C2H2-171 : A novel human cDNA representing a developmentally regulated poz domain/zinc finger protein preferentially expressed in brain

We describe a novel human zinc finger cNDA, C2H2-171. This cDNA represents an mRNA which encodes a protein of 484 amino acids and a calculated molecular weight of 54 kD. Four zinc finger-like domains are found in the C-terminal end of the protein. At the N-terminus, C2H2-171 contains a POZ/tramtrack-like domain similar to that found in the tumor associated zinc finger proteins LAZ-3/BCL-6 and PLZ-F, as well as in non-zinc finger proteins. C2H2-171 RNA is preferentially expressed in the brain, and increases during the course of murine development, with maximal expression in the adult. C2H2-171 RNA is differentially expressed in brain regions, with the highest level of expression in the cerebellum. C2H2-171 RNA was expressed at high levels in primary cerebellar granule cell neurons compared to astrocytes. The gene encoding C2H2-171 is highly conserved in vertebrates, and maps to the terminus of human chromosome 1 (1q44-ter). This chromosomal location is associated with a number of cytogenetic aberrations including those involving brain developmental anomalies and tumorigenesis. These data suggest that C2H2-171 may play an important role in vertebrate brain development and function.     

A calcium-channel blocker, amlodipine, attenuates insulin antinatriuresis but does not modulate insulin-mediated attenuation of cardiovascular reactivity in healthy man

Background: Insulin exerts an antinatriuretic effect when administered acutely in vivo. Interestingly, insulin fails to reduce sodium excretion in rats receiving verapamil. The present study was undertaken in order to investigate whether the calcium-channel blocker amlodipine attenuates the antinatriuretic effect of insulin in humans. Method: Eight healthy lean men (32±2 years) were investigated on three different occasions; i.e. time-control, insulin infusion alone, and insulin infusion following pretreatment with amlodipine (5 mg x 1 during 10 days). During the experiments renal haemodynamics (insulin and PAH clearances) and segmental tubular sodium handling (sodium and lithium clearances) were investigated. The cardiovascular reactivity was also assessed by a graded noradrenaline infusion at the end of each experiment. Results: Insulin infusion alone was accompanied by a significant 50% reduction in urinary sodium excretion. Following amlodipine pretreatment, euglycaemic insulin infusion was associated with an attenuated antinatriuretic response and the cumulative sodium excretion following 135 min of insulin infusion was significantly higher (24±4 vs 18± mmol; P <0.05) as compared to insulin infusion alone. No significant differences in the proximal and distal tubular sodium handling respectively, were seen following CCB pretreatment. The results also show that the doses of noradrenaline required to increase the basal mean arterial blood pressure by 10 mmHg (262±38 vs 150±25 ng/g/min; p <0.05) and by 20 mmHg (431±36 vs 350±38 ng/kg/min; P<0.05) respectively, were significantly higher during the insulin infusion than during the time-control experiment. Pretreatment with amlodipine did not further modulate the cardiovascular reactivity. Conclusion: Pretreatment with a calcium-channel blocker, amlodipine, attenuates the antinatriuretic effects of insulin leading to a significantly higher cumulative sodium excretion at the end of insulin infusion, which may be of clinical importance. Moreover, insulin attenuates the cardiovascular reactivity to a graded noradrenaline infusion, suggesting that insulin causes vasodilatation in healthy man.     

Gaucher disease: diagnosis and treatment

Gaucher's disease is the most common lysosomal storage disorder. It was identified in 1882 by Phillipe Gaucher, a French dermatologist. However, it was not until 1965 that Gaucher disease was found to be due to a deficiency in the enzyme glucocerebrosidase (EC 3.2.1.45) which breaks down glucocerebroside, a cell membrane component. The deficiency in this enzyme leads to an accumulation of glucocerebroside within the lysosomes of macrophages throughout the body. Gaucher's disease is classified into three types: type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). Of the three, type 1 is the most common, affecting one in 40,000-200,000 people and having a high prevalence among Ashkenazi Jews, affecting one in 450-1500. The signs and symptoms of type 1 disease demonstrate marked heterogeneity, from asymptomatic or mildly symptomatic, to severe disability with disfigurement and even death. Hepatosplenomegaly and thrombocytopenia are well documented. Less well-recognized are often insidious skeletal complications which affect the majority of type 1 patients and which are its most debilitating feature. In addition to clinical suspicion, some morphologic, hematologic and biochemical indicators can help establish the diagnosis. However, definitive diagnosis is only made by determining the catalytic activity of the lysosomal enzyme glucocerebrosidase. Confirmation of heterozygosity requires the use of molecular biotechnology methods. About 150 mutations of the glucocerebrosidase gene have been identified in patients with Gaucher's disease, some of which are predictive of phenotype. The history of treatment of Gaucher disease started with splenectomy and continued with bone marrow transplantation, before the recent introduction of safe and effective enzyme replacement therapy. In Croatia, nine patients with type 1 Gaucher's disease have been identified so far. Seven patients are on enzyme replacement therapy, and past results demonstrated significant improvement in all clinical symptoms, without development of any side effects. However, new treatments, such as substrate balance therapy and gene therapy, may become available within the next few years. The place, if any, that such therapies will have in the treatment of patients with Gaucher's disease will be dependent on the results of clinical studies currently in progress.     

Occupational physical demands and hip osteoarthritis

The authors investigated the influence of physical strain at work on radiological signs of hip osteoarthritis. The study included 295 men and 298 women aged over 45 from an urban area who were classified in four groups according to physical demands of their occupation. The evaluation included clinical and radiological signs of hip osteoarthritis. The association between hip osteoarthritis and occupation was analysed using logistic regression. Though not significantly, radiological signs of hip osteoarthritis were common in subjects who worked in a standing position (odds 1.45 for men, 1.50 for women). Clinical signs of osteoarthritis in women were significantly associated with performance in a standing position (odds 3.00), whereas in men the association was more significant for jobs with high physical strain (odds 2.19). There was a sustained trend toward an increase in health risk with years of work in all job categories. Occupation did not appear to influence the development of radiological hiposteoarthritis, but the authors did establish association between clinical signs of hip osteoarthritis and work.