Longitudinal study of the risks related to the consumption of water not conforming to bacteriological norms

A prospective follow-up study lasting 18 months in 1983-1984 was conducted in 50 villages in order to assess the risk related to the consumption of drinking water which did not meet the bacteriology standards. 119 physicians, 52 pharmacists and 118 primary-school teachers enumerated the cases of acute gastro-intestinal diseases observed among a population of 29,272 inhabitants. A weekly water sample was analysed in each village as to the presence of four indicator germs of fecal contamination: total plate count, total coliforms, fecal coliforms (thermotolerant) and fecal streptococci. 1,950 cases of acute gastro-intestinal diseases were registered by the physicians and pharmacists during a population experience of 1,873,303 persons-weeks, i.e. an incidence density of 1.06 X 10(-3) cases per person-week. The risk notified by the school teachers among children aged 7 to 11 was higher: 16.3 X 10(-3) cases per child-week. The villages were classified in 3 groups, according to the proportion of substandard samples: "good", "intermediate", and "bad" categories. The relative risk contrasting the "bad" and "good" villages was 3.5 for the cases notified by the physicians and the pharmacists among the general population (95% confidence interval = 2.5-4.8); it was 1.7 for the cases reported by the teachers among the children (95% confidence interval = 1.5-1.9). This concordant difference was very significant but not constant across the 18 months of the survey. The authors conclude that the bacteriology standards are a relevant indicator of a health hazard.     

Serum IgE in immune deficiency disorders

Serum IgE was measured in forty-eight patients with primary and in four patients with secondary hypogammaglobulinaemia. The presence of malabsorption, giardiasis, nodular lymphoid hyperplasia of the small bowel, eczema, drug reactions and depression of cell-mediated immunity was not related to the level of serum IgE. There was no relationship between the concentration of serum IgA, IgM and IgE. Patients experiencing anaphylactic type reactions following gammaglobulin injections did not tend to have a higher serum IgE. Despite very low or unrecordable levels of serum IgG, IgA and IgM, serum IgE was detected in all but three patients.     

Localization of RNA polymerases on influenza viral ribonucleoproteins by immunogold labeling

Monospecific antisera for the influenza polymerase proteins and high resolution immunoelectron microscopy have been used to investigate the topographical distribution of the polymerase molecules on influenza ribonucleoproteins (RNPs). Antibodies to PB1, PB2, and PA identify a single polymerase binding site located at, or very close to, the end of each RNP. Double labeling experiments confirm that all three polymerases are at the same end of each RNP and that they are in close association.     

A mouse model of AChR deficiency syndrome with a phenotype reflecting the human condition

The two subtypes of mammalian muscle nicotinic acetylcholine receptors (AChR) are generated by the substitution of the epsilon (adult) subunit for the gamma (fetal) subunit within the AChR pentamer. Null mutations of the adult AChR epsilon-subunit gene are the most common cause of the AChR deficiency syndrome. This is a disorder of neuromuscular transmission characterized by non-progressive fatigable muscle weakness present throughout life. In contrast with the human disorder, mice with AChR epsilon-subunit null mutations die between 10 and 14 weeks of age. We generated transgenic mice that constitutively express the human AChR gamma-subunit in an AChR epsilon-subunit 'knock-out' background. These mice, in which neuromuscular transmission is mediated by fetal AChR, live well into adult life but show striking similarities to human AChR deficiency syndrome. They display fatigable muscle weakness, reduced miniature endplate potentials and endplate potentials, reduced motor endplate AChR number and altered endplate morphology. Our results illustrate how species differences in the control of ion-channel gene expression may affect disease phenotype, demonstrate that expression of adult AChR subtype is not essential for long-term survival, and suggest that in patients with AChR deficiency syndrome, up-regulation of the gamma-subunit could be a beneficial therapeutic strategy.     

Dorsomedial telencephalon of lungfishes: A pallial or subpallial structure? criteria based on histology,connectivity, and histochemistry

The dorsomedial telencephalon of lepidosirenid lungfishes has been interpreted in two divergent ways: earlier investigators regarded it as a subpallial (septal) structure; more recently, it has been reinterpreted as the medial pallium (hippocampus). To resolve this question, we identified parameters that are conclusive in their association with either the medial pallium or the septum in anamniotes. The present study examines the position of ependymal thickenings and the distribution of acetylcholinesterase (AchE) in the cerebral hemispheres of the African lungfish Protopterus, the Australian lungfish Neoceratodus, and the amphibian species Xenopus and Ambystoma. In addition, projections from the hypothalamus (paraventricular organ) to the telencephalon are investigated in Protopterus. Ependymal specializations are located dorsally and ventrally in the lateral ventricles of amphibians, but laterally and medially in lungfishes. In Protopterus, the paraventricular organ projects to the medial telencephalic hemisphere, but not to the dorsal roof. High levels of AchE are present in restricted neuropil regions of the medial hemisphere and in the ventral and ventrolateral telencephalon, but they are lacking in the dorsal roof. Intensely AchE-stained neuronal cell bodies are located in the ventral telencephalon (rostrally) and the dorsomedial telencephalon (at mid-level). In Neoceratodus, AchE staining is pronounced in the septal area, but absent in the pallium. The terminal nerve proper lacks AchE stain in Protopterus; nerve fibres of the preoptic nerve are AchE-positive in both lungfish species. In Xenopus, AchE staining of fibers and terminals is restricted to the subpallium (medial septum, tuberculum olfactorium, striatum, nucleus accumbens, and medial amygdala); cell bodies are AchE positive in parts of the subpallium and rostral pallium. Comparison of cytological, histochemical, and "connectional" parameters substantiates the interpretation that the dorsomedial telencephalon of lungfishes represents a subpallial, but not a "medial pallial" structure. The dorsomedial part of the lepidosirenid telencephalon corresponds to the septum in the most plesiomorphic living lungfish, Neoceratodus forsteri, but it differs considerably from the dorsomedial telencephalon (medial pallium) in amphibians.     

Effect of toremifene on antipyrine elimination in the isolated perfused rat liver

Summary Toremifene is a triphenylethylene antioestrogen with significant antitumour activity. It is structurally very similar to tamoxifen. Both drugs undergo extensive hepatic metabolism and tamoxifen is known to inhibit hepatic mixed-function oxidases (MFO). Using the isolated perfused rat-liver model, we investigated the effect of toremifene on the elimination of antipyrine, a standard marker of MFO activity. Perfusate consisted of 20% red cells in a modified Krebs-Henseleit buffer, and 80 ml was recirculated at 14 ml/min for 3 h. High but clinically relevant steady-state toremifene levels of 3 and 10 g/ml were achieved using bolus plus constant infusion into the reservoir. Elimination of 2.5 mg antipyrine was not inhibited by steady-state toremifene, but methanol (maximal perfusate concentration, 1.29%), the vehicle used for toremifene administration, caused a statistically significant increase in the antipyrine elimination half-life (mean, 1.4±0.2 h for controls vs 2.2±0.3 h for methanol;P<0.05,n=4). Whereas the methanol had no apparent effect on liver viability as assessed by bile flow and perfusate back-pressure, toremifene at a steady-state concentration of 10 g/ml caused a statistically significant decrease in bile flow (value at 180 min, 0,22±0.05 ml/h as compared with 0.52±0.06 ml/h in the methanol control;P<0.05) and a statistically significant increase in perfusate back-pressure (value at 180 min, 17.5±1.8 cm vs 11.0±2.6 cm in the methanol control;P<0.05). Therefore, toremifene used at high doses can impair liver function in the isolated perfused rat liver, but it does not have any effect on antipyrine elimination.