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)

Pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. Diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprim-sulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing.
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PMID:New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. 1171 41

Preventing transmission of multidrug-resistant tuberculosis is critical because of treatment toxicity, cost, and the lack of effective therapy for latent infection. We attempted to determine the extent of transmission in Los Angeles County by comparing relatedness of multidrug-resistant tuberculosis cases using restriction fragment length polymorphism and by cross-matching contact information to the Tuberculosis Registry. Strain typing was done on isolates of 102 pulmonary multidrug-resistant cases identified between August 1993 and 1998. Seventy-one (70%) of the cases had cavitary lesions on chest radiograph, and 94 (92%) had sputa smear-positive for acid fast bacilli. Fifteen (15%) of the cases were known to be infected with human immunodeficiency virus. Four molecular clusters of two cases each and one closely related pair were identified among the 102 cases; contact investigation successfully identified all clusters but one. Among 946 contacts identified and cross-matched with the county's Tuberculosis Registry, one secondary case due to drug-resistant Mycobacterium bovis was found. To summarize, a very high proportion of pulmonary multidrug-resistant tuberculosis cases in Los Angeles County were infectious. Molecular strain typing indicated limited spread of disease, although it underestimated transmission compared with contact investigation. We believe aggressive surveillance and case management were critical to limiting the spread of multidrug- resistant tuberculosis.
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PMID:Limited transmission of multidrug-resistant tuberculosis despite a high proportion of infectious cases in Los Angeles County, California. 1255 33

Simian immunodeficiency virus (SIV)-infected macaques develop an encephalitis (SIVE) that is pathologically virtually indistinguishable from that associated with HIV infection, with multinucleated giant cells (MNGCs) being the principal histopathological manifestation. To dissect SIV variants responsible for MNGC development, we examined the relationships between env sequences transcribed in individual MNGCs and those from genomic DNA of brain and spleen tissues. The brain-specific variant found in all brain clones was dominant among the clones from MNGCs, suggesting a role in the formation of giant cells. Furthermore, two additional minor groups of sequences were present in MNGCs. One group consisted of sequences closely related to those from spleen, indicating recent and probably multiple episodes of neuroinvasion. The second group represented clones similar or identical to the initial inoculum. The survival of archival sequences and their activation presumably by the fusion of productively and quiescently infected macrophages/microglia identify the central nervous system as a possible anatomical reservoir for latent infection.
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PMID:Simian immunodeficiency virus encephalitis: analysis of envelope sequences from individual brain multinucleated giant cells and tissue samples. 1208 36

Simian immunodeficiency virus (SIV) as well as human immunodeficiency virus (HIV) induce polyclonal B-cell activation and are associated with the appearance of lymphomas in their respective hosts in either the presence or the absence of other co-infecting viruses such as Epstein-Barr virus (EBV). However, the pathogenic role of these retroviruses in the development of lymphoproliferative disorders remains poorly understood. To explore the virus-B-cell interactions, two immortalized lymphoblastoid B-cell lines (SL-P1 and SL-691) were established from cynomolgus monkeys that were naturally co-infected with a simian type D retrovirus-2 (SRV-2) and with the herpes virus Macaca fascicularis (HVMF-1). We addressed their susceptibility to SIV infection and the phenotypic modifications associated with SIV infection. In response, both cell lines (1) were co-infected with HVMF-1 (latent infection) and with SRV-2 (productive infection), (2) had a transformed phenotype because they did not require exogenous growth factors, and (3) when injected into mice with severe combined immunodeficiency (SCID), generated serially transplantable tumors. The B-cell origin of SL cells was demonstrated by the presence of rearrangements of the IgH gene and by the expression of typical B-cell lineage markers, such as CD20. SL-P1 and SL-691 could be discriminated on the basis of different expressions of CD23 and CD40 and of kappa- and lambda-chains. Most importantly, SL-691 cells, but not SL-P1 cells, were susceptible to chronic noncytolytic SIV infection. This infection occurred in a CD4/CCR5/CXCR4-independent manner and was associated with the upregulated expression of CD23 and CD40 cell surface markers. In addition, CD20 expression, which progressively disappeared in SL-691 noninfected cells, was maintained in the SIV-infected counterpart. These findings support the hypothesis that SIV induce phenotypic perturbations in B cells that might eventually contribute to the development of lymphoproliferative disease.
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PMID:Infection of simian B lymphoblastoid cells with simian immunodeficiency virus is associated with upregulation of CD23 and CD40 cell surface markers. 1221 Apr 40

