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Biomedical subjects

J Turner

Publications and source records attributed to J Turner.

At least 55 records · Page 3Linked to original sources
PubMed2001

Tryptophan and 5-hydroxytryptophan for depression.

BACKGROUND: 5 Hydroxytryptophan (5-HTP) and tryptophan are so-called natural alternatives to traditional antidepressants, used to treat unipolar depression and dysthymia. OBJECTIVES: To determine whether 5-HTP and tryptophan are more effective than placebo, and whether they are safe to use to treat depressive disorders in adults. SEARCH STRATEGY: Trials were searched in computerized general (Medline, Psychlit, and Embase) and specialized databases (Cochrane Controlled Clinical Trials Register, Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trial Register); by checking reference lists of relevant articles; by handsearching relevant specialist journals; and by contacting relevant authors where appropriate. Publications in all languages were sought. SELECTION CRITERIA: Trials were included if they were randomized, included patients with unipolar depression or dysthymia, compared preparations of 5-HTP or tryptophan with placebo, and included clinical outcomes assessed by scales assessing depressive symptoms. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the three reviewers, onto data collection forms. Inclusion criteria were applied to all potential studies independently and a coefficient of agreement (Kappa) was calculated for them. Disagreement was resolved by reaching consensus. Trial quality was scored according to risk of bias. Analysis for 5-HTP and tryptophan were combined due to the small number of included trials. MAIN RESULTS: 108 trials were located using the specified search strategy. Of these, only two trials, involving a total of 64 patients, were of sufficient quality to meet inclusion criteria. The available evidence suggests these substances were better than placebo at alleviating depression (Peto Odds Ratio 4.10; 95% confidence interval 1.28-13.15; RD 0.36; NNT 2.78). However, the evidence was of insufficient quality to be conclusive. REVIEWER'S CONCLUSIONS: A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present.

5-Hydroxytryptophan↗
PubMed2001

The CtBP family: enigmatic and enzymatic transcriptional co-repressors.

Transcription factors that associate with DNA sequences in promoters and enhancers often recruit co-regulators that modulate their activity. Many of these co-regulators have intrinsic enzymatic activity and influence gene expression by modifying chromatin and altering its structure. Recently, a new family of co-repressors, the C-terminal binding proteins, has been described. These proteins recognize Pro-X-Asp-Leu-Ser (PXDLS) motifs in DNA-binding proteins and function as transcriptional co-repressors in Drosophila, Xenopus and mammals. The precise mechanisms by which they influence transcription are still under investigation. CtBP proteins dimerize and can contact histone deacetylases; hence they may operate by linking deacetylases to DNA-bound factors. But it appears that CtBP proteins also have intrinsic enzymatic activity. They have significant homology to D-isomer-specific 2-hydroxy acid dehydrogenases, and remarkably one family member, rat CtBP, has been shown to have a second role, functioning as an acyl transferase in Golgi maintenance. These observations raise the possibility that CtBP proteins might regulate gene expression directly by means of their enzymatic activities, in addition to serving as simple bridging proteins. Supplementary material for this article can be found on the BioEssays homepage at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/v23_8.684.

Alcohol Oxidoreductases↗
PubMed2001

Tuberculosis in aged gammadelta T cell gene disrupted mice.

In young mice exposed to aerosol infection with Mycobacterium tuberculosis removal of the gammadelta T cell population by targeted gene disruption does not affect the expression of host resistance, but does influence the integrity of the early granulomatous response. The current study demonstrates that in aged gammadelta T cell gene disrupted mice similar immunopathologic changes ensued in both gene knockout and wild type control mice. Changes in cell surface marker expression, evident in other gene knockout models, was not observed in the aged gammadelta T cell knockout mice. These data imply that gammadelta T cell functions previously observed in young mice become much less important as the animal ages.

Aging↗
PubMed2001

The progression of chronic tuberculosis in the mouse does not require the participation of B lymphocytes or interleukin-4.

