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)

Genetic diagnosis is a revolutionary method that makes possible simultaneous viral isolation (detection) and identification. The method is so specific, sensitive, and rapid (non-culture) that leads not only to the diagnosis of viral infection, but also to prediction of the chemotherapy, monitoring during the therapy, and judging the efficacy of the treatment. Moreover, it contributes to understanding the disease pathophysiology. The qualitative results are sufficient for diagnosis, but quantitative analysis is sometimes necessary for the prediction of the efficacy and monitoring during treatment. It occasionally requires the numbers of genomic expression, the number of DNA/RNA copies, and the detection of point mutations for drug resistance. Many emerging and re-emerging infectious diseases, such as AIDS and viral hepatitis, are induced by viral infection via blood. The main causative agents of blood-borne viral infection are hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T cell leukemia virus type 1 (HTLV1), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human parvovirus B19. They play main roles in viral hospital infection. The risk of them being transmitted by transfusion of screened blood is very low, but it is always possible that infection may occur in a window period even after extensive blood screening tests. Therefore, to shorten a window period, genetic examinations will be accepted for screening tests in the near future. Prioritization of genetic examinations is needed to select the adequate method and sampling. After examinations, false positive and false negative results have to be extensively read out whether due to contamination or inhibition by agent such as heparin and hemoglobin. The causative virus should be decided by carefully eliminating passenger viruses or latent viruses. Because genetic examinations are so useful but occasionally yield false positive and negative results, genetic diagnosis should be judged totally by combination with other examinations, clinical signs, and clinical symptoms.
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PMID:[The role of genetic diagnosis in clinics--from the choice of ordering until reading the data]. 1059 Jun 77

Viruses are etiologically linked to approximately 20% of all malignancies worldwide. Retroviruses account for approximately 8%-10% of the total. For human T-cell leukemia virus 1 (HTLV-I), the viral regulatory tax gene product is responsible for enhanced transcription of viral and cellular genes that promote cell growth by stimulating various growth factors and through dysregulation of cellular regulatory suppressor genes, such as p53. After a long latent period, adult T-cell leukemia/lymphoma (ATL) occurs in 1 per 1000 carriers per year, resulting in 2500-3000 cases per year worldwide and over half of the adult lymphoid malignancies in endemic areas. Human immunodeficiency virus 1 (HIV-1) accounts for a significant cancer burden, and its transactivating regulatory protein Tat enhances direct and indirect cytokine and immunological dysregulation to cause diverse cancers. Kaposi's sarcoma (KS) is a very rare tumor except after HIV-1 infection, when its incidence is greatly amplified reaching seventy thousand-fold in HIV-infected homosexual men. Human herpesvirus 8 (HHV-8), which is also known as Kaposi's sarcoma-associated virus (KSHV), is a necessary but not sufficient etiological factor in KS. The dramatic decline of KS since the introduction of highly active antiretroviral therapy (HAART) could be due to suppression of HIV-1 tat. B-cell non-Hodgkin's lymphoma occurs as their first acquired immunodeficiency syndrome-defining diagnosis in 3%-4% of HIV-infected patients. Hodgkin's lymphoma is also associated with HIV infection but at a lower risk. Human papillomaviruses are linked to invasive cervical cancer and anogenital cancers among HIV-infected patients. Human retroviruses cause malignancy via direct effects as well as through interactions with other oncogenic herpesviruses and other viruses.
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PMID:Human retroviruses: their role in cancer. 1059 Oct 85

The interaction between human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia-lymphoma virus type I (HTLV-I) has generated substantial interest. However, there is disagreement on the in vivo consequences of the double infection. We investigated the interactions between HIV-1 and HTLV-I in monocyte-derived macrophages cultured in vitro. For study, the T cell-tropic strain IIIB and the macrophagetropic strain Ada-M of HIV-1 were used. The HTLV-I was prepared from the supernatants of the virus-producing MT-2 cell line. We found that coinfection of macrophages with T cell-tropic HIV-1 and HTLV-I significantly enhanced HIV-1 replication, whereas double infection of the cells with macrophage-tropic HIV-1 and HTLV-I resulted in marked upregulation of HTLV-I production. Stimulatory interactions between HIV-1 and HTLV-I were mediated by their trans-acting proteins. Results of study on nuclear translocation of proviral DNA showed that the tax gene product of HTLV-I was able to facilitate the nuclear import of the reverse-transcribed HIV-1(IIIB) DNA. In contrast, the HIV-1 Tat protein did not increase the intranuclear trafficking of HTLV-I DNA, which suggests another mechanism for HTLV-I enhancement by the tat gene product. In conclusion, this study provides possible mechanisms whereby coinfection of an individual with HIV-1 and HTLV-I may influence the clinical outcome of double infection.
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PMID:Differential patterns of interaction between HIV type 1 and HTLV type I in monocyte-derived macrophages cultured in vitro: implications for in vivo coinfection with HIV type 1 and HTLV type I. 1060 88

