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Biomedical subjects

J E Clark

Publications and source records attributed to J E Clark.

At least 37 records · Page 2Linked to original sources
PubMed1998

Heme oxygenase-1 induction in skeletal muscle cells: hemin and sodium nitroprusside are regulators in vitro.

The heat shock protein heme oxygenase-1 (HO-1) is regulated by a variety of physiological and pharmacological factors. In skeletal muscle tissue, HO-1 has been shown to be induced only by exercise and electrical stimulation in vivo. Both hemin and sodium nitroprusside (SNP) are potent inducers of HO-1 in other tissues. In this study, we examined the effects of these two agents on HO-1 induction in L6.G8 rat skeletal myoblast cells. Hemin and SNP increased cellular heme oxygenase activity in both a time- and concentration-dependent manner. Increases in the HO-1 mRNA level and protein expression accompanied changes in heme oxygenase activity. The ability of SNP to induce HO-1 in L6.G8 cells was reduced by coincubation with hydroxocobalamin, a known nitric oxide (NO) scavenger, suggesting that NO itself may be involved in HO-1 gene stimulation. These results indicate that HO-1 expression is sensitive to both hemin and SNP in skeletal myoblast cells and may indicate an important regulatory mechanism of heme catabolism in skeletal muscle tissue.

Animals↗
PubMed1998

A UK centre's experience of mycobacterial infections in HIV-infected patients.

A descriptive retrospective review of 26 patients with mycobacterial infection; 7 Mycobacterium tuberculosis (MTB), 17 Mycobacterium avium complex (MAC), one M. xenopei and one M. kansasii. Diagnosis of non-tuberculous mycobacteria (NTM) was made mainly from blood in 68%, with biopsy material initially useful in 68%. All MTB were fully sensitive. No patients received MAC chemoprophylaxis, yet resistance to rifabutin, ciprofloxacin and ethambutol was noted. It is important to examine the UK experience of mycobacterial infection; individual centres may find it useful to review infecting organisms and resistance patterns.

AIDS-Related Opportunistic Infections↗
PubMed1997

Involvement of the heme oxygenase-carbon monoxide pathway in keratinocyte proliferation.

It has been suggested that nitric oxide (NO), a small gaseous molecule with a multiplicity of cellular functions, plays an important part in the regulation of cellular proliferation. We have examined the effect of the NO donor sodium nitroprusside (SNP) on heme oxygenase-1 (HO-1) expression in human epidermal keratinocytes and investigated the contribution of the heme oxygenase pathway in the control of keratinocyte proliferation. Incubation of keratinocytes with 0.5 mM SNP resulted in a 2.5-fold increase in heme oxygenase activity which was reflected by a significant increase in HO-1 protein expression, as measured by Western blot. This effect was associated with a 200% increase in keratinocyte proliferation. The proliferative effect of the NO donor was totally abolished by co-incubation of SNP with tin protoporphyrin IX, a potent inhibitor of heme oxygenase, or hydroxocobalamin, a NO scavenger. These results suggest that the heme oxygenase pathway is involved in keratinocyte proliferation mediated by NO.

Carbon Monoxide↗
PubMed1997

Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells. Involvement of superoxide and peroxynitrite anions.

Thiols are very important antioxidants that protect cells against oxidative insults. Recently, a different and new physiological role has been defined for these compounds because of their involvement in nitric oxide (NO) binding and transport in biological systems. In view of these characteristics, we examined the effect of thiols and NO on the expression of the inducible form of heme oxygenase (HO-1), a stress protein that degrades heme to carbon monoxide and biliverdin. Cultured bovine aortic endothelial cells exposed to the NO donors sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) resulted in increased heme oxygenase activity and HO-1 expression. Co-incubation with N-acetylcysteine, a precursor of glutathione synthesis, significantly attenuated heme oxygenase induction by SNP and SNAP, and a reduction in heme oxygenase activity was also observed when cells were preincubated with N-acetylcysteine for 16 h prior to exposure to NO donors. This effect appears to be associated with NO stabilization by thiols through the formation of S-nitrosothiols. Hydroxocobalamin, a specific NO scavenger, significantly decreased endothelial heme oxygenase activity, indicating a direct involvement of NO released by NO donors to regulate the expression of this stress protein. Moreover, superoxide anion (O-2) and its reaction product with NO, peroxynitrite (ONOO-), were found to partially contribute to the observed NO-mediated activation of endothelial heme oxygenase. Thus, we suggest the existence of a dynamic equilibrium among free NO, O-2, and endogenous glutathione, which might constitute an interactive signaling mechanism modulating stress and adaptive responses in tissues.

Acetylcysteine↗
PubMed1996

Uncemented press-fit total hip arthroplasty using the Identifit custom-molding technique. A prospective minimum 2-year follow-up study.