The aging process is associated with alterations in the immune system. Some of the changes reported are an increase in the proportion of B lymphocytes, and a shift to a TH2-like cytokine environment. It has been hypothesized that the development of immunopathology within the lung during tuberculosis is linked to increased interleukin-4 (IL-4) production. In addition, a role for B cells in maintaining granuloma integrity has been recently proposed. This study investigated the role of B cells and IL-4 during the long-term course of chronic tuberculosis in mice and showed that the course of Mycobacterium tuberculosis infection in the lungs was not influenced by the absence of B lymphocytes or the TH2 cytokine IL-4.

Animals↗
PubMed2001

Cloning and analysis of the spinosad biosynthetic gene cluster of Saccharopolyspora spinosa.

BACKGROUND: Spinosad is a mixture of novel macrolide secondary metabolites produced by Saccharopolyspora spinosa. It is used in agriculture as a potent insect control agent with exceptional safety to non-target organisms. The cloning of the spinosyn biosynthetic gene cluster provides the starting materials for the molecular genetic manipulation of spinosad yields, and for the production of novel derivatives containing alterations in the polyketide core or in the attached sugars. RESULTS: We cloned the spinosad biosynthetic genes by molecular probing, complementation of blocked mutants, and cosmid walking, and sequenced an 80 kb region. We carried out gene disruptions of some of the genes and analyzed the mutants for product formation and for the bioconversion of intermediates in the spinosyn pathway. The spinosyn gene cluster contains five large open reading frames that encode a multifunctional, multi-subunit type I polyketide synthase (PKS). The PKS cluster is flanked on one side by genes involved in the biosynthesis of the amino sugar forosamine, in O-methylations of rhamnose, in sugar attachment to the polyketide, and in polyketide cross-bridging. Genes involved in the early common steps in the biosynthesis of forosamine and rhamnose, and genes dedicated to rhamnose biosynthesis, were not located in the 80 kb cluster. CONCLUSIONS: Most of the S. spinosa genes involved in spinosyn biosynthesis are found in one 74 kb cluster, though it does not contain all of the genes required for the essential deoxysugars. Characterization of the clustered genes suggests that the spinosyns are synthesized largely by mechanisms similar to those used to assemble complex macrolides in other actinomycetes. However, there are several unusual genes in the spinosyn cluster that could encode enzymes that generate the most striking structural feature of these compounds, a tetracyclic polyketide aglycone nucleus.

Amino Acid Sequence↗
PubMed2001

Pentoxifylline treatment of mice with chronic pulmonary tuberculosis accelerates the development of destructive pathology.

It is well established in animal models that production of the cytokine tumour necrosis factor-alpha (TNF-alpha) is essential to the proper expression of acquired specific resistance following infection with Mycobacterium tuberculosis. This gives rise to an apparent state of chronic disease which over the next 100-200 days is characterized by slowly worsening pathological changes in the lung. To determine whether continued TNF-alpha production was harmful during this phase mice were treated with a TNF-alpha inhibitor, pentoxifylline. It was observed that although this therapy did not alter the numbers of bacteria recovered from the lungs of the infected mice, tissue damage within the lung was accelerated. These data thus demonstrate that production of TNF-alpha, already known to be important during the early expression of resistance to tuberculosis, remains important and beneficial during the chronic stage of the disease.

Animals↗
PubMed2001

The General Medical Council's Performance Procedures: peer review of performance in the workplace.

The General Medical Council procedures to assess the performance of doctors who may be seriously deficient include peer review of the doctor's practice at the workplace and tests of competence and skills. Peer reviews are conducted by three trained assessors, two from the same speciality as the doctor being assessed, with one lay assessor. The doctor completes a portfolio to describe his/her training, experience, the circumstances of practice and self rate his/her competence and familiarity in dealing with the common problems of his/her own discipline. The assessment includes a review of the doctor's medical records; discussion of cases selected from these records; observation of consultations for clinicians, or of relevant activities in non-clinicians; a tour of the doctor's workplace; interviews with at least 12 third parties (five nominated by the doctor); and structured interviews with the doctor. The content and structure of the peer review are designed to assess the doctor against the standards defined in Good Medical Practice, as applied to the doctor's speciality. The assessment methods are based on validated instruments and gather 700-1000 judgements on each doctor. Early experience of the peer review visits has confirmed their feasibility and effectiveness.

