Interaction between smoking and the stromelysin-1 (MMP3) gene 5A/6A promoter polymorphism and risk of coronary heart disease in healthy men

Smoking is a major risk factor for coronary heart disease (CHD), but this risk may be modified by an individual's genotype. A common functional 5A/6A polymorphism in the promoter of the stromelysin-1 (matrix metalloproteinase 3, MMP3) gene has been identified. The 6A allele has been consistently associated with faster progression of angiographically determined CHD, while the 5A allele has recently been associated with risk of acute myocardial infarction (MI) in patients with unstable angina. To date there has been no prospective study of the relationship of this genotype to CHD risk in smokers and non-smokers. DNA was available from 2,743 middle-aged men, free of CHD at baseline, recruited through nine general practices in the UK for prospective surveillance. To date there have been almost 24,000 person-years of follow-up with 125 CHD events (fatal and non-fatal MI, sudden coronary death, need for coronary artery surgery or new major ECG Q-wave abnormality). Men with events were each matched for age, practice and cholesterol level with three healthy men. Smoking habit was determined by questionnaire. 5A/6A genotype was determined using a heteroduplex generator method. Associations between genotype and disease outcome, according to smoking status, were assessed using conditional logistic regression. Overall, current smoking was associated with a relative risk (RR) of 1.99 (95% CI 1.30-3.06) as compared with never-smokers and ex-smokers combined (p&0.002). In non-smoking men, and after adjustment for conventional risk factors, compared with the 5A5A group, the RR was 1.37 (0.64-2.94) in those with the genotype 5A6A and 3.02 (1.38-6.61) in those with the genotype 6A6A. Smoking increased risk 1.4 fold in the 5A6A group to 1.91 (1.84-4.36), by 1.3 fold in the 6A6A group to 4.01 (1.57-10.24), but by 3.81 fold (1.54-9.40) in the 5A5A group (smoking-genotype interaction p = 0.01). The data indicate a key role for stromelysin in the atherosclerotic process. Men with the stromelysin genotype 5A5A represent 29% of the general population, and their high risk, if smokers, provides a further strong argument for smoking avoidance.     

The Personality Assessment Inventory in individuals with traumatic brain injury.

This study examined the Personality Assessment Inventory (PAI) in 95 individuals who had suffered a traumatic brain injury (TBI). Participants were recruited from a rehabilitation hospital (n=60) and a military hospital (n=35); despite differences in demographics and injury characteristics groups did not differ on any of the clinical scales and were thus combined. In the combined group, the highest mean clinical scale elevations were on Somatic Complaints, Depression, and Borderline Features and the most common configural profiles, based on cluster analysis, were Cluster 1 (no prominent elevations), Cluster 6 (social isolation and confused thinking), and Cluster 2 (depression and withdrawal). Factor analysis indicated a robust three-factor solution that accounted for 74.86 percent of the variance and was similar to findings from the psychiatric and non-psychiatric populations in the standardization sample. The above findings are compared with the previous literature on psychopathology in TBI, particularly in regards to the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), as well as previous psychometric research on the PAI.     

Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates

Titers of lymphocytic choriomeningitis virus (LCMV) were determined on adherent fibroblast cell lines in 24- or 96-well plates. After absorption of virus by cells and 48 h incubation under a methylcellulose overlay, cell monolayers were fixed with 4% formaldehyde in phosphate-buffered saline, permeabilized by incubation in 0.5% Triton X-100 in balanced salt solution and then stained with a monoclonal rat anti-LCMV and a peroxidase-labeled second stage antibody. The sensitivity of the assay is within a factor of 2-4 of conventional plaquing methods. The method also detects poorly or non-plaquing LCMV isolates, and therefore drastically reduces the need for titration of LCMV in mice. The method is quicker (2-3 days), as compared to conventional methods (4-6 days) and less expensive in terms of work and materials.     

Risk of infection after penetrating abdominal trauma

To identify the risk factors for the development of postoperative septic complications in patients with intestinal perforation after abdominal trauma, and to compare the efficacies of single-drug and dual-drug prophylactic antibiotic therapy, we studied 145 patients who presented with abdominal trauma and intestinal perforation at two hospitals between July 1979 and June 1982. Logistic-regression analysis showed that a higher risk of infection (P less than 0.05) was associated with increased age, injury to the left colon necessitating colostomy, a larger number of units of blood or blood products administered at surgery, and a larger number of injured organs. The presence of shock on arrival, which was found to increase the risk of infection when this factor was analyzed individually, did not add predictive power. Patients with postoperative sepsis were hospitalized significantly longer than were patients without infection (13.8 vs. 7.7 days, P less than 0.0001). Both treatment regimens--cefoxitin given alone and clindamycin and gentamicin given together--resulted in similar infection rates, drug toxicity, duration of hospitalization, and costs.     

