A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease.

Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR. All eight genes are involved in the early development of the enteric nervous system, and most act through two distinct biochemical pathways mediated by RET and EDNRB. Mutations in RET and EDNRB account for up to 50% and 5% of HSCR cases in the general population, respectively. Interaction between these two signaling pathways could modify RET expression and, therefore, HSCR phenotype. Here, we report the case of a 1-year-old Taiwanese boy who presented with abdominal distension since birth and bilious vomiting after feeding. HSCR (short-segment type) was diagnosed based on X-ray, lower gastrointestinal series and biopsy findings. Mutation analysis revealed a heterozygous T>C missense mutation in exon 1 of the EDNRB gene, that substitutes the highly conserved cysteine-90 residue in the extracellular domain of the G protein-coupled receptor with an arginine residue (C90R). No RET gene mutation was detected in this patient.     

A prospective treatment study of premenstrual symptoms using a triphasic oral contraceptive.

Eighty-two women with complaints of moderate to severe premenstrual symptoms were recruited for a double-blind, controlled trial of a triphasic oral contraceptive (o.c.). Subjects made daily ratings of symptoms for at least one baseline cycle and were then randomly assigned to receive either placebo or o.c. for three months. Twenty-three women dropped out of the study (18 o.c., 5 placebo), 13 failed to show prospective confirmation of moderate to severe premenstrual symptoms, and one placebo subject had an anovulatory cycle. Forty-five women with prospectively-confirmed premenstrual changes (20 o.c., 25 placebo) completed the study. Premenstrual breast pain and bloating were significantly reduced with active treatment compared to placebo (p less than 0.03) but there were no beneficial effects of the o.c. over placebo for any of the mood symptoms. Women who received o.c.s reported decreased sexual interest after starting treatment and this effect was independent of any adverse influence on mood.     

Detrimental effects of cigarette smoking on lower extremity wound healing

The authors review the detrimental effects of cigarette smoke and its constituents to normal physiology. Nicotine and carbon monoxide, principle components of cigarette smoke appear to exert an influence on wound repair by inhibiting epithelization, damaging blood cellular components, and creating a cellular hypoxia. Recommendations for perioperative cessation of smoking by the patient are made.     

Latex condom deterioration accelerated by environmental factors: I. Ozone

Commercial non-lubricated latex condoms were unpackaged and exposed in an environmental chamber to ozone levels (0.3 ppm) commonly present in urban smog conditions. Deterioration was observed by scanning electron microscopy after 18 hours exposure. Loss of mechanical strength was quantitated by measurement of the air pressures necessary to burst the condom and volumes at burst. After 24 hours exposure to ozone the latex surface was covered with craters and after 48 hours the pressure required to burst the condom was 44% that of control samples. Data suggest the need for study of the effectiveness of lubrication and packaging in protecting condoms from environmental factors which may accelerate deterioration.     

Prion protein is ubiquitinated after developing protease resistance in the brains of scrapie-infected mice

Although the key event in the pathology of prion diseases is thought to be the conversion of cellular prion protein (PrP(C)) to the protease-resistant scrapie species termed PrP(Sc), the factors that contribute to neurodegeneration in scrapie-infected animals are poorly understood. One probable determinant could be when the accumulation of PrP(Sc) in infected brain overwhelms the ubiquitin-proteasome system and triggers the degenerative cascade. In the present study, it was found that in mouse brains infected with the ME7 scrapie strain, the level of ubiquitin protein conjugates increased significantly at approximately 144 days post-infection (pi) when clinical signs first become apparent. This elevation correlated with the detection of protease-resistant PrP(Sc) and a decline in two endopeptidase activities associated with proteasome function. However, ubiquitination of PrP was only detected at the terminal stage, 3 weeks after the development of clinical symptoms (approximately 165 days pi). These results suggest that ubiquitination of PrP is a late event phenomenon and this conjugation occurs after the formation of protease-resistant PrP(Sc). Whether this post-translational modification and the impairment of proteasome function are pivotal events in the pathogenesis of prion diseases remains to be determined.     

Malignancy may adversely influence the quality and behaviour of oocytes

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age- matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.      

Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition

Background  

The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease.