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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 127 records · Page 7Linked to original sources
PubMed1998

An archaeal aerotaxis transducer combines subunit I core structures of eukaryotic cytochrome c oxidase and eubacterial methyl-accepting chemotaxis proteins.

Signal transduction in the archaeon Halobacterium salinarum is mediated by three distinct subfamilies of transducer proteins. Here we report the complete htrVIII gene sequence and present analysis of the encoded primary structure and its functional features. HtrVIII is a 642-amino-acid protein and belongs to halobacterial transducer subfamily B. At the N terminus, the protein contains six transmembrane segments that exhibit homology to the heme-binding sites of the eukaryotic cytochrome c oxidase. The C-terminal domain has high homology with the eubacterial methyl-accepting chemotaxis protein. The HtrVIII protein mediates aerotaxis: a strain with a deletion of the htrVIII gene loses aerotaxis, while an overproducing strain exhibits stronger aerotaxis. We also demonstrate that HtrVIII is a methyl-accepting protein and demethylates during the aerotaxis response.

Amino Acid Sequence↗
PubMed1998

Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS.

The chemokine receptors CCR5 and CXCR4 are co-receptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage-tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV-1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4-positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Effects of continuous ambulatory peritoneal dialysis and kidney transplantation on advanced glycation endproducts in the skin and peritoneum.

Advanced glycation endproducts (AGE) form as a result of non-enzymatic reaction of reducing sugars with proteins. Patients with chronic renal failure (CRF) have elevated AGE in plasma, skin and peritoneum. We measured AGE in the skin and peritoneum of individuals with CRF, patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and in renal transplant recipients (TR). Pentosidine concentration and collagen-linked fluorescence (CLF) were measured. Pentosidine and CLF correlated in all patient groups (CRF r=0.688, p<0.01; CAPD r=0.674, p<0.05; TR r=0.811, p<0.01). Successful kidney transplant reduced AGE levels in the skin (CRF 11.7 +/- 4.51 U/mg; TR 5.02 +/- 3.13 U/mg, p<0.00001) and peritoneum (CRF 17.5 +/- 6.16 U/mg, TR 9.4 +/- 4.97 U/mg, p<0.0001). However in contrast to the TR group, CLF in peritoneum increased following CAPD (CRF 17.5 +/- 6.16 U/mg; CAPD 24.2 +/- 10.4 U/mg; p=0.06). Our results suggest that AGE might be formed in the peritoneum during CAPD treatment.

Adolescent↗
PubMed1997

Structural and functional investigations on the role of zinc in bifunctional rat peptidylglycine alpha-amidating enzyme.

Bifunctional peptidylglycine alpha-amidating enzyme (alpha-AE) catalyzes the two-step conversion of C-terminal glycine-extended peptides to C-terminal alpha-amidated peptides and glyoxylate. The first step is the ascorbate-, O2-, and copper-dependent hydroxylation of the alpha-carbon of the glycyl residue, producing an alpha-hydroxyglycine-extended peptide. The second step is the ascorbate-, O2-, and copper-independent dealkylation of the carbinolamide intermediate. We show that alpha-AE requires 1.1 +/- 0. 2 mol of zinc/mol of enzyme for maximal (S)-N-dansyl-Tyr-Val-alpha-hydroxyglycine dealkylation activity. Treatment of the enzyme with EDTA abolishes both the peptide hydroxylation and the carbinolamide dealkylation activities. Addition of Zn(II), Co(II), Cd(II), and Mn(II) partially restores carbinolamide dealkylation activity to the EDTA-treated enzyme. Addition of Co(II) produces the greatest restoration of dealkylation activity, 32% relative to a control not treated with EDTA, while Mn(II) addition results in the smallest restoration of dealkylation activity, only 3% relative to an untreated control. The structure and coordination of the zinc center has been investigated by X-ray absorption spectroscopy. EXAFS data are best interpreted by an average coordination of 2-3 histidine ligands and 1-2 non-histidine O/N ligands. Since catalytic zinc centers in other zinc metalloenzymes generally exhibit only O/N ligands to the zinc atom, a zinc-bound water or hydroxide may serve as a general base for the abstraction of the hydroxyl proton from the carbinolamide intermediate. Alternatively, the zinc may function in a structural role.

Amides↗
PubMed1997

Genetics of common disease: implications for therapy, screening and redefinition of disease.

Susceptibility to most common human diseases is, at least in part, determined by genetic factors. Rapid progress is being made in defining these genetic determinants for a range of diseases including breast cancer, colon cancer, diabetes, arthritis and dementia. The ability to define susceptibility in genetic terms has already led to a reclassification of some of these diseases on genetic and mechanistic grounds. This information is likely to have a profound effect on our approach to human diseases as it will allow a better definition of these disorders, permitting more effective therapeutic intervention, and will lead to both a more precise understanding of the natural history of these diseases and the possibility of identifying populations at risk. An understanding of the mechanisms underlying disease susceptibilty will also improve our ability to develop rational therapeutic interventions for many of these diseases. The role of genetic screening in these common diseases will be discussed, particularly in regard to the application of health care in populations.

