Oral cyclosporin does not arrest progression of androgenetic alopecia.
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Biomedical subjects
Publications and source records attributed to J Green.
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To study the relations of antibody production to long-term outcomes after interferon (IFN) treatment in patients with chronic hepatitis C (CH-C), we used ELISA to measure the levels of antibodies against HCV core protein and peptides. Samples from 21 complete responders and 36 non-responders were collected before IFN therapy, soon after the end of IFN therapy and 6 months later. Using a set of 19 synthesized HCV core peptide antigens, we found that anti-P2 (11-25a.a.) was the most prevalent of all IgG antibodies (93%: 39/42). Among complete responders, IgG1 anti-P2 levels had fallen by the end of IFN therapy (from 79.8 +/- 60.4-46.1 +/- 44.2: P < 0.01), and were lower still 6 months after the end of IFN therapy (31.0 +/- 35.2: P < 0.001); this change was the greatest of all antibodies studied. Among the non-responders, there was no change within the follow-up period. Soon after the end of IFN therapy, IgG1 anti-P2 levels were more than 30% lower than the initial value in more than two-thirds of the complete responders, but in only one-third of the non-responders (14/20 vs. 8/25: P < 0.05). Six months after the end of IFN therapy, IgG1 anti-P2 levels were more than 30% lower than the initial value in more than 85% of the complete responders, but in only 12% of the non-responders (17/20 vs. 3/25: P < 0.001). In conclusion, the changes in levels of IgG1 anti-P2 paralleled the activity of chronic hepatitis C after IFN therapy, and IgG1 anti-P2 levels may be markers of the efficacy of IFN therapy.
The yfiD gene of Escherichia coli has an unusual promoter architecture in which an FNR dimer located at -93.5 inhibits transcription activation mediated by another FNR dimer bound at the typical class II position (-40.5). In vitro transcription from the yfiD promoter indicated that FNR alone can downregulate yfiD expression. Analysis of yfiD::lac reporters showed that five turns of the DNA helix between FNR sites was optimal for downregulation. FNR heterodimers, in which one subunit carried a defective repression surface, revealed that the upstream subunit of the -40.5 dimer and the downstream subunit of the -93.5 dimer were most important for downregulating yfiD expression. Deletion of the C-terminal domain of the alpha-subunit of RNA polymerase (RNAP) did not affect FNR-mediated repression, suggesting that repression is mediated through FNR-FNR and not FNR-RNAP interactions. Maximum yfiD::lac expression was observed in cultures exposed to 10 microM oxygen. More or less oxygen reduced expression dramatically. This pattern of response was dependent on the combination of a high-affinity site at the activating class II position and a lower affinity site at the upstream position.
Misconceptions exist in the community regarding factors that exacerbate acne vulgaris. In particular stress, diet, lifestyle and personal hygiene are often erroneously claimed to be important factors. In order to investigate whether these common misconceptions persist in medical graduates, we analysed the answers of 215 sixth year medical students, who all subsequently graduated from The University of Melbourne, to a short-answer question on acne management and exacerbating factors in one of their final year examination papers. With respect to exacerbating factors, 67% of students identified stress, 10% identified lifestyle factors (smoking and alcohol consumption), and 25% claimed poor facial hygiene exacerbated acne. Diet was stated to be an important factor by 41% of students, of whom 12% specifically mentioned chocolate. Persistence of these misconceptions among medical graduates is likely to perpetuate misinformation in the community.
