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)

Epstein-Barr virus (EBV) has been detected in the large majority of HIV-related primary central nervous system lymphomas (PCNSL) suggesting a pathogenetic role of the virus. Unlike HIV-related PCNSL, conflicting data exist with regard to the presence of EBV in non immunodeficiency-related (sporadic) PCNSL. For this reason, a population based material of 41 sporadic PCNSL was analysed for the presence of EBV genome (EBER, BHLF) using RNA in situ hybridisation (RISH). Furthermore, the expression of the gene products of the bcl-2 oncogene and the p53 tumor suppressor gene and the tumor growth fraction reactive with the monoclonal antibody Ki-67 have been evaluated. All cases but two were EBV genome negative. In the two positive cases less than 5% of tumor cells showed EBER positivity. In contrast, more than 75% of cells morphologically belonging to the tumor-cell population stained positively for EBER in two cases of HIV related PCNSL. Immunostaining for the bcl-2 oncoprotein was positive in 28 (72%) of 39 cases examined. In most cases more than 75% of tumor cells showed cytoplasmic expression. Of 37 cases investigated for p53 expression, 21 (57%) stained positively. However, in the large majority of positive cases less than 10% of the neoplastic cells stained. The percentage of Ki-67 positive cells ranged between 10% and 80% with a mean of 50%. The expression of the p53 and bcl-2 oncoproteins and the growth fraction did not have any prognostic impact. We conclude that the EBV genome is rarely detected in sporadic PCNSL, indicating that a pathogenetic role of EBV is unlikely. Like extracerebral B-cell lymphomas a large fraction of PCNSL expresses the p53 and bcl-2 oncoproteins, a feature, however, which does not seem to have prognostic implications.
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PMID:Primary central nervous system lymphomas in immunocompetent individuals: histology, Epstein-Barr virus genome, Ki-67 proliferation index, p53 and bcl-2 gene expression. 966 83

Patients with HIV infection are at high risk for the development of high-grade B-non-Hodgkin's lymphoma (B-NHL). The aim of this study was identification of a predictive diagnostic marker for HIV-associated B-cell lymphomas, using simian-immunodeficiency-virus (SIV)-infected Rhesus monkeys as a well-established in vivo model of HIV-associated lymphomagenesis. We infected 26 monkeys (Macaca mulatta) with SIVmax and measured serum levels of sCD23 longitudinally until necropsy. Of the 26 monkeys, 9 developed high-grade B-NHL, which was preceded by lymphadenopathy (NHL+/LA+) (group 1). Among the 17 animals that remained without clinical evidence of lymphoma during the observation period, 8 developed LA (group 2) and 9 were NHL- and LA-negative (NHL-/LA-) (group 3). Elevation of sCD23 serum levels preceded B-cell lymphoma development, with a median of 44 U/ml in group 1 vs. 7 U/ml and 8 U/ml in groups 2 and 3 respectively, 32 weeks after infection. Differences in the serum level of sCD23 between group 1 vs. groups 2 and 3 became statistically significant 32 to 56 weeks after infection. At necropsy, serum levels of sCD23 were significantly higher in group 1 than in group 2 or group 3; 6/6 samples of SIV-associated B-NHL were positive for gene transcription of CD23 and its receptor CD21 as assessed by RT-PCR. The data point to a potential role of sCD23 as a predictive marker for the development of HIV-associated B-NHL. Moreover, the in vivo model of SIV-infected monkeys suggests the possibility of exactly analyzing the pathobiological role of sCD23 in the lymphomagenesis of SIV-associated B-NHL.
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PMID:Elevated serum level of soluble CD23 precedes development of B-non-Hodgkin's lymphoma in SIV-infected Rhesus monkeys. 968 7

