Emergence and scattering of multiple neurofibromatosis (NF1)-related sequences during hominoid evolution suggest a process of pericentromeric interchromosomal transposition

Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase activating protein family and is considered to be a tumor suppressor gene. Its very high rate of de novo mutation in humans led us to study a specific feature of this gene: the presence of numerous NF1-related sequences. According to our results, the human genome contains at least 11 NF1-related sequences, nine of which are scattered near centromeric sequences of seven different chromosomes. These NF1-related sequences, whose extent is quite varied according to loci, are unprocessed copies of the NF1 gene, and bear numerous mutations. A phylogenetic analysis of the six largest sequences indicates that they are all derived from a common ancestor, which would have appeared 22-33 million years ago, and was subsequently duplicated several times during hominoid evolution. The most recent duplication and interchromosomal transposition occurred in the last million years suggesting that the process could still be ongoing. Intriguing similarities between the evolution of alpha- satellite DNA and NF1-related sequences suggest the involvement of a common genetic mechanism for the generation and pericentric spreading of these NF1 partial copies.      

DISEASE-MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID ARTHRITIS: CURRENT CONCEPTS

SUMMARY Disease-modifying antirheumatic drugs are used in virtually all patients with established rheumatoid arthritis. An increasingly large number of new drugs is now available. Furthermore, old therapies are being used in novel ways. Treatment is now begun earlier and patients are rarely left untreated. This report summarises recent developments regarding the drugs currently in use and those that may be available in the near future.     

An analysis of the action of an analogue of almitrine bismesylate in the rat model of hypoxic lung disease.

Chronically hypoxic (CH) and normoxic control rats were used to assess the action of S9581, a water-soluble analogue of almitrine bismesylate. S9581 increased ventilation (Ve) by 34% in control and 20% in CH rats. During acute hypoxia Ve was raised and S9581 caused a further increase of 20% in both groups. Low doses of S9581 and almitrine enhanced the hypoxic ventilatory response in CH rats while high doses depressed it in both groups. Effects of S9581 on the pulmonary circulation were assessed in the isolated perfused lung of rats. As with almitrine a complex relationship of dose-dependent vasoconstriction and dilatation was revealed. In low doses, S9581 enhanced the hypoxic pulmonary vasoconstrictor response to 2% O2 whilst this was attenuated by high doses in both control and CH rats. S9581 seemed to act like almitrine bismesylate on both the ventilation (peripheral chemoreceptor) and the pulmonary circulation. For studying almitrine-like activity the water solubility of S9581 provides considerable advantages for the researcher.     

Multiple Correlates of Cigarette Use Among High School Students

A cross-sectional survey research design measured factors related to cigarette use among 2,212 senior high school students. Results showed 14.3% of the sample smoked cigarettes at least occasionally, with 5.3% reporting they were daily smokers. About 12.8% indicated they were ex-smokers. Males and females smoked at almost equal rates, and the percentage of 10th grade student smokers was slightly higher (16.4%) than the percentage of juniors and seniors who smoked. Approximately 22% of Hispanic students, 15% of Caucasian students, and 4.5% of African-American students reported smoking cigarettes at least occasionally. An initial regression analysis used 21 variables to predict cigarette smoking. A more parsimonious regression model (R2 = .28), using variables from the initial regression analysis with significance levels of .01 or less, indicated the most important predictors of cigarette use were ethnic group, attitude toward females who smoke, close friends' use of cigarettes, personal use of marijuana, best friend's use of cigarettes, personal use of alcohol, and school self-esteem. Implications for school health programs are addressed.     

Psychological outcomes of a pulmonary rehabilitation program

This study assessed physiologic, psychological, and cognitive functioning in outpatients with COPD. Sixty-four subjects, 53 to 82 years of age, participated in the 30-day exercise rehabilitation program. The program consisted of exercise, education and psychosocial counselling. Participants were assessed prior to beginning the program and at the end of 30 days. Assessments at both times included physiologic functioning (bicycle ergometry testing, pulmonary function tests, 12-min walk), psychological well-being (anxiety, depression, psychiatric symptoms, perceived well-being) and an abbreviated neuropsychological test battery. Results indicate significant improvement in physical endurance and pulmonary function, significant reductions in symptoms of depression and anxiety, and improvement in measures of general well-being and neuropsychological functioning. The study suggests that exercise rehabilitation of older adults with COPD contributes not only to improvements in physical functioning and endurance, but also to enhanced cognitive functioning and psychological well-being.