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)

Feline leukemia virus (FeLV) infection in cats serves as a valuable animal model system for understanding the mechanisms of human diseases such as cancer and immunodeficiency. We have used experimental infection with molecularly cloned viruses to isolate and characterize novel FeLV variants that evolved in vivo and that were associated with the development of thymic lymphoma. One variant, FeLV-81T, contained a mutated envelope gene that conferred cytopathicity, enhanced replication rate, and syncytium induction in feline T cells, and is reminiscent of immunodeficiency-inducing strains of FeLV. Another variant transduced a portion of the feline Notch2 gene, which was expressed as a novel truncated protein in the cell nucleus and which we believe functioned as an oncogene in the development of T cell malignancy. Understanding how FeLV variants that either stimulate or destroy lymphocytes evolve and interrelate during disease progression will help elucidate the mechanisms of retroviral pathogenicity.
Leukemia 1996 Dec
PMID:Viral genetic variation, AIDS, and the multistep nature of carcinogenesis: the feline leukemia virus model. 894 23

Cyclin-dependent kinase inhibitors (CDKIs) can be classified into two groups based on the structure of the proteins. One group includes the p21 (CIP1, WAF1, CAP20), p27 (Kip1), and p57 (Kip2) CDKIs, which contain a homologous amino-terminal cyclin-dependent kinase (cdk) inhibitory domain. The p16 (INK4A), p15 (INK4B), and p18 (INK4C) CDKIs, which have an ankyrin repeat motifs, belong to the other group. The p16 and p15 CDKI genes are very frequently altered in a variety of cancers including hematopoietic malignancies. The p19 (INK4D) gene is a newly cloned CDKI which belongs to the latter group. To determine if p19 genetic alterations play a role in hematopoietic malignancies, we examined DNA from 45 childhood newly diagnosed acute lymphocytic leukemias (ALLs), 30 acute myeloblastic leukemias (AMLs), 10 chronic myelocytic leukemias (CMLs), 45 adult T cell leukemias (ATLs), 70 non-Hodgkin's lymphomas (NHLs), and 20 multiple myelomas (MM) as well as 14 ALL, 20 AML, two ATL, and five lymphoma cell lines. Using Southern blot analysis, one homozygous deletion of the p19 gene was detected in a human immunodeficiency virus (HIV)-related Burkitt-like lymphoma sample. No point mutations in any of the samples were found by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Our investigation suggests that alterations of p19 do not play an important role in the development of most hematopoietic malignancies.
Leukemia 1996 Dec
PMID:Alterations of the cyclin-dependent kinase inhibitor p19 (INK4D) is rare in hematopoietic malignancies. 894 28

The long-term outcome of patients with hairy cell leukemia resistant to interferon-alpha (IFN-alpha) following treatment with deoxycoformycin (DCF) was examined, and the kinetics of recovery of lymphocyte subsets and factors influencing the rate of recovery investigated. Between May 1986 and May 1989, 15 patients with histologically confirmed hairy cell leukemia resistant to IFN-alpha received DCF 4 mg/m2 every 2 weeks with 12 cycles planned. All 15 patients were evaluable for response and have been followed for a median of 88 months (range, 72 to 106 months) from the start of therapy. Fourteen patients responded to DCF, all attaining complete remission (CR) (response rate 93%; 95% confidence interval, 69% to 100%). Seven patients have developed recurrent disease after 45 to 74 months. Using the method of Kaplan and Meier, the median remission duration is 74 months and, at 8 years, 46% (95% confidence interval, 33% to 59%) of patients are projected to be in ongoing CR. The seven relapsing patients have responded to treatment with 2-chlorodeoxyadenosine (2-CdA) and all 15 patients remain alive. After DCF, nadir CD4+ and CD8+ lymphocyte counts were significantly lower than prior to therapy (P < 0.0001 and P = 0.05, respectively), but returned to baseline levels during follow-up. Median times to attainment of the lower limit of the normal range of CD4+ and CD8+ lymphocytes were 54 and 36 months, respectively. Those patients who had previously undergone splenectomy (n=7) had higher baseline CD4+ (P= 0.073) and CD8+ (P= 0.043) lymphocyte counts and more rapid recovery of both CD4+ (P= 0.027) and CD8+ lymphocyte counts (P = 0.016) than non-splenectomized patients. One elderly patient (age, 78 years) was diagnosed with subsequent malignancy. No late opportunistic infections were observed. Resistance to IFN-alpha does not impair subsequent responsiveness of patients with hairy cell leukemia to treatment with DCF. Responses are durable and without evidence of long-term sequelae. CD4+ and CD8+ lymphocyte subsets recover slowly without clinical manifestations of immunodeficiency. Splenectomized patients appear to have higher baseline lymphocyte counts and more rapid lymphocyte recovery following treatment with DCF.
Leukemia 1997 Jan
PMID:Response duration and recovery of CD4+ lymphocytes following deoxycoformycin in interferon-alpha-resistant hairy cell leukemia: 7-year follow-up. 900 17

