A progesterone-induced endometrial homolog of a new candidate tumor suppressor, DMBT1

We have previously prepared and characterized a subtracted library enriched for endometrial progesterone (P)-dependent genes in the rhesus monkey. One of the fragment clones (H3) that we selected for sequencing from this library was found to be homologous to human DMBT1, a recently isolated member of the scavenger receptor cysteine-rich superfamily and a new putative tumor suppressor. In this report, we provide evidence that H3 is the rhesus monkey homolog of DMBT1. Additional sequence data of H3 (1071 bp) showed a striking homology with DMBT1 (92% identical). Semiquantitative kinetic PCR of estrogen-dominant vs. P-dominant endometrial complementary DNA populations showed that the H3 gene was up-regulated 5-fold by normal secretory P levels. In situ hybridization with unique probes to H3 confirmed the up-regulation by P in the endometrium and a restricted expression in the stromal compartment. Another recent report suggested the presence of an endometrial tumor suppressor in the same chromosomal region as DMBT1 (10q23-26); deletions in this region were associated with endometrial cancers. Together, these studies potentially provide a molecular link to the protective effect of the action of P on unopposed estrogen exposure in reproductive tract cancers in women.     

Diagnosing breast implant rupture with MR imaging, US, and mammography

A total of 135 symptomatic women with 262 breast implants were examined with magnetic resonance (MR) imaging performed with a body coil, ultrasound (US), or both to determine imaging features of implant rupture. Surgical proof was available for 33 women with 62 implants; 24 were ruptured and 38 were intact. Complicated internal structure was the most reliable predictor of implant rupture: Diffuse low-level echoes were seen on sonograms in 56% of ruptured implants; internal membranes (which correspond to the collapsed implant shell) were seen on MR images in 58% of ruptured implants. Fluid droplets were seen within the silicone in 26% of ruptured implants on MR images. Irregular implant contour can be a sign of rupture but is unreliable. Fluid collections around silicone implants are not a sign of rupture. At present, neither US nor conventional MR imaging with a body coil is sufficiently reliable to advocate routine screening of asymptomatic women with breast implants. Evaluation with MR imaging performed with a surface coil is more reliable.     

Information analysis of Fis binding sites

Originally discovered in the bacteriophage Mu DNA inversion system gin, Fis (Factor for Inversion Stimulation) regulates many genetic systems. To determine the base frequency conservation required for Fis to locate its binding sites, we collected a set of 60 experimentally defined wild-type Fis DNA binding sequences. The sequence logo for Fis binding sites showed the significance and likely kinds of base contacts, and these are consistent with available experimental data. Scanning with an information theory based weight matrix within fis, nrd, tgt/sec and gin revealed Fis sites not previously identified, but for which there are published footprinting and biochemical data. DNA mobility shift experiments showed that a site predicted to be 11 bases from the proximal Salmonella typhimurium hin site and a site predicted to be 7 bases from the proximal P1 cin site are bound by Fis in vitro. Two predicted sites separated by 11 bp found within the nrd promoter region, and one in the tgt/sec promoter, were also confirmed by gel shift analysis. A sequence in aldB previously reported to be a Fis site, for which information theory predicts no site, did not shift. These results demonstrate that information analysis is useful for predicting Fis DNA binding.     

Effect of vitamin B6 supplementation in McArdle's disease: a strategic case study

A patient-blind study into the effect of a 10-week cessation of long-term vitamin B6 supplementation on B6 status and performance in McArdle's disease is reported. Muscle performance was assessed both subjectively and objectively by an ischaemic fatiguing protocol of the adductor pollicis muscle. Nine weeks after withdrawal of supplementation, vitamin B6 status had changed from adequacy to inadequacy and the force loss during the ischaemic fatiguing protocol had increased at all frequencies studied. The patient reported decreased exercise tolerance after 7 weeks and by the tenth week was experiencing an increase in muscle cramps. Vitamin B6 status and muscle performance may be linked in McArdle's disease and there is potential for enhancement of performance by B6 supplementation.     

The large window ductus: a surgical trap

A rare window type of patent ductus arteriosus is reported that was large (15 mm in maximal transverse dimension) but had virtually no length and hence was externally invisible. The smaller aortic isthmus (4 mm in diameter), which was intrapericardial, was mistaken for the ductus and was inadvertently clip-occluded, leading to death. After a specific diagnosis is made, the large window ductus should be patched on cardiopulmonary bypass with a transpulmonary approach.     

Nitric oxide synthase inhibitor, aminoguanidine, reduces inflammation and demyelination produced by Theiler''s virus infection

The paper presents current methods of treatment of anxiety disorders: psychotherapeutic and pharmacologic. Therapy of panic disorder differs from therapy of generalised anxiety disorder, the two main categories of anxiety disorders. An anxiety often is present in somatic diseases. Benzodiazepines are the most often used medicines against anxiety.     

Medium-intensity light produces circadian rhythm adaptation to simulated night-shift work

The study presented here compared the acute performance-impairing, subject-rated, and observer-rated effects of quazepam (15, 30, and 45 mg), triazolam (0.1875, 0.375, and 0.5625 mg), zolpidem (7.5, 15, and 22.5 mg), and placebo in nine healthy, non-drug-abusing humans. Quazepam, a trifluoroethylbenzodiazepine, was chosen for study because, when compared with triazolam, a triazolobenzodiazepine, it is a relatively weak benzodiazepine-receptor ligand, and it may bind selectively to the BZ1 benzodiazepine-receptor subtype. Zolpidem, an imidazopyridine, is the most commonly prescribed hypnotic and was chosen for study because it is biochemically distinct from benzodiazepine hypnotics and also purportedly binds selectively to the BZ1 benzodiazepine-receptor subtype. Triazolam was chosen as the reference compound because it binds nonselectively to BZ1 and BZ2 benzodiazepine-receptor subtypes. Triazolam, zolpidem, quazepam, and placebo were administered orally in a double-blind, crossover design. Triazolam and zolpidem produced orderly dose- and time-related impairment of learning, performance, and recall, and produced sedative-like subject- and observer-rated drug effects. The behavioral pharmacologic profile of zolpidem and triazolam was indistinguishable in that at peak effect, the absolute magnitude of drug effect was comparable across the various measures. Quazepam, by contrast, did not impair performance on any task to a statistically significant degree, nor did it produce significant sedation as measured by subject- and observer-rated drug-effect questionnaires. Whether these effects are a result of the unique benzodiazepine-receptor binding profile of quazepam or the testing of insufficient dosages is unknown. Future research could extend the findings presented here by testing higher dosages of quazepam.