasia and 7 of 7 cases with invasive cancer evidenced also nuclear staining. Normal exfoliated cells did not stain even when obtained from tissue adjacent to the tumor mass. Patients with ICP10 positive atypical cells had antibody to ICP10 as determined by the Western blot assay. Serologic analyses indicated that there was a good correlation between: (i) the Western blot and the CF assay previously used to detect antibody to AG-4 (Aurelian, et al, Cancer, 48, 455, 1981) and (ii) cervical anaplasia and ICP10 seropositivity. A similar correlation with cervical anaplasia was not observed with respect to antibody to two other viral proteins (ICP12/14 and 68K).

Antibodies, Monoclonal↗

Stability of catecholamines in whole blood, plasma, and platelets.

Checking catecholamine stability in whole blood, plasma, and platelets, we found that specimens stored at room temperature or frozen for periods ranging from 1.5 h to three weeks show no significant difference in measured catecholamine concentration. The implications of these findings are discussed.

Adrenal Gland Neoplasms↗

Glucose tolerance and plasma lipid distributions in rats fed a high-sucrose, high-cholesterol, low-chromium diet.

Male Sprague-Dawley rats were fed either a low-chromium (60 to 100 micrograms per kg of diet) or chromium-supplemented (5 mg per kg of diet), high-sucrose, high-cholesterol diet from weaning until age 18 months. Rats that were pair- and meal-fed the low-chromium diet had higher one-hour postprandial plasma glucose concentrations than their supplemented partners at ages 4 and 8 months (P less than 0.05), but not at age 12 months. One-hour postgavage (250 mg glucose/100 g body wt) glucose concentrations did not differ between dietary groups at 12 months. Plasma cholesterol concentrations increased up to age 12 months, but neither they nor postprandial triglyceride concentrations differed significantly between dietary groups. Ad libitum feeding of the low-chromium and chromium-supplemented diets was initiated at age 14 months in order to determine whether there were differences due to dietary chromium content which might not be manifest on the pair-feeding regimen. Animals of both dietary groups had significant weight gain by age 16 months, but their one-hour postgavage plasma glucose concentrations did not differ significantly. Plasma cholesterol concentrations increased significantly following institution of ad libitum feedings, but neither they nor lipoprotein cholesterol or triglyceride distributions differed significantly between dietary groups. Experimental conditions, methods, and results from this study and previous studies are compared and critically examined. We suggest that other factors in addition to dietary chromium content may contribute to the differences in glucose tolerance and plasma cholesterol concentrations described in such studies and that there is a need for improved documentation of glucose intolerance and tissue chromium concentrations in this animal model.

Animals↗

An analysis of 12 months admissions to a regional infection unit with an open door admission policy.

All admissions to the Aberdeen Infection Unit over a period of 12 months have been analysed. Forty per cent of the patients proved to have non-infectious conditions although most were referred as having an infectious disease. Those patients with infectious diseases were younger and had a shorter stay in hospital. Also there was seasonal variation in the time of their admission as well as a low mortality rate when compared with older patients with non-infectious disease admitted over the same period. Cross infection did not arise in spite of patients sharing accommodation.

Cross Infection↗

The distribution of catecholamines between platelets and plasma in normal human subjects.

We have used high-performance liquid chromatography with electrochemical detection to measure content of adrenaline and noradrenaline in platelets in 13 normal subjects at rest. Subjects were exercised to raise plasma catecholamine levels and promote the platelet release reaction. There was a significant positive correlation between plasma noradrenaline concentrations and platelet noradrenaline content. Platelet/plasma concentration ratios were 1855 for noradrenaline and 268 for adrenaline at rest and 473 and 152 respectively after exercise. Plasma noradrenaline levels positively correlated with age. Determination of platelet factors released to the plasma showed increases of beta-thromboglobulin and platelet factor 4 with exercise, whereas thromboxane B2 remained unchanged. No change in platelet catecholamine levels occurred with exercise and no correlations were observed between platelet catecholamines and released platelet factors. These data suggest that plasma catecholamine levels influence platelet content and that noradrenaline and adrenaline are concentrated in platelets.

Adult↗

Multistep transformation by defined fragments of herpes simplex virus type 2 DNA: oncogenic region and its gene product.

Diploid Syrian hamster embryo cells transfected with Bgl II C fragment of herpes simplex virus type 2 DNA acquired a neoplastic phenotype. Cultures transfected with its left-hand 64% subclone EcoRI/HindIII fragment AE (0.419-0.525 map unit) grew into established but nontumorigenic lines. Transfection of EcoRI/HindIII AE-immortalized cells with a 4.4-kilobase Sac I/BamHI subfragment within BamHI E (0.554-0.584 map unit; overlaps the right-hand 16% of Bgl II C) converted them to tumorigenicity. The 4.4-kilobase subfragment encodes a 144-kDa protein immunologically and structurally similar to an infected cell protein designated ICP 10. DNA extracted from cells transformed with the 4.4-kilobase subfragment exhibited discrete hybridizing bands homologous to BamHI E fragment. Monoclonal antibody to ICP 10 precipitated a 144-kDa protein from the transformed cells and stained them in immunofluorescence. A tumor derivative established with the transformed cells did not stain with this antibody, but approximately equal to 25% of the cells stained with a monoclonal antibody to c-myc protooncogene products.

Animals↗