Clinical Competence↗
PubMed2001

Adverse impact of cigarette smoking on dimensions of health-related quality of life in persons with HIV infection.

Because effects of cigarette smoking on health-related quality of life (HRQL) have not been well described, we carried out a cross-sectional assessment of HRQL using the Medical Outcomes Survey Scale adapted for patients with human immunodeficiency virus (MOS-HIV questionnaire) in 585 HIV-infected homosexual/bisexual men, injection drug users, and female partners enrolled in a multicenter, prospective study of the pulmonary complications of HIV infection. Mean scores for the following dimensions of HRQL were calculated: general health perception, quality of life, physical functioning, bodily pain, social functioning, role functioning, energy, cognitive functioning, and depression. A multivariate model was used to determine the impact on HRQL of the following factors: smoking, CD4 loss, acquired immune deficiency syndrome (AIDS) diagnoses, number of symptoms, study site, education, injection drug use, gender, and age. Current smoking was independently associated with lower scores for general health perception, physical functioning, bodily pain, energy, role functioning, and cognitive functioning (all with p < 0.05). We conclude that patients with HIV infection who smoke have poorer HRQL than nonsmokers. These results support the use of smoking cessation strategies for HIV-infected persons who smoke cigarettes.

Adult↗
PubMed2001

p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron chelator.

Iron is involved in essential biochemical reactions ranging from respiration to DNA synthesis. Consequently, iron deprivation has been proposed as a strategy for inhibition of tumor cell growth. We recently described a novel iron chelator, tachypyridine [N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane], and demonstrated that it not only inhibited growth of cultured tumor cells, but was actively cytotoxic. Here we explore the mechanisms underlying tachpyridine cytotoxicity. Using several criteria, including time-lapse video microscopy, DNA staining and TUNEL assays, tachpyridine was shown to specifically induce apoptotic cell death. Further, unlike numerous cytotoxic chemotherapeutic drugs which induce apoptosis by activating p53-dependent pathways, tachpyridine-mediated cell death did not require p53 activation. Although immunoblotting revealed rapid accumulation of p53 following treatment with tachpyridine, p21(WAF1) was not induced. Further, neither cytotoxicity nor apoptosis required p53. p53 null human lung cancer H1299 cells transfected with an ecdysone-inducible p53 exhibited equivalent sensitivity to tachpyridine in the presence and absence of p53, demonstrating the lack of requirement for p53 in an isogenic cell system. Further, time-lapse video microscopy and TUNEL assays demonstrated that both p53 null and p53 wild-type cells underwent apoptotic cell death in response to tachpyridine. In addition, in 55 human cancer cell lines the mean GI(50) of tachpyridine in cells with mutant p53 was virtually identical to the GI(50) in cells with wild-type p53. These results demonstrate that tachpyridine initiates an apoptotic mode of cell death that does not require functional p53. Since over 50% of human tumors contain a functionally defective p53 that reduces sensitivity to commonly used chemotherapeutic agents, such as etoposide and cisplatin, the ability of tachpyridine to induce apoptosis independently of p53 may offer an advantage in anti-tumor therapy.

Anticarcinogenic Agents↗
PubMed2001

One-step disposable chambers for sperm concentration and motility assessment: how do they compare with the World Health Organization's recommended methods?

The World Health Organization suggests that 'one-step' type disposable chambers lack the accuracy and precision of the haemocytometer method for assessing sperm concentration. The purpose of this particular study was to compare sperm concentration measurements and motility using the Neubauer((R)) haemocytometer with those obtained using three 'one-step' methods: the Microcell((R)) slide, Leja((R)) slide and a plain glass slide with a 22x22 mm coverslip. A total of 200 sperm concentration measurements and 100 motility assessments were performed on all chambers. Paired comparisons showed enormous discrepancies between the counts, particularly between the Neubauer((R)) and other chambers (P < 0.0001). This discrepancy was less pronounced in oligozoospermic samples, and samples with low (<30% progression) motility but more pronounced in normozoospermic samples and those with good motility (>50% progression). In addition, concentration assessments from a fresh undiluted and unfixed semen sample on the Microcell((R)) slide were found to be significantly lower than both fixed counts on the same slide (P = 0.011) and the initial laboratory reading on the Neubauer((R)) chamber (P = 0.009). No differences were observed in progressive motility between the different chambers and a plain glass slide. There appears to be little comparison between the haemocytometer and either re-useable or disposable one-step chambers. The unfortunate consequence of this is that diagnostic semen analysis and guidelines for allocation of patients to appropriate treatment groups will vary from centre to centre, depending on the method used and may, on occasion, be erroneous.

