Intensive training of patients with hypertension is effective in modifying lifestyle risk factors.

The burden of insufficiently treated arterial hypertension is still underestimated. In addition to pharmacological therapy, patient training is a valuable therapeutic option. During 1998-1999, the Institute for Preventive Medicine conducted an intensive training programme in cooperation with regional practitioners. The goal of this programme was to educate patients about their disease and motivate them to comply with the therapy. To evaluate the effectivity of this programme, 126 patients with arterial hypertension were trained. They received eight training sessions of 90 min each. In 90 patients blood pressure measurements before and 6 months after training were available. In addition, data concerning health status and lifestyle risk factors were analysed with standardised questionnaires. There was a marked reduction in blood pressure after 6 months (152+/-6/89+/-10 vs. 145+/-12/85+/-8 mmHg, P<0.001). In parallel, mean body weight declined by 0.9 +/- 2.9 kg (P<0.001) and body mass index (BMI) by 0.33+/-1.04 kg/m2 (P<0.001). Further analysis revealed that weight loss was more marked in obese patients (P< 0.01) than in lean subjects. Similarly, the decline of blood pressure was also greater in obese patients, but did not reach statistical significance. The activity score for physical exercise increased overall from 2.1+/-0.4 to 2.8+/-3.1 h/week (P<0.01). Moreover, knowledge about hypertension increased as well (P<0.01). Of all the quality life measurements, the vitality index improved from 53+/-19 to 59+/-19 (P<0.05) according to the patients' self-estimation. In conclusion, training of hypertensive patients has a profound effect on blood pressure control. It motivates patients to change lifestyle risk factors, namely to lose weight, and increases the patients' physical activity level, thereby decreasing the patients' blood pressure. Thus, intensive training programmes are effective and should be used on a widespread basis.

[Results of an intensive training program for hypertension at the Institute for Preventive Medicine]. / Ergebnisse der Intensiv-Hypertonieschulung des Instituts für präventive Medizin.

BACKGROUND AND OBJECTIVE: The burden of insufficiently treated arterial hypertension is still underestimated. During 1998 to 1999 we conducted an intensive training program in cooperation with regional practitioners. The aim of this program was to educate the patients about their disease and motivate them to comply with therapy. The effectivity of this program yet needs to be evaluated. PATIENTS AND METHODS: 146 patients (mean age 62 years; 57 male, 89 female) with arterial hypertension were trained. They received 8 training units of 90 min each. Before training and 6 months after training data concerning health status and life style risk factors were assessed with questionnaires. RESULTS: There was a marked reduction in blood pressure after 6 months (152/89 mmHg vs 145/85 mmHg, p < 0.001). The mean body weight also declined on the average by 0.9 kg (p < 0.001). Physical exercise spent per week increased from mean 2.0 to 2.8 hours (p < 0.01). Moreover, knowledge about hypertension increased (p < 0.001). The established questionnaire SF-36 revealed a better score for vitality (p < 0.05) six months after therapy than before. CONCLUSION: Our intensive training program of patients with arterial hypertension has profound effects on their systolic and diastolic blood pressure. It also motivates patients to change life style. Our data suggest that intensive training programs should be developed on a widespread basis.

Equine infectious anemia virus transactivator is a homeodomain-type protein.

Lentiviral transactivator (Tat) proteins are essential for viral replication. Tat proteins of human immunodeficiency virus type 1 and bovine immunodeficiency virus form complexes with their respective RNA targets (Tat responsive element, TAR), and specific binding of the equine anemia virus (EIAV) Tat protein to a target TAR RNA is suggested by mutational analysis of the TAR RNA. Structural data on equine infectious anemia virus Tat protein reveal a helix-loop-helix-turn-helix limit structure very similar to homeobox domains that are known to bind specifically to DNA. Here we report results of gel-shift and footprinting analysis as well as fluorescence and nuclear magnetic resonance spectroscopy experiments that clearly show that EIAV Tat protein binds to DNA specifically at the long terminal repeat Pu.1 (GTTCCTGTTTT) and AP-1 (TGACGCG) sites, and thus suggest a common mechanism for the action of some of the known lentiviral Tat proteins via the AP-1 initiator site. Complex formation with DNA induces specific shifts of the proton NMR resonances originating from amino acids in the core and basic domains of the protein.

