Search PubMed⌕ Search

Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 325 records · Page 18Linked to original sources
PubMed1998

Impaired glycolysis and protein catabolism induced by acid in L6 rat muscle cells.

BACKGROUND: In skeletal muscle, metabolic acidosis stimulates protein degradation and oxidation of branched-chain amino acids. This could occur to compensate for impairment of glucose utilization induced by acid. METHODS: To test this hypothesis, glycolysis and protein degradation (release of [14C]-phenylalanine) were measured in L6 skeletal muscle cells cultured in Eagle's minimum essential medium at pH 7.1 or 7.5 for up to 3 days. RESULTS: No marked changes in total DNA or in cell viability were detected, nor was there any significant effect on intracellular pH or the water content of the cells (which is thought to be a key regulator of protein turnover, especially in liver). In spite of this, acid stimulated protein degradation, induced net protein loss from the cultures, inhibited glucose uptake and glycolysis (lactate output) and was associated with increased [1-14C]-leucine oxidation. Effects on protein degradation and glycolysis were gradual, reaching a maximum after 20-30 h. To investigate whether glycolytic flux itself can influence protein degradation, increased glycolysis was simulated by adding glucose (20 mmol L-1) or pyruvate (1 mmol L-1) to the medium. At pH 7.1, neither addition had any effect on protein degradation. CONCLUSION: Although acid-induced protein wasting is associated with impaired glycolysis, no obligatory coupling exists between glycolytic flux and protein degradation.

Acidosis↗
PubMed1998

Glycogen depletion patterns in trained rats adapted to a high-fat or high-carbohydrate diet.

Male Sprague-Dawley rats (n = 48, > 200 g) were progressively treadmill trained over 5 wk where they were running 60 min/d, 5 d/wk. One-half of the group consumed a high-fat diet (HF, 78.7% of energy), while one-half consumed a high-carbohydrate diet (HC, 68.7% of energy). On the day of the experiment, 6 rats per diet were run at 29 m/min, 8% grade for 0, 10, 20, or 60 min. Immediately post-exercise rats were anesthetized, and soleus (S), red vastus lateralis (RV), and white vastus lateralis (WV) muscles were removed. There were no significant differences between diets for S glycogen pre-, during, or post-exercise. RV glycogen (micromol x g(-1) wet wt) was lower (p < 0.05) at rest for the HF (27.5 +/- 3.9, Mean +/- SEM) vs the HC (37.6 +/- 3.5), but similar to HC at 60 min (11.0 +/- 1.9, HF; 8.6 +/- 1.3, HC). RV glycogen use rates (nmol x g(-1) x min(-1)) were lower for the HF (985 +/- 295, 356 +/- 61) than the HC (1593 +/- 144, 1055 +/- 272) for 0-10 and 11-20 min, respectively. Resting WV glycogen was lower for the HF (25.3 +/- 1.6) vs the HC (40.7 +/- 5.8), while post exercise values were similar (17.0 +/- 4.4, HF; 15.7 +/- 2.0, HC). WV glycogen use was negligible from 0-10 and 11-20 min in the HF compared to the HC (280 +/- 169 and 1601 +/- 177 nmol x g(-1) x min(-1), respectively). These data indicate that muscle glycogen is spared during the early stages of prolonged exercise in HF adapted rats and that the sparing occurs according to expected muscle recruitment patterns.

Adaptation, Physiological↗
PubMed1998

Current controversies in the white dot syndromes. Multifocal choroiditis, punctate inner choroidopathy, and the diffuse subretinal fibrosis syndrome.

The white dot syndromes are inflammatory diseases of unknown etiology which share several clinical features. The presence or absence of visual field defects, abnormal electroretinograms, lesions on indocyanine green angiography, and specific antiretinal antibodies may give us clues to their pathogenesis. Careful prospective studies into these features may enable us to differentiate between these diseases and facilitate further research toward developing effective treatments.

Choroid Diseases↗
PubMed1998

Radiation-induced germline instability at minisatellite loci.

