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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 469 records · Page 26Linked to original sources
PubMed1995

Patterns of cytokine expression in community-acquired pneumonia.

BACKGROUND: Pneumonia continues to be a major cause of disease and death among patients worldwide. Aspects of the host response to infection, such as the release of cytokines, may be contributing to the persistent morbidity and mortality. METHODS: Plasma levels of cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were measured in critically ill patients with pneumonia (ICUP; n = 12) and less severely ill patients with pneumonia (NONICUP; n = 8), and in 2 additional control groups of patients, viz, severely ill postoperative patients without evidence of infection (POSTOP; n = 11) and less severely ill patients with nonpneumonia infections (NONP; n = 9). All four groups of patients were studied in a multivariate one-way analysis of variance using the parameter vector: plasma IL-1 beta, IL-6, TNF-alpha, systolic blood pressure, diastolic blood pressure, plasma urea, creatinine, and temperature. Thereafter the significance of individual parameters were assessed by univariate analysis and pairwise comparisons. RESULTS: All cytokine concentrations were highest in the ICUP group. In the case of IL-1 beta, levels were significantly higher in the ICUP group when compared with the noninfected POSTOP group. The acute physiology and chronic health evaluation (APACHE) II scores were identical in these two groups (17 +/- 3 [SD] and 10 +/- 1, respectively, not significantly different). Intermediate levels were found in those groups with intermediate levels of infection. The IL-6 levels were not significantly different between the groups and in particular, the levels in the ICUP and POSTOP groups were similar. The TNF-alpha levels tended to mimic those of IL-1 beta, although the significant difference found was between the ICUP and NONICUP groups which had significantly different APACHE II scores (17 +/- 3 vs 4.4 +/- 1, respectively). No association between cytokine levels and patient mortality was demonstrated. CONCLUSION: Among the cytokines, IL-1 beta appeared to be associated with the severity of infection, IL-6 appears to reflect severity of stress whether of infection or noninfective origin, and TNF-alpha may be a marker of severity of pneumonia.

APACHE↗
PubMed1995

Stimulation of tyrosinase in human melanocytes by pro-opiomelanocortin-derived peptides.

Human melanocytes, maintained on bovine corneal endothelium-derived extracellular matrix for at least 4 days in the absence of phorbol 12-myristate 13-acetate (PMA) and cholera toxin (CT), displayed increased tyrosinase activity when exposed to several pro-opiomelanocortin-derived (POMC) peptides. Melanocytes from 9 of 14 donors showed significantly increased tyrosinase activity after treatment with adrenocorticotropic hormone (ACTH; mean increase 320 +/- 107 (S.E.M.)% of control, P < 0.005), while melanocytes from 8 of 13 donors increased tyrosinase in the presence of diacetyl-melanocyte stimulating hormone (di-MSH; mean increase 223 +/- 31 (S.E.M.)% of control, P < 0.005). Maximal increases in tyrosinase were seen after treatment with 10(-10) M ACTH and with 10(-6) M di-MSH. In two cell cultures which showed tyrosinase stimulation, melanin synthesis was similarly increased in the presence of added POMC peptides. PMA but not CT increased tyrosinase activity in melanocytes cultured under these conditions. In the presence of staurosporine, an inhibitor of protein kinase C (PKC), the magnitude of the increase in tyrosinase due to PMA, ACTH and di-MSH was significantly reduced. These results indicate that tyrosinase activity in melanocytes from most human donors, under appropriate conditions, is susceptible to the stimulatory effects of POMC peptides, that ACTH is considerably more potent than di-MSH in this test system and that in human cells the PKC pathway may be important in modulating melanogenesis.

Adrenocorticotropic Hormone↗
PubMed1995

Comparison of evaluation-selection systems for maximizing genetic response at the same level of inbreeding.

