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

Development of a vaccine for acquired immunodeficiency syndrome (AIDS) has proven difficult, and so alternative approaches such as idiotypic manipulation have been suggested. As applied to AIDS, this approach could involve immunizing with an anti-CD4 antibody resembling gp120, to induce anti-idiotypic antibodies which would bind to gp120. The CD4 binding site on gp120 is conserved, and so, such an immune response should protect against all variants. Induction of anti-human immunodeficiency virus (HIV) immunity has been reported using anti-Leu3a, and this result has led to testing in humans. Negative results obtained by others have been attributed to differences in immunization protocols. Because of the importance of this question, we reinvestigated the potential of anti-Leu3a to induce anti-HIV antibodies, compared with control immunizations with OKT4A (another anti-CD4 antibody) and the irrelevant Ig MOPC-21. Responses to anti-Leu3a showed induction of high-titer anti-idiotypic activity, and included combining-site-related activity. Yet sera showed no binding to gp160 above controls and no detectable neutralizing activity in a sensitive HIV plaque assay, so the anti-idiotypes induced were not internal images of CD4. We conclude that the pronounced anti-HIV responses reported with anti-Leu3a cannot be generalized, and thus that anti-Leu3a does not offer promise as an HIV vaccine. However, these results do not negate the promise of the idiotypic approach, and a vaccine for AIDS based on idiotype manipulation remains a possibility.
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PMID:Anti-Leu3a induces combining site-related anti-idiotypic antibody without inducing anti-HIV activity. 201 15

7,8-Disubstituted guanine ribonucleosides represent a class of B lymphocyte agonists that utilize a protein kinase C-independent signaling pathway. These compounds provide an alternate T helper signal for B cells and enhance antigen-specific humoral responses in the murine model and in an IL-2-dependent human model in vitro. They effectively restore high level immune responses in a variety of murine models of immunodeficiency both in vivo and in vitro. In this study we examined the potential of these compounds to improve antibody responses generated by cultured cells from patients with common variable immunodeficiency (CVI). The inability to mount normal humoral responses to antigen was confirmed in nine patients with diagnosed CVI (CVI: 37 +/- 16, normal 653 +/- 116 plaque-forming cells (PFC)/culture; P less than 0.001). In cultured lymphocytes from eight of the nine patients studied, a normal level or greater responses to nominal antigen could be elicited by antigen in the presence of the immunostimulatory nucleoside 7-methyl-8-oxoguanosine (7m8oGuo). The average response to antigen increased from 37 +/- 16 without nucleoside to 1733 +/- 488 PFC/culture in its presence (P less than 0.002). Restoration of specific immune responses was an antigen-dependent and nucleoside dose-dependent event. Signaling by 7m8oGuo rendered the response to antigen protein kinase C independent in cultures of cells from normal donors as well as from CVI patients. These data substantiate (i) that a non-C-kinase signaling pathway for antigen-dependent differentiation exists, (ii) that this pathway can function normally in B cells from patients with CVI when triggered appropriately, and (iii) that 7,8-disubstituted guanine ribonucleosides can convert a C-kinase-dependent signaling event to a C-kinase-independent signaling event. Substituted guanine ribonucleosides may have potential as immunotherapeutic agents for patients with CVI.
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PMID:Protein kinase C independent restoration of specific immune responsiveness in common variable immunodeficiency. 201 9

