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

Human immunodeficiency virus (HIV), an etiologic agent of AIDS, belongs to lentivirus subfamily of retroviruses. In striking contrast to oncoviruses HIV does not transform cells but instead causes chronic progressive diseases. This feature is demonstrable in vitro by dramatic cytopathic effects upon virus/cell coculture. Since virus-producing cells are generally destroyed, HIV must be transmitted to other cells after replication in order to maintain the infection. However, after viral infection, AIDS requires a long period of time before becoming full-brown. The virus appears to establish latent infection and stay dormant in many cells until activation signals have been received. We found that tumor necrosis factor can activate such latent HIV and selectively kill HIV-infected cells. The mechanism of cell death was recently cleared as Apoptosis.
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PMID:[Tumor necrosis factor and AIDS]. 846 53

The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic.
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PMID:Pathogenesis of human immunodeficiency virus infection. 846 5

Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (1O2) as one of the major oxidative species. Because this oxidant can be generated either extracellularly or intracellularly, it can cause severe damage to various biological macromolecules, even to those deeply embedded inside the cells such as DNA. Sublethal biological modifications induced by different DNA-damaging agents can promote various cellular responses initiated by the activation of various cellular genes and certain heterologous viruses. Since 1O2 fulfils essential prerequisites for a genotoxic substance, we have examined the effects of an oxidative stress, mediated by this species, on cells harbouring a heterologous promoter-leader sequence derived from the human immunodeficiency virus type 1 (HIV-1). Our results demonstrate that HIV-1 long terminal repeat (LTR), integrated into the cellular DNA of epithelial cells, can be transactivated following an oxidative stress mediated by 1O2. In addition, using HIV-1 latently infected promonocytes or lymphocytes, it can be shown that virus reactivation can be induced through a sublethal dose of 1O2 generated intracellularly. An extracellular generation of 1O2 can promote a substantial lethal effect without HIV-1 reactivation. These data may be relevant to the understanding of the events converting a latent infection into a productive one and to the appearance of the acquired immune deficiency syndrome.
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PMID:HIV-1 promoter activation following an oxidative stress mediated by singlet oxygen. 849 40

Tuberculosis, a bacterial disease caused by the Mycobacterium tuberculosis complex, is becoming an increasingly common opportunistic disease in persons infected with the human immunodeficiency virus (HIV). M. tuberculosis is transmitted from person-to-person by airborne droplet nuclei. Persons who are exposed to these droplet nuclei in poorly ventilated environments are at risk of becoming infected with M. tuberculosis. HIV infection is probably the most significant risk factor associated with progression from latent M. tuberculosis infection to active disease. Thus, HIV-infected persons should avoid exposure to M. tuberculosis, they should be screened for evidence of latent infection with the tuberculin skin test, and they should be offered preventive therapy. Because many severely immunosuppressed anergic HIV-infected persons have been found to have an increased risk of developing active tuberculosis, decisions to use preventive therapy should be individualized on the basis of the local prevalence of tuberculosis and drug-resistance patterns. Persons with active tuberculosis should receive at least 6 months of treatment with recommended regimens, preferably with directly observed therapy, to ensure adequate bacteriologic response, completion of therapy, and cure. Chronic suppressive therapy after completion of therapy is currently not recommended.
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PMID:Tuberculosis as an opportunistic disease in persons infected with human immunodeficiency virus. 854 15