Gender-specific and gonadectomy-specific effects upon swim analgesia: role of steroid replacement therapy

Both gender-specific and gonadectomy-specific effects have been observed for the analgesic responses following continuous and intermittent cold-water swims (CCWS and ICWS respectively): female rats display significantly less analgesia than males, and gonadectomized rats display significantly less analgesia than sham-operated controls. The present study evaluated the effects of steroid replacement therapy with testosterone propionate (TP: 2 mg/kg, SC) upon CCWS and ICWS analgesia on the tail-flick and jump tests and hypothermia in sham-operated or gonadectomized male and female rats. Thirty days following surgery, rats received either no treatment, a sesame oil vehicle or TP for 14 days prior to, and then during testing. Relative to the no treatment condition, repeated vehicle injections in sham-operated rats eliminated the gender-specific, but did not affect the gonadectomy-specific effects upon CCWS and ICWS analgesia. TP reversed the deficits in CCWS and ICWS analgesia observed in both castrated and ovariectomized rats on both pain tests. TP only potentiated CCWS analgesia in sham-operated males on the tail-flick test. TP potentiated CCWS and ICWS hypothermia in gonadectomized rats and in male sham-operated rats. These data indicate that gonadal steroids play a major modulatory role in the etiology of swim analgesia, and that the observed gender effects are sensitive to possible adaptational variables.     

Inhibition of vaccinia virus late protein synthesis by isatin-beta-thiosemicarbazone: characterization and in vitro translation of viral mRNA.

Thespecific effect of istin-βthiosemicarbozone (IBT) was manifested after vaccinia virus late protein synthesis had commenced. At 6 hr after infection, viral protein synthesis was inhibited by about 9596. We confirmed that λ portion of the virus-specific RNA appears to be degraded (B. Woodson and W. K. Joklik, 1965, Proc. Nat. Acad. Sci. USA 54,946–953). Nevertheless, the amount of viral RNA that was capped, properly methylated, and polyadenylylated, was reduced by only about 50%. Moreover, RNA from IBT-treated cells stimulated cell-free protein synthesis to one-half the level obtained with RNA from control cells. Polyacrylamide gel electrophoretic analysis further demonstrated that RNA from IBT-treated cells was translated into late viral proteins in vitro. Thus, it seems possible that the inhibition of protein synthesis in IBT-treated cells does not result entirely or directly from either an inhibition of mRNA synthesis or from λ depletion of mRNA caused by accelerated degradation. An alternative possibility, that accelerated degradation is secondary to λ more immediate effect of the drug on protein synthesis, was considered.     

Haematological characteristics of captive Parma wallabies (Macropus parma)

 Blood was collected from 31 Parma wallabies from five different captive populations. The morphology of erythrocytes, leucocytes and platelets was similar to that previously described for macropodids. The effects of location (population), anaesthesia and analyser on the haematological characteristics of the wallabies were considered. Location had an affect on many of the values, anaesthesia affected some of the leucocyte values, and analyser had little effect. Received: 22 November 2002 / Accepted 13 February 2003 Acknowledgements We thank Mrs R. Power, Ms S. Bayliss, Ms T. Smith and Mrs P. Slack for technical assistance, Mr D. Hopcroft for assistance with electron microscopy and Mr D. Hedderly for performing the statistical analyses.     

Mental health of parents caring for infants

The postpartum period is a sensitive time due to the presence and demands of the developing infant. The care provided by a mother to her infant during this period may be compromised if she is suffering from postnatal depression or postpartum psychosis. Evidence has been emerging which suggests that postnatal depression and postpartum psychoses have adverse effects on the quality of the mother-infant relationship and also on the infant's subsequent cognitive and emotional development. Presented is a review of the literature relating to how these conditions impact on parenting and infant outcomes, what measures are in place to detect these conditions and evidence-based models of best clinical practice are proposed.     

A human B cell differentiation antigen selectively expressed on mature B cells identified by a monoclonal antibody (HB-2)

A monoclonal IgM antibody (HB-2), produced against a membrane antigen on the Raji, B cell line, reacted by indirect immunofluorescence with 2 to 40% of lymphoblasts from the B cell lines, Raji, Daudi, SN-1036, and SB but not with other types of cell lines, including pre-B, myeloid, melanoma, or T cells. HB-2 antibody reacted with 10 ± 3% of normal blood mononuclear cells, and was unreactive with monocytes, granulocytes, platelets, or erythrocytes. Two-color immunofluorescence revealed that HB-2 antigen expression was confined to cells bearing surface Ig. An interesting finding was the fact that 25% of plasmablasts induced by pokeweed mitogen also expressed the HB-2 antigen. However, pre-B and plasma cells from normal bone marrow did not express the HB-2 antigen either on their membrane surface or in their cytoplasm. Analysis of 85 leukemias revealed that the HB-2 antigen was expressed on acute and chronic B cell leukemias and Burkitt's lymphomas, but not on malignacies of pre-B, T, myelocytic, or plasma cells. The results suggest that expression of the HB-2 antigen is confined to mature B cells.