Despite the fact that there are 8 million new cases of tuberculosis (TB) annually and 3 million deaths, TB has been a neglected public health priority, primarily because effective chemotherapy has led to a dramatic decrease in cases in industrialized countries and most cases in developing countries occur in adults. It has only been recently that the emergence of multi-drug resistant TB and the rapid disease progression in HIV-infected persons has led to the application of the methods of modern basic science to TB. Population movement among refugees and immigrants and the neglect of the public health infrastructure have also led to increases in the number of cases worldwide. TB and HIV interact in 4 ways: TB may become reactivated in an HIV-infected person; there may be a primary TB infection, an HIV-positive person may suffer reinfection; or TB may alter the natural history of the HIV infection. In developing countries, the TB seen in association with HIV is believed to be reactivation of latent infection. HIV seropositivity is associated with a 30-50% lifetime risk of TB as compared with a 10% risk in the uninfected. Reactivation of TB in HIV positive people causes an additional 250,000 cases in Africa each year. HIV changes the course of TB; first time exposure is associated with 30-40% attack rates, short incubation periods, and rapid progression of the disease. It is also suggested that TB may hasten the progression of HIV, although this has not been proved. HIV-associated cases of TB will continue to increase in Africa, but in the future the largest number of co-infected persons will be in Asia. The clinical manifestations of HIV-related TB become more severe according to the progression of the immunodeficiency. Patients dying of AIDS who also have TB usually have extremely heavy mycobacterial burdens with widespread, probably incurable, TB. Being HIV-positive is also associated more often with sputum-negative pulmonary or extrapulmonary TB and with atypical radiological manifestations such as absence of cavitation, absence of localization to the upper zones, and the presence of hilar adenopathy, effusions, or infiltrates. Diagnosis may, therefore, be more difficult in cases of HIV infection. Although a greater mortality is found in HIV-positive patients (perhaps associated with complications of other bacterial infections), TB can be treated successfully in HIV-infected people. The World Health Organization recommends short-course chemotherapy of isoniazid, rifampicin, ethambutol, and pyrazinamind for 2 months followed by 4 months of isoiazid and rifampicin or 6 months of isoniazid and ethambutol. The risk of recurrence is greater if non-rifampicin regimens are used and is 3-34 times greater than in seronegative cases. Treatment is complicated by the fact that 18-20% of HIV-positive people have adverse reactions to thiacetazone which presents as a skin condition and can lead to death. Proposed solutions to this problem are to replace thiacetazone with another drug, replace thiacetazone only in HIV-positive persons (testing all patients for HIV), or educating staff and patients about the need to discontinue the drug if a rash occurs. Donor funding will be necessary to adopt a single worldwide approach with the least side effects. Policy decisions must also be made to create a programmatic approach to preventing HIV-associated TB.
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PMID:The new tuberculosis. 1231 74

The human immunodeficiency virus type 1 (HIV-1) Tat protein is essential for viral replication and stimulates transcription of the integrated provirus by recruiting the kinase complex TAK/P-TEFb, composed of cyclin T1 (CycT1) and Cdk9, to the viral TAR RNA element. TAK/P-TEFb phosphorylates the RNA polymerase II complex and stimulates transcriptional elongation. In this report, we investigated the regulation of TAK/P-TEFb in primary human macrophages, a major target cell of HIV infection. While Cdk9 levels remained constant, CycT1 protein expression in freshly isolated monocytes was very low, increased early during macrophage differentiation, and, unexpectedly, decreased to very low levels after about 1 week in culture. The kinase activity of TAK/P-TEFb paralleled the changes in CycT1 protein expression. RNA analysis indicated that the transient induction of CycT1 protein expression involves a posttranscriptional mechanism. In transient transfection assays, the ability of Tat to transactivate the HIV long terminal repeat (LTR) in the late differentiated macrophages was greatly diminished relative to its ability to transactivate the HIV LTR in early differentiated cells, strongly suggesting that CycT1 is limiting for Tat function in late differentiated macrophages. Interestingly, lipopolysaccharide, a component of the cell wall of gram-negative bacteria, reinduced CycT1 expression late in macrophage differentiation. These results raise the possibility that regulation of CycT1 expression may be involved in establishing latent infection in macrophages and that opportunistic infection may reactivate the virus by inducing CycT1 expression.
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PMID:Transient induction of cyclin T1 during human macrophage differentiation regulates human immunodeficiency virus type 1 Tat transactivation function. 1236