Since the onset of the acquired immune deficiency syndrome (AIDS) epidemic fifteen years ago, much has been learned about the effects of the human immunodeficiency virus (HIV) in the nervous system. This review summarizes the pathology findings in the central nervous system (CNS). There is now abundant evidence that HIV can infect the CNS directly, leading to a characteristic HIV encephalitis (HIVE) which occurs in 10-50 p. 100 of AIDS autopsy series. Multinucleated giant cells are the pathognomonic feature of HIVE and are found predominantly in the central white matter and deep grey matter. Evidence of productive HIV infection in the CNS is confined to cells of the microglial/macrophage lineage, from which the giant cells are almost certainly derived. These cells are known to express both CD4 and beta-chemokine receptors, which act in conjunction to permit HIV entry. Restricted infection of astrocytes has also been identified by a variety of methods. HIVE is frequently associated with white matter damage ranging from inflammatory (microglia, macrophages and sparse lymphocytes) to degenerative (myelin loss and axonal damage) pathology. Although giant cells are seen less frequently in neocortical grey matter, significant neuronal loss has been established in a number of studies. Recent investigations using markers of apoptosis, (including TUNEL, Bcl-2 and BAX), have established the presence of DNA damage in some neurons and in other cell types. Axonal damage has also been confirmed by evidence of amyloid precursor protein expression. The CNS is also vulnerable to opportunistic infections and high grade B-cell lymphomas as a result of the immune suppression of advanced HIV infection. Cytomegalovirus (CMV) infection is reported in 10-30 p. 100 of AIDS cases at autopsy, toxoplasma in 10-25 p. 100, progressive multifocal leucoencephalopathy in about 5 p. 100 and lymphomas, usually primary, in up to 10 p. 100. A wide variety of other infections has also been reported. These may coexist with HIVE and may be difficult to diagnose in life. CMV gives rise to microglial nodular encephalitis, ventriculitis, necrotising encephalitis and myelo-radiculitis. Presymptomatic HIV positive patients do not show HIVE or opportunistic infections or lymphomas in the CNS. They frequently display a low-grade T-cell infiltrate in the leptomeninges and parenchyma, particularly around vessels. This lymphocytic infiltrate has been attributed to presumed early invasion of the CNS by HIV although the exact timing of entry is uncertain. It is possible that reported abnormalities in presymptomatic cases such as gliosis, microglial activation and rising proviral load may anticipate the onset of HIVE but most studies show that significant CNS damage and HIV-related pathology is confined to patients with AIDS. HIV-related pathology in the spinal cord includes not only HIV myelitis, opportunistic infections and lymphomas, but also vacuolar myelopathy (VM) which affects predominantly the dorsolateral white matter tracts. The cause of VM is not understood and has not been unequivocally linked with HIV infection. It is noted that none of these neuropathological features (including HIVE) correlates exactly with the clinical expression of AIDS-related dementia (ARD). The exact contribution of macrophage activation and cytokine release, astrocytic infection, neuronal loss and axonal damage to the neuropsychiatric syndromes of advanced HIV infection remain to be determined. While the current understanding of the pathogenesis of HIVE and ARD is beyond the scope of this review it is axiomatic that accurate documentation of neuropathology findings will help to resolve the outstanding dilemmas relating to HIV infection of the CNS. There is considerable optimism that progress in therapeutic regimes for HIV-infected patients will succeed in eliminating the virus from the blood and from lymphoid tissue. (ABSTRACT TRUNCATED)
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PMID:The neuropathology of adult HIV infection. 993 3

Gastrointestinal lymphomas comprise a group of distinctive clinicopathological entities of B- or T-cell type, with primary gastrointestinal Hodgkin's disease being extremely uncommon. Most low-grade B-cell gastrointestinal lymphomas are of mucosa-associated lymphoid tissue (MALT) type, so called because they recapitulate the features of MALT rather than those of lymph nodes. Paradoxically, however, most MALT lymphomas arise in the stomach, which normally contains no organized lymphoid tissue. Gastric MALT lymphomas appear to arise in MALT acquired as a reaction to infection of the stomach by Helicobacter pylori and their growth can be inhibited by eradication of this organism from the stomach. Low-grade MALT lymphomas, which usually have a very favorable clinical course, may undergo high-grade transformation but high-grade diffuse large B-cell lymphomas may also arise de novo. Immunoproliferative small intestinal disease (IPSID) is a special form of MALT lymphoma characterized by synthesis of alpha heavy-chain immunoglobulin and a restricted geographic distribution. Other B-cell lymphomas that tend to arise in the gastrointestinal tract include mantle cell lymphoma, which presents as lymphomatous polyposis, Burkitt's lymphoma, and B-cell lymphomas associated with immunodeficiency states. Enteropathy (celiac disease)-associated T-cell lymphoma (EATL) is the most common primary gastrointestinal T-cell lymphoma This is a clinically aggressive tumor that arises from the intraepithelial T-cell population.
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PMID:Gastrointestinal lymphomas of T- and B-cell types. 1007 40