Humans↗
PubMed2001

The activity of vancomycin against heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus explored using an in vitro pharmacokinetic model.

Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) may account for treatment failure with vancomycin and act as a precursor of vancomycin-intermediate or -resistant S. aureus. The activity of vancomycin was assessed against vancomycinsusceptible, hVISA and VISA strains in a dilutional pharmacokinetic model. Over a 48 h period, total bacteria and cells with a vancomycin-intermediate phenotype were quantified. Total counts of hVISA were reduced by vancomycin in a similar way to a vancomycin-susceptible control. The vancomycin-intermediate sub-population was eradicated from the model within one dose interval. Exposure to low vancomycin concentrations did not result in an increase in the proportion of cells which were vancomycin intermediate. Short-term exposure of hVISA to vancomycin at gradient concentrations did not increase the proportion of cells with vancomycin-intermediate phenotype.

Anti-Bacterial Agents↗
PubMed2001

Supplementation of islet culture medium with insulin may have a beneficial effect on islet secretory function.

Recent reports suggest that apoptosis resulting from the disruption of the normal cell-matrix relationship (anoikis) during islet isolation could lead to a loss of islet tissue in culture. Insulin is known to have a role in cell growth and survival, and this study was undertaken to assess any beneficial effect on islets by supplementing the islet culture medium with insulin. Human and porcine islets were cultured in medium supplemented with 0, 10, 100, and 1,000 ng x mL(-1) insulin. Secretory function was assessed by perifusion at days 1 and 8. The results demonstrated a significant variation in stimulation index between isolations for human islets, but there was no effect relating to the concentration of insulin in the medium or time in culture. For porcine islets, there was a significant (p < 0.001) improvement in secretory function for islets cultured in 10 and 100 ng x mL(-1) insulin, relative to 0 and 1,000 ng x mL(-1) insulin. There was no interisolation variation or effect of time in culture. In conclusion, the secretory function of porcine islets benefited from the addition of 10 to 100 ng x mL(-1) insulin to the culture medium, but interisolation variation in human islet secretory function did not allow any specific effect of the insulin to be determined.

Animals↗
PubMed2001

Single-copy IMH3 allele is sufficient to confer resistance to mycophenolic acid in Candida albicans and to mediate transformation of clinical Candida species.

Parasexual genetic analysis of Candida albicans utilized the dominant selectable marker that conferred resistance to mycophenolic acid. We cloned and sequenced the IMH3(r) gene from C. albicans strain 1006, which was previously identified as resistant to mycophenolic acid (MPA) (A. K. Goshorn and S. Scherer, Genetics 123:213-218, 1989). MPA is an inhibitor of IMP dehydrogenase, an enzyme necessary for the de novo biosynthesis of GMP. G. A. Kohler et al. (J. Bacteriol. 179:2331-2338, 1997) have shown that the wild-type IMH3 gene, when expressed in high copy number, will confer resistance to this antibiotic. We demonstrate that the IMH3(r) gene from strain 1006 has three amino acid changes, two of which are nonconservative, and demonstrate that at least two of the three mutations are required to confer resistance to MPA. We used this gene as a dominant selectable marker in clinical isolates of C. albicans and Candida tropicalis. We also identified the presence of autonomously replicating sequence elements that permit autonomous replication in the promoter region of this gene. Finally, we found the excision of a phi-type long terminal repeat element outside the IMH3 open reading frame of the gene in some strains. We used the IMH3(r) allele to disrupt one allele of ARG4 in two clinical isolates, WO-1 and FC18, thus demonstrating that a single ectopic integration of this dominant selectable marker is sufficient to confer resistance to MPA.