PURPOSE: To review the results of recent studies on radiation-induced germline instability at mammalian minisatellite loci. RESULTS: Evidence has been obtained recently that germline mutation at minisatellites is remarkably sensitive to ionizing radiation, in both mice and humans. In mice, an elevated mutation rate was found after acute irradiation of pre-meiotic spermatogonia, with a doubling dose of 0.33 Gy, a value close to those obtained in mice after acute spermatogonia irradiation using other systems for mutation detection. In humans, analysis of germline mutation rate at minisatellites among children born in areas of the Mogilev district of Belarus, which was heavily polluted after the Chernobyl accident, has shown a twofold higher mutation rate in exposed families compared with non-irradiated families from the United Kingdom. Within the Belarus cohort, the mutation rate was significantly greater in families exposed to a higher parental radiation dose, consistent with radiation induction of germline mutation. The data in this study also demonstrate the indirect nature of radiation-induced germline mutation at mammalian minisatellite loci suggesting a strong similarity with the phenomenon of genomic instability in somatic cells. CONCLUSIONS: Minisatellite loci provide a powerful system for the efficient monitoring of germline mutation in humans and are capable of detecting induced mutations in relatively small population samples.

Animals↗
PubMed1998

Linkage analysis of X-linked cone-rod dystrophy: localization to Xp11.4 and definition of a locus distinct from RP2 and RP3.

Progressive X-linked cone-rod dystrophy (COD1) is a retinal disease affecting primarily the cone photoreceptors. The COD1 locus originally was localized, by the study of three independent families, to a region between Xp11.3 and Xp21.1, encompassing the retinitis pigmentosa (RP) 3 locus. We have refined the COD1 locus to a limited region of Xp11.4, using two families reported elsewhere and a new extended family. Genotype analysis was performed by use of eight microsatellite markers (tel-M6CA, DXS1068, DXS1058, DXS993, DXS228, DXS1201, DXS1003, and DXS1055-cent), spanning a distance of 20 cM. Nine-point linkage analysis, by use of the VITESSE program for X-linked disorders, established a maximum LOD score (17.5) between markers DXS1058 and DXS993, spanning 4.0 cM. Two additional markers, DXS977 and DXS556, which map between DXS1058 and DXS993, were used to further narrow the critical region. The RP3 gene, RPGR, was excluded on the basis of two obligate recombinants, observed in two independent families. In a third family, linkage analysis did not exclude the RPGR locus. The entire coding region of the RPGR gene from two affected males from family 2 was sequenced and was found to be normal. Haplotype analysis of two family branches, containing three obligate recombinants, two affected and one unaffected, defined the COD1 locus as distal to DXS993 and proximal to DXS556, a distance of approximately 1.0 Mb. This study excludes COD1 as an allelic variant of RP3 and establishes a novel locus that is sufficiently defined for positional cloning.

Alleles↗
PubMed1998

Metabolizable energy of high non-starch polysaccharide-maintenance and weight-reducing diets in men: experimental appraisal of assessment systems.

We have examined the reliability of several food energy assessment systems for healthy men. The predictions of metabolizable energies were compared with determinations made in energy balance studies with three maintenance diets (12 MJ/d); one of the diets was moderate in non-starch polysaccharide (NSP; 2.1% of gross energy) and two were higher in NSP (3.5-4.6% of gross energy). A fourth diet was a submaintenance (6 MJ/d) high NSP (7% gross energy) diet. Discrepancies between the different food energy assessment systems and the determined metabolizable energy values ranged between 0 and 15%. With the maintenance diets, the Atwater specific factor system had errors generally within 6% of the determined value and a limit of agreement (bias +2SD) for diets of 10%. This accuracy compares with errors of 2% for both the originally published assessment of this system and a more recent general formula; both systems were without bias with increasing NSP content of the diets but the latter had limits of agreement within 3%. In contrast, the Atwater general, the European general and a recent FDA general formula showed increasing bias with increasing NSP intake. All of the general energy assessment systems overpredicted metabolizable energy from the high NSP submaintenance diet, which shows that even the least biased and most reliable energy assessment system that we identified applies to maintenance diets only; thus a correction has to be made for submaintenance diets.

Adult↗
PubMed1998

The economic perspective.

The rationale for the economic perspective on screening is presented and the particular relevance of economic evaluation highlighted. The principles of economic evaluation are described in terms of measuring and valuing the costs and outcomes associated with screening. The different types of economic evaluation are described with discussion of data sources. The problematic issues associated with time preferences and discounting and with the measurement and valuation of outcomes other than true positives are discussed. Issues associated with antenatal screening, in particular the inclusion of averted costs due to the termination of an affected pregnancy and the inclusion and valuation of the unborn child's utility, are also raised.