HIV-infected patients are at high risk of developing diffuse large B-cell lymphomas (DLBCL). It is currently unclear whether these lymphomas represent Epstein-Barr virus (EBV)-driven lymphoproliferations that develop in the setting of immunodeficiency, or whether these tumours are more closely related to the DLBCL seen in the general population. To clarify this issue, 12 HIV-related DLBCL from 11 patients were analysed for the presence of clonally rearranged and somatically mutated immunoglobulin heavy chain (IgH) genes and their association with EBV was determined. Eleven of the 12 tumour samples displayed monoclonal rearrangements of the IgH genes, with or without a moderate number of somatic mutations in the CDRII and in the FWIII regions (average four mutations). One patient presented two successive lesions; whereas the initial tumour showed an oligoclonal IgH rearrangement, the lymphoma at relapse proved to harbour a monoclonal B-cell population. Ten of 12 tumour samples expressed the EBV encoded small RNAs (EBERs), and six of these EBV-positive cases displayed, in addition, an expression of the EBV encoded nuclear antigen 2 (EBNA-2). The results obtained from HIV-related DLBCL are at variance to those described for DLBCL occurring in the general population, since the latter contain significantly more somatic IgH mutations in the CDRII and in the FWIII regions and are only rarely associated with EBV. It is concluded from these findings that HIV-related DLBCL represent a distinct group of B-cell lymphomas, a significant fraction of which most likely originates from EBV-driven lymphoproliferations, and that half of the cases derive from pre-germinal centre B-cells.
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PMID:Common and HIV-related diffuse large B-cell lymphomas differ in their immunoglobulin gene mutation pattern. 1039 55

Interleukin-16 (IL-16), produced by activated CD8+ T lymphocytes, is inhibitory to human immunodeficiency virus-1 (HIV-1) replication. In an attempt to determine whether human B cells express and secrete IL-16, a wide panel of B-cell lines derived from patients with acquired immune deficiency syndrome (AIDS)-associated B-cell lymphomas (AABCL) (n = 5) and from non-AABCLs (n = 8) were studied. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, we were able to observe ubiquitous expression of IL-16 mRNA. Kinetic studies on constitutive mRNA turnover and secretion for IL-16 suggests that the optimum expression is at 24 hr. Interestingly, we report, for the first time, IL-16 secretion by human B-cell lines.
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PMID:Human B-cell lines constitutively express and secrete interleukin-16. 1069 46

Human immunodeficiency virus 2 (HIV-2) is endemic in West Africa and is a causative agent of the acquired immunodeficiency syndrome. Only a small number of HIV-2-infected patients have been described in detail. Non-Hodgkin's lymphoma (NHL) is the second most common neoplasm occurring in HIV-1-infected patients, but its incidence seems to be lower in HIV-2-infected individuals. We report an HIV-2-infected patient from Cape Verde (West Africa) with separate and distinct systemic and primary central nervous system large B-cell lymphomas and review the findings of cases of HIV-2-associated lymphomas reported in the literature. Different clonal rearrangements of the immunoglobulin heavy chain gene could be detected in the two lymphomas of our patient by polymerase chain reaction and sequence analysis. These data indicate the presence of two clonally unrelated large B-cell lymphomas in the same patient, which is an unusual finding. Neither Epstein-Barr virus nor human herpesvirus 8 could be detected in the tumor tissues or the cerebrospinal fluid. HIV-2 infection should be considered in patients with NHL, especially in those from West Africa.
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PMID:Clinicopathological characterization of an HIV-2-infected individual with two clonally unrelated primary lymphomas. 1107 59