Alleles↗
PubMed2001

Temporal and spatial arrangement of lymphocytes within lung granulomas induced by aerosol infection with Mycobacterium tuberculosis.

The progression of the immune response in the lungs after aerosol infection with Mycobacterium tuberculosis is a complex cellular event dominated by macrophages and lymphocytes. Although the phenotype of lymphocytes participating in this response is becoming increasingly well characterized, the dynamic influx of these cells during the infection and their spatial arrangements within the lung tissue are still poorly understood. This study shows that in the first month after aerosol infection with M. tuberculosis there was a steady increase in the percentages of total CD3+, CD3+ CD4+ and CD3+ CD8+ cells, with consistently larger numbers of CD3+ CD4+ cells than of CD3+ CD8+ cells. As granuloma formation continued, the granuloma was found to consist of macrophages, CD4, and CD8 T cells, as well as a smaller number of B cells. Whereas CD4 T cells formed organized aggregates, CD8 T cells were fewer and more scattered and tended to be more prominent toward the periphery of the granulomas. The possible ramifications of the juxtapositions of these two major T-cell subsets are discussed.

Animals↗
PubMed2001

Immunological basis for reactivation of tuberculosis in mice.

In this study different inbred strains of mice appeared to control and contain a low dose aerosol infection with Mycobacterium tuberculosis in a similar manner, giving rise to a chronic state of disease. Thereafter, however, certain strains gradually began to show evidence of regrowth of the infection, whereas others consistently did not. Using C57BL/6 mice as an example of a resistant strain and CBA/J mice as an example of a strain susceptible to bacterial growth, we found that these animals revealed distinct differences in the cellular makeup of lung granulomas. The CBA/J mice exhibited a generally poor lymphocyte response within the lungs and vastly increased degenerative pathology at a time associated with regrowth of the infection. As a possible explanation for these events, it was then observed that the CBA/J mouse strain was also less able to upregulate adhesion molecules, including CD11a and CD54, on circulating lymphocytes. These results therefore suggest that a failure to control a chronic infection with M. tuberculosis may reflect an inability to localize antigen-specific lymphocytes within the lung.

Animals↗
PubMed2001

Health care utilisation of infants with chronic lung disease, related to hospitalisation for RSV infection.

AIMS: To compare the use of health care resources and associated costs between infants with chronic lung disease (CLD) who had or had not an admission with a proven respiratory syncytial virus (RSV) infection. METHODS: Review of community care, outpatient attendances, and readmissions in the first two years after birth. PATIENTS: 235 infants (median gestational age 27 weeks) evaluated in four groups: 45 infants with a proven RSV admission (RSV proven); 24 with a probable bronchiolitis admission; 60 with other respiratory admissions; and 106 with non-respiratory or no admissions. RESULTS: The RSV proven compared to the other groups required more frequent and longer admissions to general paediatric wards and intensive care units, more outpatient attendances and GP consultations for respiratory related disorders, and had a higher total cost of care. CONCLUSION: RSV hospitalisation in patients with CLD is associated with increased health service utilisation and costs in the first two years after birth.

Analysis of Variance↗
PubMed2001

Phenylethylamine, a possible link to the antidepressant effects of exercise?

OBJECTIVES: To determine in this pilot study whether aerobic exercise affects phenylacetic acid concentration in the urine. METHODS: Twenty healthy men provided 24 hour urine samples on two consecutive days for the determination of phenylacetic acid levels. Before and during day 1, subjects refrained from physical activity; on day 2 subjects ran on a treadmill at 70% of their maximal heart rate reserve (MHRR) for 30 minutes. RESULTS: The 24 hour mean urinary concentration of phenylacetic acid was increased by 77% after exercise. CONCLUSION: As phenylacetic acid concentration in urine reflects phenylethylamine level, which is known to have antidepressant effects, phenylethylamine may be linked to the therapeutic effects of physical exercise on depression.

Adolescent↗