Cerebral ischemia induces transient intracellular redistribution and intranuclear translocation of the raf proto-oncogene product in hippocampal pyramidal cells

Summary In this report we describe changes in the intracellular redistribution of raf serine/threonine protein kinase (product of the raf proto-oncogene family) in hippocampal neurons following cerebral ischemia in Mongolian gerbils. For immunohistochemical localization studies polyclonal antisera specific for each of the A, B, and Raf-1 isotypes of raf, as well as a pan-raf antisera, were employed. Of these, only sera recognizing B-raf, as well as the general v-raf (raised against the conserved C-terminal region) were positive, indicating that B-raf is the major isotype in this neuronal region. Three different ischemie models were used (repeated 3 times for two min and single 5 or 15 min occlusions, of the common carotid arteries) to demonstrate that ischemie insult causes redistribution of raf protein kinase into the cell nucleus of hippocampal neurons. Increased amounts of raf protein in the nuclei of pyramidal cells following ischemia was confirmed by Western blot analysis of isolated nuclear fractionations. Moreover, an elevation in the level of nuclear raf protein also was detected in the contralateral (i.e. non-occluded hemisphere) neurons of CA1 and CA3 subfields 4 days after the ischemie insult indicating a possible transsynaptic increase in the amount of raf protein along with redistribution. The intranuclear translocation of the immunoreactive material started from the perinucleolar rim and with time extended throughout the nucleus. Enhanced levels and altered redistribution of the raf polypeptide in the nuclei of pyramidal cells of the CA3 subfleld appears to be reversible and returns to the normal level 12 days following the ischemic insult. In addition to triggering the above changes in the intracellular redistribution of raf, ischemie insult also caused an increase in the level of B-raf protein in reactive astrocytes.     

Analysis of human rotavirus strains prevailing in Bangladesh in relation to nationwide floods brought by the 1988 monsoon.

The virologic character of human rotavirus strains prevailing in Bangladesh was investigated in relation to the devastating nationwide floods brought by the 1988 monsoon. Human rotaviruses contained in stool specimens that were collected from inpatients with infantile and adult diarrhea in two hospitals in Mymensingh over a 13-month period (January 1988 to January 1989) and in one hospital in Dhaka over a 3-month period (February to April 1988) were examined for their subgroup, VP7 serotype, and RNA electropherotype. In concurrence with the spread of the flood (from the middle of August 1988), the number of infantile and adult diarrhea patients increased greatly. At the same time, the proportion of rotavirus-positive specimens in all diarrhea cases also increased remarkably, reaching 54 and 45% in September and October, respectively. An electrophoretic analysis of viral RNA revealed 17 distinct patterns of viral RNA (14 long and 3 short electropherotypes) and a considerable number of mixed electropherotypes, suggesting the simultaneous infection of some patients with more than two rotavirus strains. It was noteworthy that electropherotypes of rotavirus strains prevailing in the community changed considerably after the spreading of the flood and that the frequency of virus specimens showing mixed electropherotypes increased significantly during the flood period. These results suggest that sudden environmental change caused by the devastating floods seriously affected the epidemiology of rotavirus infections by increasing the opportunity of transmission of the virus and by reducing the resistance of the host to infection. In both pediatric and adult patient groups, serotypes 1 and 2 were the most frequent ones detected, followed by serotype 4.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interleukin-6 production by thyroid epithelial cells. Enhancement by interleukin-1.

Interleukin-1 is a potent inhibitor of thyroglobulin and cAMP production in human thyroid cells and the inhibitory effect is enhanced by tumor necrosis factor-alpha and interferon-gamma. In the present study secondary cultures of human thyroid cells produced interleukin-6 and the production was significantly increased after exposure of the cells to recombinant interleukin-1 alpha and -1 beta. This increase was dose-dependent and concomitant of the IL-1 induced decrease in cAMP and thyroglobulin production. Both tumor necrosis factor-alpha and -beta also augmented interleukin-6 production, but less potently than interleukin-1. Interferon-gamma did not affect the production of interleukin-6. The rat thyroid cell line FRTL-5 produced interleukin-6 spontaneously, and the production was enhanced after addition of recombinant interleukin-1 beta. A pathogenetic role of interleukin-6 in autoimmune thyroid disease is suggested.     

The prognostic value of hypocholesterolemia in hospitalized patients

Clinical observations show that severe illness often leads to hypocholesterolemia. To verify this finding and to define the relationship between serum cholesterol and a patient's prognosis, a study was conducted in two large hospital populations. Of 24,000 and 61,463 adult patients (populations I and II) an average of 3.8% and 3.6% died in hospital, respectively. The mean serum cholesterol levels of patients who died was significantly lower than that of those who survived (163.6 mg/dl versus 217.8 mg/dl;P < 0.0001). The average cholesterol of surviving patients was similar to that of 6,543 healthy controls. During hospitalization serum cholesterol levels of 100 mg/dl were encountered in 1.2% and 3.6% of patients of populations I and II, respectively. The mortality of these hypocholesterolemic patients was about tenfold higher than average and showed a strong, inverse, linear relationship with serum cholesterol concentrations. Patients whose serum cholesterol level dropped to less than 45 mg/dl did not survive. These data show that in severely ill patients serum cholesterol may decline to very low concentrations, and the prognosis is reflected by the degree of hypocholesterolemia, which thus may serve as a clinically useful prognostic parameter. Correspondence to: E. Windler