Formation and stability of linear plasmids in a recombination deficient strain of yeast

Summary Natural termini from macronuclear DNA of the ciliated protozoans Tetrahymena thermophila and Oxytricha fallax can support telomere formation in yeast. However, plasmids carrying these ciliate termini are modified by the addition of DNA which hybridizes to the synthetic oligonucleotide poly [d(C-A)], a sequence which also hybridizes to terminal restriction fragments from yeast chromosomes but not to Tetrahymena or Oxytricha macronuclear DNAs. Thus, in yeast, the creation of new telomeres on ciliate termini involves the acquisition of yeast-specific terminal sequences presumably by either recombination or non-templated DNA synthesis. The RAD52 gene is required for the majority of yeast mitotic and meiotic recombination events. Moreover, the absence of an active RAD52 gene product results in high rates of chromosome loss. Here we demonstrate that terminal restriction fragments from Tetrahymena macronuclear ribosomal DNA (rDNA) support the formation of modified telomeres in a yeast strain carrying a defect in the RAD52 gene. Moreover, linear plasmids bearing these modified ciliate termini are stably propagated in rad52 ^– cells.     

Neuropathies in the rheumatoid patient: a case of the heavy hand

Rheumatoid Arthritis (RA) is a common inflammatory arthritis' with pain and loss of function among its most disabling symptoms. These are mostly secondary to inflammation or mechanical damage to the joints. However it is also important to consider disease complications as a cause of symptoms, especially when the response to treatment is suboptimal. We report an RA patient whose symptoms were resistant to standard therapy, and were actually due to peripheral neuropathy.     

Physiotherapists in private practice in France

In France, most of the physiotherapists providing ambulatory care are in private practice: they are paid on a fee-for-service basis by the patients who are reimbursed by the Sickness Insurance Fund. A survey on a sample of 2000 (out of 40,000) private practitioners was undertaken in early 2004. As concerns their workload, only 4% think that it is "not sufficient" whereas 66% estimate it "certainly sufficient". Such a feature is noteworthy, as private practitioners are most often fearful of lack of work. In the coming years, one physiotherapist out of 10 envisages to increase his workload, whereas 27% are in favour of a reduction. Furthermore, the survey shows that more than one third of private physiotherapists plan to offer to patients services which are not listed in the contractual agreement document signed by their profession and the Sickness Insurance Fund. The trend is most noticeable among the young practitioners. As the feeling of medical doctors shortage is currently widespread in France, the public debates are focused on the issue of task delegation. After the survey, 54% private physiotherapists are in favour of task delegation, 24% have an opposite opinion and 22% do not express a clear-cut position. However, an in-depth analysis of the written answers to the question shows that a large majority do not accept to replace medical doctors for performing the tasks which are of a subordinate level, are not significant or are time-consuming (e.g. filling out the administrative forms). The question of vocabulary is fundamental in the matter. Moreover, a process of task delegation implies that certain tasks carried out by an overburdened profession are transferred to an other profession less heavily surcharged. Is it the case of French private physiotherapists whose two thirds declare that "their workload is certainly sufficient"?     

Fluconazole prophylaxis prevents invasive fungal infection in high-risk, very low birth weight infants

OBJECTIVES: To evaluate the benefit of fluconazole prophylaxis in preventing invasive fungal infection in very low birth weight (VLBW) infants with central vascular access. STUDY DESIGN: A 3-year baseline period (1998 to 2000) was compared with a subsequent 3-year period (2001 to 2003) during which a different protocol for preventing invasive fungal infection was used. All infants with a birth weight < 1500 g and with central vascular access were eligible for the study. Fluconazole (Diflucan R) was administered for 28 days at a dose of 6 mg/kg every third day during the first week and daily after the first week. RESULTS: There were no significant differences between the baseline and the fluconazole groups in demographic characteristics or risk factors for fungal infection. Fungal infection developed in 9 of the infants in the baseline group and in none of those in the fluconazole group (P=.003). A trend of decreasing mortality rate between the 2 groups (12.6% vs 8.1%; P=.32) was observed but was not statistically significant. No adverse effects of fluconazole therapy were documented. CONCLUSIONS: Fluconazole prophylaxis appeared to be beneficial in preventing invasive fungal infection in VLBW infants.     

Nicotine addiction and comorbidity with alcohol abuse and mental illness

The World Health Organization estimates that one-third of the global adult population smokes. Because tobacco use is on the rise in developing countries, death resulting from tobacco use continues to rise. Nicotine, the main addictive component of tobacco, initiates synaptic and cellular changes that underlie the motivational and behavioral alterations that culminate in addiction. Nicotine addiction progresses rapidly in adolescents and is most highly expressed in vulnerable people who have psychiatric illness or other substance abuse problems.     

Analysis of genetic polymorphisms in acetylcholinesterase as reflected in different populations

Acetylcholinesterase (AChE) plays a crucial physiological role in termination of impulse transmission at cholinergic synapses through rapid hydrolysis of acetylcholine. In addition, it was implicated in amyloid plaque formation, a hallmark of Alzheimer's disease (AD), and most of the drugs used in AD treatment are AChE inhibitors. Thus ACHE is an obvious candidate gene for pharmacogenetic study of AD treatment. However, AChE is a highly conserved molecule, and only a few naturally occurring genetic polymorphisms have been reported in the human gene. The goals of this study were to make a systematic effort to identify natural single nucleotide polymorphisms (SNPs) in the human ACHE gene, and to reveal their population specific architecture. To this end, the genomic coding sequences for AChE of 96 unrelated control individuals from three distinct ethnic groups, African Americans, Ashkenazi Jews and Israeli Arabs, were analyzed. Thirteen ACHE SNPs were identified, ten of which are newly described, and five of which should produce amino-acid substitutions (Arg34Gln, Gly57Arg, Glu344Gly, His353Asn and Pro592Arg). Population frequencies of 11 of the 13 SNPs were established in four different populations, African Americans, Ashkenazi Jews, Sephardic Jews and Israeli Arabs; 17 haplotypes and 5 ethno-specific alleles were identified, and a cladogram of ACHE haplotypes was constructed. Among the SNPs resulting in an amino-acid substitution, three are within the mature protein, mapping on its external surface; they are thus unlikely to affect its catalytic properties, yet could have antigenic consequences or affect putative protein-protein interactions. Furthermore, the newly identified SNPs open the door to a study of the possible association of AChE with deleterious phenotypes - such as adverse drug responses to AChE inhibitors employed in treatment of AD patients and hypersensitivity to pesticides.     

New insight into the pathophysiology of severe hypothyroidism in an infant with multiple hepatic hemangiomas

We report on an infant with severe acquired hypothyroidism resulting from both increased activity of type 3 iodothyronine deiodinase and increased production of TSH-like hormone from hepatic hemangiomas. The combination of these two mechanisms in a patient with hepatic hemangiomas has not been reported previously.