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Biomedical subjects

P Clarke

Publications and source records attributed to P Clarke.

At least 109 records · Page 6Linked to original sources
PubMed1995

Configuration and terminal sequences of the simian varicella virus genome.

The simian varicella virus (SVV) genome is a linear DNA molecule consisting of a unique short (Us) and a unique long (UL) region. The Us is bounded by internal (IR) and terminal inverted repeats and inverts such that virion DNA contains equimolar amounts of two genome isomers. We have sequenced the right and leftward termini and the UL-IR junction region of the SVV genome. A sequence motif common to other herpesviruses, consisting of A and T residues surrounded by G+C-rich regions, was found near the rightward terminus of the SVV genome. Sequence analysis showed no repeats surrounding the UL region of the genome. Nucleic acid hybridization and polymerase chain reaction (PCR) amplification using primers from the right and leftward ends of the SVV genome indicated that the UL region inverts. PCR amplification also showed that, compared with virion DNA, SVV genomes with connected termini are increased in infected cell DNA, suggesting the presence of circular or concatemeric genomic molecules.

Base Sequence↗
PubMed1995

Failure of macrophage activation in experimental obstructive jaundice: association with bacterial translocation.

Bacterial translocation from the gastrointestinal tract and macrophage activation are central to current theories of sepsis. The relevance of both in obstructive jaundice is unclear. The effect of bile duct ligation for 7 days on bacterial translocation to mesenteric lymph nodes and on macrophage activation in a rat model was examined. Compared with an incidence of zero in sham-ligated controls, bile-duct ligated rats had a 67 per cent incidence of Gram-negative colonization of mesenteric lymph nodes. This was associated with a significant (P < 0.001) decrease in macrophage tumour necrosis factor, superoxide anion and nitric oxide production compared with that in sham controls. Spontaneous bacterial translocation occurs in experimental obstructive jaundice and is associated with marked suppression of macrophage activation. This suggests a mechanism whereby jaundiced patients may be more susceptible to persistent infection but relatively protected against uncontrolled sepsis.

Animals↗
PubMed1995

High-dose interleukin 2 promotes bacterial translocation from the gut.

Toxicity associated with high-dose recombinant interleukin 2 (rIL-2) therapy simulates a sepsis syndrome, but the mechanism remains unclear. We hypothesised that translocated gut-origin bacteria may be important. Fifty-one male rats were randomised to receive rIL-2 by intraperitoneal injection at doses (IU) of 10(5) (n = 15), 10(4) (n = 8), 10(3) (n = 8) or 10(2) (n = 8) twice daily, or a saline bolus (n = 12). After 5 days, ileal histomorphology was assessed and the mesenteric lymph node complex cultured. Results showed that colonisation of mesenteric lymph nodes with Escherichia coli occurred in all rats treated with 10(5) IU of rIL-2, and in 62%, 37% and 12% of rats treated with decreasing doses of rIL-2. No translocation was observed in control animals. An increase in submucosal lymphatics and occasional mucosal disruption was seen only in the group receiving 10(5) IU. These data show that rIL-2 promotes bacterial translocation and suggests a mechanism that may fuel high-dose rIL-2 toxicity in man.

Animals↗
PubMed1995

Configuration of latent varicella-zoster virus DNA.

The configuration of latent varicella-zoster virus (VZV) DNA was analyzed by PCR. Template DNA for both internal and terminal VZV primers was present in a 1:1 ratio in ganglionic DNA, compared with a 15:1 ratio in DNA extracted from VZV virions, indicating that the VZV genomic termini are adjacent in latently infected human ganglia.

Adult↗
PubMed1995

Pancreatic duct: MR cholangiopancreatography with a three-dimensional fast spin-echo technique.

PURPOSE: To determine the role of three-dimensional fast spin-echo magnetic resonance (MR) cholangiopancreatography in the evaluation of the normal and abnormal pancreatic duct. MATERIALS AND METHODS: A non-breath-hold MR cholangiopancreatographic technique with use of a body coil was compared with direct pancreatography performed with endoscopic retrograde cholangiopancreatography in 37 patients. RESULTS: MR cholangiopancreatograms of satisfactory quality were obtained in 92% of patients. Sensitivity for detection of pancreatic duct dilatation (n = 15) was 100% and 87% (observers 1 and 2, respectively). Among patients with pancreatic duct strictures (n = 8), 75% of the strictures were detected; there was a single false-positive finding. Specificity for both observers was 69% for the maximum intensity projection reconstructions and increased to 81% with review of the source images. Four of six cases of pancreas divisum (67%) and two cases of pancreatic duct stones were demonstrated. Interobserver agreement was moderate to substantial, as assessed with kappa-analysis. CONCLUSION: MR cholangiopancreatography can accurately demonstrate the normal pancreatic duct as well as various pancreatic duct abnormalities.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1994

Ultrastructural localization of BHRF1: an Epstein-Barr virus gene product which has homology with bcl-2.

