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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 307 records · Page 17Linked to original sources
PubMed1995

Chemotherapy for chronic bronchitis. Controversies.

Chronic bronchitis is a common inflammatory disease of the airways characterised by cough, sputum production and associated features such as dyspnoea and respiratory obstruction. It has a poor prognosis once fully developed and imposes a heavy financial burden on affected societies. Chronic bronchitis is subject to periodic exacerbations in which the role of bacterial infection and the rightful place of antibiotic therapy is only slowly emerging, largely due to the non-homogeneity of the populations under study. Haemophilus influenzae is implicated as the pathogen in more than half of all bacterial exacerbations, Streptococcus pneumoniae and Moraxella catarrhalis accounting for a further third. Viruses and mycoplasmas are also involved. Some 18-25% of patients receiving domiciliary therapy may fail to respond to initial treatment, calling into question the efficacy of antibiotics in acute exacerbations. In part this may relate to sub-optimal respiratory pharmacokinetics as most antibiotics are quite effective against sensitive respiratory pathogens in vitro. However, bacterial resistance rates against traditional agents are rising rapidly in Europe and new agents are needed to counter this threat. Paradoxically few such agents have been shown to improve on the results of amoxycillin and other standard drugs, probably because most trials include patients with exacerbations of only mild-to-moderate severity due to sensitive pathogens. Since recent large scale studies have demonstrated the efficacy of antibiotic therapy compared with placebo in defined exacerbations, use of these definitions has allowed more realistic assessment of new agents which, in terms of improved antibacterial potency and respiratory pharmacokinetics, should offer superior efficacy. Regression analysis of a large scale general practice survey in the UK has now shown the frequency of exacerbations and the presence of co-morbid conditions to correlate significantly with a poor therapeutic outcome and thus, by implication, with severity. Future trials of antibacterial chemotherapy for acute bacterial exacerbations of chronic bronchitis should incorporate such criteria so that real differences between existing and improved compounds can be assessed.

Anti-Bacterial Agents↗
PubMed1995

Organochlorine contaminants in fish from an arctic lake in Alaska, USA.

A wide range of organochlorine pesticides and polychlorinated biphenyls (PCBs) were measured in muscle tissue and livers of lake trout (Salvelinus namaycush) and Arctic grayling (Thymallus arcticus) from Schrader Lake in Arctic Alaska. Results confirm the long-range transport of these contaminants to a US Arctic freshwater system. The most abundant group of compounds in all tissues was composed of PCBs. Mean concentrations of the sum of a selected group of PCB congeners ranged from 3.2 ng/g in grayling liver to 22.8 ng/g in trout liver and from 1.3 ng/g in grayling muscle to 6.6 ng/g in trout muscle (wet wt.). The second most abundant group was composed of chlordane-related compounds. No significant correlations of organochlorine concentrations with fish weight or length were observed for the data set as a whole. There were marked differences in sigma PCB, sigma chlordane and p,p'-DDE concentrations between species. The biomagnification factors for these compounds are similar to ratios reported for other aquatic systems. Comparisons showed that contaminant concentrations in lake trout from Schrader Lake were similar to levels found in burbot and slightly higher than levels in whitefish reported in Canadian studies from the Mackenzie River Delta.

Alaska↗
PubMed1995

The MLC1f/3f gene is an early marker of somitic muscle differentiation in Xenopus laevis embryo.

cDNAs clones encoding the MLC1f and MLC3f proteins of Xenopus laevis have been isolated from a stage 42 cDNA library. Sequence analysis reveals that the amphibian MLC1f and MLC3f isoforms are similar to the mammalian and avian cognates. The two isoforms share a common 141-amino-acid carboxy-terminal regions. These are 49 and 9 residues long for the MLC1f and MLC3f isoforms, respectively. This suggests a genomic organization similar to the mammalian and avian genes, with two promoters and alternative splicing. The developmental expression of the MLC1f/3f mRNAs was studied by Northern blot and RNase protection and their spatial expression analyzed by in situ hybridization. Both the MLC1f and MLC3f mRNAs can be detected in the developing embryo from the end of gastrulation and accumulate rapidly in the somitic mesoderm. Expression of the MLC1f/3f gene can also be detected in animal cap explants which have been induced to form mesodermal derivatives by exposure to activin A or bFGF. However, unlike other muscle-specific markers, neither transcript from the MLC1f/3f gene can be detected in embryonic or adult cardiac muscle, their expression being restricted to somitic muscle. Together, these data demonstrate that expression of the MLC1f/3f gene provides a sensitive and specific marker for skeletal muscle differentiation. Ectopic expression of myogenic factors in animal caps induces the expression of the MLC1f/3f gene, suggesting that the amphibian gene, like its mammalian and avian counterparts, is a regulatory target for members of the MyoD family of transcription factors.

