Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sections of normal and diseased brain and kidney tissues were screened for the presence of JC virus (JCV) DNA by using the polymerase chain reaction. As expected, all samples obtained from patients with progressive multifocal leukoencephalopathy (PML) tested positive when multiple JCV-specific primer and probe combinations were used. Unexpectedly, more than 50% of non-PML-affected brains were also found to harbor low levels of JCV DNA. To confirm that the positive signals seen in the tissue sections were not the result of contamination, amplified DNA was cloned and sequenced and in some cases was shown to represent strains of JCV not identified previously. Two predominant regulatory region configurations of JCV have been detected in the human host: archetype JCV, which is excreted in the urine of normal and immunocompromised individuals, and "PML-type" JCV found in diseased brains. This latter group of variants appears to derive from archetype JCV by the deletion and duplication of sequences within the promoter-enhancer region. In the present study, the archetype strain of JCV was identified only in normal kidney samples; JCV DNA found in non-PML-affected brain specimens and in kidney tissue from patients with PML resembled that of strains isolated from PML-affected brain tissue. Our findings indicate that JCV reaches the brain more frequently than previously thought and may persist at this site without causing demyelinating disease. A subsequent episode of prolonged immunodeficiency or a direct interaction with an immunocompromising agent (e.g., human immunodeficiency virus type 1) might activate the latent JCV infection and lead to the development of PML.
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PMID:JC virus DNA is present in many human brain samples from patients without progressive multifocal leukoencephalopathy. 132 40

A population-based case control study of intermediate- and high-grade lymphoma in the County of Los Angeles, CA, was initiated in 1989. Human immunodeficiency virus (HIV)-positive lymphoma patients are compared to HIV-negative lymphoma patients, to HIV-positive controls with acquired immunodeficiency syndrome but without lymphoma, and to HIV-positive asymptomatic individuals. The HIV-negative lymphoma cases are compared to neighborhood controls, who are matched in terms of age, sex, race/ethnicity, and socioeconomic status. All cases are reviewed for pathology by a single group of pathologists. All cases and controls are studied for HIV, Epstein-Barr virus (EBV), and human herpesvirus 6 antigens and antibodies. Tissues from HIV-positive and -negative cases are studied for immunoglobulin gene rearrangement, presence of EBV and HIV, c-myc oncogene rearrangements, and karyotypic analysis. To date, with 294 lymphoma cases and 181 control cases interviewed, high-grade lymphoma has been diagnosed in 82% of the HIV-positive cases versus 40% of the HIV-negative cases (P = 0.001). Although elevated titers of EBV-viral capsid antigen were demonstrated in 82% of HIV-positive versus 50% of HIV-negative lymphoma cases, the geometric mean titer of EBV-viral capsid antigen is similar among HIV-positive lymphoma cases and HIV-positive controls. The geometric mean titer of human herpesvirus 6 antibodies was similar in HIV-positive and HIV-negative lymphoma cases and in the control populations. Monoclonality was demonstrated in all cases of lymphoma. EBV genome was demonstrated within lymphoma DNA in 68% of HIV-positive and 15% of HIV-negative lymphoma cases. Further study will be required to elucidate the full mechanisms of pathogenesis of the acquired immunodeficiency syndrome-related lymphomas.
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PMID:Epidemiological and biological study of acquired immunodeficiency syndrome-related lymphoma in the County of Los Angeles: preliminary results. 132 9

To investigate the association between human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV), simultaneous determinations of HIV antigen (HIV Ag) p24 and EBV DNA were performed in lymphocyte culture supernatants from 63 individuals at risk of HIV infection. In vitro data, together with HIV immune status results, were subjected to a statistical analysis. HIV infection was identified in 49 patients (78%); of these, in vitro EBV DNA was found in 44 individuals (90%), while in only 3 of the 14 non-infected ones (21%). Statistical analysis demonstrated a close relationship between evidence of HIV infection and in vitro detection of EBV DNA (87.3% concordant with 95% confidence interval: 76.5%-94.5%). Furthermore, a strong dependence was revealed between the presence of EBV DNA and HIV Ag in culture (p less than 0.00001). These results indicate the existence of in vitro viral interactions, with likely in vivo implications in the pathogenesis and evolution of HIV infection.
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PMID:Evidence of an in vitro association between human immunodeficiency virus antigen P24 and Epstein-Barr virus DNA. 132 86