Adult T-cell leukemia/lymphoma(ATL) was first discovered and reported in Japan, where it has a high incidence in the southwestern region of the country. The retrovirus human T-cell leukemia virus type I(HTLV-I) is considered to be related to its etiology. ATL shows divers clinical features. It can be divided into four types of smoldering, chronic, acute, and lymphoma. ATL cells originate from the CD4-positive subset of peripheral T cells showing a characteristic notch in the nucleus and a tendency for lobulation. A definit diagnosis of ATL is made by documenting the presence of HTLV-I proviral DNA in the DNA of leukemic or lymphoma cells. Crinico-Pathological aspects of ATL are more complexed than other types of lymphoma because of the verity of the disease type, state of immunodeficiency, hypercalcemia, cytokine activation, and so on.
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PMID:[Clinico-pathological aspects of adult T-cell leukemia/lymphoma(ATL)]. 1074 Nov 41

Infection with human T cell leukemia virus type 1 (HTLV-1) can result in the development of HAM/TSP, a nonfatal, chronic inflammatory disease involving neuronal degeneration and demyelination of the central nervous system. Elevated levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 observed in the cerebrospinal fluid of HAM-TSP patients suggest that cytokine dysregulation within the CNS is involved in neuropathogenesis. HTLV-1 infection and enhanced expression of TNF-alpha by microglial cells, astrocytes, and macrophages has been hypothesized to lead to the destruction of myelin and oligodendrocytes in the CNS. Although the association of HTLV-2 infection and development of neurological disease is more tenuous, HTLV-2 has also been found to be associated with peripheral neuropathies. To investigate the roles of HTLV Tax(1) and Tax(2) in the induction of cytokine disregulation in these cell types, we are currently developing gene delivery vectors based on human immunodeficiency virus type-1 (HIV-1) capable of stably coexpressing the HTLV-1 or -2 tax and eGFP reporter genes in primary human cells. Transduction frequencies of up to 50%, as assessed by eGFP expression, can be achieved in human monocyte-derived macrophages and in explanted cultures of human microglia. Preliminary data suggest that Tax(1) expression is sufficient to up-regulate the proinflammatory cytokine profile in explanted human microglial cells. Future experiments will compare and evaluate the effect of tax(1) and tax(2) gene expression on the cellular proinflammatory cytokine expression profile, as well as demonstrate the effects of transducing human fetal astrocytes and PBMC-derived macrophages.
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PMID:HTLV type 1 Tax transduction in microglial cells and astrocytes by lentiviral vectors. 1108 Aug 25

Lymphomas in persons with AIDS are mostly B-cell types, but T-cell lymphomas have also been reported. We examined T-cell lymphoma risk in the 2-year period after AIDS onset by linking 302,834 adults with AIDS to cancer registry data. Of 6,788 cases of non-Hodgkin's lymphoma (NHL) with specified histologies, 96 (1.4%) were T-cell lymphomas. Assessment was based on clinical diagnosis and histology because T-cell marker data were inadequate, but when present, marker data supported the T-cell diagnosis. The relative risk of T-cell lymphoma, estimated by standardized incidence ratio, was 15.0 (95% confidence interval: 10.0--21.7). Risks were increased for all subtypes, including mycosis fungoides, peripheral lymphomas, cutaneous lymphomas, and adult T-cell leukemia/lymphoma (ATLL). HIV-related immunodeficiency could be important, but differences between the population developing AIDS and the general population (e. g., immigration from the Caribbean region for ATLL) might independently increase T-cell lymphoma risk.
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PMID:Risk of T-cell lymphomas in persons with AIDS. 1131 81

