Huntington's disease (HD) is a fatal, dominantly inherited disorder caused by polyglutamine repeat expansion in the huntingtin (htt) gene. Here, we observe that HD mice develop hypothermia associated with impaired activation of brown adipose tissue (BAT). Although sympathetic stimulation of PPARgamma coactivator 1alpha (PGC-1alpha) was intact in BAT of HD mice, uncoupling protein 1 (UCP-1) induction was blunted. In cultured cells, expression of mutant htt suppressed UCP-1 promoter activity; this was reversed by PGC-1alpha expression. HD mice showed reduced food intake and increased energy expenditure, with dysfunctional BAT mitochondria. PGC-1alpha is a known regulator of mitochondrial function; here, we document reduced expression of PGC-1alpha target genes in HD patient and mouse striatum. Mitochondria of HD mouse brain show reduced oxygen consumption rates. Finally, HD striatal neurons expressing exogenous PGC-1alpha were resistant to 3-nitropropionic acid treatment. Altered PGC-1alpha function may thus link transcription dysregulation and mitochondrial dysfunction in HD.
Serum analyte measurement is a useful, noninvasive method for monitoring disease in a mouse model of bacterial-induced IBD.
Ten isolates of an antigenically intermediate strain of adenovirus were recovered from eight persons who presented febrile upper respiratory illness, pneumonia, or multisystem disease between November 1976 and August 1978. Six isolates were recovered from four members of an extended family in which the other nine members all had serologic evidence of infection; the other four isolates were epidemiologically unrelated. The isolates were placed in hemagglutination group IB on the basis of results of differential hemagglutination tests. All isolates were identified as adenovirus 21 by serum-neutralization tests and as types 21, 34, or 35 by hemagglutination-inhibition tests with reference rabbit and horse antisera. Conversely, rabbit antiserum to the intermediate strain had high titers of neutralizing antibody to adenovirus 21 and high titers of hemagglutination-inhibiting antibody to adenoviruses 21 and 35. The patients' serologic responses were similar. Thus, the isolates were typed as adenovirus 21/H21 + 35 and are the first such intermediate strains recorded.
By means of a continuous canine kidney cell line (MDCK), influenza viruses were rapidly isolated from specimens collected from patients with respiratory disease. The cell line proved more sensitive than either eggs or rhesus monkey cells for currently circulating influenza A and B strains. Influenza viruses caused a distinct cytopathology within 5 days of inoculation if trypsin-ethylenediamine-tetraacetic acid was incorporated into the medium. Sufficient hemagglutinin was produced on the initial tissue culture passage to allow direct identification of isolates by hemagglutinin inhibition tests. A variety of other respiratory viruses replicated in MDCK, and over a 10-month period 211 of 600 specimens (35%) yielded viruses.
LPA, a simplified LPA (SLPA) perforaed at the bedside by house officers, and CIE assays which were developed in this laboratory are sensitive in vitro to 0.2 nglml. 0.5 nglml and 1 ngl ml of HIB capsular antigen respectively. The sensitivity and specificity of these assays were canpared prospectively in 106 episodes of suspected HIB infections. Nineteen immunosuppressed patients with v a r i c e l l a zoster were enrolled i n a randomized crossover 10 da t r i a l o f adenine arabinoside. Of 14 w i t h reticuloendothelia! malignancy, 7 were receiving a c t i v e chemotherapy. Age, sex, underlylng disease, and preceding chemotherapy were comparable f o r both randomization groups. Eight patients received drug over the f i r s t 5 days and placebo the next 5; while 11 received the exact opposite regimen. I n s p i t e o f natural healing i n the placebo group, adenine arabinoside s i g n i f i c a n t l y accelerated cutaneous healing for the elimination o f virus from vesicles (P = 0.015) and cessation o f new vesicle formation (P = 0.026). Although pustulation was not s t a t i s t i c a l l y accelerated, a l l treated patients had completely pustulated by the time o f crossover. Five patients, a l l w i t h reticuloendothelial cancer, developed pneumonitis and, because o f the crossover received adenine arabinoside during t h e i r disease course. The mean duration o f pneumcnitls was 5.6 days + 2.1 (range: 3 t o 8). Resolution was temporally associated w i t h -therapy. There were no study deaths. C l i n i c a l and laboratory evidence o f t o x i c i t y was i n s i g n i f i c a n t a t the dose employed. These data f o r therapy o f primary v a r i c e l l a zoster i n f e c t i o n support the larger study demonstrating accelerated healing and satisfactory therapeutic index i n herpes zoster w i t h adenine arabinoside. months of age was similar to that seen in infants 12-14 months of age. Our findings also suggest factors other than age which may be important in the occurrence of rubeola vaccine failures. LPA AND SLPA are more sensitive than CIE in the diagnosis of HIB infections, especially in non-meningitic disease (p = 0.005). The LPA assay is simple enough for bedside use, specific, and will detect almost all invasive HIB infections. cines provide a model for determining v i r a l and host factors i n Adenine arabinoside was evaluated f o r the treatment of lerpes the control of primary infection. An attenuated parainfluenza 3 simplex encephalitis i n a randomized controlled study. Of 50 (para 3) vaccine was given intranasally (104-5 TCID~g/dose) t o 16 patients w i t h a presunptive c l i n i c a l diagnosis and undergoing children ages 13 t o 35 months-with 5 additional placebo inocub r a i n biopsy, 25 cases were proved by f s o l a t f o n of virus from the l a t e d controls studied f o r transmission and i n t e r c u r r e n t i l l n e s s . b r a i n specimen. Adenine arabinoside treatment reduced m o r t a l i t y P r i o r natural para 3, as judged by prevaccination serum antibody, f r a ...
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