Human herpesvirus 6 (HHV-6) prototype isolate GS is a newly identified lymphotropic herpesvirus and several subsequent herpes isolates were recognized as HHV-6 by their hybridization to a HHV-6(GS) DNA probe pZVH14. DNA restriction analysis and in vitro tropism studies show that HHV-6 isolates can be divided into two groups, designated group A and group B. Antigenic relationships among 15 HHV-6 isolates belonging to these two groups were examined using rabbit antibodies against HHV-6(GS) infected cells, 11 monoclonal antibodies against three glycoproteins and four non-glycoproteins of HHV-6(GS), and sera from 136 healthy adults. More than 20 polypeptides from all these isolates were immunoprecipitated by rabbit polyclonal antibodies against HHV-6(GS) infected cells. Reactivities of monoclonal antibodies segregated these isolates into the same two groups. Group A contains HHV-6(GS), HHV-6(U1102) from a Ugandan acquired immunodeficiency syndrome (AIDS) patient, and nine other HHV-6 isolates from various disorders. HHV-6(Z-29) from a Zairian AIDS patient, HHV-6(SF) isolated from the saliva of a human immunodeficiency virus (HIV)-infected individual, HHV-6(OK) from a child with exanthem subitum, and HHV-6(DC) from a leukopenia patient are in group B. Eighty-one percent of the sera showed similar antibody titer in immunofluorescence assay with group A HHV-6(GS) and group B HHV-6(Z-29) infected cells and 19% of the sera showed two- to four-fold antibody titer differences. The mobilities of many of the polypeptides immunoprecipitated from group A HHV-6(GS) and group B HHV-6(Z-29) infected cells were different and sera showed differences in the quantities and nature of polypeptides immunoprecipitated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antigenic relationships among human herpesvirus-6 isolates. 132

2',3'-Dideoxy-3'-thiacytidine (cis-(+/-)-SddC) was found to have potent activity against hepatitis B virus and human immunodeficiency viruses in culture. Recent studies by us identified (-)-SddC as the stereoisomer responsible for the antiviral effect and showed that the cytotoxicity was mainly caused by (+)-SddC. Metabolism studies showed that these drugs were converted to their monophosphates, diphosphates, and triphosphates. The enzyme responsible for the formation of monophosphates was identified to be cytoplasmic deoxycytidine kinase in CEM cells. Uptake studies showed that the intracellular concentration of (-)-SddC and its metabolites was approximately 5-fold higher than that of (+)-SddC metabolites. (-)-SddCTP was more potent than (+)-SddCTP in inhibiting hepatitis B virus replication; (+)- and (-)-SddCTP exhibited minimal inhibition on polymerases alpha and delta, more inhibition on beta, and strong inhibition on gamma. In all cases, (+)-SddCTP was found to be more inhibitory than (-)-SddCTP to all four polymerases. (+)-SddCMP competed with dCTP for incorporation into DNA by DNA polymerase gamma and beta and served as a chain terminator; however, similar incorporation was not detected using other polymerases. The selective inhibition of DNA synthesis in isolated mitochondria by (+)- and (-)-SddCTP suggests a stereospecificity on the mitochondrial uptake of deoxynucleoside triphosphates.
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PMID:Biochemical pharmacology of (+)- and (-)-2',3'-dideoxy-3'-thiacytidine as anti-hepatitis B virus agents. 133 Oct 54

Human papillomavirus (HPV) DNA was found in cervicovaginal lavage fluids from 9 of 11 human immunodeficiency virus type 1 (HIV-1)-seropositive female prostitutes with cervical intraepithelial neoplasia (CIN) in Kinshasa, Zaire. Since 7 yielded complex nucleic acid hybridization results consistent with mixed HPV infections, limited sequencing of HPV DNA was used to identify the HPVs present. Three of HPV 16 and 1 each of HPV 18, 31, 33, and 56 and ME180-HPV were identified by sequencing in 8 samples. Each of these genotypes has been found in specimens from HIV-1-seronegative women with CIN. Some DNAs had nucleic acid and amino acid sequence variations relative to the reference HPVs, but the variants were closely related to variants that have been found in HIV-1-seronegative women. Variant amino acids were found predominantly at three positions in one 40-amino-acid segment of the L1 open reading frame sequenced. The predominant HPV 16 variant observed has been found rarely in other countries.
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PMID:Genotypes and sequence variants of human papillomavirus DNAs from human immunodeficiency virus type 1-infected women with cervical intraepithelial neoplasia. 133 Dec 47