BACKGROUND: Patients undergoing successful kidney transplantation often manifest overt hypophosphatemia associated with exaggerated phosphaturia during the early post-transplant period (2 weeks to 3 months). The mechanism for this phenomenon has not been fully elucidated. We tested the hypothesis that a circulating serum factor [non-parathyroid hormone (non-PTH)], which operates during chronic renal failure (CRF) to maintain phosphate (Pi) homeostasis, can increase fractional excretion of Pi (FE(PO4)) in normal functioning kidney grafts during the early post-transplant period, thereby causing phosphaturia and hypophosphatemia. METHODS: Five groups of patients were studied: control subjects (group 1, N = 16), "early" (2 weeks to 1 month) post-transplant patients (group 2, N = 22), "late" (9 to 12 months) post-transplant patients (group 3, N = 14), patients with advanced CRF (glomerular filtration rate = 30 to 40 mL/min; group 4, N = 8), and patients who suffered from end-stage renal failure and were treated by chronic hemodialysis (group 5, N = 14). Group 2 manifested significant hypophosphatemia and phosphaturia when compared with groups 1 and 3 (Pi = 0.9 +/- 0.003 mg/dL, FE(PO4) = 68+/- 5%, P < 0.0005 vs. groups 1 and 3). Sera were taken from each of the five subject groups and applied to the proximal tubular opossum kidney (OK) cells. The activity of Na/Pi-type 4 (that is, OK-specific type II transporter) was evaluated by measuring Na(+)-dependent (32)Pi flux. The expression of Na/Pi type II mRNA and the abundance of Na/Pi protein were determined by Northern and Western blot assays, respectively. RESULTS: When compared with sera from groups 1 and 3, 10% sera taken from groups 2, 4, and 5 (incubated overnight with OK cells) inhibited (32)Pi flux by 25 to 30% (P < 0.0003). Both Na/Pi mRNA and the expression of Na/Pi protein were markedly augmented under the same conditions (P < 0.05 groups 2, 4, and 5 vs. groups 1 and 3). Time-course analysis revealed that the up-regulation of Na/Pi protein by sera from groups 2, 4, and 5 was observed as early as four hours of incubation, whereas augmented abundance of Na/Pi mRNA was only seen after eight hours of incubation. The addition of PTH (1-34) to sera from groups 2, 4, and 5 abolished the augmented expression of NaPi protein. We labeled OK cell surface membrane proteins with N-hydroxysuccinimide bound to biotin (NHS-SS-biotin). Biotinylated transporters incubated with the different sera were precipitated by strepavidin and identified by Western blot analysis. Cells incubated in sera from group 2 showed increased membrane bound transporter when compared with control sera, whereas the intracellular pool of the transporter was comparable between the two groups. CONCLUSION: A non-PTH circulating serum factor (possibly phosphatonin) that increases FE(PO4) during CRF is also responsible for phosphaturia and hypophosphatemia in the early period following successful kidney transplantation. The putative factor inactivates Na/Pi activity along with inhibition of the transporter trafficking from the cell membrane into the cytosol.
Nail art or nail technology is a form of nail decoration which frequently entails applying extensions to the natural nail and then adding decorative effects. There have been a number of outbreaks of infection which have implicated nail art. These infections are likely to be as a result of difficulties in cleaning and maintaining the nail extensions. Nail art appears to be incompatible with clinical care.
Iodine deficiency disorder (IDD) is currently an important public health problem in Turkey. The use of iodized salt is a sample and cheap solution. The purpose of this study was to determine the prevalence of iodized salt use in the Trabzon region and the effect of a local mass-media education program in increasing usage. The overall aim was to use the findings to inform future health management and health education activities, and shape further development of the IDD program. Prior to the intervention, the prevalence of iodized salt consumption was 54.5%. Following the 3-month education program it increased to 62.4%. There was a significant difference in the pre- and post-intervention findings (P = 0.00237). The results show that the use of local mass media is effective in raising the prevalence of iodized salt use. Local mass media could therefore be used as part of a national strategy to prevent iodine deficiency disorders.
OBJECTIVE: To investigate health gain and its predictors during inpatient and associated day patient treatment. METHOD: Consecutive admissions to two inpatient units for children and young adolescents in northwest England were studied (N = 55). Ascertainments were made from multiple perspectives, including family, teacher, clinician, and an independent researcher. Measures were taken at referral, admission, discharge, and 6-month follow-up; health gain was inferred from change scores on measures. Recruitment lasted from late 1995 to 1997; follow-up was completed during 1998. Independent variables tested as predictors included assessments of presenting symptoms, therapeutic alliance, and family functioning. RESULTS: Significant health gain during hospitalization was found on most measures and sustained to follow-up. There was no symptom change during the waiting-list control condition. Health gain was predicted independently by child and parental therapeutic alliance with the unit early in hospitalization and by preadmission family functioning. Externalizing problems did well if accompanied by good alliance. CONCLUSIONS: Assessment of health gain from multiple perspectives is possible and valuable. Inpatient treatment has significant therapeutic effect. Predictors for health gain lie in process variables of therapeutic alliance and family functioning rather than presenting symptoms. The results are discussed in relation to clinical practice and future research.
The purpose of these studies was to examine how women and men react and accommodate to gender-preferential language in e-mail messages. In Experiment 1, participants wrote messages to two assigned "netpals." These netpals were actually one of the experimenters. For each participant, one netpal used female-preferential language and the other used male-preferential language. Analyses revealed that the netpals' language style, and not the participants' gender, predicted the language used by participants in their e-mail replies. Female and male participants used the gender-preferential language that matched the language used by their netpals. In Experiment 2, the gender labels and language styles of netpals were independently manipulated. As before, linguistic style had the greatest impact on participants' language use. These results have implications for how people think about gendered behavior, and highlight how gendered language is constructed in social interaction.
