Novel deletion mutations of the DAX1 (NR0B1) gene in two Taiwanese families with X-linked adrenal hypoplasia congenita

OBJECTIVE: To analyze the DAX1 (NROB1) gene in Taiwanese families with adrenal hypoplasia congenita. PATIENTS AND METHODS: Two unrelated Taiwanese patients were followed up at our pediatric endocrine clinic. Both patients presented with adrenal crisis. One patient entered puberty spontaneously. However, arrest of puberty was noted in the following years and hypogonadotropic hypogonadism was confirmed by GnRH test. The other patient was still prepubertal. Sequencing of the DAX1 (NROB1) gene was carried out in both patients and their respective family members. RESULTS: Two different novel mutations were identified. The first patient had one base (G) deletion at nucleotide 159, resulting in a frame-shift and a premature stop codon at position 84. The other patient had one base (G) deletion at nucleotide 831, leading to a frameshift and a premature stop codon at position 371. Family studies revealed that their mothers and sisters were heterozygotes for the mutations while their maternal grandmothers did not carry the mutations. CONCLUSIONS: Two Taiwanese patients with adrenal hypoplasia congenita were detected to have novel mutations of the DAX1 (NR0B1) gene. Family studies suggested that such mutations resulted from de novo mutation of the DAX1 (NROB1) gene in their mothers. These data indicate that molecular analysis of the DAX1 (NR0B1) gene is important for the diagnosis and genetic counseling of children with primary adrenal insufficiency.     

Neonatal autoimmune disease: influence of CD4+ CD25+ regulatory T cells

Although previous studies have emphasized the tolerogenic property of murine neonatal immune system, recent studies indicate that neonatal mice are prone to autoimmune disease. This chapter will summarize the evidence for neonatal propensity to autoimmune ovarian disease (AOD) and describe the new finding that autoantibody can trigger a T cell-dependent autoimmune disease in neonatal but not adult mice. Based on depletion or addition of the CD4+ CD25+ T cells, disease resistance of older mice is explicable by the emergence of CD4+ CD25+ regulatory T-cell function after day 5, whereas disease susceptibility is associated with resistance to regulation by CD4+ CD25+ T cells.     

Violations of exhibiting and FDA rules at an American Psychiatric Association annual meeting

We conducted a cross-sectional study of all exhibit booths for the 24 pharmaceutical companies at the 2002 American Psychiatric Association (APA) convention. We collected and categorized one of each item distributed by the companies at each booth. A total of 268 items were collected from 24 companies (median=8). The most common categories of items were "reprints or pamphlets" (37%) and "noneducational gifts" (27%), including music CDs and invitations to dinners and museums. There were a total of 16 violations of the APA's own exhibit rules: eight companies had one violation and two companies had four violations. Four companies engaged in FDA-prohibited off-label promotion; one also violated the APA code. Over half of all companies (54%) were in violation of either APA rules or FDA regulations. The APA's voluntary code has failed to adequately reduce inappropriate promotional activity at the annual APA meeting.     

Hyperbaric oxygen protects against lipopolysaccharide-stimulated oxidative stress and mortality in rats

Free radicals and proinflammatory mediators have been implicated in the pathogenesis of endotoxic shock, a disease with high mortality caused by Gram-negative bacterial endotoxin. Hyperbaric oxygen is used as an adjuvant therapy for various inflammatory diseases and shows beneficial effects in lipopolysaccharide-induced shock syndrome. However, the underlying mechanisms for these effects are still to be defined. In this study, we investigated the effect of hyperbaric oxygen on inflammatory mediators, free radicals, and mortality in endotoxic rats. Wistar-Kyoto rats were injected with lipopolysaccharide (10 mg/kg) and then exposed to aminoguanidine, an inhibitor of inducible nitric oxide (NO) synthase (bolus injection 2 h after lipopolysaccharide), or hyperbaric oxygen (2 ATA for 60 min 1, 4, 9, and 24 h after lipopolysaccharide). Plasma tumor necrosis factor alpha (TNF-alpha), NO, and superoxide anion were detected and the vasorelaxation response and survival rate were assessed. The results demonstrated that increases in plasma TNF-alpha and NO, and the vasohyporeactivity induced by lipopolysaccharide treatment were significantly inhibited by hyperbaric oxygen and aminoguanidine. Mortality and vascular superoxide anion production of lipopolysaccharide treatment were also markedly reduced by hyperbaric oxygen treatment, but were not restored by aminoguanidine. None of the parameters was changed by hyperbaric oxygen treatment alone. Thus, repeated hyperbaric oxygen exposure significantly attenuated the inflammatory mediators, free radicals, and mortality in endotoxic rats.     

Molecular and epidemiologic analysis of a county-wide outbreak caused by <Emphasis Type="Italic">Salmonella enterica</Emphasis> subsp. <Emphasis Type="Italic">enterica</Emphasis> serovar Enteritidis traced to a bakery

Background  

An increase in the number of attendees due to acute gastroenteritis and fever was noted at one hospital emergency room in Taiwan over a seven-day period from July to August, 2001. Molecular and epidemiological surveys were performed to trace the possible source of infection.