Genetic Diseases, Inborn↗
PubMed1997

Methadone maintenance and drug-related crime.

Using data from an evaluation of methadone maintenance treatment, this study investigated factors associated with continued involvement in crime during treatment, and in particular whether there appeared to be differences in effectiveness of treatment between different methadone clinics. The methodology was an observational study, in which 304 patients attending three low-intervention, private methadone clinics in Sydney were interviewed on three occasions over a twelve month period. Outcome measures were self-reported criminal activity and police department records of convictions. By self-report, crime dropped promptly and substantially on entry to treatment, to a level of acquisitive crime about one-eighth that reported during the last addiction period. Analysis of official records indicated that rates of acquisitive convictions were significantly lower in the in-treatment period compared to prior to entry to treatment, corroborating the changes suggested by self-report. Persisting involvement in crime in treatment was predicted by two factors: the cost of persisting use of illicit drugs, particularly cannabis, and ASPD symptom count. Treatment factors also were independently predictive of continued involvement in crime. By both self-report and official records, and adjusting for subject factors, treatment at one clinic was associated with greater involvement in crime. This clinic operated in a chaotic and poorly organized way. It is concluded that crime during methadone treatment is substantially lower than during street addiction, although the extent of reduction depends on the quality of treatment being delivered.

Adult↗
PubMed1997

The effect of dominant vestigial alleles upon vestigial-mediated wing patterning during development of Drosophila melanogaster.

The vestigial gene product is required for the completion of wing development in Drosophila melanogaster. In the absence of vestigial gene expression, cells within the larval wing and haltere imaginal discs fail to proliferate normally thus producing adults with severely reduced wings. Of a large number of vestigial mutations that have been characterized, only two are currently known to exist, vestigial(U) and vestigial(W), which manifest a significant dominant phenotype. Both are associated with chromosomal inversions that fuse the majority of the vestigial coding regions to other genes; mastermind in vestigial(U) and invected in vestigial(W) Examination of vestigial expression in the presence of these dominant alleles shows alterations in the disc-specific expression of vestigial during later stages of larval development. These patterning disruptions are specific to cells of the wing imaginal disc, as significant suppression of total levels of vestigial expression within entire larvae could not be detected. This dominant interference of vestigial patterning appears to be mediated in part by the vestigial coding sequences that are within the gene fusions. Further evidence that the dominant phenotype is the result of disrupted vestigial patterning comes from observations that the dominant alleles can be partially suppressed by mutations within the Drosophila-epidermal growth factor receptor gene. Mutagenesis of vestigial(U) and vestigial(W) produced a series of alleles with partially dominant phenotypes that restored various amounts of the adult wing. These phenotypes can be correlated with alterations in specific portions of the vestigial sequences associated with the dominant alleles. In the presence of these partially dominant alleles, wing imaginal discs have significantly more cells which express vestigial compared with the number associated with the original dominant phenotype. Additionally, eliminating some of the dominant effect causes alterations in the patterns of early stage apoptotic cell death associated with dominant vestigial alleles. Utilizing these new vestigial alleles, it is possible to correlate the consequence of altered vestigial expression to subsequent changes in patterning of the wing disc.

Animals↗
PubMed1997

Breast cancer management: is volume related to quality? Clinical Advisory Panel.

A method of carrying out region-wide audit for breast cancer was developed by collaboration between the cancer registry, providers and purchasers as part of work to fulfill the 'Calman-Hine' recommendations. In order to test the audit method, a retrospective audit in North Thames East compared practice in 1992 against current guidelines. The analysis compared care in specialist and non-specialist centres. A stratified random sample comprising 28% of all breast cancer patients diagnosed in 1992 was selected from the population-based Thames Cancer Registry. The data for 309 patients with stage I-III tumours were analysed by hospital type using local guidelines. No difference between specialist (high volume) and non-specialist centres was detected for factors important in survival. Pathological staging was good with over 70% reporting tumour size and grade. A small number of patients were undertreated; after conservative surgery, 10% (19) of women did not receive radiotherapy, and 15% (8) of node-positive premenopausal women did not receive chemotherapy or ovarian ablation. In contrast, a significant trend with hospital volume was found for several quality of life factors. These included access to a specialist breast surgeon and specialist breast nurses, availability of fine-needle aspiration (FNA), which ranged from 84% in high-volume to 42% in low-volume centres, and quality of surgery (axillary clearance rates ranged from 51% to 8% and sampling of less than three nodes from 3% to 25% for high- and very low-volume centres respectively). Confidential feedback of results to surgeons was welcomed and initiated change. The summary information gave purchasers information relevant to the evaluation of cancer services. While the audit applied present standards to past practice, it provided the impetus for prospective audit of current practice (now being implemented in North Thames).