Use of improved methods of genetic evaluation and intense selection lead to higher rates of genetic change but also lead to higher rates of inbreeding. A number of methods have been proposed to attain high rates of genetic response with moderate or low inbreeding (i.e., restrict the number of close relatives selected, use false high heritability in the genetic evaluation, use assortative mating, adjust estimated breeding values for the relationship with those already selected, avoid matings of related individuals, and increase the number of parents selected). These various methods were compared here using stochastic simulation of an infinitesimal genetic model. The results were studied graphically plotting response against inbreeding, so allowing comparison of the methods at each of a range of inbreeding levels. None of the methods was best over all conditions. At high rates of inbreeding and with a fixed number of sires, several of the methods gave large decreases in inbreeding for small losses in response. However, these were matched by simply increasing the number of sires selected. There is an optimum response-inbreeding "front" attained by several methods, and this front seems hard to breach. Characterization of the front would be useful in designing selection programs.

Algorithms↗
PubMed1995

Metal ion release from mechanically-disrupted human arterial wall. Implications for the development of atherosclerosis.

Oxidation of low density lipoproteins (LDL) in blood vessel walls plays a significant role in the development of atherosclerosis. LDL oxidation in vitro is greatly accelerated by the presence of "catalytic" iron or copper ions, which have already been shown to be present within advanced atherosclerotic lesions. We demonstrate here that mechanical damage to human arterial wall samples (both normal and early or intermediate atherosclerotic lesions) causes release of "catalytic" iron and copper ions, to an extent increasing with the damage. It may be that traumatic (e.g. during angioplasty) or other injury to the vessel wall contributes to the generation of metal ions that can facilitate LDL oxidation and other free radical reactions, so promoting atherosclerosis.

Arteries↗
PubMed1995

Fasting insulin concentration is related to cardiovascular reactivity to exercise in children.

OBJECTIVE: One mechanism through which hyperinsulinemia is linked to hypertension is through its stimulation of sympathetic nervous activity. Thus, insulin concentration may be correlated with indices of sympathetic activity before it is associated with resting blood pressure. We tested this hypothesis by determining the relationship of insulin concentration and sympathetically mediated cardiovascular reactivity to exercise in children. DESIGN: Survey. SETTING: General community. PARTICIPANTS: Volunteer sample of 46 black and white boys and girls, 9 to 11 years of age. INTERVENTIONS: None. Fasting insulin concentration was the main independent variable. MAIN OUTCOME MEASURES: Systolic blood pressure and heart rate during a standard submaximal bout of treadmill exercise, and systolic blood pressure at peak effort. RESULTS: The hypothesis was tested by multiple regression analyses controlled for resting values. Insulin contributed significantly to the regression models for submaximal heart rate (P < .001), submaximal systolic blood pressure (P = .001), and peak systolic blood pressure (P = .006). CONCLUSIONS: Fasting insulin concentration is associated with cardiovascular reactivity to exercise in young children. This supports the hypothesis that the relationship between hyperinsulinemia and hypertension is mediated by sympathetic nervous tone and that the process begins in childhood. Because percent body fat was positively associated with both insulin and cardiovascular reactivity to exercise, prevention of childhood obesity may be a valuable prophylactic measure for these health problems.

Analysis of Variance↗
PubMed1995

Inhibition of HIV-1 in CEM cells by a potent TAR decoy.

TAR decoys are short RNA oligonucleotides, corresponding to the HIV TAR sequence, which inhibit HIV expression and replication by blocking the binding of the HIV regulatory protein Tat to the authentic TAR region. In previous studies, TAR decoys expressed from a tRNA polIII promoter were moderately effective at inhibiting HIV in isolated human T cell lines and less effective at inhibiting HIV in peripheral blood CD4+ T cells. In this study, a series of modifications was introduced into the tRNA expression cassette in order to improve their effectiveness. These modifications included the addition of sequences which are predicted to have stem-loop secondary structures and addition of a wild-type tRNA processing site. TAR decoy RNA expressed in CEM cells from modified tRNA-based expression cassettes yielded five- to 20-fold more TAR transcripts than unmodified tRNA-based expression cassettes. HIV replication, as measured by a flow cytometric method to quantify intracellular viral p24 expression, was significantly reduced in polyclonal populations of CEM cells expressing a modified tRNA-TAR transcript that contains a wild-type tRNA processing site and stem-loops 5' and 3' to the TAR sequence. Similar modifications to the tRNA expression cassette also increased the intracellular concentration of a random test oligonucleotide, indicating that this improved expression system may also be useful for antisense and ribozyme based gene inhibition strategies.