Human cytomegalovirus (HCMV) infects about 60% of adults in developed world and more than 90% of developing countries population. In the immunocompetent host, initial infection and reactivation of latent infection are usually asymptomatic. However, in hosts with impaired cellular immune functions, such as transplant recipients, patients infected with human immunodeficiency virus (HIV) or undergoing anticancer chemo- and/or radiotherapy, the full pathogenic potential of the virus may be realized. HCMV is also among the most common causes of viral intrauterine infection affecting from 0.4 to 2.3% of live-born infants. Though in pregnant, immunocompetent women infections with HCMV are usually asymptomatic, severe infections may occur among congenitally infected fetuses and infants due to immaturity of their immune system. Approximately 40% of mothers with primary HCMV infections during gestation transmit virus to their infants. Although only 10% of infected infants are symptomatic at birth, 20 to 30% of these die. In addition, 5 to 15% of asymptomatic neonates are at risk of developing congenital anomalies later. In this outline we present anti-CMV drugs currently in clinical use and give examples of new molecules under laboratory and clinical development.
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PMID:[Drugs against human cytomegalovirus]. 1247 80

The presence of latent reservoirs has prevented the eradication of human immunodeficiency virus (HIV) from infected patients successfully treated with anti-retroviral therapy. The mechanism of postintegration latency is poorly understood, partly because of the lack of an in vitro model. We have used an HIV retroviral vector or a full-length HIV genome expressing green fluorescent protein to infect a T lymphocyte cell line in vitro and highly enrich for latently infected cells. HIV latency occurred reproducibly, albeit with low frequency, during an acute infection. Clonal cell lines derived from latent populations showed no detectable basal expression, but could be transcriptionally activated after treatment with phorbol esters or tumor necrosis factor alpha. Direct sequencing of integration sites demonstrated that latent clones frequently contain HIV integrated in or close to alphoid repeat elements in heterochromatin. This is in contrast to a productive infection where integration in or near heterochromatin is disfavored. These observations demonstrate that HIV can reproducibly establish a latent infection as a consequence of integration in or near heterochromatin.
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PMID:HIV reproducibly establishes a latent infection after acute infection of T cells in vitro. 1268 19

Whether infection with Mycobacterium avium complex (MAC) among patients with acquired immune deficiency syndrome results from recent exposure to virulent strains or reactivation of latent infection acquired years earlier is unknown. To address this question, tissue samples from 47 simian immunodeficiency virus (SIV)-infected and 63 SIV-uninfected rhesus macaques were cultured. MAC was cultured from 14 SIV-uninfected macaques (22.2%) and 32 SIV-infected macaques (68.1%); median bacterial burdens were 33.3 and 998.7 cfu/g, respectively. Genetically distinct strains of MAC were identified for 13 SIV-uninfected macaques (20.6%) and 15 SIV-infected macaques (31.9%). A genetically identical MAC strain (K128A) was identified for 25 SIV-infected macaques (53.2%) and 1 SIV-uninfected macaque (1.6%). Multivariate analysis identified infection with SIV/Delta(B670), diagnosis of an SIV-related tumor or opportunistic infection, and birth on site as risks for MAC infection. SIV-uninfected and SIV-infected macaques yielding unique strains of MAC were considered to have latent and reactivation infection, respectively, whereas animals infected with strain K128A were considered to have recent infection, demonstrating that both mechanisms occur among rhesus macaques.
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PMID:Latent infection as a source of disseminated disease caused by organisms of the Mycobacterium avium complex in simian immunodeficiency virus-infected rhesus macaques. 1275 Oct 32

This prospective study examined the persistence and transition of Epstein-Barr virus (EBV) in human immunodeficiency virus (HIV)-seropositive subjects with and without oral hairy leukoplakia, a replicative EBV-associated epithelial disease. The intrahost molecular epidemiology of EBV infection was characterized in subjects treated with valacyclovir to suppress EBV replication. Tongue epithelial tissues of HIV-seropositive subjects were found to support not only EBV replication but also persistent, nonproductive EBV infection. EBV appeared to enter the tongue from the blood reservoir of infection and, possibly, from exogenous sources as well. EBV transition from the blood to the tongue appeared to occur even during valacyclovir-mediated suppression of EBV replication, suggesting EBV entry into tongue epithelial tissue as a cell-associated latent infection. In conclusion, these results describe the persistence and transition of EBV as a dynamic interaction between the blood and epithelial reservoirs of EBV infection and suggest a role for entry, persistence, and reactivation of oral epithelial EBV in the pathogenesis of oral hairy leukoplakia.
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PMID:Persistence and transition of Epstein-Barr virus genotypes in the pathogenesis of oral hairy leukoplakia. 1521 77


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