This report updates and replaces previous recommendations regarding the use of Bacillus of Calmette and Guerin (BCG) vaccine for controlling tuberculosis (TB) in the United States (MMWR 1988;37:663-4, 669-75). Since the previous recommendations were published, the number of TB cases have increased among adults and children, and outbreaks of multidrug-resistant TB have occurred in institutions. In addition, new information about the protective efficacy of BCG has become available. For example, two meta-analyses of the published results of BCG vaccine clinical trials and case-control studies confirmed that the protective efficacy of BCG for preventing serious forms of TB in children is high (i.e., > 80%). These analyses, however, did not clarify the protective efficacy of BCG for preventing pulmonary TB in adolescents and adults; this protective efficacy is variable and equivocal. The concern of the public health community about the resurgence and changing nature of TB in the United States prompted a re-evaluation of the role of BCG vaccination in the prevention and control of TB. This updated report is being issued by CDC, the Advisory Committee for the Elimination of Tuberculosis, and the Advisory Committee on Immunization Practices, in consultation with the Hospital Infection Control Practices Advisory Committee, to summarize current considerations and recommendations regarding the use of BCG vaccine in the United States. In the United States, the prevalence of M. tuberculosis infection and active TB disease varies for different segments of the population; however, the risk for M. tuberculosis infection in the overall population is low. The primary strategy for preventing and controlling TB in the United States is to minimize the risk for transmission by the early identification and treatment of patients who have active infectious TB. The second most important strategy is the identification of persons who have latent M. tuberculosis infection and, if indicated, the use of preventive therapy with isoniazid to prevent the latent infection from progressing to active TB disease. Rifampin is used for preventive therapy for persons who are infected with isoniazid-resistant strains of M. tuberculosis. The use of BCG vaccine has been limited because a) its effectiveness in preventing infectious forms of TB is uncertain and b) the reactivity to tuberculin that occurs after vaccination interferes with the management of persons who are possibly infected with M. tuberculosis. In the United States, the use of BCG vaccination as a TB prevention strategy is reserved for selected persons who meet specific criteria. BCG vaccination should be considered for infants and children who reside in settings in which the likelihood of M. tuberculosis transmission and subsequent infection is high, provided no other measures can be implemented (e.g., removing the child from the source of infection). In addition, BCG vaccination may be considered for health-care workers (HCWs) who are employed in settings in which the likelihood of transmission and subsequent infection with M. tuberculosis strains resistant to isoniazid and rifampin is high, provided comprehensive TB infection-control precautions have been implemented in the workplace and have not been successful. BCG vaccination is not recommended for children and adults who are infected with human immunodeficiency virus because of the potential adverse reactions associated with the use of the vaccine in these persons. In the United States, the use of BCG vaccination is rarely indicated. BCG vaccination is not recommended for inclusion in immunization or TB control programs, and it is not recommended for most HCWs. Physicians considering the use of BCG vaccine for their patients are encouraged to consult the TB control programs in their area.
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PMID:The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices. 860 27

The Epstein-Barr virus (EBV) carrier state is characterized by latent infection of the general B-cell pool and by chronic virus replication at oropharyngeal sites. In Caucasian populations, most healthy carriers seem to harbor one dominant transforming virus strain, usually of type I rather than type 2, which persists over time and is detectable both in the blood and in the throat. This finding implies that once the virus carrier state is established, both viral reservoirs are largely if not completely protected from infection with additional strains. However, it is not known which facets of the immune response offer that protection. Here we address this question by a detailed study of EBV carriage in patients T-cell immunocompromised as a result of chronic human immunodeficiency virus (HIV) infection. Resident EBV strains were rescued from blood and from throat washings by using an in vitro transformation assay which aims to minimize bias toward faster-growing transformants; in this way, a mean of 16 independent isolations were made from each of 35 HIV-positive (predominantly male homosexual) patients. These virus isolates were characterized first at the DNA level by PCR amplification across type-specific polymorphisms in the EBNA2 and EBNA3C genes and across the 30-bp deletion and 33-bp repeat loci in the LMP1 gene and then at the protein level by immunoblotting for the strain-specific "EBNAprint" of EBNA1, -2, and -3C molecular weights. By these criteria, 18 of 35 patients harbored only one detectable EBV strain, usually of type 1, as do healthy carriers. However, the other 17 patients showed clear evidence of multiple infection with different EBV strains. In eight cases these strains were of the same type, again usually type 1, and were more often found coresident in throat washings than in the blood. By contrast, a further nine patients gave evidence of coinfection with type 1 and type 2 strains, and in these cases both virus types were detectable in the blood as well as in the throat. Immunological assays on these HIV-positive patients as a group showed a marked impairment of T-cell responses, reflected in reduced levels of EBV-specific cytotoxic T-cell memory, but an elevation of humoral responses, reflected in raised antibody titers to the EBV envelope glycoprotein gp340 and by the maintenance of virus neutralizing antibodies in serum. We infer that selective impairment of the T-cell system predisposes the host to infection with additional exogenously transmitted EBV strains.
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PMID:Frequency of multiple Epstein-Barr virus infections in T-cell-immunocompromised individuals. 876 91

The incidence of tuberculosis (TB) in patients with human immunodeficiency virus (HIV) infection has increased in recent years, raising issues regarding preventive therapy for TB in this high-risk patient population. To determine if an HIV-positive individual is at risk for reactivation of latent infection, testing with purified protein derivative (PPD) is recommended; however, many people with impaired cell-mediated immunity due to HIV are anergic. Strategies regarding PPD testing and criteria for HIV-positive patients are presented. Isoniazid has been the accepted drug for use as prophylaxis for TB in immunocompetent patients, and there is evidence that isoniazid is also effective in HIV-positive, PPD-positive patients. Data from efficacy and feasibility trials and the risks and benefits of preventive therapy with isoniazid are discussed. Because of toxicity and compliance problems with isoniazid, there is a continuing need for development of alternative therapies. The results of some preliminary studies of newer therapies are presented here.
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PMID:Prophylaxis for tuberculosis in Europe--ongoing research. 878 58

