11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction

The evolutionary theory of aging predicts that the equilibrium gene frequency for deleterious mutations should increase with age at onset of mutation action because of weaker (postponed) selection against later-acting mutations. According to this mutation accumulation hypothesis, one would expect the genetic variability for survival (additive genetic variance) to increase with age. The ratio of additive genetic variance to the observed phenotypic variance (the heritability of longevity) can be estimated most reliably as the doubled slope of the regression line for offspring life span on paternal age at death. Thus, if longevity is indeed determined by late-acting deleterious mutations, one would expect this slope to become steeper at higher paternal ages. To test this prediction of evolutionary theory of aging, we computerized and analyzed the most reliable and accurate genealogical data on longevity in European royal and noble families. Offspring longevity for each sex (8409 records for males and 3741 records for females) was considered as a dependent variable in the multiple regression model and as a function of three independent predictors: paternal age at death (for estimation of heritability of life span), paternal age at reproduction (control for parental age effects), and cohort life expectancy (control for cohort and secular trends and fluctuations). We found that the regression slope for offspring longevity as a function of paternal longevity increases with paternal longevity, as predicted by the evolutionary theory of aging and by the mutation accumulation hypothesis in particular.     

Recycling of L-citrulline to sustain nitric oxide-dependent enteric neurotransmission

Neurons that synthesize nitric oxide from arginine produce stoichiometric amounts of citrulline. We investigated whether nitric oxide-releasing enteric neurons have the capacity to recycle citrulline to arginine and thereby sustain nitrergic neurotransmission. Argininosuccinate synthetase-like immunoreactivity and argininosuccinate lyase-like immunoreactivity, enzymes capable of citrulline to arginine conversion, were both localized in discrete populations of myenteric and submucosal neurons in the canine proximal colon. Argininosuccinate synthetase-like immunoreactivity and argininosuccinate lyase-like immunoreactivity co-localized with neuronal beta-nicotinamide adenine dinucleotide phosphate diaphorase staining, a marker for nitric oxide synthase. The functional significance of argininosuccinate synthetase-like immunoreactivity and argininosuccinate lyase-like immunoreactivity was shown by testing the effects of exogenous citrulline on responses to enteric inhibitory nerve stimulation, which were assessed by measuring contractions, inhibitory junction potentials and electrical slow waves. As shown previously, arginine analogues (L-nitroarginine methyl ester or L-nitroarginine; 100 microM) inhibited nitric oxide-dependent responses, and excess L-arginine restored inhibitory responses. Citrulline alone (0.1-2 mM) had no effect on nitrergic transmission under control conditions, but in the presence of L-nitroarginine methyl ester or L-nitroarginine, citrulline (0.1-2 mM) restored nitrergic transmission in a concentration-dependent manner. Other neutral amino acids (L-serine, L-leucine) did not mimic the effects of citrulline. Taken together, these data suggest that enteric nitrergic neurons have the enzymatic apparatus and functional capability of recycling citrulline to arginine.     

Neurologic paraneoplastic syndromes with neurotologic manifestations

Evidence supports the hypothesis that autoimmune mechanisms are operational in the etiopathogenesis of certain neurologic paraneoplastic syndromes (PNSs), including paraneoplastic encephalomyelitis (PEM) and paraneoplastic cerebellar degeneration (PCD). The antibodies (Anti-Hu and Anti-Yo), the antigens (Hu and Yo), and complementary DNA clones encoding Hu and Yo, central to PEM and PCD, respectively, have been isolated. In contrast, the antigens, and antibodies if any, involved in autoimmune cochleovestibular dysfunction remain unknown. The temporal bone histopathology and neuropathology of 2 patients, 1 with PEM and 1 with PCD, who developed signs and symptoms of cochleovestibular dysfunction, are reviewed and contrasted to the literature. It is concluded that both auditory and vestibular symptomatology and pathologic alterations can be seen in association with neurologic PNSs and that studies using the antigens and antibodies involved in neurologic PNSs may provide a new perspective on the investigation of autoimmune cochleovestibular dysfunction.     

The killing of Helicobacter pylori by low-power laser light in the presence of a photosensitiser

Activation and proliferation of human T lymphocytes in vitro can be obtained by various stimuli including specific antigens, mitogens, and cytokines. Here we describe the effect of interleukin-10, interleukin-12 and tumor necrosis factor-alpha on the interleukin-2 dependent proliferation and function of established human CD4+ and CD8+ alloreactive T-cell clones in the absence of antigen presenting cells. IL-12 and TNF-alpha both demonstrated an inhibitory effect on the proliferation of CD8+ cytotoxic T lymphocyte clones, whereas IL-10 enhanced the proliferation. IL-12-induced inhibition of CD8+ CTL clones was not mediated by the endogenous production of TNF-alpha by these clones. The strong inhibitory effect of IL-12 and TNF-alpha did not result in apoptosis. These cytokines did not alter the cytotoxicity of CD8+ CTL clones. When CD4+ T-cell clones were tested in the absence of APC, no significant change in IL-2-dependent proliferation due to IL-10, IL-12, and TNF-alpha could be measured. Since these effects on established CTL clones are in contrast to the effects of IL-10, IL-12, and TNF-alpha during the induction phase of immune responses, a dichotomy of immunomodulatory cytokines such as IL-10, IL-12, and TNF-alpha early and late in the immune response is suggested.     

Linking assembly code to PASCAL programs for microprocessors

High level languages used for programming microprocessors still need some assembly code to cover all the programming requirements and aspects. Using assembly code in a high level language program introduces certain difficulties and disadvantages. Practical suggestions to minimise the use of assembly code procedures in a high level language program is presented. (The high level language discussed is pascal/64000.)     

Epidermolysis bullosa junctionalis progressiva in three siblings

Three siblings of Swiss origin with epidermolysis bullosa junctionalis progressiva are described. The following clinical features were present from school age: dystrophy of the nails, non-scarring blistering of the skin, mild skin atrophy, hypodontia and dental caries. Light microscopy showed subepidermal blistering. Direct immunofluorescence was negative. On indirect immunofluorescence staining of a fresh spontaneous blister, bullous pemphigoid antigen and laminin were localized to the blister roof, and collagen IV and collagen VII to the blister base, indicating junctional splitting. Electron microscopy revealed a normal dermo-epidermal junction zone, including normal hemidesmosomes. There were no deposits of electron-dense amorphous material.     

Internal audit in a microbiology laboratory

AIM: To set up a programme of internal laboratory audit in a medical microbiology laboratory. METHODS: A model of laboratory based process audit is described. Laboratory activities were examined in turn by specimen type. Standards were set using laboratory standard operating procedures; practice was observed using a purpose designed questionnaire and the data were analysed by computer; performance was assessed at laboratory audit meetings; and the audit circle was closed by re-auditing topics after an interval. RESULTS: Improvements in performance scores (objective measures) and in staff morale (subjective impression) were observed. CONCLUSIONS: This model of process audit could be applied, with amendments to take local practice into account, in any microbiology laboratory.