Antiviral Agents↗
PubMed1995

Evaluating nursing care: reflection in practice.

Reflective practice involves examining everyday events. Critical awareness is essential in a period of rapid change. Analysing events in nursing care can identify new ways of working in the future.

Aged↗
PubMed1995

Learning about yourself helps patient care. Using self-awareness to improve practice.

1. Nurses must be able to communicate effectively with patients, relatives and other staff. 2. Self-awareness is the recognition of the physical, social, psychological and spiritual aspects of the individual. 3. Using a journal helps develop critical faculties and enhances personal and professional development. 4. Reflective practice allows people to examine and explore their feelings, beliefs and attitudes.

Humans↗
PubMed1995

Controversies in the management of retroperitoneal hemorrhage associated with pelvic fractures.

Pelvic fractures present major therapeutic challenge requiring systematic diagnostic and management strategies. This article describes a 50-year-old female with a massive pelvic fracture after being crushed under the wheels of a bus. All aspects of her management are presented in detail. The current indications and role of exploratory laparotomy, internal and external fixation, and diagnostic and therapeutic angiography are discussed.

Fatal Outcome↗
PubMed1995

P1 blood group phenotype, secretor status in patients with urinary tract infections.

We have examined the distribution of P antigen, Lewis blood group phenotypes and secretor status of 65 patients with E. coli UTI (20 asymptomatic bacteriuria, 20 cystitis and normal radiology, 25 reflux nephropathy) and 45 controls who have never experienced a UTI episode. The distribution of Lewis blood group antigens was similar in all UTI groups and in the controls. The incidence of non-secretors in the reflux nephropathy group was similar to that in controls (24% versus 31%). The P1 phenotype was present in 100% of patients with asymptomatic bacteriuria, 80% with cystitis and controls and only 44% with reflux nephropathy. The combined P1/non-secretor phenotype was observed in 45% of patients with asymptomatic bacteriuria, 30% with cystitis, 12% with reflux nephropathy and in 22% of control healthy individuals. P2/secretor phenotype was demonstrated in 44% of patients with reflux nephropathy and in only 11% of controls. Our data suggest that having P2 blood group protects against asymptomatic colonization of the urinary tract, but is associated with the type of infection responsible for scarring in reflux nephropathy. It also appears that being a non-secretor does not predispose to renal scarring and that combined P2/secretor phenotype may be linked with susceptibility to reflux nephropathy.

ABO Blood-Group System↗
PubMed1994

Autoregulation of endothelin-1 secretion by cultured human keratinocytes via the endothelin B receptor.

We investigated endothelin-1 (ET-1) receptor expression on normal human keratinocytes (HK). We show that HK express the ETB receptor isoform and respond to ET-1 with a 2.7-fold increase in intracellular free calcium. HK did not respond to ET-1 with increased proliferation; however, 30 nM ET-1 caused a 51.7% decrease in ET-1 accumulation in HK-conditioned medium. We propose that HK ET-1 receptors function in autocrine regulation of ET-1 secretion.

Cell Division↗
PubMed1994

Activity of two-chain recombinant human cytomegalovirus protease.

The human cytomegalovirus UL80 protease was expressed in Escherichia coli and purified by metal-chelate chromatography using a histidine tag engineered at the amino terminus. Cleavage of the 30-kDa protease at an internal site, VEA/A144, resulted in the recovery of 16- plus 14-kDa two-chain protease. The amino-terminal 16-kDa chain and the carboxyl-terminal 14-kDa chain remained associated as an active enzyme that was modified specifically at Ser132 on the 16-kDa chain by [3H]diisopropyl fluorophosphate. Disruption of the cleavage site by mutation from VEA/A to AEA/A facilitated the recovery of active 30-kDa one-chain enzyme that could be similarly modified at Ser132 by [3H]diisopropyl fluorophosphate. Both one- and two-chain enzymes cleaved recombinant assembly protein at the maturation site, VNA/S, and a peptide, GVVNASARL, mimicking this site. Internal processing does not inactivate the protease but forms a two-chain enzyme that retains activity.

