Smoking and nicotine addiction: a pediatric epidemic with sequelae in adulthood

Pediatric addiction to nicotine from cigarette smoking is a major public health problem, extracting a tremendous societal toll in terms of human suffering, a loss of future productivity, and the consumption of scarce health care resources. Teenagers smoke 1.1 billion packs of cigarettes yearly and will account for more than $200 billion in future health care costs. Recent behavioral studies confirm nicotine's ability to induce in adolescents both the tolerance and abstinence phenomena typical of other addicting substances. A range of adverse health effects, first detectable in adolescent cigarette smokers, extend into adulthood. Through the effects of environmental smoke or smoking during pregnancy, adolescent smokers affect not only their own health, but that of friends, family members, and even their own fetuses and children. Additional research into effective prevention and smoking cessation programs is urgently needed to forestall the ravaging of yet another generation by this preventable and deadly habit.     

Self-incompatibility alleles from Physalis: implications for historical inference from balanced genetic polymorphisms

Balanced genetic polymorphism has been proposed as a source from which to infer population history complementary to that of neutral genetic polymorphism, because genetic polymorphism maintained by balancing selection permits inferences about population size over much longer spans of time. However, empirical data for both S genes and major histocompatibility complex genes do not fit expectations of coalescent theory. Species-specific gene genealogies have longer terminal branches than expected, indicating an apparent slowdown in the origination of new alleles. Here, we present evidence that divergent S alleles were selectively maintained in Physalis cinerascens during a reduction in population size, generating longer terminal branches in the S gene genealogy relative to the congener Physalis crassifolia. Retention of divergent alleles during reduction in the number of alleles violates assumptions of the coalescent model used to estimate effective population size. Recent theoretical and empirical results are consistent with the proposition that nonrandom sorting is a general property of balanced genetic polymorphisms, suggesting that studies of balanced polymorphism that infer the absence of population bottlenecks may overestimate effective population size.     

Purification and properties of mycobacterial GDP-mannose pyrophosphorylase

The enzyme that catalyzes the formation of GDP-d-mannose from GTP and alpha-d-mannose-1-P was purified about 2300-fold to near homogeneity from the soluble fraction of Mycobacterium smegmatis. At the final stage of purification, a major protein band of 37 kDa was observed and this band was specifically labeled, and in a concentration-dependent manner, by the photoaffinity probe 8-N3-GDP[32P]-d-mannose. The purified enzyme was stable for several months when kept in the frozen state. The 37-kDa band was subjected to protein sequencing and one peptide sequence of 25 amino acids showed over 80% identity to GDP-mannose pyrophosphorylases of pig liver and Saccharomyces cerevesiae. In contrast to some other bacterial GDP-mannose pyrophosphorylases, the mycobacterial enzyme was not multifunctional and did not have phosphomannose isomerase or phosphoglucose isomerase activity. Also, in contrast to the pig liver enzyme which uses mannose-1-P or glucose-1-P plus GTP to synthesize either GDP-mannose or GDP-glucose, the mycobacterial enzyme was specific for mannose-1-P as the sugar phosphate substrate. The enzyme was also relatively specific for GTP as the nucleoside triphosphate substrate. ITP was about 18% as effective as GTP, but ATP, CTP, and UTP were inactive. The activity of the enzyme was inhibited by GDP-glucose and glucose-1-P, although neither was a substrate for this enzyme. The pH optimum for the enzyme was 8.0, and Mg2+ was the best cation with optimum activity at about 5 mM. This enzyme is important for producing the activated form of mannose for formation of cell wall lipoarabinomannan and various mannose-containing glycolipids and polysaccharides.     

Angiotensin-converting enzyme gene polymorphism and cardiovascular disease

1. The crucial role played by the renin-angiotensin-aldosterone system in the cardiovascular system and the immense therapeutic potential of angiotensin-converting enzyme inhibitors and, more recently, angiotensin II receptor blocking agents, in both heart failure and post-myocardial infarction is becoming increasingly evident. Polymorphisms within the genes controlling this enzyme system are candidates for the elucidation of the pathogenesis of cardiovascular disease and this link is both intriguing and provocative. Recently, an association between a polymorphism of the angiotensin-converting enzyme gene and phenotypic expression of cardiovascular disease, namely myocardial infarction, was reported. Since then, several small case-controlled studies have confirmed an association with manifestations of ischaemic heart disease or various other cardiac end-points. However, in a large prospective study the angiotensin-converting enzyme gene conferred no appreciable risk. 2. Our aim was to review the evidence that links polymorphisms of the angiotensin-converting enzyme gene with cardiovascular disease. We searched the Medline database (1990-1997) using the key words myocardial infarction, ischaemic heart disease, angiotensin-converting enzyme and polymorphisms and performed a search of the reference citation of relevant articles. We selected clinical studies on cardiovascular disease related to the angiotensin-converting enzyme genotype. 3. Taken together, the available evidence supports the notion that the DD-angiotensin-converting enzyme genotype adversely influences specific cardiovascular diseases but appears to do so in specific geographical areas and in particular patient subgroups. It is not yet known whether it does this through an interaction with other genes or by as yet unexplained biochemical mechanisms. 4. We should regard the current data with the angiotensin-converting enzyme genotype as an intriguing clue in the pathogenesis of cardiovascular disease. However, the main factor against this potential benefit is that the impact of the DD genotype appears to be small and its clinical manifestations rather heterogeneous.     

Long-term intravesical oxybutynin chloride therapy in children with myelodysplasia

PURPOSE: We evaluated the clinical use of long-term intravesical oxybutynin chloride in the treatment of neurogenic bladder dysfunction in children with myelodysplasia who could not tolerate oral anticholinergics. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients recommended for intravesical oxybutynin chloride therapy. A total of 12 girls and 18 boys 1 to 17 years old was recruited for study. Oxybutynin chloride (5 mg.) was instilled 2 times daily and pretreatment cystograms were compared to followup urodynamic studies. Duration of therapy was 2 to 26 months (mean 13, median 12). RESULTS: Mean total capacity plus or minus standard deviation increased from 209 +/- 103 to 282 +/- 148 ml. (p < 0.01), mean safe capacity increased from 157 +/- 105 to 234 +/- 147 ml. (p < 0.01) and mean age adjusted safe capacity increased from 76 +/- 36 to 115 +/- 62%. Of the 29 patients who were incontinent 3 (10%) achieved continence and 19 (65%) reported a decreased use of sanitary pads. None of the patients had systemic side effects related to intravesical treatment. CONCLUSIONS: We believe that intravesical oxybutynin chloride is a viable treatment option for patients with myelodysplasia in whom oral therapy fails.