Amino Acid Sequence↗
PubMed1995

An empirical examination of factors influencing prediction of carcinogenic hazard across species.

This study was stimulated by a recent U.S. Environmental Protection Agency (EPA, 1994) statement in draft environmental carcinogen risk assessment guidelines: "Several kinds of observations from animal studies can contribute to the judgment whether animal responses indicate a significant carcinogenic hazard to humans." We have investigated each of these kinds of observation using the cancer bioassay data system database. We obtained concordances from rat to mouse (and vice versa) for various subgroups of chemicals as follows: chemicals that induced tumors at multiple sites, chemicals that induce cancer in both sexes, chemicals that display reduced latency, and chemicals increasing the rates of rare tumors. The concordances are much higher for these chemical subgroups than the chemical groups that induce tumor at a single site, in only one sex, or without reduced latency, respectively. Thus, our findings support some of the EPA's suggested factors.

Animals↗
PubMed1995

XIdx, a dominant negative regulator of bHLH function in early Xenopus embryos.

We have identified a divergent member of the Xenopus Id family, XIdx, which disrupts binding of myogenic factor/E-protein complexes to DNA in vitro and inhibits transactivation of the E-box regulated cardiac actin gene by MyoD in embryonic tissue. XIdx transcripts accumulate from the early neurula stage in discrete domains of the anterior neural plate and subsequently identify regions of the developing nervous system, including the eye rudiments and the rhombencephalon. These results suggest that bHLH proteins and their Id protein regulators may participate in patterning of embryonic neural tissue. Phylogenetic analysis indicates that XIdx is the product of a novel Id gene and is distinct from XId2, which is expressed primarily in the developing pronephros.

Amino Acid Sequence↗
PubMed1995

The use of ultra-low-dose aprotinin to reduce blood loss in cardiac surgery.

One hundred patients due to undergo primary cardiac surgery were prospectively randomized to receive aprotinin or placebo. In the aprotinin group, 250,000 kallikrein inhibitory units (KIU) of aprotinin were added to the cardiopulmonary bypass prime solution. A further 250,000 KIU of aprotinin were infused intravenously over 30 minutes immediately before the start of cardiopulmonary bypass. The control group received 0.9% saline in equal volumes at identical times. The study was designed to have a 90% chance of demonstrating a 30% reduction in blood loss. No significant differences were found between the two groups. The median blood loss in the aprotinin group was 750 mL (interquartile range 556 to 1025 mL, 95% confidence interval 600 to 800 mL). In the control group, the median blood loss was also 750 mL (interquartile range 500 to 988 mL, 95% confidence interval 625 to 925 mL). In the aprotinin group, 12 patients received postoperative autotransfusion of shed mediastinal blood of median volume of 665 mL (interquartile range 500 to 925 mL, 95% confidence interval 450 to 1000 mL). In the control group, 14 patients received postoperative autotransfusion of mediastinal blood of median volume of 663 mL (interquartile range 600 to 800 mL, 95% confidence interval 600 to 700 mL). Five patients in the aprotinin group and seven patients in the control group required postoperative homologous blood transfusion. Reassessment of inclusion criteria showed a 19% reduction in blood loss in patients undergoing only aortocoronary bypass receiving aprotinin compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗
PubMed1995

Quantitative determination of functional thiol groups on intact cell surfaces by resonance Raman spectroscopy.

The sensitivity and selectivity of resonance Raman spectroscopy, combined with electronic spectroscopy, has been used to develop a method to quantify the membrane thiol population in situ in viable erythrocytes. This technique is based on the thiol-disulfide reaction of Ellman's reagent (5,5'-dithio-bis-2-nitrobenzoic acid). It has the advantage that continuous monitoring of lysis is simple and a correction can be made for any interference resulting from lysis. In addition, the extent of reaction can be expressed as a ratio of the reagent signal, providing an internal calibrant.