Oral candidiasis is a common fungal infection in patients infected with the human immunodeficiency virus (HIV). Although rare at the time of primary HIV infection, it is frequently found throughout the asymptomatic phase and is predictive of progressive immunodeficiency. However, the precise immune defect which results in outgrowth of commensal Candida albicans in HIV infection has not been identified. Mice infected with the Du5H(G6T2) mixture of mouse leukemia viruses develop a syndrome, designated murine AIDS (MAIDS), that has many of the immune abnormalities found in HIV infection. Retrovirus-infected C57BL/6 mice were examined for their ability to resist the development of oral candidiasis from the carrier state established after a self-limiting acute infection and to clear a subsequent secondary inoculum of oral C. albicans. Most of the mice orally colonized with C. albicans and then inoculated with the retrovirus mixture maintained a low-level oral carriage of C. albicans, while 30% of coinfected mice developed recurring 2- to 3-week episodes of acute Candida proliferation, separated by transient recoveries to the carrier state. The frequencies of CD4+ and CD8+ lymphocytes were, respectively, unchanged and significantly decreased (P < 0.05) in both cervical lymph nodes and spleens of coinfected mice compared to the corresponding frequencies in C. albicans-carrying, virus-free, age-matched control animals. Secretion of gamma interferon by concanavalin A (ConA)-stimulated spleen cells from Candida-carrying, retrovirus-infected mice was significantly decreased (P < 0.05) compared to that of C. albicans-carrying, retrovirus-free mice, in accordance with known abnormalities associated with MAIDS. However, production of this cytokine by ConA-stimulated or unstimulated cervical lymph node cells from coinfected mice was enhanced compared to that of virus-free animals colonized with C. albicans. Acquired resistance to reinfection with C. albicans was maintained in retrovirus-infected mice and was associated with a mucosal recruitment of CD8+ cells not observed in control mice. These results suggest that alterations in mucosal immunity which occur in MAIDS differ substantially from defects observed at other sites and that surrogate epithelial defense mechanisms may function locally to limit Candida proliferation.
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PMID:Oral carriage of Candida albicans in murine AIDS. 900 28

A rapid (within 1 h) and profound cytotoxic cell death of immature TdT+CD4+CD8+ and/or TdT+CD4+ thymic T cell type leukemia cell lines, and of normal thymocyte populations rich in TdT+CD4+CD8+ cells was induced by contact with some human immunodeficiency virus type-1 (HIV-1) carrier T cell clones. This cytotoxic reaction, without requiring a complete viral replication cycle in the thymic T cells, did not occur in any mature CD4+CD8+ and/or CD4+ T cells which are otherwise permissive for virus infection. Although it was not an antigen-specific cytotoxic reaction, the rapid and profound thymic T cell destruction was shown, at the individual clonal level, to be triggered specifically by the binding of CD4 molecules on thymic T cells with gp120/gp160 on HIV-1 carrier clones. The present study suggesting direct elimination of immature T cells by contact with some HIV-1-infected T cells, may provide a novel insight into the mechanism responsible for the mature CD4+ T cell depletion in HIV-1 infection.
Leukemia 1997 May
PMID:In vitro study using leukemia cell line panel to demonstrate rapid thymic T cell death due to contact with HIV-1 carrier cell clones. 918 Feb 97

The localization of mammalian retroviruses to specified immune organs has significant implications on the pathophysiology of retroviral associated diseases. Human T-cell Lymphotropic Virus Type I (HTLV-I) is considered a CD4+ lymphotropic virus although the virus has been shown to infect a large variety of cells in vitro. Similarly, the human immunodeficiency virus (HIV), once thought to be harbored only in CD4+ peripheral blood lymphocytes (PBL) has been shown to be present in latent form in lymph nodes of HIV infected patients. HTLV-I Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a chronic progressive neurologic disorder of the central nervous system and is believed to result from infection of HTLV-I in association with an immunopathogenic or autoimmune mechanism. Here we describe experiments which utilize the in situ hybridization/polymerase chain reaction technology to demonstrate extensive HTLV-I infection of bone marrow in HAM/TSP patients. We discuss these results in the context of HTLV-I associated neurologic disease and extend these observations to other disorders of potential retroviral etiology and autoimmune involvement.
Leukemia 1997 Apr
PMID:Immunopathogenesis of HTLV-I associated neurologic disease: massive latent HTLV-I infection in bone marrow of HAM/TSP patients. 920 3