Breast Neoplasms↗
PubMed1997

Increasing vancomycin resistance in Enterococcus spp. in Australia: facing the challenge in the laboratory.

High level vancomycin resistance in enterococci (VRE) is increasing in Australia. If the spread of VRE is to be checked, then it is vital for laboratories to be able to detect it promptly and accurately. We have established a rapid and accurate screening method using Enterococcosel agar supplemented with 6 mg/l vancomycin. It can recover VRE from spiked feces, it may be used to screen feces for carriage of VRE and it is not subject to the confounding effects which feces introduce to broth enrichment culture.

Australia↗
PubMed1997

Pre-AIDS deaths in HIV infection related to intravenous drug use.

We prospectively collected data on deaths in the Edinburgh City Hospital HIV cohort of patients (60-70% acquired via injection drug use) from October 1986 to September 1994. Sixty-four patients (25% of all HIV deaths or 2.5/100 person-years) had died without an AIDS diagnosis, and 42 (66%) of these had autopsy data available. Some pre-AIDS deaths (20% or 0.5/100 person-years) were the expected consequence of underlying medical conditions diagnosed during life: the remainder (80% or 1.98/100 person-years) were sudden or unexpected. Examining the underlying conditions, drug overdoses accounted for 45% or 1.1/100 person-years; bacterial sepsis, 25% or 0.6/100 person-years; liver disease, 26% or 0.6/100 person-years; and an undiagnosed AIDS condition, 9% or 0.2/100 person-years. Drug overdoses were the commonest cause of pre-AIDS death in this cohort of patients predominantly infected via IDU, but many of the sudden deaths had significant underlying pathology, which may have increased their susceptibility to an overdose of drugs. In future, death before an AIDS diagnosis should be classified into Medical or Expected Non-AIDS (MNA or ENA) and Sudden Non-AIDS (SNA).

Bacterial Infections↗
PubMed1997

Moclobemide in social phobia: a controlled dose-response trial.

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.

Adult↗
PubMed1997

p53 gene product expression in resected non-small cell carcinoma of the lung, with studies of concurrent cytological preparations and microwave antigen retrieval.

AIM: To document the frequency and extent of p53 gene product expression in paraffin sections of resected non-small cell carcinoma of the lung and in cytological preparations of the same tumours; to determine the effect of microwave antigen retrieval on antigen detection. METHODS: Representative paraffin sections of 50 non-small cell carcinomas were stained with an antibody to p53 gene product (DO-7) both with and without prior microwave antigen retrieval. Cytoblocks and cell smears obtained from 19 cases were similarly stained. RESULTS: Using a histochemical scoring system (0-300) which takes into account staining intensity and extent, 78% (n = 39) of microwave pretreated paraffin sections and 52% (n = 26) of non-pretreated sections scored between 5 and 300; p = 0.001; 56% (n = 28) of microwave pretreated sections and only 2% (n = 1) of non-pretreated sections scored between 100 and 300 (p = 0.0001); 75% of direct smears of tumours and 80% of cytoblocks stained similarly to the paraffin sections of the resected specimens. No smears or cytoblocks stained positively when the sections of the resected specimen were negative. CONCLUSIONS: As up to 78% of non-small cell lung carcinomas overexpress p53 gene product, this may prove to be a valuable diagnostic method in biopsy or cytological material when the morphological diagnosis is uncertain. Microwave antigen retrieval is effective on formalin fixed tissue.

Adenocarcinoma↗
PubMed1997

Genetic mapping of susceptibility loci in the genes involved in rheumatoid arthritis.

Eighty-nine multicase rheumatoid arthritis families, each containing at least one affected sib pair, have been studied for evidence of genetic linkage to a panel of 315 microsatellite DNA markers. The families were located through the UK national data repository of the Arthritis and Rheumatism Council. Microsatellites were genotyped by semiautomated technology using Applied Biosystems sequencers (ABI 373). Using the SIBPAIR statistical package, linkage to HLA was confirmed (p < 0.0003). Several possible linkages outside HLA were noted, including at least one (p < 0.004) that merits further investigation.

Arthritis, Rheumatoid↗
PubMed1997

A longitudinal study of the attitudes of the dental profession towards competition and advertising.

In 1985, members of the dental profession and of four other professional groups in New Zealand were surveyed to establish their attitudes towards the developing commercialisation of their professions, particularly towards advertising. This survey was repeated in 1988, and repeated again in 1994. The results of the three surveys are presented in this paper. Over the survey period there has been a steady, if undramatic, movement of attitudes to a position that is more favourable towards the concept of an openly competitive profession. The use of informative advertising by dental practices had gained widespread acceptance by 1994, but there was still considerable opposition to persuasive advertising. However, there are still areas of professional practice, notably matters concerned with fees, where there is widespread opposition to competition and advertising.

Advertising↗