A nested polymerase chain reaction (PCR) was evaluated for the detection of cytomegalovirus (CMV) DNA in cerebrospinal fluid (CSF). CSF and serum samples from 19 AIDS patients with intracerebral CMV infection diagnosed at autopsy were retrospectively examined. As controls, CSF and serum samples from 15 AIDS patients with only extracerebral CMV involvement at autopsy, from 10 AIDS patients without CMV infection at autopsy, and from 10 anti-human immunodeficiency virus-negative patients without ongoing CMV infection, were studied. CMV DNA was detected from patients with intracerebral CMV infection in 9 of 9, 5 of 6, and 1 of 4 CSF samples collected, respectively, 1-30, 30-90, and 90-300 days before death. Twelve of 13 sera from these patients were CMV PCR-positive. None of the control patients had CMV DNA in CSF. PCR was positive in 6 of 8 sera from AIDS patients with only extracerebral CMV infection and in serum from 1 AIDS patient without CMV involvement at autopsy. CMV PCR on CSF is highly sensitive and specific. It should be considered a rapid and reliable diagnostic method for CMV infection of the central nervous system.
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PMID:Cytomegalovirus infection of the central nervous system in patients with AIDS: diagnosis by DNA amplification from cerebrospinal fluid. 133 Dec 53

The utility of amplification of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid (CSF) for the diagnosis of HCMV central nervous system (CNS) disease in AIDS patients was studied. CSF specimens from 30 patients with neurologic dysfunction were assayed by polymerase chain reaction (PCR), and the results were correlated with histopathologic findings, CSF culture, and clinical manifestations. PCR was positive in all 11 patients who had histopathologic evidence of HCMV CNS disease, including 4 who were CSF culture-negative. Three patients with HCMV polyradiculopathy had CSF positive by PCR. Nine patients negative for HCMV by neuropathologic study and an additional 7 patients with HCMV-unrelated clinical diagnosis were all CSF PCR-negative, despite concomitant systemic HCMV infection in 7. In addition, 24 asymptomatic human immunodeficiency virus-infected individuals were CSF PCR-negative. CSF PCR appears to be a sensitive and specific diagnostic method for detection of HCMV CNS disease in AIDS patients.
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PMID:Diagnosis of human cytomegalovirus central nervous system disease in AIDS patients by DNA amplification from cerebrospinal fluid. 133 Dec 54

A polymerase chain reaction (PCR)-based method was used to detect cytomegalovirus (CMV) DNA in 82 cerebrospinal fluid (CSF) samples from 67 patients infected by human immunodeficiency virus (HIV). The test was positive for 14 patients, 8 of whom had CMV-related neurologic disease proven by viral culture of CSF or histologic examination. Encephalitis was the most frequent manifestation in patients with positive PCR results, but CMV DNA was also present in some patients with peripheral neuropathy or polyradiculomyelitis. All patients with proven CMV neurologic disease were positive by PCR. In contrast, viral culture was negative for 4 of the 8 patients and pathologic studies were available only for 5. The specificity of the PCR-based assay could not be assessed precisely because of the lack of a reference standard, but the results correlated well with clinical course and results of the other methods. These findings suggest that the PCR-based method may be a useful noninvasive tool for the rapid diagnosis of CMV-related neurologic disease.
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PMID:Rapid detection of cytomegalovirus DNA in cerebrospinal fluid of AIDS patients with neurologic disorders. 133 Dec 55

Dominant negative or trans-dominant mutants of viral proteins represent a new and exciting potential approach to antiviral therapy. Unfortunately, the extreme specificity of a given dominant negative mutant limits its general utility in treating a broad spectrum of viral diseases, since it can typically interfere with the activity of only a single viral polypeptide encoded by a single virus. However, it seems likely that dominant negative mutants of promiscuous viral trans-activator proteins, which by definition would repress rather than activate gene expression, should be able to inhibit infectious virus production for a number of different viruses. One such dominant negative mutant, derived from the herpes simplex virus type 1 (HSV-1) regulatory protein ICP0, was found previously to behave as a powerful repressor of gene expression from an assortment of HSV-1 and non-HSV-1 promoters in transient expression assays. In the present study, this ICP0 mutant was found to be capable of inhibiting the replication of both HSV-1 and a completely unrelated virus, human immunodeficiency virus, in cell culture. The properties of this dominant negative mutant indicate that it may have potential as a means of treating diseases caused by a number of DNA and RNA viruses. Moreover, a truncated form of ICP0 which can hypothetically be created by alternative splicing was found to possess similar inhibitory capabilities, suggesting that a virus-encoded version of this dominant negative mutant may play a role in down-regulating HSV-1 gene expression during infection in vivo.
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PMID:Antiviral properties of a dominant negative mutant of the herpes simplex virus type 1 regulatory protein ICP0. 133 Dec 97


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