Comparisons of the protein sequences and gene structures of the known creatine kinase isoenzymes and other guanidino kinases revealed high homology and were used to determine the evolutionary relationships of the various guanidino kinases. A 'CK framework' is defined, consisting of the most conserved sequence blocks, and 'diagnostic boxes' are identified which are characteristic for anyone creatine kinase isoenzyme (e.g. for vertebrate B-CK) and which may serve to distinguish this isoenzyme from all others (e.g. from M-CKs and Mi-CKs). Comparison of the guanidino kinases by near-UV and far-UV circular dichroism further indicates pronounced conservation of secondary structure as well as of aromatic amino acids that are involved in catalysis.

Amino Acid Sequence↗

PubMedDate not supplied

Significance of respiratory syncytial virus (RSV) infection in the 1st year of life.

BACKGROUND: In this study we investigated the frequency, symptoms and predisposing factors of respiratory syncytial virus (RSV) infection during the 1st year of life in infants with obstructive airway disease in comparison with infants without airway disease. PATIENTS: We enrolled 216 infants in their 1st year of life, who were hospitalized because of obstructive airway disease. As an age- and sex-balanced control group, we examined 133 infants hospitalized for other reasons than airway disease. METHOD: A deep pharyngeal swab was taken from all infants and immediately examined for the presence of RSV antigen by using an enzyme immunoassay (Directigen). Patient data were surveyed by a questionnaire. RESULTS: The frequency of RSV infections among infants with obstructive airway disease (34.3%; n = 74) differed significantly from the control group (15%; n = 20; p < 0.01). The frequency of RSV-infected infants with obstructive airway disease decreased with age ranging from 39.1% in trimenon I to 29.0% in trimenon IV. This trend was not observed in the control group. With respect to clinical symptoms and risk factors, there were no differences between RSV-infected versus noninfected infants. CONCLUSION: RSV is an important agent causing lower obstructive airway disease (34.3% of all patients). There are no specific symptoms that can be used for diagnosing RSV infection. In order to prevent other patients on the ward from contracting nosocomial RSV infection and in the light of therapeutic options, one should test newly admitted patients presenting with symptoms of an obstructive airway disease for RSV antigen. On a ward with high-risk patients, we would recommend the use of an RSV test for all new patients.

Age Factors↗

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Umbilical vein and placental vessels from newborns with hereditary haemorrhagic telangiectasia type 1 genotype are normal despite reduced expression of endoglin.

Hereditary haemorrhagic telangiectasia, HHT, is an autosomal dominant disorder that affects approximately 1 in 8000 people. HHT1 is associated with mutations in the ENG (Endoglin) gene and with haploinsufficiency. The disorder is characterized by focally dilated vessels, which can lead to arteriovenous malformations and serious complications even in young children. In the current study, umbilical cord and placenta samples from newborns with ENG mutations were analyzed to estimate the level of corresponding protein and look for potential vascular dysplasia. We confirmed, using metabolic labelling and flow cytometry, that endoglin levels were significantly reduced to median values of 47 per cent (range 32-56 per cent) and 58 per cent (46-90 per cent), respectively, in human umbilical vein endothelial cells derived from newborns with ENG mutations (HHT1 group; n=18) relative to samples from newborns shown not to have the familial mutation (non-HHT group). We also quantified the relative expression of endoglin by estimating the endoglin/PECAM-1 staining ratio in tissue sections. We observed significantly lower values in the HHT1 group, compared to the non-HHT group for the umbilical vein (n=9; median 0.6 vs 0.9; ranges 0.2-1.0 and 0.5-1.5) and for placental stem villus vessels (n=9 and 10; median 0.42 vs 0.93; ranges 0.24-0.58 and 0.56-1.18). No differences in the estimated umbilical vein cross-sectional area and in the proportion of vessels present in placental villi were observed in sections from the HHT1 group relative to the non-HHT group. Thus, blood vessels from HHT1 individuals are maintained intact in the umbilical vein and placenta during pregnancy and delivery, despite a significant reduction in endoglin expression.