We have studied the relationship of antibodies reacting with human retroviral core proteins to the disease outcome in Finnish mycosis fungoides (MF) patients in a prospective manner. Antibodies recognizing human T-cell leukaemia/lymphoma virus I (HTLV-I) or human immunodeficiency virus type 1 (HIV-1) core proteins were found in 12 of 14 MF patients as shown by the Western blot method. The antibody reactivities showed three patterns: three patients had antibodies cross-reacting with the gag-encoded core proteins of both HTLV-I and HIV-1; seven patients showed antibodies reacting with HTLV-I core proteins only; and the sera of two patients reacted with HIV p24 core protein only. When following the clinical course of these patients, we found that the three patients with antibodies cross-reacting with both viruses had the most fulminant clinical course, and the overall duration of MF was, on average, 4 years less than in the rest of the patients. None of the patients, however, became leukaemic, or showed any other features suggestive of acute T-cell leukaemia/lymphoma (ATL). Two patients, who did not show anti-retroviral antibodies during the follow-up, had a stable disease with plaque-type skin lesions. Histological or immunohistological typing of the skin infiltrates did not correlate with the disease outcome or the above antibody patterns. Our results thus raise the possibility that an unknown retrovirus, immunologically related to the known human retroviruses, may be aetiologically linked to MF.
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PMID:Antibodies against retroviral core proteins in relation to disease outcome in patients with mycosis fungoides. 208 36

Oral hairy leukoplakia occurs almost exclusively in human immunodeficiency virus (HIV)-infected patients and is predictive for the development of acquired immunodeficiency syndrome (AIDS). It presents as a white plaque with a rough surface, most commonly on the sides of the tongue. The eruption is frequently overlooked, and, because it is commonly mistaken for oral candidiasis, its true incidence is unknown. The leukoplakia is the result of permissive infection of epithelial cells by the Epstein-Barr virus. Antiviral therapy that inhibits Epstein-Barr virus replication can result in clinical improvement. Oral hairy leukoplakia provides a unique clinical model for investigations on the pathogenesis of Epstein-Barr virus infection.
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PMID:Oral hairy leukoplakia. 216 9

An investigation of the potential spread of iatrogenic infections through contaminated multidose vials was performed. Contamination of a multidose vial was hypothesized to occur after a single syringe is used to inject an infected patient with medication, and the same syringe subsequently is used to withdraw additional medication from the multidose vial. If the contaminated multidose vial is used for another patient, an iatrogenic infection may be spread. Laboratory study of this injection technique found that viral plaque-forming units could be transmitted to a multidose vial in this manner. A survey of 100 fellows of the American Academy of Dermatology from the United States found that 24% of the respondents used this potentially unsafe procedure. The potential for iatrogenic spread of the human immunodeficiency virus and hepatitis B virus is described. Recommendations to avoid patient infection are made.
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PMID:Iatrogenic contamination of multidose vials in simulated use. A reassessment of current patient injection technique. 217 97

To explore the biologic significance of the presence of a heterogeneous human immunodeficiency virus (HIV) population within infected individuals with regard to ultimate disease progression, the effect of coinfection of more than one variant of HIV on infectivity and cytopathogenicity in CD4-positive cells was examined. Using the lowest and highest infectious clones of HIV obtained by the plaque-cloning method, a clear consistent synergism of infectivity and cytopathic effects was detected when different cell lines were coinfected with a mixture of the two clones. These data suggest that the emergence of a highly infectious variant of HIV due to mutation may modify the infectivity of a minimally infectious latent variant with the final progression of HIV infection to overt AIDS.
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PMID:Synergistic infectivity of highly and minimally infectious clones of human immunodeficiency virus in vitro. 218 23

The observation that human immunodeficiency virus resistant to zidovudine can be isolated from patients with AIDS or AIDS-related complex during prolonged zidovudine treatment was made with a plaque reduction assay employing a CD4-expressing HeLa cell line. Fifty percent inhibitory concentrations of zidovudine for isolates from untreated patients ranged from 0.01 to 0.05 microM. In contrast, most isolates from these patients showed decreased sensitivity after 6 months or more of zidovudine administration. Isolates from several patients showed progressive, stepwise reductions in sensitivity. Zidovudine-resistant isolates exhibited cross resistance to 3'-azido-2',3'-dideoxyuridine and 3'-azido-2',3'-dideoxyguanosine but not to dideoxycytidine, dideoxyinosine, foscarnet (phosphonoformate), or several other compounds. The clinical implications of these findings have yet to be determine. Studies are in progress to assess sensitivity patterns of isolates from patients who are at earlier stages of human immunodeficiency virus disease or who are receiving other drug therapy and to characterize the mutations and mechanisms accounting for resistance.
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PMID:Zidovudine resistance of human immunodeficiency virus. 201 26