Fifty-three primary uncemented custom-molded Identifit (Depuy, Warsaw, IN) hip arthroplasties were evaluated prospectively at a mean follow-up period of 30 months. The custom technique provided the capability to reproduce the unique femoral offset, version, and height in each hip and to achieve high percentages of femoral canal fill. Surgical time for unilateral cases was a mean 153 minutes. Clinical results, however, were disappointing. Nine hips (17%) required stem revision for persistent thigh pain and limping. Of the remaining 44 hips, the mean Harris hip score was 83, and 20% experienced moderate to severe thigh pain and 50% had a limp. Radiographically, 65% of the stems had subsided and 27% had migrated into valgus. Survivorship analysis predicted an 80% stem survival rate at 43 months. A precise fit and fill of the femoral canal is not in itself sufficient for femoral implant stability in total hip arthroplasty surgery.

Adult↗
PubMed1996

Vowel classification in children.

Research into the developing vowel system has assumed greater importance in recent years with growing evidence for a more important theoretical role for vowels in child phonology. One limitation of acoustic studies in child speech has been the practical difficulties associated with formant-based analysis and the experiments reported in this paper compare the reliability of critical bands and formant frequencies as acoustic correlates of vowel identity in children. Gaussian classification of vowels in/CVd/Australian English words was carried out using data collected from 4-year-old children and male and female adults. The results show that the use of critical bands for the classification of vowels in children is a robust technique which requires less experimenter intervention in the analysis procedure than the use of formant frequencies, while achieving similar results. The ability to utilize an automatic methodology such as critical band analysis can provide a very powerful tool for large-scale studies in this area.

Child, Preschool↗
PubMed1996

Lymphadenopathy.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗
PubMed1995

Non-tuberculous mycobacterial lymphadenopathy.

The surgical and antimicrobial treatment of non-tuberculous mycobacterial lymphadenopathy in 17 children was reviewed. Node excision was curative, but most nodes were still incised leaving discharging lesions. Standard antituberculous treatment was unhelpful, but a new macrolide/quinolone combination appeared to be effective in three cases.

Antitubercular Agents↗
PubMed1994

For young jumpers, differences are in the movement's control, not its coordination.

Previous research on the development of jumping has indicated that the coordination of the jump is stable from its inception, but that individual differences lie in the control of the task. The purpose of this study was to examine control in the vertical jump as performed by novice jumpers. Two groups of children who varied in their ability to regulate the takeoff angle were compared on measures of coordination and control. The children's groups were also compared to a group of skilled adults. Both children's groups demonstrated temporal coordination patterns comparable to the adult pattern, though the children were distinguished from the adults on selected spatial (control) measures. The results indicate that a mature pattern of coordination for the jump exists at the earliest stages of the behavior's appearance in the movement repertoire. The novice, however, lacks the ability to precisely control, or tune, the movement to task demands.

Child, Preschool↗
PubMed1994

Parenting satisfaction and efficacy among caregivers of children with diabetes.

This study assessed parenting satisfaction and efficacy in 53 parents of children with diabetes and 39 parents of physically healthy children. In addition, the relationship between parenting self-esteem and perceptions of child behavior, child age, disease duration, and metabolic control were examined. Parents of children with diabetes reported significantly lower levels of parenting satisfaction and efficacy compared to parents of healthy children, and their negative parental cognitions are most influenced by perceptions of more internalizing child problems, shorter diabetes duration, and poorer metabolic control. Parenting self-esteem was significantly inversely correlated with both internalizing and externalizing child behavior problems for parents of healthy children. The clinical implications of poor parental cognitions and directions for future research are highlighted.

Caregivers↗
PubMed1994

Effects of 17-octadecynoic acid, a suicide-substrate inhibitor of cytochrome P450 fatty acid omega-hydroxylase, on renal function in rats.

This study evaluated the ability of 17-octadecynoic acid (17-ODYA) to inhibit the metabolism of arachidonic acid by cytochrome P450 in renal cortical microsomes of rats, and characterized the effects of intrarenal infusion of this substance on renal hemodynamics and the excretion of water and electrolytes. 17-ODYA was a potent inhibitor (IC50 < 100 nM) of the formation of 20-hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids by rat renal cortical microsomes incubated with arachidonic acid. Infusion of 17-ODYA (16.5 nmol/min; n = 8) directly into the renal cortical interstitium of rats produced a diuresis and a natriuresis which were associated with an increase in renal papillary blood flow in the absence of changes in renal blood flow, cortical blood flow or glomerular filtration rate. 17-ODYA inhibited the omega-hydroxylation of arachidonic acid by microsomes prepared from the infused kidney by 61.3 +/- 9.2% (n = 7) relative to that observed in the contralateral kidney, whereas infusion of vehicle (n = 6) or palmitate (n = 4) had no effect on renal metabolism of arachidonic acid by cytochrome P450. Infusion of 17-ODYA (33 nmol/min) into the renal artery of rats also increased urine flow and sodium excretion, whereas renal blood flow and glomerular filtration rate were not significantly altered. Papillary blood flow increased 36% during infusion of 17-ODYA into the renal artery, and renal interstitial hydrostatic pressure increased from 8.7 +/- 1.1 to 13.8 +/- 1.5 mm Hg. These results suggest that endogenous cytochrome P450 metabolites of arachidonic acid influence renal medullary hemodynamics and the excretion of water and electrolytes.

