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)

Tat protein of the human immunodeficiency virus type-1 (HIV-1) plays a critical role in the regulation of viral transcription and replication. In addition, Tat regulates the expression of a variety of cellular genes and could account for AIDS-associated diseases including Kaposi's Sarcoma and non-Hodgkin's lymphoma by interfering with cellular processes such as proliferation, differentiation, and apoptosis. The molecular mechanisms underlying the pleiotropic activities of Tat may include the generation of functional heterodimers of Tat with cellular proteins. By screening a human B-lymphoblastoid cDNA library in the yeast two-hybrid system, we identified E2F-4, a member of E2F family of transcription factors, as a Tat-binding protein. The interaction between Tat and E2F-4 was confirmed by GST pull-down experiments performed with cellular extracts as well as with in vitro translated E2F-4. The physical association of Tat and E2F-4 was confirmed by in vivo binding experiments where Tat.E2F-4 heterodimers were recovered from Jurkat cells by immunoprecipitation and immunoblotting. By using plasmids expressing mutant forms of Tat and E2F-4, the domains involved in Tat.E2F-4 interaction were identified as the regions encompassing amino acids 1-49 of Tat and amino acids 1-184 of E2F-4. Tat x E2F-4 complexes were shown to bind to E2F cis-regions with increased efficiency compared with E2F-4 alone and to mediate the activity of E2F-dependent promoters including HIV-1 long terminal repeat and cyclin A. The data point to Tat as an adaptor protein that recruits cellular factors such as E2F-4 to exert its multiple biological activities.
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PMID:Physical and functional interaction of HIV-1 Tat with E2F-4, a transcriptional regulator of mammalian cell cycle. 1205 84

Dysphonia and airway obstruction are rarely caused by Kaposi's Sarcoma (KS). We present the case of a 40 year old man receiving his diagnosis of human immunodeficiency virus (HIV) after presenting with hoarseness caused by laryngeal KS. HIV may contribute to KS growth by stimulating excess production of angiogenic lymphokines and monokines and by decreasing immune surveillance. Histopathology reveals proliferating endothelial cells, fibroblasts, thin vascular slits, and extravasated erythrocytes. A wide variety of localized treatment options exist, while chemotherapeutic agents and alpha-interferon are used for multifocal or widespread disease.
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PMID:Dysphonia due to Kaposi's sarcoma as the presenting symptom of human immunodeficiency virus. 1533 Nov 14

Both the incidence and prevalence of human immunodeficiency virus infection are increasing in the world. Diseases of ENT districts are more frequent in human immunodeficiency virus-infected patients and involve all the otolaryngological sites. The otorhinolaryngological manifestations in association with HIV infection are mainly atypical, so common in the clinical practice, really aspecific and very frequent in ENT daily routine (such as sinusitis, otitis, etc.) and, therefore, immunodeficiency may not be suspected. In other cases, ENT evidence is more peculiar or unusual, such as opportunistic infections, rare neoplasm and tumours with an unusual course, giving a very high suspect of a human immunodeficiency virus-related infection. The most frequent malignant neoplasm is Kaposi's Sarcoma which is extremely rare in non-human immunodeficiency virus-infected subjects; the second most frequent is non-Hodgkin's lymphoma with 50% in extranodal sites (oral and maxillary sinus). Following a review of the literature, modifications caused by current antiretroviral treatment on head and neck manifestations of human immunodeficiency virus infection have been evaluated. Highly active antiretroviral therapy is a new therapeutic strategy, based on poly-chemo-therapeutic schemes, providing simultaneously two or more anti-retroviral drugs. We have used highly active antiretroviral therapy in human immunodeficiency virus infection since 1997, substituting previous mono-chemotherapy based on Zidovudine or Didanosine alone. Highly active antiretroviral therapy is extremely efficient in reducing the viral load of human immunodeficiency virus and increasing CD4+ T-lymphocyte count. These biological effects are associated with an improvement in immune functions. To evaluate the effects of highly active antiretroviral therapy on otorhinolaryngological manifestations in human immunodeficiency virus infection, we performed a retrospective study on 470 adults, observed over 14 years (1989-2002) and constantly receiving the same treatment, with follow-up from 7 to 80 months. A total of 250 subjects underwent mono-antiretroviral chemotherapy (1989-1996), while 220 underwent highly active antiretroviral therapy (1997-2002). The results of the retrospective study showed that highly active antiretroviral therapy has greatly improved the control of the immune-deficiency (increasing the range of CD4+), reducing the number of otorhinolaryngological manifestations (also tumours). On the other hand, 2 patients presented sudden unilateral hearing loss following treatment: toxicity due to association of new drugs cannot be excluded.
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PMID:Human immunodeficiency virus infection: personal experience in changes in head and neck manifestations due to recent antiretroviral therapies. 1608 Mar 13