To perform a human immunodeficiency virus (HIV) plaque assay in nonadherent host cells, we developed a novel technique in which HIV-infected MT-2 cells were formed into monolayers by centrifugation through molten agarose. Infection, formation of cell monolayers, and enumeration of plaques all took place in 96-well microtiter plates. When this process was preceded by 18 h of incubation of HIV with patient serum samples, neutralizing antibody titers between 1:10 and 1:5,000 could be accurately determined in patient serum samples. In addition to the determination of neutralizing antibody titers (with the use of various serum dilutions and a constant virus concentration), neutralization indices could also be determined with different virus dilutions and a single dilution of patient serum.
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PMID:Application of a rapid microplaque assay for determination of human immunodeficiency virus neutralizing antibody titers. 222 85

Mice infected i.v. with high doses of lymphocytic choriomeningitis virus (LCMV; 10(5)-10(6) plaque-forming units) 8-10 days prior to challenge with the methylcholanthrene-induced fibrosarcoma tumor cell line MC57G or the melanoma cell line B16 tumor cells showed an enhanced tumor susceptibility with respect to both growth kinetics of the tumor and the minimal dose necessary for tumor take. After transient initial growth, MC57G tumor cells were all rejected by uninfected C57BL/6 mice by day 14. Mice preinfected i.v. with LCMV 3 weeks before or at the time of tumor challenge, but not those infected 2 months before or 7 days after, showed increasing tumor growth, the tumor take being 100% for 10(6), 50% for 10(5) and 37% for 10(4) MC57G tumor cells injected into the footpad compared with resistance to 10(6) cells in normal mice. B16 melanoma cells also grew more rapidly in LCMV-preinfected mice and by day 40 tumors were established with about 100 times fewer cells, i.e. about 10(3) compared with 3 x 10(4)-3 x 10(5) for uninfected mice. Analysis of the growth of tumor cells in normal and in LCMV-carrier mice revealed that the latter mice were not more susceptible to LCMV-infected than to uninfected MC57G. Since LCMV-carrier mice fail to mount LCMV-specific T cell responses, these results suggest that anti-LCMV-specific T cells may be responsible for acquired immunodeficiency hampering immune surveillance against the tumors studied.
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PMID:Enhanced tumor susceptibility of immunocompetent mice infected with lymphocytic choriomeningitis virus. 228 3

Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection developed persistent disseminated hyperkeratotic papules that failed to heal with intravenous or high-dose oral acyclovir therapy. Varicella zoster virus, resistant to acyclovir in vitro, was isolated from skin lesions of all four patients. Three patients were adults in whom the acquired immunodeficiency syndrome (AIDS) had been diagnosed 12 to 20 months before isolation of acyclovir-resistant varicella zoster virus. The fourth patient was a perinatally HIV-infected child who developed primary varicella infection at age 7 years when profoundly immunosuppressed (absolute CD4+ lymphocyte count less than 50 cells/microL). Mean antiviral susceptibilities (ED50 values) of the four clinical isolates compared with the ED50 values of the reference strain Oka were 85 compared with 3.3 mumol/L for acyclovir, 1.4 compared with 0.8 mumol/L for vidarabine, and 123 compared with 117 mumol/L for foscarnet. When assayed by [125I]-dC plaque autoradiography, 90% to 100% of the viral isolate populations had altered or no measurable thymidine kinase function. Acyclovir-resistant varicella zoster virus infection may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with the appearance of atypical hyperkeratotic papules.
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PMID:Acyclovir-resistant varicella zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS). 229 95


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