Genetically susceptible C57BL/6 (B6) mice that are infected with the LP-BM5 isolate of murine retroviruses develop profound splenomegaly, lymphadenopathy, hypergammaglobulinemia, terminal B-cell lymphomas, and an immunodeficiency state bearing many similarities to the pathologies seen in AIDS. Because of these similarities, this syndrome has been called murine AIDS (MAIDS). We have previously shown that CD154 (CD40 ligand)-CD40 molecular interactions are required both for the initiation and progression of MAIDS. Thus, in vivo anti-CD154 monoclonal antibody (MAb) treatment inhibited MAIDS symptoms in LP-BM5-infected wild-type mice when either a short course of anti-CD154 MAb treatment was started on the day of infection or a course was initiated 3 to 4 weeks after LP-BM5 administration, after disease was established. Here, we further characterize this required CD154-CD40 interaction by a series of adoptive transfer experiments designed to elucidate which cellular subsets must express CD154 or CD40 for LP-BM5 to induce MAIDS. Specifically with regard to CD154 expression, MAIDS-insusceptible B6 nude mice reconstituted with highly purified CD4+ T cells from wild-type, but not from CD154 knockout, B6 donors displayed clear MAIDS after LP-BM5 infection. In contrast, nude B6 recipients that received CD8+ T cells from wild-type B6 donors did not develop MAIDS after LP-BM5 infection. B6 CD40 knockout mice, which are also relatively resistant to LP-BM5-induced MAIDS, became susceptible to LP-BM5-induced disease after reconstitution with highly purified wild-type B cells but not after receiving purified wild-type dendritic cells (DC) or a combined CD40+ population composed of DC and macrophages obtained from B6 SCID mouse donors. Based on these and other experiments, we thus conclude that the cellular basis for the requirement for CD154-CD40 interactions for MAIDS induction and progression can be accounted for by CD154 expression on CD4+ T cells and CD40 expression on B cells.
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PMID:Characterization of the CD154-positive and CD40-positive cellular subsets required for pathogenesis in retrovirus-induced murine immunodeficiency. 1126 47

Nasal natural killer (NK) lymphoma associated with Epstein-Barr virus (EBV) is a rare lymphoma that has not yet been reported in patients with human immunodeficiency virus (HIV). This report describes the first case, to our knowledge, of nasal NK cell lymphoma in an HIV-positive patient. A 50-year-old African man presented with an obstructive nasopharyngeal tumor, leading to the diagnosis of HIV infection. Nasal biopsy specimens showed NK cell lymphoma, confirmed on nasal tissues by morphologic, immunohistochemical, and polymerase chain reaction studies using a denaturing gradient gel electrophoresis technique that showed no T-cell receptor gamma rearrangement. The EBV was detected by in situ hybridization. The patient received chemotherapy but died from infection. To our knowledge, this is the first reported case of nasal NK cell lymphoma associated with EBV in an HIV patient. Involvement of EBV in HIV non-B-cell lymphomas may represent a further manifestation of opportunistic EBV infection arising in these patients.
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PMID:Nasal natural killer lymphoma associated with Epstein-Barr virus in a patient infected with human immunodeficiency virus. 1130 Sep 39

ATM, the gene mutated in the human immunodeficiency disorder ataxia-telangiectasia (A-T), plays a central role in recognizing ionizing radiation damage in DNA and in controlling several cell cycle checkpoints. We describe here a murine model in which a nine-nucleotide in-frame deletion has been introduced into the Atm gene by homologous recombination followed by removal of the selectable marker cassette by Cre-loxP site-specific, recombination-mediated excision. This mouse, Atm-DeltaSRI, was designed as a model of one of the most common deletion mutations (7636del9) found in A-T patients. The murine Atm deletion results in the loss of three amino acid residues (SRI; 2556-2558) but produces near full-length detectable Atm protein that lacks protein kinase activity. Radiosensitivity was observed in Atm-DeltaSRI mice, whereas the immunological profile of these mice showed greater heterogeneity of T-cell subsets than observed in Atm(-/-) mice. The life span of Atm-DeltaSRI mice was significantly longer than that of Atm(-/-) mice when maintained under nonspecific pathogen-free conditions. This can be accounted for by a lower incidence of thymic lymphomas in Atm-DeltaSRI mice up to 40 weeks, after which time the animals died of other causes. The thymic lymphomas in Atm-DeltaSRI mice were characterized by extensive apoptosis, which appears to be attributable to an increased number of cells expressing Fas ligand. A variety of other tumors including B-cell lymphomas, sarcomas, and carcinomas not seen in Atm(-/-) mice were observed in older Atm-DeltaSRI animals. Thus, expression of mutant protein in Atm-DeltaSRI knock-in mice gives rise to a discernibly different phenotype to Atm(-/-) mice, which may account for the heterogeneity seen in A-T patients with different mutations.
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PMID:Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype. 1138 91


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