BHRF1 is an Epstein-Barr virus encoded protein which has a 38% sequence similarity with bcl-2 over the carboxyl portion. Like bcl-2, BHRF1 has been shown to suppress programmed cell death from apoptosis. Previously BHRF1 has been detected in mitochondrial, microsomal, and nuclear compartments by cell fractionation analysis. In this study we have used the technique of immunoelectron microscopy to define the ultrastructural distribution of the BHRF1 product in the EBV converted cell lines B95.8 and P3HR-1. The BHRF1 product was localized at the periphery of the mitochondria in a pattern similar to that of bcl-2 and by analogy with bcl-2 this is likely to be the functional destination. Sequence analysis of the BHRF1 protein disclosed similarity with the recently described bcl-2 homologues bcl-x (32%) and bax (34%) over the carboxyl portion, with several domains of complete identity. BHRF1 appears to be a member of a gene family involved in the regulation of programmed cell death. The identity between BHRF1 and bcl-2, an apparent shared ability to abrogate apoptosis, and the common ultrastructural localization is compelling and suggests that bcl-2 and BHRF1 are both functionally and mechanistically similar.

Amino Acid Sequence↗
PubMed1994

Sclerosing peritonitis: identification of diagnostic, clinical, and radiological features.

Sclerosing peritonitis is a rare, but serious complication of peritoneal dialysis. To attempt the early identification of patients at risk of developing this life-threatening problem, we performed a cross-sectional study of 15 patients: five had died of sclerosing peritonitis, four had stopped peritoneal dialysis because sclerosing peritonitis was suspected, and six were considered to be at increased risk because of more than 4 years on peritoneal dialysis. We examined the duration of dialysis, number of episodes of peritonitis, strength of peritoneal dialysis bags, the type of dialysate, and the use of beta blockers. We also used a number of radiologic investigations, including abdominal x-ray, a measure of colonic transit using radiopaque markers, abdominal ultrasound, and computed tomography scanning. Of the clinical features, only duration of dialysis could be shown to be an important risk factor. We identified a number of radiologic features that we believe to be early signs of peritoneal sclerosis. The two computed tomography scans that were available from the deceased patients demonstrated peritoneal thickening, as did those from three of the four living patients who stopped peritoneal dialysis with suspected disease and from two of the six patients who had been on peritoneal dialysis for over 4 years. Ultrasound demonstrated a characteristic trilaminar appearance in four patients, but was unable to be demonstrated without peritoneal fluid in situ. Delayed colon transit was demonstrated in three of the four living patients with clinically suspected disease. Radiologic screening to detect sclerosing peritonitis early in high-risk patients requires further study.

Adult↗
PubMed1993

DNA sequence of a simian varicella virus gene that encodes a homologue of varicella zoster virus IE62 and herpes simplex virus ICP4.

Clinical and biological studies indicate that simian varicella virus (SVV) infection of primates is the counterpart of human varicella zoster virus (VZV) infection. We have identified an SVV open reading frame (ORF) that is homologous to the VZV protein IE62 and herpes simplex virus (HSV) ICP4. Like the genes encoding the VZV and HSV proteins, the SVV gene is located in the repeat region of the virus genome. Its expression in SVV-infected cells yields a 4.2-kb transcript. DNA sequencing of the SVV gene reveals a coding region 3834 nucleotides in length and a G+C content of 60.3%. Like ICP4 homologues in other herpesviruses, the SVV protein has five regions, two of which (regions 2 and 4) are highly conserved. The SVV protein also contains a run of serine residues in its amino terminus that is characteristic of herpesvirus ICP4 homologues. The SVV protein shows an overall homology of 24% to HSV ICP4 and 53% to VZV IE62.