A number of immunodeficiency states--both inherited (such as agammaglobulinaemia, Bloom's syndrome, hereditary telangiectasia) and acquired (e.g. immunosuppressive therapy) have been associated with varieties of cancers. HIV induces more profound immunodeficiency state and it should not be difficult to imaging why cancer diagnosis is made in over 40% of HIV infected patients. Impairment of normal function of natural killer cells as a result of lack of helper signals from CD4+ T-lymphocytes may be a major mechanism of increased susceptibility to cancer development in HIV infected patients. Although many neoplastic diseases could occur at a frequency not higher than would be expected by chance alone, the biological behaviour of such malignancies tend to be more aggressive. Three neoplastic diseases are associated so commonly with HIV infection that each of them has become recognized as an AIDS defining illness. These are Kaposi's Sarcoma (KS), Non-Hodgkin's Lymphoma (NHL) and Cervical Carcinoma. Both KS and NHL were recognized as AIDS associated cancers from the onset of the epidemic in 1981 but carcinoma of the cervix became AIDS defining in 1993. The epidemiology, aetiopathogenesis, clinical manifestation, diagnostic tools and modalities of therapeutic intervention for KS and NHL form the subject of this review.
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PMID:AIDS-associated malignancies. 1805 Jul 76

Around the world, infection is one of the most important causes of cancer. Almost one in every five malignancies can be attributed to infectious agents. Among infection-related neoplasms, cancers of the stomach, liver and cervix uteri detain the highest incidence figures, and are known to be largely attributable to Helicobacter pylori, hepatitis B and C viruses, and human papilloma virus, respectively. Other infectious organisms can also cause cancer; these include the Epstein-Barr virus (nasopharyngeal carcinoma, and different types of lymphoma), Human herpes virus-8 (Kaposi's Sarcoma), human T-cell leukemia virus type I (leukaemia, lymphoma), liver flukes (cholangiocarcinoma) and schistosomiasis (bladder cancer). Infection with human immunodeficiency virus, although strongly associated with an excess of cancer incidence at many cancer sites, is probably not carcinogenic per se, but acts mainly via immunodeficiency. The burden of infection-related cancers is still underestimated worldwide, due to the use of conservative population prevalence and risk ratio estimates. Furthermore, associations with new infectious agents remain yet to be explored.
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PMID:Infections and cancer: established associations and new hypotheses. 1880 2

Immunosuppressive agents are used for treatment of a variety of autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosis (SLE), and psoriasis, as well as for prevention of tissue rejection after organ transplantation. Recrudescence of herpesvirus infections, and increased risk of carcinogenesis from herpesvirus-associated tumors are related with immunosuppressive therapy in humans. Post-transplant lymphoproliferative disorder (PTLD), a condition characterized by development of Epstein Barr Virus (EBV)-associated B-lymphocyte lymphoma, and Kaposi's Sarcoma (KS), a dermal tumor associated with Kaposi Sarcoma-associated virus (KSHV), may develop in solid organ transplant patients. KS also occurs in immunosuppressed Acquired Immunodeficiency (AIDS) patients. Kaposi Sarcoma-associated virus (KSHV) is a herpes virus genetically related to EBV. Murine gammaherpes-virus-68 (MHV-68) is proposed as a mouse model of gammaherpesvirus infection and recrudescence and may potentially have relevance for herpesvirus-associated neoplasia. The pathogenesis of MHV-68 infection in mice mimics EBV/KSHV infection in humans with acute lytic viral replication followed by dissemination and establishment of persistent latency. MHV-68-infected mice may develop lymphoproliferative disease that is accelerated by disruption of the immune system. This manuscript first presents an overview of gammaherpesvirus pathogenesis and immunology as well as factors involved in viral recrudescence. A description of different types of immunodeficiency then follows, with particular focus on viral association with lymphomagenesis after immunosuppression. Finally, this review discusses different gammaherpesvirus animal models and describes a proposed MHV-68 model to further examine the interplay of immunomodulatory agents and gammaherpesvirus-associated neoplasia.
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PMID:Is murine gammaherpesvirus-68 (MHV-68) a suitable immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence? 2451 28

Kaposi's Sarcoma (KS) is a malignancy that generally effects the skin, and can be systemic with internal organ involvement. It originates from the vascular endothelium. KS's relationship with human immunodeficiency virus (HIV) infection is well known. Isolated scrotal KS in the urogenital system is quite rare and scrotal KS in an HIV-negative patient is limited to a few cases. In this case report, the biopsy result from the violescent nodular lesions on the scrotum of the HIV-negative 81-year-old patient was found compatible with KS and a pathology was not detected in the systemic screening. With a diagnosis of isolated scrotal KS, the patient underwent surgical excision aimed at the lesions on the scrotum. KS is rare in HIV-negative patients and it is associated with human herpes virus-8 infection.
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PMID:Scrotal Kaposi's Sarcoma in HIV-negative patient: A case report and review of the literature. 2951 91

Non-Hodgkin Lymphoma (NHL) is a neoplasm associated with a group of malignancies called AIDs-Defining Malignancies (ADMs) in Human-Immunodeficiency Virus (HIV) -patients. Similar to the case of NHL in Latin America, particularly in Peru, the amount of research done on others ADMs is limited, especially in the case of Kaposi's Sarcoma (KS). Prior investigations have talked about the great potential risk that represents this illness in latin american population, but topics as prognosis factors are yet to be well defined. In this letter, we address the importance of investigation in this area and include previously reported data that may enlighten the current national standpoint.
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PMID:Letter to the editors regarding the paper: Prognostic factors in HIV-positive patients with non-Hodgkin lymphoma: a Peruvian experience. 3055 26


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