Structure and promoter organization of the human monoamine oxidase A and B genes.

Monoamine oxidase (MAO) A and B play an important role in regulating levels of biogenic amines. MAO A and B cDNAs have been cloned and the deduced amino acids share 73% sequence identity. The genes for MAOA and B are comprised of 15 exons interspersed by 14 introns, span at least 60 kb and exhibit identical exon-intron organization. These findings suggest that the MAOA and MAOB genes are derived from the duplication of a common ancestral gene. The core promoter region of MAOA is comprised of two 90 bp repeats, each of which contains two Spl elements and lacks a TATA box. The MAOB core promoter region contains two sets of overlapping Spl sites which flank a CACCC element all upstream of a TATA box. The different organization of the MAOA and MAOB promoters may underlie their different cell and tissue specific expression.     

Outcome for patients colonised with Burkholderia cepacia in a Birmingham adult cystic fibrosis clinic and the end of an epidemic.

BACKGROUND: There has been increasing concern since 1979 about the emergence of Pseudomonas cepacia (Burkholderia cepacia) in patients with cystic fibrosis in the UK and elsewhere. Colonisation of the sputum has been shown to be associated with increased morbidity and mortality. Evidence suggests person to person transmission and some centres have segregated those colonised with B cepacia from other patients with cystic fibrosis. The outcome of patients colonised by B cepacia has been studied, together with the effects of strict segregation. METHODS: The outcome in 18 patients with sputum colonised by B cepacia was compared with that in age, sex, and severity matched controls with no evidence of B cepacia colonisation by a retrospective case note study. RESULTS: No difference between cases or controls were found in the 24 month period prior to colonisation by B cepacia in lung function, number of days in hospital, or outpatient visits. Colonisation led to an increased rate of loss of lung function and utilisation of hospital services. There was an increase in the numbers of transplants and deaths amongst the cases. Since 1992 there have been only three new cases of B cepacia colonisation and the incidence and prevalence of the organism has fallen dramatically since segregation commenced. CONCLUSIONS: B cepacia appears to be linked to the decline in colonised individuals. There was no evidence that colonisation occurred in patients declining for other reasons. B cepacia colonisation confers a worse prognosis than Pseudomonas aeruginosa alone. Segregation appears to limit the spread of the organism from infected individuals to other patients with cystic fibrosis.     

Serum measurements of soluble CD23 in HIV infection.

A gradual reduction in cell-mediated immunity is thought to occur with the progression of human immunodeficiency virus (HIV) infection. This suggests a selective attrition of the Th1 subset. The regulation of the soluble form of the low-affinity receptor for IgE (sCD23) by the opposing actions of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) allows the assessment of the overall balance of Th1 to Th2 activity in a given disease. In order to investigate this further we employed an enhanced chemiluminescent ELISA to analyse serum levels of sCD23 in male subjects with and without HIV infection. Serum levels of sCD23 were similar in 34 HIV seronegative homosexuals, 39 homosexuals with asymptomatic HIV infection, 27 homosexuals with acquired immune deficiency syndrome (AIDS) and 20 healthy controls. This suggests that HIV has no predilection for either the Th1 or Th2 subsets of CD4 T cells.     

Enterotoxins and toxic-shock syndrome toxin-1 in non-enteric staphylococcal disease.

Over the 7 years 1985-91, 997 strains of Staphylococcus aureus from 962 patients with diseases other than food poisoning have been tested for the production of enterotoxins and toxic shock syndrome toxin-1 (TSST-1) and phage typed. In all, 128 cases could be classified as confirmed or probable toxic shock syndrome (TSS) but a further 199 cases were classified as possible or unconfirmed TSS. In 219 cases, an alternative diagnosis could be supported and 45 cases were classified as sudden infant death syndrome. In 371 cases, insufficient information for classification was available. Strains of phage group I producing TSST-1 were associated with menstrual TSS. Many menstrual TSS cases were aged less than 20 and were using non-introducer tampons. When all strains were reviewed, strong associations were observed between TSST-1 production and phage group I strains, enterotoxin B production and group V strains, enterotoxin C and phage-type 95 strains and between enterotoxin A without TSST-1 and phage group III strains.     

小鼠胸腺和脾脏细胞的体外转化培养

建立了小鼠脾脏、胸腺细胞体外转化微量培养系统,确定了最佳实验条件.点蜡法充CO_2,简便易行,效果好.RPMI-1640培养基内补充胎牛血清,其浓度确定为在脾细胞培养为10%,在胸腺细胞培养为20%.脾细胞培养最适细胞密度为2～5×10~6/ml,Con A最适量为2～4μg/培养;胸腺细胞培养细胞最适密度为1×10~7/ml,Con A最适量为2～4μg/培养.两种已知免疫活性的药物在脾细胞培养体系有明确肯定的反应.     

The chief medical residency in Canada: comparison of opinions between physicians-in-chief and chief medical residents.

