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J Rogers

Publications and source records attributed to J Rogers.

At least 199 records · Page 11Linked to original sources
PubMed1996

Kinetic basis for the substrate specificity during hydrolysis of phospholipids by secreted phospholipase A2.

Kinetics of hydrolysis of aqueous dispersions of arsono-, sulfo-, phosphono- and phospholipids by phospholipase A2 from pig pancreas are characterized in terms of interfacial rate and equilibrium parameters. The enzyme with or without calcium binds with high affinity to the aqueous dispersions of the four classes of anionic lipids and shows the same general kinetic behavior. The rate of hydrolysis of anionic substrates does not show an anomalous change at the critical micelle concentration because the enzyme is present in aggregates even when bulk of the substrate is dispersed as a solitary monomer. Apparent affinities of the enzyme for the interface of different anionic lipids are virtually the same. Also, affinities of these substrates for the active site of the enzyme at the interface are comparable. However, a significant change in the catalytic turnover rate is seen as the sn-3 phosphodiester group is modified; the apparent maximum rate at saturating bulk substrate concentration, V(M)app values, increase in the order: homo- and arsonolipids < sulfo- < phosphono- < phospholipids. Not only the basis for the sn-2 enantiomeric selectivity but also the decrease in the rate of hydrolysis with the increasing chain length is due to a decrease in the value of V(M)app. Results show that even when the bulk concentration of anionic phospholipid is below cmc, hydrolysis occurs in aggregates of enzyme and substrate where the chemical step of the turnover cycle remains rate-limiting, which provides a basis for the assumption that V(M)app is directly related to Kcat. The fact that Kcat depends on the nature of the head group (phosphate, phosphonate, sulfate, arsonate) implies that the head group plays a critical role in the rate-limiting chemical step of the catalytic cycle, possibly during the decomposition of the tetrahedral intermediate. The significance of these results for the microscopic steady-state condition for hydrolysis at the micellar interface, mechanism of esterolysis by phospholipase A2, and inhibitor design are discussed.

Animals↗
PubMed1996

Inhibition of the self-cleavage reaction of the human hepatitis delta virus ribozyme by antibiotics.

Human hepatitis delta virus (HDV) poses a health threat in populations where chronic hepatitis B is endemic. It is a single-stranded RNA virus of 1700 nucleotides and both genomic and antigenomic sequences contain ribozymes which are important for viral replication. Using ribozyme constructs we show that several classes of antibiotics inhibit the self-cleavage reaction of the HDV ribozyme. Antibiotics of the aminoglycoside, peptide and tetracycline classes all inhibit HDV cleavage in vitro at micromolar concentrations. Neomycin (an aminoglycoside) inhibits HDV self-cleavage with a Ki value of 28 (+/- 10) microM. Neomycin inhibition can be reversed by increasing magnesium ion concentration in a competitive manner. Lead acetate cleaves positions G76, A42 and G28, which surround the ribozyme cleavage site. Both Mg2+ and neomycin prevent lead cleavage. Footprinting experiments using base-specific chemical probes revealed enhanced modifications of a set of bases by neomycin, overlapping with the above mentioned lead cleavages. These observations may indicate that neomycin directly displaces divalent metal ions essential for catalysis.

Anti-Bacterial Agents↗
PubMed1996

Developmentally regulated expression of IGF binding protein-3 (IGFBP-3) in human placental fibroblasts: effect of exogenous IGFBP-3 on IGF-1 action.