Calibration↗
PubMed1995

The effect of variations in the expression of pili on the interaction of Neisseria meningitidis with human nasopharyngeal epithelium.

Bacterial adherence is essential to colonization of the nasopharynx by Neisseria meningitidis, and pili may facilitate adherence. Scanning electron microscopy and immunogold labeling were used to study the interaction of 2 piliated and 1 nonpiliated variant of N. meningitidis with nasopharyngeal mucosa in an adenoid organ culture system with an air-mucosal interface. Meningococcal infection caused epithelial damage, loss of ciliated epithelium, and ciliary disorganization, which progressed with time and were greater with the piliated strains. Pili increased adherence of meningococci to the mucosa, and there was tropism of piliated strains for nonciliated cells containing microvilli, damaged epithelium, and sites of cell separation. Bacterial adherence was associated with a change in the appearance of the microvilli.

Adenoids↗
PubMed1995

The effects of low concentrations of antibiotics on epithelial damage caused by non-typable Haemophilus influenzae and bacterial morphology.

Sterile culture filtrates from non-typable Haemophilus influenzae (NTHi) grown in medium containing no antibiotics or 0.25 MIC of amoxycillin, ciprofloxacin or loracarbef were examined for their effect on the ciliary beat frequency (CBF) and structure of human respiratory epithelium. CBF slowing was significantly (P < 0.05) less with 0.25 MIC of all three antibiotics. The epithelium was significantly (P < 0.05) less disrupted with ciprofloxacin. The morphology of NTHi infecting human adenoid organ cultures after 24 h with or without 0.25 MIC of the same antibiotics was measured by scanning electron microscopy. Only ciprofloxacin caused a significant (P < 0.05) change in morphology.

Anti-Bacterial Agents↗
PubMed1995

Epidemiology of AIDS.

This presentation provides an overview of the epidemiology of human immunodeficiency virus (HIV) disease in the United States, followed by a discussion highlighting the extent of HIV disease globally.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Interaction of pneumolysin-sufficient and -deficient isogenic variants of Streptococcus pneumoniae with human respiratory mucosa.

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia, and pneumolysin, a hemolytic toxin, is thought to be an important virulence factor. We have studied the interaction of a pneumolysin-sufficient type II S. pneumoniae strain (PL+) and an otherwise identical pneumolysin-deficient derivative (PL-) with human respiratory mucosa in an organ culture with an air interface for up to 48 h. Ciliary beat frequency (CBF) was measured by a photometric technique, and adherence to and invasion of the epithelium were assessed by scanning and transmission electron microscopy. PL+ and PL- caused a progressive fall in CBF compared with the control which became significant (P < 0.01) at 24 h for PL+ and at 48 h for PL-. At 24 h, there was a significant increase in the percentage of the mucosa of the organ culture that was damaged for PL+ compared with the control (P < 0.01) and PL- (P < 0.02). At 48 h, there was a significant increase in mucosal damage for both PL+ (P < 0.005) and PL- (P < 0.05) compared with the control. At 24 and 48 h, PL+ and PL- adhered predominantly to mucus and damaged cells. PL+ infection alone caused separation of tight junctions between epithelial cells, and at 48 h PL+ cells were adherent to the separated edges of otherwise healthy unciliated cells. PL+ and PL- both caused damage to the epithelial cell ultrastructure. S. pneumoniae infection caused patchy damage to the respiratory mucosa and a lowered CBF. These changes were more severe and occurred earlier with the pneumolysin-sufficient variant.

Adenoids↗
PubMed1995

Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium.

The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.

Aspergillus fumigatus↗
PubMed1995

Cell cycle kinetics in pterygium at three latitudes.

The cell cycle kinetics of 93 specimens of pterygial tissue, as well as 19 specimens of normal conjunctiva, from patients at three sites representing three different latitudes (Singapore, 1 degree; Hong Kong, 22 degrees; and Little Rock, Arkansas, 34 degrees) were evaluated by flow cytometry. The results showed no difference in cellular proliferation patterns between pterygial and conjunctival tissue at any of the sites, suggesting that pterygium is not a disorder of excess cellular proliferation. Transmission electron microscopy showed extracellular matrix to be a prominent component of pterygium. Cellular proliferation patterns of primary and recurrent pterygium were not significantly different from each other. Factors associated with increased incidence of pterygium included male sex, outdoor occupation, and advanced age.

Adult↗