Antigens, CD↗

PubMedDate not supplied

Educational support groups of patients with ankylosing spondylitis: a preliminary report.

Educational support groups (ESGs) for patients with ankylosing spondylitis were found to significantly (P less than 0.01) increase knowledge about the disease and its treatment. Compliance of participants with their prescribed exercise programs was improved, although the improvement did not achieve statistical significance. Compliance with prescribed application of heat to joints was not changed. Control patients showed no substantial changes in knowledge or compliance. Although analysis of pretest and posttest responses on a questionnaire did not indicate that the ESGs enhanced the patients' ability to cope with ankylosing spondylitis or their perception of the adequacy of family relationships with regard to the disease, verbal feedback concerning these areas was positive in most cases. Patients did not express negative feelings about the thought of meeting another person with ankylosing spondylitis whose disease was less severe or whose coping ability was greater or less than their own. Two patients who initially believed that they would feel threatened if they were to meet a more severely ill patient relinquished that concern after ESG participation.

Adult↗

PubMedDate not supplied

The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity.

Ha-ras is a member of a multigene family in man which encode highly related proteins of 189 amino acids (p21). In vitro, ras proteins bind GTP, and p21 mutants with treonine at position 59 autophosphorylate at that residue. Mutation (at amino acids 12 or 61) and elevated expression of ras genes result in cell transformation in culture, and are also observed in many types of human tumours. Normal and mutant transforming ras proteins show no differences in localization, lipidation or GTP binding. However, mutations at position 12 in recombinant (Thr 59) p21 molecules were observed to affect autophosphorylation. We have expressed the full-length normal and T24 transforming (Gly----Val at position 12) Ha-ras proteins in Escherichia coli and have purified them to homogeneity (ref. 19 and M.G. et al., in preparation); these proteins bound GTP with approximately molar stoichiometry and with an affinity comparable to partially purified mammalian proteins. Microinjection of the T24 protein into quiescent rodent fibroblasts resulted in a rapid alteration in cell morphology, stimulation of DNA synthesis and cell division; in contrast, little response was observed with the normal protein. We now report that the normal ras protein has an intrinsic GTPase activity, yielding GDP and Pi. In contrast, the T24 transforming protein is reduced 10-fold in this activity. We suggest that this deficiency in GTPase is the probable cause for the transforming phenotype of the T24 protein.

Amino Acid Sequence↗

PubMedDate not supplied

Sympathetic inhibition with methyldopa in heart failure.

The hypothesis that withdrawal of increased sympathetic activity may be beneficial in heart failure was tested by administration of the centrally acting adrenergic inhibitor methyldopa. Fourteen subjects with chronic, stable New York Heart Association Functional Class 2 or 3 heart failure receiving digitalis and diuretics were randomized to methyldopa (n = 8) 500-1000 mg daily or placebo (n = 6). Clinical, hemodynamic, neurohumoral, and platelet alpha 2-receptor effects were studied after chronic (3 weeks) administration. Sympathetic inhibition did not alter symptom status or exercise duration but reduced plasma norepinephrine concentration during exercise and permitted the same level of exercise to be attained at a lower pressure-rate product, indicating reduced myocardial oxygen consumption. Left ventricular ejection fraction and stroke volume tended to increase, and systemic vascular resistance tended to decrease during exercise after methyldopa administration, suggesting enhanced vasodilation. Upright plasma renin activity increased from 8.2 +/- 2.2 to 13.3 +/- 3.0 ng/nl/h (p = 0.03) after methyldopa, but plasma antidiuretic hormone concentration changed insignificantly. In a subset of patients, platelet alpha 2-receptor density and affinity were unaltered. Renal function was also unchanged. Thus, sympathetic inhibition induced by methyldopa in selected patients with chronic, stable heart failure does not worsen symptom status or exercise performance, and may produce a beneficial effect by withdrawal of excess sympathetic activity with reduction of plasma norepinephrine levels.

Adult↗

PubMedDate not supplied

An evaluation of community-based mental health programs: long-range effects.

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Community Mental Health Services↗