Homology modeling of adenylosuccinate synthetase from Saccharomyces cerevisiae reveals a possible binding region for single-stranded ARS sequences.

Adenylosuccinate synthetase from Saccharomyces cerevisiae was investigated in order to find a structural explanation for its ability to bind specifically to single-stranded ARS elements (autonomously replicating sequences). Using the E. coli enzyme as template, a model for the structure of adenylosuccinate synthetase from S. cerevisiae was generated and subsequently refined by molecular dynamics techniques. The resulting three-dimensional structure offers an explanation for the DNA binding activity of the yeast enzyme by revealing a distinct basic region that is not present in the homologous enzymes from other organisms. The model is also in good agreement with biochemical data available for a mutant protein in which Glycine 252 is replaced by Aspartate. On the basis of the model a significant structural distortion near the catalytic center was predicted for this mutant, corresponding well to the enzymatic inactivity observed. The mutant enzyme shows larger structural fluctuations than the wild-type protein according to the results of two independent molecular dynamics simulations.

[Clonal analysis in cells using PCR and laser microdissection]. / Klonalitätsanalysen in Geweben durch PCR und Laser-Mikrodissektion.

Clonality represents one of the hallmarks of neoplastic cell growth. X-chromosomal inactivation patterns have been used to determine clonality in various tumors. This approach is limited by admixture of polyclonal non-tumor stroma cells among which the monoclonal proliferation may be missed. In order to overcome this limitation, we combined a sensitive PCR based DNA analysis with a highly selective microdissection technique using a laser beam. In sections of intraductal mammary carcinomas tumor cell complexes of at least 100 cells were isolated by removing the surrounding stroma by laser irradiation. Thereby, tumor cells could be isolated without contaminating non-neoplastic elements. Clonality in these cells was determined using two X-chromosomal polymorphic sites-phosphoglycerate kinase 1 (PGK1) and human androgen receptor (HUMARA). Control experiments could show the polyclonal nature of the surrounding tissue. Moreover, complete destruction of DNA by laser irradiation was assured. The technique requires a certain amount of cells and DNA in order to avoid artefacts that result from preferential amplification of exclusively one X-chromosomal allele in small samples. We conclude that combination of laser-microdissection with PCR analysis of X-chromosomal inactivation patterns enables the detection of clonal cell populations in heterogeneous tissues. Studies of clonality in borderline cases between reactive and neoplastic proliferations or premalignant lesions are made possible by this technique.

Enzymatic properties and inhibition by single-stranded autonomously replicating sequences of adenylosuccinate synthase from Saccharomyces cerevisiae.

Adenylosuccinate synthase (ASS) from Saccharomyces cerevisiae has been shown to bind specifically to the T-rich side of the autonomously replicating sequence (ARS) core consensus sequence [Zeidler, R., Hobert, O., Johannes, L., Faulhammer, H. & Krauss, G. (1993) J. Biol. Chem. 268, 20191-20197]. We have cloned and sequenced the gene for ASS and have studied in detail the enzymatic properties and DNA-binding activity of ASS. The deduced amino acid sequence of the yeast ASS is highly similar to the same enzymes from other sources from which it is however distinguished by its more basic nature. We show that the enzymatic activity of ASS is inhibited in a highly specific manner by the binding of a 44-base DNA oligonucleotide carrying the ARS core consensus sequence. Other nucleic acids, rNTP and dNTP are not able to mimic the specific inhibitory effect. Single-base substitutions in the ARS core sequence lead to a tenfold reduction in inhibition. The inhibition data corroborate the earlier report on the DNA-binding specificity of this enzyme. The homologous enzymes from Escherichia coli and Dictyostelium discoideum do not show specific binding to single-stranded ARS sequences and their enzymatic activity is not influenced by the presence of a 44-base DNA oligonucleotide carrying the ARS core consensus sequence. Treatment of ASS with alkaline phosphatase leads to a loss of DNA binding and to a loss of the inhibition by DNA of the enzymatic activity which suggests that the DNA-binding activity but not the enzymatic activity may be regulated by the phosphorylation status of the protein.