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)

The infectious aspects of cancer in humans were epidemiologically pioneered by Dr. David Burkitt through his observations of lymphomatous tumors seen in children in equatorial Africa. Years, later, the Epstein-Barr virus (EBV) was shown to be intimately associated with such tumors and is now recognized as a component of some B-cell lymphomas and nasopharyngeal carcinoma. Still the questions of an active, passive, or accessory role persist. The ability of this virus to cause immunosuppressive hemopoietic disturbances in individuals infected with EBV but not developing cancer raise questions about host susceptibility, host immune response, and possible coconspiring, infectious, oncogenic agents. Recent associations of EBV antibody found in diseases, such as squamous cell carcinoma of the head and neck and acquired immunodeficiency syndromes, point to its possible accessory role as an immunosuppressive agent. The ability of EBV to spread by extracellular and intracellular mechanisms demonstrates its variable infectious potential. Numerous EBV-transformed human cell lines attest to its ability to confer "immortality" with uncontrolled growth patterns. This review critically examines the association of EBV with various malignancies, the type of evidence which links it there, and the implications for further investigations and therapy.
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PMID:Epstein-Barr virus-associated malignancies. 303 69

A working group of the acquired immunodeficiency syndrome (AIDS) advisory group to the health administration of Denmark has been studying the advantages and disadvantages of routine tests of certain groups. One advantage of offering routine human immunodeficiency virus (HIV) tests to all pregnant women is that it makes it possible to follow the course of the epidemic. Secondly, it makes it possible for an individual woman to get an abortion if she is HIV-positive. On the other hand, routine HIV tests may keep female drug addicts who do not wish to be tested out of the pregnancy health care system. A specific problem is the greater number of false positives among pregnant women that among other groups. Normally tests are repeated immediately and again several months later if a new test is ambiguous but this possibility does not apply to pregnant women since the time limit for having an abortion will be exceeded. Still another advantage of offering routine HIV tests to pregnant women is that it will contribute to making HIV tests more routine, which will generally be an advantage to the AIDS campaign. A tentative conclusion is that it will be more productive to have routine HIV tests in venereal disease clinics where there is a higher percentage of population at risk.
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PMID:[A work group reviews the AIDS testing of selected groups]. 338 19

Toxiusol, a natural product isolated from the Red Sea sponge Toxiclona toxius, has been shown to be a potent inhibitor of various viral reverse transcriptases (RT) [i.e., of human immunodeficiency virus (HIV-1), equine infectious anemia virus, and murine leukemia virus] and cellular DNA polymerases (i.e., of DNA polymerases alpha and beta and Escherichia coli DNA polymerase I). A thorough investigation of the mode of inhibition was conducted with HIV-1 RT-associated DNA polymerase activity. The inhibition is unaffected by the nature of template-primer used. The inhibitory active site of toxiusol is attributable to the polar moieties at the benzene ring. The presence of either sulfate groups in the natural lead compound or hydroxyl groups in the corresponding hydroquinone is critical, because both compounds are equally effective at low micromolar concentrations. Conversely, the presence of acetyl groups in the same position in the derivative toxiusol diacetate lowers significantly or abolishes the inhibitory activity. Toxiusol binds the HIV-1 RT irreversibly and in a noncompetitive way with high affinity (Ki = 1.2 microM), probably through polar groups. The replacement with acetyl moieties in the analog toxiusol diacetate hampers the binding of the inhibitor to the enzyme (Ki increases to about 26 microM). Still, the compound binds irreversibly, probably through its hydrophobic structure skeleton. Toxiusol diacetate loses its ability to inhibit the first step in the DNA polymerization process (that is, the formation of the DNA-enzyme complex as measured by a gel retardation assay), which contributes to its poor inhibitory capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of inhibition of HIV reverse transcriptase by toxiusol, a novel general inhibitor of retroviral and cellular DNA polymerases. 753 6

Recent reports document that US hospitals vary considerably, notably by ownership, in the number of acquired immunodeficiency syndrome (AIDS) patients they treat. Still, little is known about other types of hospital response to human immunodeficiency virus (HIV) and AIDS and the relative strength of ownership as a determining factor. With annual survey data from the American Hospital Association the authors examine the formal adoption of HIV-related services among urban US hospitals at the turn of the decade. Descriptive analyses of 2 years of data (1988 and 1991) are presented. A multivariate logistic regression analysis, conducted on the 1991 data, tests for unique ownership effects on the likelihood that hospitals are heavy investors in HIV-related care. Patterns of service adoption for 1991 strongly resemble those for 1988. Nearly three fourths of urban US hospitals offer general inpatient AIDS care, and over half provide HIV testing. Few urban hospitals offer outpatient services; even fewer operate AIDS units. A substantial minority report no formal adoption of HIV-related services. For-profit hospitals stand out as least likely to formally adopt these HIV-related services. Those adopting a comprehensive set of HIV-related services typically are public or secular, not-for-profit in ownership, large, affiliated with a medical school, and high volume users of Medicaid funding. The logistic regression analysis suggests that public ownership is a key determinant of greater service investment, even after controlling for other explanatory factors. This study appears to mirror a familiar pattern of hospital response to undercompensated care in the United States.
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PMID:Adoption of HIV-related services among urban US hospitals: 1988 and 1991. 766 3