Oxathlin carboxanilide analogs (UC) and alpha APA, compounds recognized as nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI), were evaluated for activity against the human immunodeficiency virus (HIV-1) and drug-resistant variants. These NNRTIs are structurally diverse but potent inhibitors of HIV-1 with efficacy in the nanomolar to low micromolar concentrations. They interact at a specific site in the pain domain of the p66 subunit of RT. Treatment of HIV-1 infected cell cultures with UC compounds resulted in the selection of drug-resistant viruses bearing specific amino acid changes at 100, 101, 103, 106, and/or 181. Since Y181C and L1001 are the most commonly observed resistance-engendering mutations, RT enzymatic analysis was correlated with molecular modeling to glean information on the structural interactions between these NNRTIs and RT. Information derived from these studies will facilitate rational drug design and the selection of complementary anti-HIV drugs for combination therapy.
Leukemia 1997 Apr
PMID:Cross-resistance analysis and molecular modeling of nonnucleoside reverse transcriptase inhibitors targeting drug-resistance mutations in the reverse transcriptase of human immunodeficiency virus. 920 8

The human immunodeficiency viruses (HIV-1) undergo high rates of variation. Only a few point mutations in the envelope gene are required to switch the tropism of HIV-1 from a growth preference for monocytes to lymphocytes or to acquire lytic properties for rapid killing of infected T4 lymphocytes. Since heterosexual transmission efficiency is high for HIV-1's that are most prevalent in Africa or Asia, but low for HIV-1 B, which dominates in the US and western Europe, we asked whether African and Asian viruses had a particular tropism for cells of the reproductive tract. Langerhans' cells (LC), showed only minimal susceptibility to infection with HIV-1B from the US, but substantially greater sensitivity for infections by HIV-1 E and HIV-1 C, subtypes that predominate in Asia and Africa.
Leukemia 1997 Apr
PMID:Genetic variation within human immunodeficiency viruses generates rapid changes in tropism, virulence, and transmission. 920 9

Infection of domestic cats with the feline immunodeficiency virus (FIV) represents an important veterinary health problem and a useful animal model for the development of vaccines against AIDS. Two experimental FIV vaccines have been developed: one consisting of fixed infected cells and the other of inactivated whole virus. Both vaccines elicited strong CTL responses to FIV and high virus neutralizing (VN) antibody titers. Over 90% of vaccinated cats were protected against intraperitoneal infection with 10 cat infectious dose 50% (10 CID50) of either homologous FIVPet or heterologous FIVDix. As a means to evaluate the mechanism of vaccine protection, cats were either passively immunized with serum antibodies or transfused with peripheral blood cells from FIV-vaccinated cats. Cats passively immunized with vaccine sera or purified vaccine antibodies were protected from homologous FIV infection at a challenge doses which infected all control cats (5 and 10 CID50). Such passive protection was not achieved against heterologous FIV challenge. More importantly, cats transfused with washed blood cells from half-matched vaccinated cat were protected from FIV challenge (20 and 50 CID50). As expected, protection was not observed in cats transfused with cells from either unmatched vaccinated or half-matched unvaccinated cats. Further, only peripheral-blood cells from vaccinated cats had FIV-specific CTL responses to both autologous and half-matched target cells. Overall, these findings suggest that both humoral and cellular immunity are required for optimal vaccine protection.
Leukemia 1997 Apr
PMID:Mechanism(s) of FIV vaccine protection. 920 11

The mechanisms responsible for development of profound immunodeficiency and extensive lymphoproliferation that characterize infection of different species with retroviruses are only partially understood. In mice, it has been shown the activities of an unusual Gag protein are necessary and sufficient to induce these abnormalities in a syndrome designated mouse AIDS (MAIDS). Current studies suggest that complex, antigen-driven interactions between T cells and B cells result in polyclonal activation of both types of lymphocytes, aberrant cytokine production and late lymphomas.
Leukemia 1997 Apr
PMID:Immunologic havoc induced by the 60 kD Gag protein of the MAIDS defective virus. 920 32


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