Clinical phenotype of nephrogenic diabetes insipidus in females heterozygous for a vasopressin type 2 receptor mutation

Nephrogenic diabetes insipidus (NDI) usually shows an X-linked recessive mode of inheritance caused by mutations in the vasopressin type 2 receptor gene (AVPR2). In the present study, three NDI families are described in which females show clinical features resembling the phenotype in males. Maximal urine osmolality in three female patients did not exceed 200 mosmol/kg and the absence of extra-renal responses to 1-desamino-8-d-arginine vasopressin was demonstrated in two of them. All affected females and two asymptomatic female family members were shown to be heterozygous for an AVPR2 mutation. Skewed X-inactivation is the most likely explanation for the clinical manifestation of NDI in female carriers of an AVPR2 mutation. It is concluded that, in female NDI patients, the possibility of heterozygosity for an AVPR2 gene mutation has to be considered in addition to homozygosity for mutations in the aquaporin 2 gene.     

Contribution to the structural characterization of eucaryotic PSI reaction centre—I. Critical analysis of the polypeptidic composition of different P700 enriched fractions

In thylakoid membranes, several peptides of high MW are present which may interfere with the study of CP1's components. Modifying Cleveland's technique [7] for limited proteolysis, we have characterized the polypeptides found in the 60 kD region. Some may result from incomplete washing of the CF1 while others come from the CP1; indeed, this chlorophyll protein complex, which has a higher MW (above 100 kD), very often undergoes a dissociation into smaller components of about 60 KD MW.Analysis of the protein content of different preparations commonly used to obtain PSI reaction centre enriched fractions has been performed. The and subunits of CF1 are among the main contaminants of most of these preparations. A further purification step is described which can be applied to all these preparations, but numerous peptides are still present in the active fractions. It is most unlikely that all these polypeptides are required for the primary photochemical event, and this emphasizes the necessity to find a new simple method to purify PSI reaction centres.     

Circadian complexes: Circadian rhythms under common gene control

Summary Circadian rhythms for food and water consumption were measured in five inbred strains of mice under a photoperiod of 16 h light and 8 h dark (16:8 LD), and under constant light (LL).Significant strain differences were observed which indicate that a common gene difference, or set of differences inMus musculus influences both the phase angle () associating the rhythms with the light-dark cycle, and the periods (_LL) of circadian rhythms for food and water consumption. The biological clock mechanism influenced by this genetic variance is common to both food and water circadian rhythms, and differs among the five inbred strains. A positive genetic correlation was observed between the phase angle () and the period (_LL) of each rhythm. This observation can be understood in terms of a functional relationship between phase and period proposed by Pittendrigh and Daan (1976b) for the entrainment of a circadian oscillator by a light-dark cycle in nocturnal rodents.These results suggest that circadian rhythms for food and water consumption in mice are regulated by a common physiological mechanism, and would respond to natural selection as a single circadian complex under common gene control.     

Myocardial Revascularization in Patients 70 Years of Age and Older

Myocardial revascularization has been carried out by us in 67 patients 70 years of age or older. Advanced coronary artery disease was found at angiography in more than two thirds of the patients. The postoperative morbidity and mortality compare very favorably with those in younger patients. The early and late mortality in the 67 patients was 4.5 percent and 6.0 percent, respectively. Fifty-seven survivors have been followed an average of 21 months; for most patients there has been a pronounced improvement in clinical classification. Properly selected, patients of advanced age can undergo successful revascularization surgical procedures. The adequacy of function of the left ventricle, proper timing of the surgical operation and an aggressive yet realistic approach seem to be major determinants for a good result.     

Recent time-trends of age-specific death rates for breast cancer: Quebec and other provinces, 1965 through 1974.

For the 10-year period 1965 through 1974 the age-specific death rates for cancer of the breast decreased among middle-aged women, especially at ages 40 to 49 years, in Quebec, the Maritimes and the Prairies but not in Ontario or British Columbia. In women under 35 years of age the mortality generally increased, while in women aged 60 to 64 years there was little change except in the Prairies, where the rate increased. It seems probable that the trends reflect changes in incidence rather than in case-fatality. Some, but not all, of the pattern could be explained by changes in fertility over the past 50 years.     

Regioelectronic factors in metabolic hydroxylation of aliphatic carbon atoms

EHT calculations have been performed on model molecules acting as substrates for mammalian mono-oxygenases. C_α---H bonds are consistently found to have larger overlap populations compared with C_β---H and C_γ---H bonds. It is known on the other hand that metabolic hydroxylation of aliphatic carbon atoms shows a marked regioselectivity for α-carbons. The quantum-mechanical results sustain the view that C---H bonds of relatively high electronic density are preferred target sites for the cytochrome P-450-mediated oxygenation, and that the oxygen atom being activated is transformed into an electrophilic species capable of C---H bond insertion.     

Studies on dehydro-l-ascorbic acid 2-arylhydrazone 3-oximes: Conversion into substituted triazoles and isoxazolines

l-threo-2,3-Hexodiulosono-1,4-lactone 2-(arylhydrazones) (2) were prepared by condensation of dehydro-l-ascorbic acid with various arylhydrazines. Reaction of 2 with hydroxylamine gave the 2-(arylhydrazone) 3-oximes (3). On boiling with acetic anhydride, 3 gave 2-aryl-4-(2,3-di-O-acetyl-l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones (4). On treatment of 4 with liquid ammonia, 2-aryl-4-(l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxamides (5) were obtained. Acetylation of 5 with acetic anhydride-pyridine gave the triacetates, and vigorous acetylation with boiling acetic anhydride gave the tetraacetyl derivatives. Periodate oxidation of 5 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxamides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamides, characterized as the monoacetates and diacetates. Controlled reaction of 2 with sodium hydroxide, followed by neutralization, gave 3-(l-threo-glycerol-l-yl)-4,5-isoxazolinedione 4-(arylhydrazones), characterized by their triacetates. Reaction of 2 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy-l-threo-2,3-hexodiulosono-1,4-lactone 2-(arylhydrazones); these were converted into 4-(2-O-acetyl-3-bromo-3-deoxy-l-threo-glycerol-l-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones on treatment with acetic anhydride-pyridine.