Preterm, human, placental fibroblasts exhibit growth rates, in vitro, that vary with gestational age. The observed increase in proliferation rate is associated with enhanced mitogenic responsiveness to IGF-I. IGFBPs can either potentiate or inhibit IGF action at the cellular level. The production of IGFBPs by placental fibroblasts was studied as potential modulators of their responsiveness to IGFs. Human placental fibroblasts were obtained at various gestational ages and maintained in culture. IGFBP-3 protein and mRNA expression were assessed by Northern and ligand blot analyses. First, media conditioned by fibroblasts, in culture, were subjected to ligand blot analysis. Multiple species of IGFBPs were present in each cell line tested. IGFBP-3, migrating as a doublet at approx. 38/42 kDa, was the predominant IGFBP species present. Other IGFBPs of 22-35 kDa were also present. The secretion of IGFBP-3 exhibited a marked decrease at 10-15 weeks gestation relative to 8-9 week fibroblasts but began to increase again by 19 weeks. We next studied the expression of IGFBP-3 mRNA. Total cellular RNA was obtained from rapidly growing cells and subjected to Northern analysis. Placental fibroblasts exhibited decreased steady state levels of IGFBP-3 mRNA at 10-15 weeks gestation consistent with its decreased protein expression. The ability of IGFBP-3 to influence IGF-1 stimulated DNA synthesis was studied in 10 week placental fibroblasts as measured by [3H]thymidine incorporation. IGFBP-3 inhibited IGF-1 (3.3 nM) stimulated DNA synthesis in a dose-dependent manner when added simultaneously with IGF-1 or preincubated with the cells for 48 h prior to the addition of IGF-1. By contrast, maximum effective concentrations of IGFBP-3 (52 nM) potentiated the effect of IGF-1 50-200% when preincubated with bovine fibroblasts for 48 h prior to the addition of IGF-1. These data suggest that IGFBP-3 production is developmentally regulated in human placental fibroblasts and inhibits their mitogenic response to IGF-1. The regulated expression of IGFBP-3 may contribute to the altered growth rate and IGF responsiveness exhibited by placental fibroblasts, in vitro.

Animals↗
PubMed1996

Intermembrane molecular contacts by polymyxin B mediate exchange of phospholipids.

Direct intermembrane exchange of dimyristoylphosphatidylmethanol is mediated by polymyxin B (PxB), a cationic amphipathic cyclic decapeptide. The possibility that the phospholipid exchange is mediated by solubilization of phospholipids or by fusion of vesicles is ruled out. By kinetic and spectroscopic methods it is shown that the exchange occurs directly through vesicle-vesicle contacts formed by a few PxB molecules. The contact is stable on the time scale of several minutes such that neither PxB nor the vesicles in the pair forming a contact exchange with excess vesicles. Several contacts may be formed on a vesicle, which leads to the formation of a cluster of vesicles, and the lipid molecules on the outer monolayers of vesicles exchange throughout the cluster. Kinetics of substrate replenishment during processive interfacial catalysis suggests that the exchange of anionic lipids over the contact occurs at a rate considerably faster than 300 s-1. The exchange through the contact is specific for certain lipids, and phospholipids with a modified head group or phospholipase A2 bound to a vesicle are not transferred to the other vesicle in contact. Since this phenomenon has not been described before, possible implications of direct vesicle-vesicle exchange of phospholipids through peptide-mediated molecular contacts are discussed. Such a mechanism for intermembrane transfer of phospholipids could be responsible for intracellular trafficking and sorting of phospholipids; it could be a necessary first step for the sequence of events leading to budding, vesiculation, and secretion; and PxB-mediated transfer between the inner and outer membranes of Gram-negative bacteria could also account for its antibiotic action.

Cell Membrane↗
PubMed1996

Interspecific variation at the Y-linked RPS4Y locus in hominoids: implications for phylogeny.

Within- and between-species variation in restriction endonuclease recognition sites was examined at the Y-linked RPS4Y locus of six hominoid species: human (Homo sapiens), gorilla (Gorilla gorilla), chimpanzee (Pan troglodytes), bonobo (Pan paniscus), orangutan (Pongo pygmaeus), and gibbon (Hylobates lar). RPS4Y is an expressed gene that maps to the non-recombining region of the Y chromosome. An approximately 1,490 base pair fragment of the RPS4Y gene, including all of intron 3, was amplified by PCR from DNA extracted from each of the six species. Forty-seven restriction sites were identified on the six-species composite map derived from double-digest restriction analyses of the amplified fragment. As expected, maximum parsimony analysis indicated that chimpanzee and bonobo are the two most closely related living hominoids. The same analysis suggested that the closest living relative of Homo is Gorilla, not Pan, although support for this relationship was relatively weak. These results disagree with recently published phylogenies based on analyses of mtDNA sequences (Horai et al. [1995] Proc. Natl. Acad. Sci. U.S.A. 88:7401-7404) and the Y-linked ZFY locus (Dorit et al. [1995] Science 268:1183-1185). A combined data set derived from three distinct Y-linked loci-RPS4Y, SRY, and ZFY-was also analyzed. The maximum parsimony topology for the combined data provided only weak support for a shared common ancestor for Homo and Pan subsequent to divergence from the Gorilla lineage. Taken together, the data from the Y chromosome do not provide unequivocal support for any single, dichotomously branching species tree linking Homo, Pan, and Gorilla.