We conducted a survey of physicians-in-chief (PCs) and chief medical residents (CMRs) in training programs throughout Canada to determine their attitudes toward the need for and role of CMRs in Canada and to rate the importance of CMR duties and attributes. Forty-three hospitals with 5 to 126 house staff in all eight provinces with medical schools were surveyed; 36 PCs (84%) and 29 CMRs (67%) returned a completed questionnaire. Compared with the CMRs the PCs preferred more prior training (p less than 0.03), estimated as significantly less the time spent by CMRs in required duties (p less than 0.05) and rated as more important the responsibilities of faculty-house staff liaison, house staff leader, house staff role model and teaching house staff (p less than 0.05) and the attributes of clinical judgement, medical knowledge, clinician model and research interests (p less than 0.03). All of the PCs and 97% of the CMRs rated the position as somewhat to very necessary; 83% of the PCs and 66% of the CMRs would not alter the present CMR roles. A total of 92% of the PCs felt that the position was very or somewhat advantageous with respect to a future private practice, compared with 67% of the CMRs (p less than 0.02). Increased administrative and committee duties, decreased teaching and future reductions in house staff were identified as major but reversible threats to the unique quality of the CMR position. We conclude that the CMR has a necessary, important and highly regarded role in Canadian university hospitals that could possibly be improved by regular review by the PC and CMR at each hospital to avoid the identified problems.     

A case-control study of the effect of environmental sanitation on diarrhoea morbidity in Malawi.

A case-control design has been applied in the evaluation of improved environmental sanitation on diarrhoeal diseases in rural Malawi. The study demonstrates the feasibility of using such an approach to evaluate two levels of water supply and sanitation service quickly and at moderate cost. Sample sizes would need to be increased substantially to evaluate multiple levels of service or to investigate interactions between water supply and sanitation. The results indicate that children living in families who use good quality water supplies and latrines experience 20% less diarrhoea as reported to the health clinics during the warm, rainy season.     

A cluster of bacterial genes for anaerobic benzene ring biodegradation

A reductive benzoate pathway is the central conduit for the anaerobic biodegradation of aromatic pollutants and lignin monomers. Benzene ring reduction requires a large input of energy and this metabolic capability has, so far, been reported only in bacteria. To determine the molecular basis for this environmentally important process, we cloned and analyzed genes required for the anaerobic degradation of benzoate and related compounds from the phototrophic bacterium, Rhodopseudomonas palustris. A cluster of 24 genes was identified that includes twelve genes likely to be involved in anaerobic benzoate degradation and additional genes that convert the related compounds 4-hydroxybenzoate and cyclohexanecarboxylate to benzoyl-CoA. Genes encoding benzoyl-CoA reductase, a novel enzyme able to overcome the resonance stability of the aromatic ring, were identified by directed mutagenesis. The gene encoding the ring-cleavage enzyme, 2-ketocyclohexanecarboxyl-CoA hydrolase, was identified by assaying the enzymatic activity of the protein expressed in Escherichia coli. Physiological data and DNA sequence analyses indicate that the benzoate pathway consists of unusual enzymes for ring reduction and cleavage interposed among enzymes homologous to those catalyzing fatty acid degradation. The cloned genes should be useful as probes to identify benzoate degradation genes from other metabolically distinct groups of anaerobic bacteria, such as denitrifying bacteria and sulfate-reducing bacteria.     

Adequacy of hormone replacement therapy for osteoporosis prevention assessed by serum oestradiol measurement, and the degree of association with menopausal symptoms.

BACKGROUND: Patients on hormone replacement therapy (HRT) for osteoporosis prevention rather than menopausal symptom control may be asymptomatic, despite inadequate replacement and low serum oestradiol (E2) levels. In the primary health care setting, therapeutic monitoring of HRT is not carried out routinely so that patients with serum E2 levels inadequate to protect bone may be missed. AIM: To determine the proportion of women on transdermal E2 preparations with serum E2 levels insufficient to protect bone and to assess the value of a questionnaire-derived menopausal symptom score (MSS) for detecting these patients. METHOD: A cross-sectional analysis of 45 patients aged 35-70 years using transdermal E2 preparations obtained from a computer register of 14500 patients in a suburban practice. One blood sample was obtained from each patient at the time the MSS questionnaire was completed. Serum E2 concentration was measured using a fluoroimmunoassay and compared with the MSS. Levels below 150 pmol/l were considered to be insufficient to protect bone. The diagnostic accuracy of the MSS in screening for levels below 150 pmol/l was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: The median (95% CI) serum E2 was 147 pmol/l (126-198 pmol/l) and levels were below 150 pmol/l in 24 out of 45 patients. There was no difference in the MSS (median, 95% CI) between those with serum E2 < 150 pmol/l (8.5, 5.0-17) and > or = 150 pmol/l (9.0, 5.0-14; P = 0.477). The degree of association between the serum E2 and the MSS, using the Spearman rank correlation coefficient, rs (95% CI) was small and not significant (-0.04, -0.34 to 0.26; P = 0.398). ROC curve analysis revealed an area under the curve (95% CI) of 0.51 (0.33-0.68). CONCLUSIONS: More than half the women were inadequately replaced to protect against osteoporosis. Furthermore, the MSS was of no value in screening for those with low serum E2 levels. Serum E2 levels should be monitored in women on HRT for osteoporosis prevention and the E2 dosage adjusted accordingly.