All retroviruses possess a highly error-prone reverse transcriptase, but the extent of the consequent sequence diversity and the rate of evolution differ greatly among retroviruses. Because of the high mutability of retroviruses, it is not the generation of new viral variants that limits the extent of diversity and the rate of evolution of retroviruses, but rather the selection forces that act on these variants. Here, we suggest that two selection forces--the immune response and the limited availability of appropriate target cells during transmission and persistence--are chiefly responsible for the observed sequence diversity in untreated retroviral infections. We illustrate these aspects of positive selection by reference to specific lentiviruses [human and simian immunodeficiency viruses (HIV and SIV)] and oncoviruses [feline leukemia virus (FeLV) and human T cell leukemia virus (HTLV)] that differ in their extent of variation and in disease outcomes.
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PMID:Selection forces and constraints on retroviral sequence variation. 1135 65

Viral infections represent one of the areas in which cancer research has made the greatest advances in the last 20 years. In 1981, only two viruses were known to cause human cancer, i.e., the Epstein-Barr virus (EBV) and the hepatitis B virus (HBV). By 1995, it was estimated that approximately 15% of all cancers occurring world-wide were attributable to viral infections, and the oncogenic role of seven viruses [i.e., EBV, HBV, hepatitis C virus (HCV), human papillomavirus (HPV), human immunodeficiency virus (HIV), human herpesvirus-8 (HHV-8), and human T cell leukemia virus type I (HTLV-I)] has been well-established. In this paper, the epidemiological evidence concerning some of the major aspects of the association between viruses and cancer are summarised.
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PMID:Viral infections and cancer: epidemiological aspects. 1169 28

Ku has been implicated in nuclear processes, including DNA break repair, transcription, V(D)J recombination, and telomere maintenance. Its mode of action involves two distinct mechanisms: one in which a nonspecific binding occurs to DNA ends and a second that involves a specific binding to negative regulatory elements involved in transcription repression. Such elements were identified in mouse mammary tumor virus and human T cell leukemia virus retroviruses. The purpose of this study was to investigate a role for Ku in the regulation of human immunodeficiency virus (HIV)-1 transcription. First, HIV-1 LTR activity was studied in CHO-K1 cells and in CH0-derived xrs-6 cells, which are devoid of Ku80. LTR-driven expression of a reporter gene was significantly increased in xrs-6 cells. This enhancement was suppressed after re-expression of Ku80. Second, transcription of HIV-1 was followed in U1 human cells that were depleted in Ku by using a Ku80 antisense RNA. Ku depletion led to a increase of both HIV-1 mRNA synthesis and viral production compared with the parent cells. These results demonstrate that Ku acts as a transcriptional repressor of HIV-1 expression. Finally, a putative Ku-specific binding site was identified within the negative regulatory region of the HIV-1 long terminal repeat, which may account for this repression of transcription.
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PMID:Ku represses the HIV-1 transcription: identification of a putative Ku binding site homologous to the mouse mammary tumor virus NRE1 sequence in the HIV-1 long terminal repeat. 1173 2

Retroviral RNA genomes are known to have a biased nucleotide composition. For instance, the plus-strand RNA of human immunodeficiency virus (HIV) is A-rich, and the genome of human T cell leukemia virus (HTLV) is C-rich, and other retroviruses have a U-rich or G-rich genome. The biased composition of these genomes is most likely caused by directional mutational pressure of the respective reverse transcriptase enzymes. Using a set of retroviral genomes with a distinct nucleotide composition, we performed skew analyses of the nucleotide bias along the complete viral genome. Distinct nucleotide signatures were apparent, and these typical patterns were generally conserved across the viral genome. Furthermore, it is demonstrated that this typical nucleotide bias, combined with a profound discrimination against the CpG dinucleotide sequence, strongly influences the codon usage of the retroviruses in a direct manner, and their amino acid usage in an indirect manner. The fact that both codon usage and amino acid usage are so closely entwined with the genome composition has important practical implications. For instance, the typical trends in nucleotide usage could influence the molecular phylogenetic reconstruction of the family Retroviridae.
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PMID:Codon and amino acid usage in retroviral genomes is consistent with virus-specific nucleotide pressure. 1183 46


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