Abstract Glucocorticoid receptor (GR) is emerging as a key driver of prostate cancer (PCa) progression and therapy resistance in the absence of androgen receptor (AR) signaling. Acting as a bypass mechanism, GR activates AR-regulated genes, although GR-target genes contributing to PCa therapy resistance remain to be identified. Emerging evidence also shows that African American (AA) men, who disproportionately develop aggressive PCa, have hypersensitive GR signaling linked to cumulative stressful life events. Using racially diverse PCa cell lines (MDA-PCa-2b, 22Rv1, PC3, and DU145) we examined the effects of glucocorticoids on the expression of two stress oncoproteins associated with PCa therapy resistance, Clusterin (CLU) and Lens Epithelium-Derived Growth Factor p75 (LEDGF/p75). We observed that glucocorticoids upregulated LEDGF/p75 and CLU in PCa cells. Blockade of GR activation abolished this upregulation. We also detected increased GR transcript expression in AA PCa tissues, compared to European American (EA) tissues, using Oncomine microarray datasets. These results demonstrate that glucocorticoids upregulate the therapy resistance-associated oncoproteins LEDGF/p75 and CLU, and suggest that this effect may be enhanced in AA PCa. This study provides an initial framework for understanding the contribution of glucocorticoid signaling to PCa health disparities.
A total of 63 HIV-1 strains collected in Iceland during the years 1989-96 were typed into serotypes A-E using a peptide-based enzyme immunoassay. The majority of the strains were of serotype B (66.6%). 22.2% were untypeable by this method. Until 1993 only serotype B was found, but in 1993 and after that date other serotypes, especially E (7.9%) were detected, indicating the spread of serotypes previously confined to developing countries. This may reflect the increase in the number of Icelanders travelling to distant countries and the increased immigration into Iceland from developing countries.
Summary Cultured spinal ganglia and cord from mice and hamsters were infected with mumps virus or Sendai virus. Expression of five structural proteins, the haemagglutinin-neuraminidase, fusion, nucleocapsid (NP), phospho (P) and matrix proteins was examined with monoclonal antibodies to each protein. In Sendai virus-infected mouse neurons all five viral proteins were detected. In hamster neurons infected with mumps virus all viral proteins were also expressed, but in mouse neurons only the NP and P proteins were seen. This suggests a species-specific cellular restriction of viral protein synthesis in mumps virus-infected mouse neurons. There was no, or only a slight, reduction in the number of neurons between days 4 and 20 after infection of mouse cultures with mumps virus, but the proportion of infected neurons diminished from 68% to 15% during this time.
Summary Intracerebral injection of hamster neurotropic (HNT) measles virus in weanling Balb/C mice leads to an encephalitis, which is characterized by glial activation, behavioral seizures, selective neurodegeneration, and, after approximately 7 days, death. To provide a better understanding of the underlying molecular pathology, we studied seizure evolution by continuously monitoring electroencephalographic (EEG) activity, examined neuroglia and neurons histologically, and measured the brain content of glia‐derived neuroactive metabolites of the kynurenine pathway of tryptophan degradation. Microglia and astrocytes were activated as early as postinoculation day (PID) 1, with reactive microglia lining the extent of the alveus. This was followed by a more extensive microglial activation that specifically outlined hippocampal pyramidal neurons in areas CA1‐CA3 and by increases in the hippocampal levels of the neurotoxins 3‐hydroxykynurenine (3‐HK) and quinolinic acid (QUIN). These changes preceded the onset of EEG seizures, which had a mean onset of 108 h after inoculation. Prominent hippocampal cell loss, demonstrated by Nissl‐ and silver staining, was apparent by PID 5. Thus, we speculate that early glial reactions to HNT inoculation result in the excess formation of 3‐HK and QUIN, which in turn causes subclinical seizure activity, behavioral seizures, and, eventually, neurodegeneration. In addition to its conceptual implications, our study indicates that timely interventions modulating glial activation or 3‐HK/QUIN synthesis may be of benefit in preventing or arresting seizure‐induced neuronal damage.
An important factor in the outcome of a viral infection is the occurrence of cells expressing major histocompatibility (MHC) class I and class I1 antigens, because activation and the effects or functions of T cells depend on recognition of the virus antigen in the context of MHC antigens.Under normal conditions, the nervous system has low levels of MHC antigen expression.'However, enhanced expression of both
Summary Detailed, country‐specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus ( HCV ) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use ( IDU ) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.
Abstract We studied a new commercially available thyrotropin (TSH) assay, the AquaLite Bioluminescence TSH-Immunoassay (SeaLite Inc.). This assay has a detection limit of 0.005 mIU/L and a functional sensitivity of 0.017 mIU/L and meets the requirements of a third-generation TSH assay. Using this assay, we measured serum TSH in 153 euthyroid individuals and in the following patients: 32 primary hypothyroids; 38 primary hyperthyroids; 35 with thyroid cancer receiving suppressive therapy with levothyroxine (L-T4); 33 receiving replacement L-T4 aimed at reaching and maintaining a euthyroid status; 23 with subclinical hyperthyroidism; and 52 hospitalized for nonthyroidal illnesses (NTI). The AquaLite TSH assay perfectly discriminated hypothyroid and untreated hyperthyroid patients from euthyroid subjects and clearly discriminated between overtly and mildly hyperthyroid patients. Intermethod comparisons showed that the AquaLite and the Nichols assays were more effective than the ACS-180 and the TOSOH assays in discriminating among hyperthyroid patients, including patients over-treated with L-T4.