Teenagers are a crucial target group for interventions concerning acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV). Experimenting with their burgeoning sexuality and increased ability to obtain drugs, they are prime candidates for AIDS prevention and education strategies. The intervention described in this paper is a 30-minute magic show, presented by Cyrus (or Iris) the Virus, a sinister but entertaining character portrayed by any health educator willing to spend a few hours learning the magic tricks. The tricks explain why sharing needles and choosing sexual partners based on appearance alone can result in AIDS. Cyrus also uses magic to communicate the ways that AIDS is not transmitted, how to refuse sex, and how to use condoms correctly. The show, as well as increasing the audience's knowledge about HIV, attempts to induce behavioral change by increasing participants' perceived self-efficacy--a predictor of healthful behavior. Still in its pilot phase, the show has been seen by 281 students ages 10-15 years. Viewers rate the show highly, and preliminary analysis suggests that perceived self-efficacy has been significantly improved.
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PMID:The AIDS prevention magic show: avoiding the tragic with magic. 815 67

Cell lines that are nonproductively infected with human immunodeficiency virus type 1 (HIV-1), such as the T-lymphocyte ACH2 clone, have been proposed to represent in vitro models of proviral latency. We have previously shown that such cells exhibit an aberrant pattern of viral RNA expression, with a large excess of fully spliced viral RNAs. Here, by superinfecting the ACH2 cells with a second HIV-1 virus, we demonstrate the primary mechanism of HIV-1 proviral latency in this cell line. In the dually infected cells, the exogenous virus was transcribed at high levels. However, expression from the provirus originally present in the ACH2 cells was not quantitatively increased. Still, its RNA production was shifted from a blocked early-stage to a fully productive pattern. This was interpreted to be a consequence of the high levels of Rev produced by the exogenous virus, acting in trans to promote the cytoplasmic export of all incompletely spliced viral mRNAs made in the cells. Comparable numbers of copies of each provirus were present in the dually infected cells, and both viruses grew equally well, once passed onto fresh cells. These results indicate that the low levels of transcriptional activity of the HIV-1 virus present in ACH2 cells are secondary to specific characteristics of the region of the cellular genome in which the proviral DNA is integrated.
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PMID:HIV-1 latency due to the site of proviral integration. 837 52

In the past few years, there has been a virtual explosion of information on the viral and bacterial molecules now known as superantigens. Some structures have been defined and the mechanism by which they interact with MHC class II and the V beta region of the T cell receptor is being clarified. Data are accumulating regarding the importance of virally encoded superantigens in infectivity, viral replication, and the life cycle of the virus. In the case of MMTV, evidence also suggests that superantigens encoded by a provirus may be maintained by the host to protect against future exogenous MMTV infection. Experiments in animals have also begun to elucidate the dramatic and variable effects of superantigens on responding T cells and other immune processes. Finally, the role of superantigens in certain human diseases such as toxic shock syndrome, some autoimmune diseases like Kawasaki syndrome, and perhaps some immunodeficiency disease such as that secondary to HIV infection is being addressed and mechanisms are being defined. Still, numerous important questions remain. For example, it is not clear how superantigens with such different structures, for example, SEB, TSST-1, and MMTV vSAG, can interact with MHC and a similar region of the TCR in such basically similar ways. It remains to be determined whether there are human equivalents of the endogenous murine MMTV superantigens. The functional role of bacterial superantigens also remains to be explained. Serious infection and serious consequences from toxin-producing bacteria are relatively rare events, and it is questionable whether such events are involved in the selection pressure to maintain production of a functional superantigen. Hypotheses to explain these molecules, which can differ greatly in structure, include T cell stimulation-mediated suppression of host responses or enhancement of environments for bacterial growth and replication, but substantiating data for these ideas are mostly absent. It also seems likely that only the tip of the iceberg has been uncovered in terms of the role of superantigens in human disease. Unlike toxic shock syndrome, other associations, especially with viral superantigens, may be quite subtle and defined only after considerable effort. The definition of these molecules and mechanisms of disease may result in new therapeutic strategies. Finally, it is apparent that superantigens have dramatic effects on the immune system. One wonders whether these molecules or modifications of them can be used as specific modulators of the immune system to treat disease.
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PMID:Superantigens and their potential role in human disease. 839 79