The human polyomavirus JC virus (JCV) infects myelin-producing cells in the central nervous system, resulting in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV-induced PML occurs most frequently in immunosuppressed individuals, with the highest incidence in human immunodeficiency type 1-infected patients, ranging between 4 and 6% of all AIDS cases. Although JCV targets a highly specialized cell in the central nervous system, infection is widespread, with more than 80% of the human population worldwide demonstrating serum antibodies. A number of clinical and laboratory studies have now linked the pathogenesis of PML with JCV infection in lymphoid cells. For example, JCV-infected lymphocytes have been suggested as possible carriers of virus to the brain following reactivation of a latent infection in lymphoid tissues. To further define the cellular tropism associated with JCV, we have attempted to infect immune system cells, including CD34+ hematopoietic progenitor cells derived from human fetal liver, primary human B lymphocytes, and human tonsillar stromal cells. Our results demonstrate that these cell types as well as a CD34+ human cell line, KG-1a, are susceptible to JCV infection. JCV cannot, however, infect KG-1, a CD34+ cell line which differentiates into a macrophage-like cell when treated with phorbol esters. In addition, peripheral blood B lymphocytes isolated by flow cytometry from a PML patient demonstrate JCV infection. These results provide direct evidence that JCV is not strictly neurotropic but can infect CD34+ hematopoietic progenitor cells and those cells which have differentiated into a lymphocytic, but not monocytic, lineage.
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PMID:JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: implications for viral latency. 879 45

Cytomegalovirus (CMV), as do other herpesviruses, establishes a lifelong latent infection in its natural host. While in immunologically intact hosts most CMV infections are subclinical, clinical disease follows severe immunosuppression and immunodeficiency. In these situations CMV may produce serious life-threatening disease, and virus reactivated from the latent state is often responsible. Essential to understanding this virus and its pathogenesis is the need to define particular tissue and cell types harboring viral DNA. We searched for viral DNA and RNA in subpopulations of blood cells from mice latently infected with murine CMV by using differential centrifugation and fluorescent antibody cell sorting followed by polymerase chain reaction analysis. Following intravenous inoculation, the viral DNA was found to be present in the buffy coat at and after 21 days postinfection, and both granulocytes and peripheral blood mononuclear leukocytes (PBML) were reservoirs. Further analysis of the PBML fraction by separation into Mac-1+ and Mac-1- cells revealed that monocytes harbored the DNA while lymphocytes were not sites of persistence. We conclude that in buffy coat of latently infected mice the viral DNA is present only in cells of the myeloid lineage. The relationship of this DNA to the latent infection is discussed.
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PMID:Murine cytomegalovirus DNA in peripheral blood of latently infected mice is detectable only in monocytes and polymorphonuclear leukocytes. 880 53

Patients with primary or secondary immunodeficiency are at high risk for B cell lymphoproliferative syndromes (LPS) that are generally Epstein-Barr virus (EBV)-associated. We established a cell line, termed JuWa, from an immunoblastic lymphoma that developed in a child with severe combined immunodeficiency. JuWa cells were representative of the original lymph node as shown by a similar IgH gene rearrangement pattern. The cell line exhibited the typical features of a lymphoblastoid cell line (LCL): (1) growth pattern in large clumps, (2) lack of structural chromosome abnormalities, (3) type III latency with expression of EBV-associated EBNA2 and LMP, as well as B cell activation markers CD23 and CD30, thereby showing characteristics of an EBV producer cell line, i.e. a latent infection with a small subpopulation of cells spontaneously entering the lytic cycle, (4) inducibility of the lytic cycle by IdU and TPA, leading to an increase of early antigen and viral capsid antigen-positive cells from 1 to 15-20%, and (5) elimination of the linear viral genomes by treatment with acyclovir (ACV), without affecting the circular episomal genomes. After withdrawal of ACV, viral replication resumed within 7 days. Thus, JuWa cells support the concept of the LCL-like features of LPS and lymphomas occurring in the setting of immunodeficiency. In our in vitro model, ACV treatment could effectively suppress the viral replication but not cure EBV infection of B cells.
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PMID:Epstein-Barr-virus-associated lymphoproliferative syndrome in severe combined immunodeficiency: establishment of a lymphoblastoid cell line as an in vitro model for biological and therapeutic studies. 887 15


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