Environmental factors in the development of essential hypertension

Hypertension is predominantly a disorder of populations in which the fundamental problem is the tendency for blood pressure to rise with age. This phenomenon, which varies markedly across populations, is determined largely by environmental factors. We argue that the most important factors in the development of hypertension at the population level are calorie excess (as manifest by obesity), high salt intake, low potassium intake, physical inactivity, heavy alcohol consumption and psychosocial stress. Potential interactions between these factors (and the genetic endowment) are emphasized. We consider data from studies of blood pressure in children and adolescents and from intervention studies. The hypothesis that essential hypertension is initiated in fetal life is reviewed briefly. It is clear that the current high risk approach to prevention should be supplemented by a population based approach. There is controversy however regarding the value of certain interventions, such as salt restriction, at the population level. Ultimately community intervention trials will be required to resolve these issues.     

NMR and protein folding: equilibrium and stopped-flow studies

NMR studies are now unraveling the structure of intermediates of protein folding using hydrogen-deuterium exchange methodologies. These studies provide information about the time dependence of formation of secondary structure. They require the ability to assign specific resonances in the NMR spectra to specific amide protons of a protein followed by experiments involving competition between folding and exchange reactions. Another approach is to use 19F-substituted amino acids to follow changes in side-chain environment upon folding. Current techniques of molecular biology allow assignments of 19F resonances to specific amino acids by site-directed mutagenesis. It is possible to follow changes and to analyze results from 19F spectra in real time using a stopped-flow device incorporated into the NMR spectrometer.     

Metastasis results from preexisting variant cells within a malignant tumor

Clones derived in vitro from a parent culture of murine malignant melanoma cells varied greatly in their ability to produce metastatic colonies in the lungs upon intravenous inoculation into syngeneic mice. This suggests that the parent tumor is heterogeneous and that highly metastatic tumor cell variants preexist in the parental population.     

Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol

The monoterpenes d-limonene and perillyl alcohol (POH) inhibit the growth of mammary tumors. In this investigation we tested whether POH is also effective in reducing liver tumor growth. Diethylnitrosamine was used to induce liver tumors in male Fischer 344 rats. Two weeks after diethylnitrosamine exposure was discontinued, the animals were divided into POH-treated and untreated groups. The mean liver tumor weight for the POH-treated rats after 19 weeks of POH treatment was 10-fold less than that for the untreated animals. POH did not influence tumor cell proliferation but increased the apoptotic index approximately 10-fold. The mRNA levels for the mannose 6-phosphate/insulin-like growth factor II receptor and the transforming growth factor beta type I, II, and III receptors were also significantly increased in the liver tumors from the POH-treated animals when compared to the corresponding receptor mRNA levels in the normal tissue surrounding the tumors and in the tumors of untreated animals. These results demonstrate that POH does not promote the formation of liver tumors, but rather inhibits their growth by enhancing tumor cell loss through apoptosis.     

Quality assessment instruments in nursing: towards validation

The aim of this study was to explore the validity of the nursing quality assessment instruments, Monitor, Senior Monitor and Qualpacs. This follows recommendations in the literature for the need for more comprehensive validation of instruments than has been the case hitherto. A multiple triangulation research design was used which included observation of and interviews with nurses and patients as well as administration of the instruments with the same patients and a questionnaire completed by the nurses in charge on ward organisation and their approach to nursing care. Results reported here focus on our experiences of using the instruments, their inter-rater reliability and comparisons of instrument scores within medical, surgical and elderly care wards. Difficulties were encountered in using the instruments but most of these can be overcome given sufficient time for preliminary discussions. Inter-rater reliability of all three instruments taken as a whole reached acceptable levels, although some of the section score correlation coefficients were low, especially for Qualpacs. Convergent validity was achieved for the Senior Monitor-Qualpacs comparisons in four elderly care wards. The results were less clear for the Monitor-Qualpacs comparisons in seven medical and surgical wards. Explanations for the equivocal results are suggested and subsequent hypotheses were tested which supported these explanations.     

Thumb reconstruction with a free neurovascular wrap-around flap from the big toe: long-term follow-up of thirty cases

From March 1982 to December 1992, 30 cases of thumb reconstruction with a free neurovascular wrap-around flap from the big toe were performed at Korea University Hospital. Twenty-nine of a total of 30 cases were successful and obtained excellent functional and cosmetic results. Postoperative complications included 1 case of graft failure, 6 partial skin necroses, 1 malunion, and 15 cases of resorption of iliac bone graft including 1 case of fatigue fracture of grafted bone. Even for the first metacarpal neck amputations, thumb reconstruction with a free neurovascular wrap-around flap was possible; however, limitation of motion of the reconstructed thumb and resorption of the grafted bone occurred. Thumb reconstruction with a wrap-around free flap from the big toe gives excellent cosmetic and functional results and causes minimal morbidity on the donor site.     

Genetic requirements and mutational specificity of the Escherichia coli SOS mutator activity

To better understand the mechanisms of SOS mutagenesis in the bacterium Escherichia coli, we have undertaken a genetic analysis of the SOS mutator activity. The SOS mutator activity results from constitutive expression of the SOS system in strains carrying a constitutively activated RecA protein (RecA730). We show that the SOS mutator activity is not enhanced in strains containing deficiencies in the uvrABC nucleotide excision-repair system or the xth and nfo base excision-repair systems. Further, recA730-induced errors are shown to be corrected by the MutHLS-dependent mismatch-repair system as efficiently as the corresponding errors in the rec+ background. These results suggest that the SOS mutator activity does not reflect mutagenesis at so-called cryptic lesions but instead represents an amplification of normally occurring DNA polymerase errors. Analysis of the base-pair-substitution mutations induced by recA730 in a mismatch repair-deficient background shows that both transition and transversion errors are amplified, although the effect is much larger for transversions than for transitions. Analysis of the mutator effect in various dnaE strains, including dnaE antimutators, as well as in proofreading-deficient dnaQ (mutD) strains suggests that in recA730 strains, two types of replication errors occur in parallel: (i) normal replication errors that are subject to both exonucleolytic proofreading and dnaE antimutator effects and (ii) recA730-specific errors that are not susceptible to either proofreading or dnaE antimutator effects. The combined data are consistent with a model suggesting that in recA730 cells error-prone replication complexes are assembled at sites where DNA polymerization is temporarily stalled, most likely when a normal polymerase insertion error has created a poorly extendable terminal mismatch. The modified complex forces extension of the mismatch largely at the exclusion of proofreading and polymerase dissociation pathways. SOS mutagenesis targeted at replication-blocking DNA lesions likely proceeds in the same manner.     

Quantitative cerebral magnetic resonance imaging during ACTH treatment of multiple sclerosis

Serial MR scans were performed with the 2DFT imaging method and the filtered backprojection imaging method on 12 patients with multiple sclerosis in acute phase, 4 in a relapsing/remitting form, and 8 in a progressive form, before, during and after ACTH treatment. Both T1 and T2mono relaxation times, obtained by fitting transverse magnetization decay curves with a monoexponential function within the apparently normal white matter and the areas of increased signal, were measured. With the backprojection method it was possible to fit the transverse magnetization decay curve with a biexponential function and obtain T2long and T2short relaxation times. The T2mono and T1 relaxation times of the apparently normal white matter were significantly different from those obtained for volunteers, but no significant differences were found before, during, or after treatment. The transverse magnetization decay curves of the areas of increased signal were better fitted by a biexponential function. No significant changes in these relaxation times were observed after ACTH treatment. These results argue against an anti-oedematous action of ACTH and may suggest that it has an immunosuppressant effect.