The FNR protein of Escherichia coli controls the transcription of target genes in response to anoxia. The anaerobic incorporation of oxygen-sensitive [4Fe 4S] clusters promotes dimerization, which in turn enhances DNA binding. Four potential iron ligands (C20, C23, C29 and C122) are essential for normal FNR activity in vivo. Three FNR variants (C20S, C23G and C29G) retained the ability to incorporate oxygen-sensitive [4Fe 4S] clusters and to bind target DNA with essentially unimpaired affinity, suggesting that their failure to function normally in vivo resides at a later stage in the signal transduction pathway. The C122 variant failed to assemble iron-sulphur clusters and to bind DNA. Second-site substitutions that partially restore activity to FNR(C20S) were generated by error-prone polymerase chain reaction and were located in the dimer interface, in the activating regions (AR1, 2 or 3) or close to C122. Substitutions at E47, R48, E123, I124, E127 or T128 allowed the extent of the FNR AR2 surface to be defined. Only one revertant, FNR(C20S Y69F G149S), specifically corrected the C20S defect. It was concluded that [4Fe 4S] cluster acquisition, dimerization and DNA binding are not sufficient to confer transcription regulatory activity on FNR: the iron-sulphur cluster must also be correctly liganded in order to establish effective activating contacts between FNR and RNA polymerase.
An epidemiological study of rotavirus infection was conducted on specimens collected from patients with gastroenteritis and domiciled in the rural Upper Eastern Region of Ghana during 1998. Fifty isolates, randomly selected from 165 human group A rotavirus-positive samples, were G and P characterized by a reverse transcription (RT)-PCR assay using a seminested multiplex method. Rotaviruses of the G3 genotype were found to be the predominant strain (78%), followed by G2 (14%) and G1 (2%). Mixed infections, as shown by combinations of G3 and G2 (4%) and G3 and G1 (2%), were also observed. P typing showed P[4] (72.34%) to be the prevalent strain, followed by P[6] (21.3%), P[8] (2.13%), and a combination of P[4] and P[6] (4.3%).
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract caused by an abnormal and uncontrolled immune response to one or more normally occurring gut constituents. AIM: Given the effects of transforming growth factor beta1 (TGF-beta1) on both the immune system and extracellular matrix, we postulated that alterations in TGF-beta signalling in intestinal epithelial cells may play an important role in the development of IBD. METHODS: TGF-beta signalling was inactivated in mouse intestine by expressing a dominant negative mutant form of the TGF-beta type II receptor under the control of the mouse intestinal trefoil peptide (ITF)/TFF3 promoter. Transgenic mice (ITF-dnRII) developed spontaneous colitis presenting with diarrhoea, haematochezia, and anal prolapse when not maintained under specific pathogen free (SPF) conditions. Under SPF conditions we induced colitis by mixing dextran sodium sulphate (DSS) in drinking water to examine the significance of loss of TGF-beta signalling in the pathogenesis of IBD. RESULTS: Transgenic mice showed increased susceptibility to DSS induced IBD, and elicited increased expression of major histocompatibility complex class II, generation of autoantibodies against intestinal goblet cells, and increased activity of matrix metalloproteinase in intestinal epithelial cells compared with wild-type littermates challenged with DSS. CONCLUSIONS: Deficiency of TGF-beta signalling specifically in the intestine contributes to the development of IBD. Maintenance of TGF-beta signalling may be important in regulating immune homeostasis in the intestine
BACKGROUND: Patients' evaluations are an important means of measuring aspects of primary care quality such as communication and interpersonal care. This study aims to examine variations in assessments of primary care according to age, gender, socioeconomic, and ethnicity variables. METHODS: A cross sectional survey of consecutive patients attending 55 inner London practices was performed over a 2 week period using the General Practice Assessment Survey (GPAS) instrument which assesses 13 important dimensions of primary care provision. Variations in scale scores were investigated for differences relating to age, gender, socioeconomic, and ethnic status as reported by respondents. RESULTS: A total of 7692 questionnaires were returned (71% response rate). Valid information on age, gender, socioeconomic status, and ethnicity was available for 4819 out of 5496 adult respondents. Approximately half the respondents reported their ethnic group as "white" and most of the remaining respondents reported belonging to "black" or South Asian groups. Significant differences existed between groups of patients defined by age or ethnicity for most of the scale scores examined. Black, South Asian, and Chinese respondents reported lower scores (representing less favourable assessments) than white respondents; older respondents reported more favourable evaluations of care than younger respondents; and less affluent groups reported lower scores than more affluent groups for two of the 13 dimensions. There was no significant difference between gender groups with respect to assessment of primary care. Age and ethnicity were independent predictors of respondents' assessments of primary care. CONCLUSIONS: Differences exist between identifiable subgroups of the population in their assessments of primary health care measured using the GPAS instrument. This work adds to the literature on variation in healthcare experience and the potential for patient assessment of primary care. Further work is required to investigate these differences in more detail and to relate them to differences in the nature and process of primary care provision. Primary care providers need to ensure that services provided are appropriate for all patient groups within their communities.