Amino Acid Sequence↗
PubMed1993

A double-blind, placebo-controlled crossover trial of nadolol and verapamil in mild and moderately symptomatic hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to determine whether therapy with a beta-adrenergic or calcium channel blocking agent can improve the functional capacity and quality of life of patients with mild or moderately symptomatic hypertrophic cardiomyopathy. BACKGROUND: Both beta-blockers and calcium channel blockers may alleviate symptoms in hypertrophic cardiomyopathy, but previous studies have been performed in hospitalized patients or have been open studies without control subjects. METHODS: A randomized, double-blind crossover trial of nadolol, verapamil and placebo, administered for periods of 4 weeks each, was performed in 18 patients with mild or moderately symptomatic hypertrophic cardiomyopathy (10 men, 8 women; mean age +/- SD 39 +/- 17 years). A detailed symptom assessment, bicycle exercise testing, echocardiography and Holter monitoring were performed in each period. RESULTS: Two patients withdrew from the study owing to symptomatic sinus bradycardia during nadolol therapy. Neither drug improved maximal oxygen consumption (placebo 26 +/- 8, verapamil 23 +/- 6, nadolol 21 +/- 7 ml/kg per min; p = 0.1). Peak exercise work load was reduced by > or = 10 W in 13 patients (81%) during nadolol therapy and in 4 patients (25%) during verapamil therapy (p = 0.005, nadolol vs. verapamil). Despite the effects on exercise capacity, 13 patients (81%) preferred drug treatment (8 verapamil, 5 nadolol) over placebo (p = 0.001). Verapamil improved reported performance at work compared with nadolol (p = 0.01) and tended to improve other measures of health-related behavior and symptoms compared with nadolol and placebo. CONCLUSIONS: In patients with mild or moderately symptomatic hypertrophic cardiomyopathy, exercise capacity was not improved by nadolol or verapamil, and individuals were more often impaired by nadolol than with verapamil. Nevertheless, many patients derived symptomatic benefit from drug therapy, especially with verapamil.

Adolescent↗
PubMed1992

Mutations in the araC gene of Salmonella typhimurium LT2 which affect both activator and auto-regulatory functions of the AraC protein.

The araC gene encodes a regulatory protein, AraC, that acts as both an activator and a repressor of transcription of the genes involved in the transport and catabolism of L-arabinose in Salmonella typhimurium LT2. Five araC mutants which have altered regulatory properties were characterized. All are point mutations which would result in amino acid substitutions near the C terminus of AraC. Each mutation results in altered activator and auto-regulatory AraC function in vivo. In vitro DNA-binding assays showed that three mutant AraC have measurable lowered affinity for ara controlling site DNA. The data are consistent with a model in which there is a DNA-binding domain in the C terminus of AraC which functions in both activation and repression.

Alleles↗
PubMed1992

Prevalence and distribution of latent simian varicella virus DNA in monkey ganglia.

We used polymerase chain reaction to analyze the prevalence and distribution of latent simian varicella virus (SVV) in ganglionic and nonganglionic tissues from nine African green monkeys experimentally infected with SVV. Primers specific for three different regions of the SVV genome were used for amplification. SVV DNA sequences were detected in trigeminal ganglia from seven of nine monkeys and in thoracic ganglia from seven of nine monkeys. Analysis of DNA from nonneuronal tissues of three monkeys and from adrenal glands of nine monkeys revealed the presence of SVV-specific sequences in the adrenal gland of one monkey. The results indicate that, like human varicella, SVV becomes latent primarily in ganglia at multiple levels of the neuraxis, and more than one region of the SVV genome is present in latently infected ganglia. SVV latency in primates may be a useful model for varicella latency in humans.

Animals↗
PubMed1992

Molecular analysis of simian varicella virus DNA.

Clinical and pathological studies indicate that simian varicella virus (SVV) infection in primates is the counterpart of human varicella zoster virus (VZV) infection. The SVV and VZV genomes are also similar in size and structure. To extend studies of SVV DNA, we analyzed virus DNA from African green monkey kidney cells infected with the Delta-herpes-virus strain of SVV. The infectivity of SVV DNA was 88 PFU/micrograms. The buoyant density of SVV DNA, determined by isopycnic banding in CsCl gradients, was 1.700 +/- 0.002 g/ml, corresponding to a G + C molar ratio of 40.8%. The size of SVV DNA, estimated by analysis of restriction endonuclease digestion products and pulsed-field gel electrophoresis was 125.1 and 124.9 kbp, respectively. Electron microscopy of SVV DNA revealed a long region of 110.0 kbp, a unique short (Us) region of 5.1 kbp, and inverted repeat regions of 7.5 kbp flanking the Us. An EcoRI map of SVV DNA revealed two fragments not previously reported; our complete Pstl map also shows some differences. Mapping of SVV DNA with an additional restriction enzyme, measurement of full-length SVV DNA molecules, and the first use of pulsed-field electrophoresis to size SVV DNA, confirm and extend Gray's recent finding that SVV DNA has the same size and molecular configuration as VZV. We also show for the first time that the density of SVV DNA is similar to that of VZV DNA and that SVV DNA is infectious.

Animals↗