Blood pressure reactions to acute psychological stress and future blood pressure status: a 10-year follow-up of men in the Whitehall II study

OBJECTIVE: The aim of this study was to examine whether blood pressure reactions to mental stress predicted future blood pressure and hypertension. METHODS: Blood pressure was recorded at an initial medical screening examination after which blood pressure reactions to a mental stress task were determined. A follow-up screening assessment of blood pressure and antihypertensive medication status was undertaken 10 years later. Data were available for 796 male public servants, between 35 and 55 years of age upon entry to the study. RESULTS: Systolic blood pressure reactions to mental stress were positively correlated with follow-up screening systolic blood pressure and to a lesser extent, follow-up diastolic pressure. In multivariate tests, by far the strongest predictors of follow-up blood pressures were initial screening blood pressures. In the case of follow-up systolic blood pressure, systolic reactions to stress emerged as an additional predictor of follow-up systolic blood pressure. With regard to follow-up diastolic blood pressure, reactivity did not enter the analogous equations. The same outcomes emerged when the analyses were adjusted for medication status. When hypertension at 10-year follow-up was the focus, both systolic and diastolic reactions to stress were predictive. However, with correction for age and initial screening blood pressure, these associations were no longer statistically significant. CONCLUSIONS: The results of this study provide modest support for the hypothesis that heightened blood pressure reactions to mental stress contribute to the development of high blood pressure. At the same time, they question the clinical utility of stress testing as a prognostic device.     

Distribution of alleles of the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in familial spina bifida

Spina bifida cystica (SB) is one of the most common and disabling of birth defects. Folic acid supplementation in mothers during the periconceptional period has been shown to prevent more than 70% of neural tube defects (NTD) including SB. However, the mechanism is unknown. We tested a series of multicase SB families in which 224 individuals were genotyped and a group of 215 unrelated unaffected (external) control individuals for association of SB with the T allele of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism that produces a heat-labile enzyme protein. The data were analyzed using first the transmission/disequilibrium test (TDT) and second a modified case-control study design with Monte Carlo sampling methods. No association of SB with the MTHFR T allele was found by either method. Presently, association between SB and the T allele has been found in four studies, a Dutch study, an Irish study, a North American study, and an Italian study. But no association was found in four other studies, a British study, a French study, a Turkish study, and a German study. A California population-based study found only modestly increased risk of SB with this allele that was not significant at the P < 0.05 level. The present study finds no evidence of the association. Only one other study, the German study, has used TDT analysis. The present study is the first to use a modified case-control study design with Monte Carlo sampling methods to test this association. Thus, it appears that the MTHFR T allele is a risk factor for SB in some populations but not others. Major genetic risk factors for folate-related SB remain to be found.     

SV40 defectives selected during low multiplicity passage on A172 human glioblastoma cells

The gliobastoma line, A172, is unusual among human cell lines in being permissive for SV40 infection, and differs from many host cell types in allowing the accumulation of viral defectives on low multiplicity passage. We have characterized these A172-derived defectives and find that most are reiteration mutants, containing multiple copies of both the viral replication origin (including the BglI site at map position 0.659) and sequences from the opposite side of the standard genome (around the BamHI site at map position 0.143). This distinguishes them from defectives accumulated during high-multiplicity passage in monkey cells, which generally have only reiterated origins. When well characterized, monkey cell-derived defectives (ev-1101, d₅ a₃, a′₄) were passed in A172 cells, the characterized defectives were lost, and sometimes replaced by other defectives present in the same stock. Surprisingly, this was true even when the characterized defective carried sequences from the BamHI region of standard SV40. These findings are taken to support the notion that sequences in addition to the viral replication origin are positively selected during defective propagation, but that different requirements for such sequences are set by monkey cells and A172 cells.     

The mutational specificity of l-nitroso-6-nitropyrene in the lacI gene of Escherichia coli strains deficient in nucleotide excision repair

We have examined the mutational specificity of 1-nitroso-6-nitropyrene(1,6-NONP), an activated metabolite of the carcinogen 1,6-dinitropyrene,in the lacI gene of Escherichia coli strains which are deficientin nucleotide excision repair (strain NR6113,     

Genome maps of simian virus 40 defectives propagated in human glioblastoma cells.

The DNA sequences present in four defective SV40 genomes propagated on human glioblastoma cells (A172) have been characterized by analysis of restriction enzyme digests and by hybridization to the wild-type genome. Like defectives grown on monkey cells, these molecules are 10 to 20% shorter than wild-type DNA and contain reiterations of specific segments of the nondefective genome, including multiple copies of the viral replication origin. However, unlike the monkey cell defectives, those grown on A172 cells have also retained multiple copies of the region of viral DNA around the BamHl site at map position 0.15. These defectives consist only of sequences derived from SV40 and contain no detectable host cell sequences.     

Millon Clinical Multiaxial Inventory-III subtypes of opioid dependence: validity and matching to behavioral therapies

The concurrent and predictive validity of 2 different methods of Millon Clinical Multiaxial Inventory-III subtyping (protocol sorting, cluster analysis) was evaluated in 125 recently detoxified opioid-dependent outpatients in a 12-week randomized clinical trial. Participants received naltrexone and relapse prevention group counseling and were assigned to 1 of 3 intervention conditions: (a) no-incentive vouchers, (b) incentive vouchers alone, or (c) incentive vouchers plus relationship counseling. Affective disturbance was the most common Axis I protocol-sorted subtype (66%), antisocial-narcissistic was the most common Axis II subtype (46%), and cluster analysis suggested that a 2-cluster solution (high vs. low psychiatric severity) was optimal. Predictive validity analyses indicated less symptom improvement for the higher problem subtypes, and patient treatment matching analyses indicated that some subtypes had better outcomes in the no-incentive voucher conditions.     

Translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia: Three new cases

Several recent reports have described cases of acute nonlymphocytic leukemia with a unique chromosome translocation, t(6;9)(p23;q34). We have studied three additional patients who have acute nonlymphocytic leukemia and t(6;9)(p23;q34). Our findings provide additional support for the suggestion that this translocation is yet another distinct cytogenetic abnormality associated with myeloproliferative disorders.