Animals↗
PubMed1996

Total anorectal reconstruction results in complete anorectal sensory loss.

Six patients underwent objective measurement of anorectal sensory function following abdominoperineal excision of the rectum and total anorectal reconstruction. No patient perceived neorectal distension as a desire to defaecate or as a feeling of flatus. Anal mucosal sensation was preserved in two patients in whom some anal mucosa was retained. These sensory deficiencies may result in faecal retention and incontinence in patients undergoing reconstructive surgery. The loss of rectal sensation suggests that the prime sensors of rectal filling may lie within the rectum itself.

Aged↗
PubMed1996

Use of an asialoglycoprotein receptor-targeted magnetic resonance contrast agent to study changes in receptor biology during liver regeneration and endotoxemia in rats.

The hepatic asialoglycoprotein receptor is responsible for rapid clearance of desiaylated glycoproteins from the circulation by receptor-mediated endocytosis. Previous in vitro studies in hepatocyte preparations from rats subjected to partial hepatectomy (PH) of 70% to stimulate hepatic regeneration showed decreased asialoglycoprotein (ASGP) receptor binding. We used an ASGP receptor-targeted hepatic magnetic resonance imaging (MRI) agent, BMS 180550, to demonstrate similar changes in receptor biology in vivo. BMS 180550 is an arabinogalactan-coated ultrasmall superparamagnetic iron oxide preparation. Arabinogalactan is a ligand for the ASGP receptor and, thereby, targets the contrast agent exclusively to hepatocytes. Hepatic uptake of BMS 180550 was assessed by sequential precontrast and post-contrast MRI in rats subjected to PH of 70%. In regenerating liver 1 and 3 days after PH, the maximum decrease in hepatic signal intensity (62.2% +/- 6.1 and 59.4% +/- 3.8, respectively) was significantly less than the maximum decrease seen in sham-operated animals at 1 and 3 days postsurgery (39.5% +/- 2.5 and 44% +/- 1.0, respectively). The time necessary to reach 80% of the maximum decrease in hepatic signal intensity, (t80), was less than 2 minutes in control rats and increased to 7.5 +/- 1.3 min and 11.0 +/- 2.3 minutes at 1 and 3 days post-PH, respectively. By 7 days post-PH, contrast-enhanced MRI no longer detected a difference in regenerating liver. Because BMS 180550 is taken up exclusively by the liver, clearance of the agent from the blood was used as a measure of hepatic clearance. Concentration-time curves constructed by measuring changes in blood T2 after an intravenous dose of BMS 180550 were used to determine clearance of the agent. Blood clearance of BMS 180550 in normal liver (15.4 +/- 1.08 mL/min) obeyed first-order kinetics and did not vary over the dose range tested (10 to 100 micromol/L/kg iron). One, 3, 7, and 14 days post-PH, clearance varied with dose, suggesting ASGP receptor saturation. As regeneration proceeded, the dose of contrast agent needed to cause a deviation from first-order kinetics increased, suggesting gradual recovery of ASGP receptor function. Hepatic relaxation was determined by in vitro spectroscopy 60 minutes after administration of graded doses of BMS 180550 and showed dose-dependent increases in relaxation. Kinetic analysis at 1 day post-PH demonstrated a decrease in the apparent k(m) and the maximum response, R(max), suggesting a decrease in the number of functional asialoglycoprotein receptors with concomitant increase in receptor affinity. Systemic endotoxemia, which normally accompanies hepatic regeneration induced by PH, also decreased clearance of BMS 180550 and slowed hepatic uptake of the contrast agent. Altered BMS 180550 pharmacokinetics in endotoxin-treated rats was enhanced by prior administration of small doses of competing ligand. Our studies document the value of BMS 180550 in following changes in ASGP function that accompany PH or systemic endotoxemia. This agent may be useful in assessing the degree of hepatic regeneration in patients with clinical liver disease.