Amino Acid Sequence↗
PubMed1994

26,27-Dihomo-1 alpha-hydroxy- and 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 analogs that differ markedly in biological activity in vivo.

26,27-Dihomo-1 alpha-hydroxyvitamin D2, 26,27-dihomo-24-epi-1 alpha-hydroxyvitamin D2, and 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 have been synthesized. In contrast to 1 alpha-hydroxyvitamin D2 and 24-epi-1 alpha-hydroxyvitamin D2, 26,27-dihomo-1 alpha-hydroxyvitamin D2 (1) and the 24-epi analog (2) have no activity in intestinal calcium transport, bone calcium mobilization, or skeleton mineralization. On the other hand, 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 is equal to 1,25-dihydroxyvitamin D3 in biological activity. Vitamin D 25-hydroxylase readily converts 1 alpha-hydroxyvitamin D2 to 1,25-dihydroxyvitamin D2. In contrast, the same preparations fail to hydroxylate 26,27-dihomo-1 alpha-hydroxyvitamin D2 and 26,27-dihomo-24-epi-1 alpha-hydroxyvitamin D2 on carbon 25. Thus, homologation of carbons 26 and 27 of the vitamin D compound likely sterically hinders vitamin D 25-hydroxylase.

Animals↗
PubMed1994

Synthesis and opioid activity of 7-oxygenated 2,3,4,4a,5,6,7,7a-octahydro-1H-benzofuro[3,2-e]isoquinolin-9-ols.

3-(Cyclopropylmethyl)-9-hydroxy-7-oxo-2,3,4,4a alpha,5,6,7,7a alpha- octahydro-1H-benzofuro[3,2-e]isoquinoline (4b) containing the ACNO ring system of morphine and a 7-keto function on ring C has been synthesized and found to possess potent PQW (ED50 = 0.15 mg/kg sc) and anti-Straub tail (ED50 = 0.02 mg/kg sc) activity. As compared to its 7-deoxy analog 1b, introduction of the 7-keto group did not significantly affect binding to any of the three opioid receptors (mu, kappa, and delta), but caused a 34-fold reduction in sigma-binding, suggesting reduced propensity to induce psychotomimetic effects. The C/D cis isomer of 4b (4c) was much less potent at the three opioid receptors, while displaying a slight increase in sigma affinity. Both 7-hydroxy derivatives 4e and 4f were active in anti-Straub tail assay (ED50 < or = 0.8 mg/kg sc), but only the alpha-isomer 4e demonstrated analgesic activity (PQW ED50 = 0.37 mg/kg sc) in the dose range tested. In guinea pig ileum preparations, 4e was characterized as a selective full agonist at the kappa opioid receptor (IC50 = 2.8 nM); while its beta-isomer 4f was a partial agonist (78% at 1 microM), with antagonist activity observed at both mu- and kappa-opioid receptors.

Analgesics↗
PubMed1994

Human melanoma cells express functional endothelin-1 receptors.

Current evidence suggests that endothelium-derived factors enhance human melanoma vascular invasion. Therefore, we studied human melanoma cell expression of receptors to the endothelium-derived peptide, endothelin-1 (ET-1), and determined if they respond to ET-1 with proliferation and chemokinesis. Human metastatic melanoma cell lines were found to have specific, saturable, high affinity ET-1 binding. Northern analysis and competitive inhibition studies confirmed that melanoma cells express the ETB receptor isoform. Ten nanomolar ET-1 caused an 8.2 to 25.5-fold increase in intracellular free calcium. ET-1 was found to be a weak mitogen for melanoma cells, however, melanoma cell chemokinesis was significantly increased by ET-1. These data suggest that ET-1 may be involved in providing a chemokinetic and growth factor environment that enhances perivascular proliferation and invasiveness of melanoma cells.

Calcium↗