Lymphoid neoplasia is a complex area comprising multiple diseases with varied pathology, treatment, and outcome. The non-Hodgkin's lymphomas are reviewed here. Non-Hodgkin's lymphomas, collectively, represent the sixth most common cancer in the United States as well as the sixth most common cause of cancer deaths. The overall incidence of non-Hodgkin's lymphoma has risen steadily over the past four decades. Although some of this is attributable to human immunodeficiency virus (HIV)-associated lymphoma, HIV-associated disease accounts for only a small part of the increase in lymphoma. As our knowledge of normal as well as neoplastic lymphoid development has expanded on the basis of histopathology as well as adjunct cellular and molecular techniques, multiple classifications have been proposed to take these into account. The clinical relevance to our understanding of non-Hodgkin's lymphoma is the concept that various lymphoid cancers are counterparts of stages of normal lymphoid development. Stages of lymphoid development in terms of cell surface markers and immunoglobulin gene rearrangements have been well characterized. These are particularly applicable to the early B-cell development, which is antigen-independent and occurs in the bone marrow. Diseases correlating with these stages are largely acute lymphocytic and lymphoblastic leukemia/lymphoma and high-grade lymphomas, such as Burkitt's lymphomas. Much has been learned recently about subsequent antigen-dependent B-cell development in secondary lymphoid organs to improve our understanding of the corresponding stages of B-cell neoplasia. Many of these stages correlate with more recently described entities such as mantle cell and marginal zone lymphomas. Histologic study remains crucial in determining the subtype of NHLs, whereas immunohistochemistry, surface phenotype, and molecular studies are useful in selected cases. Although some lymphoma classifications may be better in terms of understanding the lymphoma biology, the working formulation remains useful to guide clinical decision making. Lymphomas classified as low grade are considered incurable with standard therapy when diagnosed, as is usual, at advanced stages. Different subtypes may have different median survivals, but the goal has typically been palliation, whereas experimental approaches are clearly needed. Intermediate and high-grade lymphomas are potentially curable with aggressive combination chemotherapy. Recent evidence suggests that CHOP chemotherapy is as effective as more complex regimens. Still, 40% to 50% of patients are cured. Prognostic factor analysis has allowed separation of subgroups with much better survival in whom CHOP is adequate versus those with much poorer survival in whom experimental approaches are rational. Additional subtypes of lymphomas have been described and characterized since the working formulation was developed, including mucosa-associated lymphoid tissue tumors (MALT-oma), mantle zone lymphoma, anaplastic large cell lymphoma and AILD-like T-cell lymphoma. Approaches to these entities are still being optimized. Newer approaches, including high-dose therapy with stem cell support, biologic agents, and newer chemotherapeutic agents are discussed, as are special situations such as localized lymphoma of certain sites and lymphoma in immunosuppressed patients.
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PMID:Non-Hodgkin's lymphoma. 891 70

Chronic granulomatous disease (CGD) is an inherited immunodeficiency characterized by severe recurrent bacterial and fungal infections of several organs. The disease is due to the inability of phagocytic leukocytes to generate reactive oxygen species upon phagocytosis. The defect arises as a consequence of mutations of the genes encoding for the subunits of a membrane NADPH oxidase, which catalyzes the production of superoxide anion (O2-). CGD represents an ideal candidate disorder for gene therapy, since the disease has a recessive inheritance, its phenotype is exclusively expressed in phagocytic cells, and a partial correction is likely to be effective. Given the short half-life of mature phagocytes, the optimal target cell population for gene transfer is the pluripotent hematopoietic stem cell. Transduction of CD34+ hematopoietic progenitors with retroviral vectors carrying the cDNA of the defective gene results in the correction of the enzymatic defect in myeloid cells differentiated in vitro. Still, the effective development of a clinical gene therapy protocol for this disease will await a substantial improvement in our current technology for the identification and manipulation of hematopoietic stem cells, and in our understanding of their biological and molecular properties.
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PMID:Gene therapy of chronic granulomatous disease (CGD) by gene transfer into hematopoietic stem cells. 1023 75

There are continuing concerns over the safety of the nation's and the world's blood supply. The allogeneic blood supply is tested for antibodies to HIV1/2, HTLVI/II, hepatitis B, hepatitis C (HCV) and syphilis. Testing is also performed for donor ALT (SGOT) levels, for the presence of hepatitis B surface antigen, human immunodeficiency virus (HIV) p24 antigen and, using nucleic acid amplification testing (NAT), for HIV and HCV nucleic acids. Still, there are concerns regarding other pathogenic agents. Dr. Roger Dodd addresses a series of pathogens that are already known to be transmissible by transfusion. These include malaria, Chagas' disease, babesiosis, bacteria and some viral agents. The need for new donor screening assays to protect the integrity and purity of the blood supply must be balanced against the loss of potential donors and the cost of developing and implementing these new screening assays. This issue will be highlighted. Dr. Edward Snyder reviews the status of research into development of systems for pathogen inactivation (PI) of blood and its components. A proactive technology wherein PI reagents such as psoralen, riboflavin, dimethylmethylene blue or inactine are added to blood collection bags could assure multiple log reduction of a variety of pathogens including viruses, bacteria, protozoa and fungi without the need to initially pre-screen the blood for a specific pathogen. Such a program could also cover new pathogens as they enter the blood supply. As a key issue relates to the toxicology of these agents, Dr. Snyder provides data on a novel carcinogenicity assay that uses a heterozygous p53 knock-out mouse model. The criteria likely to be needed for PI technology to be adopted by the transfusion community are summarized.
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PMID:Reducing the risk of blood transfusion. 1172 97


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