Animals↗
PubMed1996

Stratum corneum lipids: the effect of ageing and the seasons.

Stratum corneum lipids play a predominant role in maintaining the water barrier of the skin. In order to understand the biological variation in the levels and composition of ceramides, ceramide 1 subtypes, cholesterol and fatty acids, stratum corneum lipids collected from tape strippings from three body sites (face, hand, leg) of female Caucasians of different age groups were analysed. In addition, we studied the influence of seasonal variation on the lipid composition of stratum corneum from the same body sites. The main lipid species were quantified using high-performance thin-layer chromatography and individual fatty acids using gas chromatography. Our findings demonstrated significantly decreased levels of all major lipid species, in particular ceramides, with increasing age. Similarly, the stratum corneum lipid levels of all the body sites examined were dramatically depleted in winter compared with spring and summer. The relative levels of ceramide 1 linoleate were also depleted in winter and in aged skin whereas ceramide 1 oleate levels increased. The other fatty acid levels remained fairly constant with both season and age, apart from lignoceric and heptadecanoic acid which showed a decrease in winter compared with summer. The decrease in the mass levels of intercellular lipids and the altered ratios of fatty acids esterified to ceramide 1, are likely to contribute to the increased susceptibility of aged skin to perturbation of barrier function and xerosis, particularly during the winter months.

Adult↗
PubMed1996

Examination of biofilm formation and risk of infection associated with the use of urinary catheters with leg bags.

Urinary catheters and legs bags were simultaneously colonized by Escherichia coli and Proteus vulgaris using a model urinary drainage system. the system was continuously supplied with filter-sterilized artificial urine using a diurnal flow pattern. The extent of colonization was determined by assessment of both planktonic and biofilm formation over time. Contamination of the catheters resulted in rapid colonization of the whole system within a 24 h period. Contamination of the leg bags resulted in an ascending biofilm formation over a four-day period. Results indicated that infection risk could be minimized by changing the catheter and leg bags at least once a week. The design of the leg bags was not found to influence the rate or extent of biofilm formation.

Animals↗
PubMed1996

Prolonged ambulatory small intestinal and colonic motility monitoring: potential in irritable bowel syndrome--first report of prolonged ambulatory oesophageal, small intestinal and colonic motility in the same patient.

Irritable bowel syndrome (IBS), which affects up to 25% of the population in western countries and accounts for up to 50% of referrals to gastroenterologist, remains mainly a diagnosis of exclusion. We have studied, for the first time, prolonged ambulatory motility recordings from the oesophagus, small intestine and colon of a patient who was referred to us with a 12-year history of abdominal pain and a presumptive diagnosis of IBS. The results indicated that the diagnosis was pseudo-obstruction syndrome rather than IBS. Wider clinical use of the new techniques of prolonged ambulatory intestinal motility monitoring in IBS would offer considerable potential not only in achieving a greater understanding of its pathophysiology but also in providing a more precise definition of clinical and therapeutic subgroups.

Colon↗
PubMed1996

Differences in patterns of care of prostate cancer, New South Wales, 1991.

BACKGROUND: In this time of uncertainty about the benefits of earlier diagnosis for prostate cancer and the optimal choice of treatment in various clinical scenarios, we addressed the hypothesis that two groups in the population, namely country dwellers and migrants from non-English-speaking countries, were less likely to be offered new methods of diagnosis and treatment for prostate cancer. METHODS: Incident cases of prostate cancer in 1991 were identified through the population-based New South Wales Central Cancer Registry. For 73% of eligible cases information relating to diagnosis, staging and treatment was abstracted onto a checklist from clinical records in urologists' consulting rooms and in public hospitals. RESULTS: Transrectal ultrasound and prostatic biopsy were used for diagnosis significantly more often in urban than in rural cases while the reverse was true for transurethral resection of the prostate. Intravenous pyelography, ultrasound (other than transrectal) and bone scans were performed for staging more frequently in urban than rural cases. Rural cases were more likely to be treated with anti-androgens than urban cases and less likely to be given luteinizing-hormone releasing hormone (LH-RH) agonists. The pattern of use of various diagnostic and staging procedures for 1991 rural cases resembled that for urban men diagnosed with prostate cancer in 1986 rather than that for 1991 urban cases. CONCLUSIONS: At least in part, these urban-rural differences could be explained by the fact that some patients in the country would have been treated by general surgeons rather than urologists. The patterns of care for non-English-speaking migrants resembled those for the Australian-born and for English-speaking migrants.