BACKGROUND/AIM: Heparin has been shown to be renoprotective in a number of experimental nephropathies. The inflammatory component in the early phase of Adriamycin (ADR) induced nephropathy has been established. A microdose of low molecular weight heparin (Fragmin; F) has been noted to exert immunomodulatory effects independent of its anticoagulant activity. We assessed the effects of microdoses of F on daily proteinuria and glomerular production of tumor necrosis factor alpha (TNF-alpha) and prostaglandins 8 and 15 days after induction of ADR nephropathy. METHODS: Following intravenous injection of ADR (7 mg/kg) to Wistar rats weighing 200 +/- 20 g, F 20 microg/day/rat s.c. was administered for 8 and 15 days (groups F8 and F15). The respective control groups (C8 and C15) received normal saline subcutaneously. Proteinuria, serum albumin, and creatinine clearance were evaluated on days 8 and 15. The production of TNF-alpha and prostaglandins from glomerular supernatants was measured by radioimmunoassay on days 8 and 15. RESULTS: F significantly reduced proteinuria (mg/day) on day 8: 13.6 +/- 1.2 in F8 versus 40.3 +/- 2.7 in C8 (p = 0.008). The glomerular production of TNF-alpha (pi/ml) was significantly lower on day 8 in rats treated with F: 356 +/- 33 in F8 versus 764 +/- 81 in C8 (p = 0.006). A decrease in the prostaglandin E2/thromboxane B2 ratio was noted in the F group between 8 and 15 days (1.1 in F8 vs. 0.9 in F15, p = 0.005) which principally reflects an increase of thromboxane B2. The antiproteinuric effect of F shown after 8 days was no longer present after 15 days (354 +/- 91 mg/day in F15 vs. 499 +/- 69 mg/day in C15, p = 0.33). The same trend was seen for the glomerular production of TNF-alpha. Light microscopy and immunohistochemistry for interstitial and glomerular macrophages were negative. CONCLUSION: The lowering effect of microdoses of F on the proteinuria seen during the early phase of ADR nephropathy may be mediated by a decreased production of glomerular TNF-alpha, supporting the anti-inflammatory action of low molecular weight heparin.
BACKGROUND: Pregnancy-induced hypertension is characterized by an increased sympathetic activity and probably by a decreased synthesis/activity of nitric oxide. The aim of the present study is to evaluate whether the beneficial action of the sympathetic antagonist methyldopa (a first-choice hypotensive agent in the treatment of PIH) may be associated to changes in nitric-oxide synthesis. METHODS: Forty pregnant Wistar rats received L-NAME (NO synthase inhibitor, 9-10 mg/kg/day) from mid-pregnancy (day 11) through to term. Some rats were treated with daltroban (TxA receptor antagonist, 60 mg/kg/day), diltiazem (calcium channel blocker, 30 mg/kg/day), methyldopa (central adrenergic antagonist, 400 mg/kg/day) or L-arginine (260 mg/kg/day) from mid-pregnancy. The effect of the different treatments on systolic blood pressure (SBP), creatinine clearance (CCR), urine protein excretion (UP) and urinary nitrate excretion (UNO(3), representing urine NO metabolite) were evaluated and the results compared with those found in normal pregnancy. Normal pregnant rats receiving similar treatment were used as controls. RESULTS: In normal pregnant (P) rats, SBP values decreased from 94 +/- 2 to 83 +/- 3 mm Hg at the end of pregnancy (p < 0.01) and CCR augmented significantly. Drug treatment had no significant effect. In NAME-treated rats, at the same period, the SBP augmented from 92 +/- 1 to 129 +/- 1.8 mm Hg (p < 0.01). At the end of pregnancy, NAME rats had significantly lower CCR values and higher UP excretion when compared with P rats. UNO(3) increased significantly in P and in P rats treated with methyldopa. As expected, in NAME rats UNO(3) excretion was significantly reduced. Treatment with methyldopa normalized SBP, improved CCR and proteinuria and was associated with an increase in UNO(3). Similar results were obtained with L-arginine treatment. Diltiazem lowered SBP significantly but had no effect on renal function or UNO(3) and daltroban had no effect. CONCLUSION: The increased UNO(3) found in NAME rats treated with methyldopa suggests that the vasoconstriction secondary to chronic NO inhibition may be partially related to an increased sympathetic activity. The efficient action of the sympathetic antagonist methyldopa may be due not only to its antihypertensive effects but also by its stimulating effect on NO synthesis leading also to an improvement of renal function.
This is the first of an occasional series of articles that will feature in full exclusively in Promotion & Education as part of the formal link between IUHPE and Health Education Research. Each article will review key issues raised by papers published recently in Health Education Research on a topic or theme of current relevance to health promotion. A brief summary will also appear in Euronews, the IUHPE Regional Newsletter for Europe.