Cost-Benefit Analysis↗
PubMed1998

A long-range restriction map across 3 Mb of the chromosome 11 breakpoint region of a translocation linked to schizophrenia: localization of the breakpoint and the search for neighbouring genes.

A balanced t(1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related mental illness in a single large Scottish pedigree. We have constructed a long-range restriction map covering at least 3 Mb of the chromosome 11 breakpoint region and conducted searches for genes whose expression could be altered by the translocation, resulting in schizophrenia. Novel transcribed sequences of unknown function clustered around putative CpG islands, located approximately 500 kb and 700 kb above the breakpoint, represent the only evidence to date for expressed genes within the mapped region.

Cells, Cultured↗
PubMed1998

Weather temperatures and sudden infant death syndrome: a regional study over 22 years in New Zealand.

STUDY OBJECTIVE: To examine and identify relationships between the sudden infant death syndrome (SIDS) and environmental temperature in Canterbury, New Zealand. DESIGN: A retrospective epidemiological study combining details of regional hourly temperature and reported SIDS cases. SETTING: Canterbury, New Zealand, between 1968 and 1989 inclusively. PARTICIPANTS: All infants reported as dying from SIDS within the Canterbury region. MAIN RESULTS: The SIDS incidence increased after months with prolonged colder minimum temperatures, confirming the seasonality of SIDS. After adjusting for this seasonality, days that showed little change in hourly temperature and days with warmer minimum temperatures recorded were seen to have a significantly increased the incidence of SIDS. No evidence was found for other relationships between the SIDS incidence and various measures of daily temperatures on the day of death, over the preceding eight days or between these days. Infants aged 12 weeks and over were more susceptible to SIDS on days when small hourly temperature changes were recorded than their younger counterparts; no other age differences emerged. CONCLUSIONS: This study confirmed that the incidence of SIDS is affected by seasonality and temperature on the day of death. In particular, after a prolonged period of cold minimum temperatures, infants were most at risk from SIDS on days on which either a warmer minimum temperature or little hourly variation in temperature were recorded. No other daily or lagged daily temperature factor (lagged up to eight days before the day of death) was statistically associated with the SIDS incidence. It is suspected that the inconsistent previously published lag effect findings actually describe some other phenomenon such as parental behaviour or infant thermoregulation.

Age Factors↗
PubMed1998

Familial dementia lacking specific pathological features presenting with clinical features of corticobasal degeneration.

A family is described in which one member presented with symptoms and signs suggestive of corticobasal degeneration and a sibling presented with features of a frontal lobe dementia. Their mother developed a presenile dementia and movement disorder. At postmortem examination the member with clinical corticobasal degeneration had non-specific pathological features. Therefore, the clinical features of corticobasal degeneration can occur with non-specific pathological changes. Within a pedigree, different members can present with different clinical syndromes, which may reflect variation in the distribution and severity of the pathological process.

Atrophy↗
PubMed1998

Inhibition of protein synthesis by acid in L6 skeletal muscle cells: analogies with the acute starvation response.

Impaired protein synthesis (PS) occurs in skeletal muscle during acute starvation. Even though it is well established that uraemic metabolic acidosis (MA) stimulates protein degradation (PD) and is a major contributor to skeletal muscle wasting in chronic renal failure, the accompanying effects of MA on PS are much less clear. Previous work has shown that, in cultured L6 skeletal muscle cells, PD and leucine oxidation are stimulated by acid. The aim of the present study was to determine whether acid (like acute starvation) can also inhibit PS. PS (14C-phenylalanine incorporation) was measured in L6 cells in MEM + 2% serum at acid pH (7.1) or control pH (7.5). After 24 h, acid inhibited PS (7.7 +/- 0.2 vs. 8.9 +/- 0.1 nmol Phe/4 h/35-mm culture well in controls, p = 0.01) and this was maintained at 72 h. In vitro this could arise because acid only inhibits the rapid PS occurring in dividing cells. However, when division was abolished with 10(-5) mol/l cytosine arabinoside, PS inhibition by acid still occurred (6.9 +/- 0.1 vs. 8.3 +/- 0.2 at control pH, p < 0.05). Acid also had no effect on the specific radioactivity of cellular phenylalanine, suggesting that the impaired PS was not a consequence of inadequate labelling of this pool. Elevated PD and impaired PS together led to loss of 7% of the total protein in only 28 h (-21 +/- 3 microg/well, p = 0.004). This combination of impaired PS with increased PD and increased leucine oxidation in response to acid resembles the response of skeletal muscle to acute starvation. These superficial similarities between the starvation state and MA suggest that fundamental metabolic signals may occur which are common to both states.