Delivery of Health Care↗
PubMed1996

Conservation of human chromosome 18 in baboons (Papio hamadryas): a linkage map of eight human microsatellites.

A panel of 25 microsatellite loci known to map to human chromosome 18 was screened for length polymorphisms in a multigenerational pedigree of baboons (Papio hamadryas). Eight of these loci were polymorphic in the baboon pedigrees, with observed heterozygosity values ranging from 0.16 to 0.88. All eight loci show strong evidence of linkage. The most likely map order among the microsatellite loci for Papio is completely compatible with the locus order found in the human genome, and sex differences in recombination rates are also similar in the two species. We conclude that the organization of the chromosomal region defined by these loci is largely conserved between baboons and humans.

Animals↗
PubMed1996

Diagnosis of neonatal congenital heart defects by remote consultation using a low-cost telemedicine link.

To determine whether telemedicine could assist in the earlier diagnosis of neonates with congenital heart disease (CHD) in an area hospital remote from a paediatric cardiologist, we established a low-cost telemedicine link between the neonatal unit of a district general hospital and the regional paediatric cardiology unit. Realtime ultrasound images of babies suspected of having CHD were obtained by a paediatrician and transmitted for realtime interpretation by a paediatric cardiologist. In a four-month pilot study, 10 neonates were studied in this way. In eight of the ten cases, the diagnosis made over the telemedicine link was confirmed subsequently in a direct examination at the regional unit. In one case the patient died before the direct examination was possible. In one case two small muscular ventricular septal defects were missed on the remote examination. Our early experience suggests that, with realtime guidance by a paediatric cardiologist, transmitted images of sufficient quality to allow confirmation or exclusion of major cardiac defects can be obtained. This form of remote consultation should improve morbidity and mortality rates by reducing the waiting time for specialist diagnosis and treatment.

Cardiology Service, Hospital↗
PubMed1996

Seasonal affective disorder: some epidemiological findings from a tropical climate.

OBJECTIVE: To determine whether a predominantly summer-focussed pattern of seasonal affective disorder (SAD) exists in tropical northern Australia. METHOD: A mail survey containing a modified form of the Seasonal Pattern Assessment Questionnaire (SPAQ) was administered to 176 households in the city of Townsville (latitude: 19 degrees south). RESULTS: Using previously reported screening criteria, 9% of respondents reported a degree of summer impairment indicative of SAD, while the incidence rate for winter SAD was 1.7%. This summer-winter ratio is typically reversed in more temperate latitudes. CONCLUSIONS: Excessive heat and humidity were reported to be the two most influential environmental factors affecting mood and behaviour. It is likely that respondents meeting criteria for summer SAD represent the extreme end of a spectrum of summer-related mood and behaviour change that affects many individuals in northern Australia. Strategies for further clinical and epidemiological research on SAD in tropical climates are proposed.

Adolescent↗
PubMed1996

Inflammation, A beta deposition, and neurofibrillary tangle formation as correlates of Alzheimer's disease neurodegeneration.

We evaluated entorhinal cortex and superior frontal gyrus for hallmarks of Alzheimer's disease (AD) pathology, including inflammation, in three patient sets: AD patients, nondemented elderly patients with few or no neurofibrillary tangles (NFTs) and amyloid beta peptide (A beta) deposits, i.e. normal controls (NC), and nondemented elderly patients with profuse entorhinal cortex NFTs and neocortical A beta deposits, i.e. high pathology controls (HPC). Membrane attack complex (C5b-9) immunoreactivity and immune activation of microglia (MHCII expression) were used as general markers for inflammation. Compared to NC patients, AD patients exhibited significant cortical synapse loss, A beta deposition, NFT formation, and inflammation. HPC patients also had significantly elevated A beta deposition and NFT formation, but there was no evidence of synapse loss and little or no evidence of inflammation. Across patients and brain regions the measures of inflammation each accounted for significant percentages of the variance in synaptophysin immunoreactivity and each was more highly correlated with synapse estimates than NFT formation or A beta deposition.

Aged↗