Animals↗
PubMed1993

Expression of rabbit cytochromes P4504A which catalyze the omega-hydroxylation of arachidonic acid, fatty acids, and prostaglandins.

The omega-hydroxylation product of arachidonic acid is thought to be a potent vasoconstrictor or a precursor thereof in kidney. In this report, we have measured the capacity of four rabbit CYP4A enzymes, each expressed in COS-1 cells, to catalyze the omega-hydroxylation of arachidonic acid. These rates were compared to those obtained for other substrates such as lauric acid, palmitic acid, and prostaglandins PGE1 and PGA1. With the exception of P4504A5, all of the enzymes tested exhibited relatively high rates for the omega-hydroxylation of arachidonic acid. P4504A5 showed very little activity toward arachidonic or palmitic acids as compared to that toward lauric acid (< 10%). In contrast, P4504A6 and P4504A7 catalyzed the omega-hydroxylation of arachidonic acid at rates that were roughly 50% of that observed for lauric acid. P4504A4 was not active toward lauric acid, but it also catalyzed the omega-hydroxylation of arachidonic acid at a rate that was roughly 20% of that exhibited for PGE1. Thus, each enzyme exhibits a distinct substrate specificity profile across this panel of substrates. A sensitive RNase protection assay was used to provide a more quantitative estimate of the relative abundance of mRNAs encoding P4504A5, P4504A6, and P4504A7 in liver and kidney from control, pregnant, and clofibrate-treated animals. CYP4A5 is the most abundant of the mRNAs, but it was not induced in kidney and only moderately (2-fold) in liver by clofibric acid. CYP4A7 exhibits a similar pattern of induction by clofibrate. In contrast, CYP4A6 is induced 12-fold in liver and 6-fold in kidney. The higher induction ratio largely reflects a lower basal level of expression for CYP4A6 than for CYP4A7 and CYP4A5. Following treatment with clofibrate, the amount of CYP4A6 mRNA is similar to those of CYP4A5 and CYP4A7. Pregnancy did not affect the expression of CYP4A5, CYP4A6, or CYP4A7, although it induced the expression of CYP4A4 to detectable levels in the liver and kidney, where it is not normally found in nonpregnant animals. Our results indicate that the enzyme whose mRNA is most highly induced by clofibric acid (P4504A6) and the enzyme selectively elevated during pregnancy (P4504A4) both exhibit relatively high rates for the omega-hydroxylation of arachidonic acid.

Animals↗
PubMed1993

Cytochrome P450 4A4: expression in Escherichia coli, purification, and characterization of catalytic properties.

Rabbit lung prostaglandin omega-hydroxylase (P450 4A4) was expressed in Escherichia coli using the isopropyl beta-D-thiogalactopyranoside (IPTG) inducible expression vector pCWori+, containing the full-length cDNA encoding the P450 4A4. The first seven codons were changed to reflect E. coli codon bias [a modification of the method of Barnes et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 5597-5601]; only the second residue of P450 4A4 was altered (Ser to Ala), while the remaining mutations were silent. This strategy was adopted in order to minimize changes in the structure of the expressed enzyme. Induction by IPTG of the apoprotein peaked after 6 h, and by including the heme precursor delta-aminolevulinic acid, enzymatic activity peaked 12 h after addition of IPTG. The isolated membrane fraction, free of cell debris, contained 12-15 nmol of P450/L of media. The expressed enzyme was purified to electrophoretic homogeneity, and kinetic and spectrophotometric data indicate that this expressed, purified enzyme is equivalent to the enzyme purified from rabbit lung. The Km for PGE1 was determined to be 3.0 microM, which is the same as that obtained for the enzyme purified from lung [Williams et al. (1984) J. Biol. Chem. 259, 14600-14608]. The CO-reduced difference spectrum of purified P450 4A4 exhibited a lambda max at 450 nm, and the absolute absorbance spectrum of the pyridine hemochromogen revealed a typical b type heme. To characterize P450 4A4 further, the catalytic activities with prostaglandin E1 (PGE1), arachidonate, 15-hydroxyeicosatetraenoic acid (15-HETE), and palmitate were investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminolevulinic Acid↗