Animals↗
PubMed1998

Extrapolation of cost-effectiveness information to local settings.

Providers and purchasers of health care are increasingly looking to the results of economic evaluations for guidance when making their decisions. In this paper the authors argue that there are dangers involved in the naive and unthinking use of published cost-effectiveness information outside the setting in which the information was generated. In considering whether the results of a published study are likely to be relevant locally, decision-makers are encouraged to assess whether the values of the key parameters reported in the published study apply locally. The possible sources of variation are described: unit cost differences; differences in the prevalence, incidence or natural history of disease; and differences in the comparators. In situations where the only source of variation is that local unit costs are different, local values can be substituted in the published analysis and local cost-effectiveness results estimated. Where the other sources of variation exist, the decision-maker is required to make an assumption about the nature of the interaction between the sources of variation and the values of the cost-effectiveness parameters. Using an example, the authors argue that local threshold analysis can aid decision-making where the policy change being considered has a high probability either of increasing effectiveness or reducing costs. Without local re-analysis, there is a danger that local policy changes in line with the recommendations of published studies will promote inefficiency. Re-analysis in the local setting is, however, reliant on authors of economic evaluations being explicit about their methods and the comparators used in their analyses.

Cost-Benefit Analysis↗
PubMed1998

Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices.

STUDY OBJECTIVES: To compare lung deposition of fenoterol or flunisolide administered from a novel, multidose inhalation device delivering liquid droplets (RESPIMAT; Boehringer Ingelheim Ltd; Bracknell, UK) or from conventional metered-dose inhalers (MDIs) with and without spacers. DESIGN: Two randomized, three-way crossover studies. SETTING: Clinical research laboratory. PARTICIPANTS: Healthy, nonsmoking volunteers. INTERVENTIONS: In one study, radiolabeled aerosols of fenoterol from the RESPIMAT device and from a conventional MDI with or without an Aerochamber spacer (Trudell Medical; London, Ontario Canada). In the second study, radiolabeled aerosols of flunisolide from a RESPIMAT device, from a RESPIMAT device modified by inclusion of a baffle/impactor in the mouthpiece, and from a conventional MDI with an Inhacort spacer (Boehringer Ingelheim; Ingelheim, Germany). MEASUREMENTS AND RESULTS: Assessment of the deposition of fenoterol or flunisolide in the lung and oropharynx using gamma scintigraphy. Safety was assessed based on reported adverse effects and spirometry (FEV1, FVC, and peak expiratory flow rate) to detect any paradoxical bronchoconstriction. The RESPIMAT device delivered significantly more fenoterol to the lungs than either an MDI alone or an MDI with Aerochamber (39.2% vs 11.0% and 9.9% of metered dose, respectively; p<0.01). Oropharyngeal deposition of fenoterol from the new device was lower than that from the MDI (37.1% vs 71.7%, respectively; p<0.01). The RESPIMAT device deposited significantly more flunisolide in the lungs compared with MDI plus spacer (44.6% vs 26.4%, respectively; p<0.01), while resulting in similar oropharyngeal deposition (26.2% vs 31.2%, respectively). Introduction of a baffle into the RESPIMAT system reduced lung deposition of flunisolide to 29.5%, and oropharyngeal deposition to 7.8% (p<0.01). CONCLUSION: The RESPIMAT device may prove to be an effective alternative to MDIs for the administration of inhaled bronchodilators and corticosteroids. The high lung deposition and low oropharyngeal deposition may lead to improved efficacy and tolerability of inhaled medications, especially corticosteroids.

Adult↗
PubMed1998

Computerized endoscopic surgical grasper.

We report a computerized endoscopic surgical grasper with computer control and a force feedback (haptic) user interface. The system uses standard unmodified grasper shafts and tips. The device can control grasping forces either by direct surgeon control, via teleoperation, or under software control. In this paper, we test an automated palpation function in which the grasper measures mechanical properties of the grasped tissue by applying a programmed series of squeezes. Experimental results show the ability to discriminate between the normal tissues of small bowel, lung, spleen, liver, colon, and stomach. We anticipate applications in telesurgery, clinical endoscopic surgery, surgical training, and research.

Endoscopes↗