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)

A 35-year-old homosexual man developed a composite nodal Kaposi's sarcoma and peripheral T-cell lymphoma that were associated with a peripheral blood CD4-positive lymphocyte count of only 43/mm3. The patient subsequently developed Pneumocystis carinii pneumonitis and eventually died due to disseminated Cryptococcus neoformans. Numerous premortem tests for the presence of human immunodeficiency virus (HIV) types 1 and 2 were negative by the enzyme-linked immunosorbent assay, Western blot, viral isolation, and polymerase chain reaction techniques. Postmortem evaluations for HIV-1, HIV-2, human T-cell lymphotropic virus (HTLV)-I, and HTLV-II also were negative by polymerase chain reaction, immunofluorescence assays, and viral isolation. A systemic infection by Mycoplasma fermentans, however, was documented by immunohistochemistry and polymerase chain reaction in premortem and postmortem tissues. This recently recognized human pathogen has produced systemic infections in patients with the acquired immunodeficiency syndrome (AIDS) and in previously healthy non-AIDS patients who characteristically have a fulminant flu-like illness. Additionally, M fermentans has enhanced the cytopathic effect of HIV in in vitro studies and has produced fatal wasting illnesses with terminal lymphopenia in inoculated adult silvered leaf monkeys. This report is the first description of an association between M fermentans infection and an AIDS-like illness in an HIV-negative individual. The etiology of the severe immunosuppression in this patient and the associated role of M fermentans remain to be determined by further investigations.
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PMID:Acquired immunodeficiency syndrome-like illness associated with systemic Mycoplasma fermentans infection in a human immunodeficiency virus-negative homosexual man. 849 93

There is a large increase in lymphoid malignancy in A-T patients and a total absence of myeloid tumors. Penetrance of the tumor phenotype is about 10% to 15% by early adulthood. The increase in lymphoid malignancy includes both B- and T-cell tumors. However, young A-T patients do not show an increased susceptibility to cALL, and the UK data suggest that B-cell lymphoma occurs in older A-T children. T-cell tumors may occur at any age and may be T-ALL, T-cell lymphoma, or T-PLL; most strikingly, there may be a fourfold to fivefold increased frequency of T-cell tumors compared with that of B-cell tumors in these patients. If this is correct, it is possible that a significant proportion of all T-ALL/T-cell lymphoma in infants might be associated with undiagnosed A-T. The age range and sex predominance for T-ALL may be different for A-T and non-A-T patients and the age range for T-PLL may also be different in A-T and non-A-T patients. There is clearly some uncertainty concerning the ratio of T-cell to B-cell tumors in A-T, but this could be clarified by the publication of all tumors that occur in the disorder. In contrast, 8 of 9 tumors reported in NBS, which shows the same cellular features as A-T, were lymphomas and none was a leukemia. There are several indicators of genetic heterogeneity in A-T that suggest that not all patients are equally susceptible to all T-cell tumor types. Concordance for tumor type within individual families suggests that particular gene defects may be associated with particular tumor types. The logical extrapolation of this argument is that some patients may not have any increased risk for B-cell tumors at all or even to all T-cell types but only to a particular type of T-cell tumor. What is the cause of the increased predisposition to leukemia/lymphoma in A-T patients? There is no evidence that the immunodeficiency in A-T is related to this predisposition. One of the major findings in all A-T patients is the increase in V(D)J-mediated chromosome rearrangement observed in T lymphocytes. Particular chromosome translocations in T cells, involving a break in a TCR gene, are characteristically associated with either T-ALL or T-PLL in non-A-T patients. The majority of T-cell tumors in A-T are T-ALL and T-cell lymphoma, about which virtually nothing is known chromosomally, and the assumption is that the increased number of translocations leads to the increased level of these tumors. In older T patients, the expansion of specific translocation T-cell clones has been followed to the point to which they develop into T-PLL. All the evidence, therefore, suggests that the A-T mutation in the homozygous state allows a large increase in production of translocations formed at the time of V(D)J recombination, and this leads to the increased predisposition to leukemia. The general increased predisposition to T-cell tumors compared with B-cell tumors in A-T patients may be related to a preferential occurrence of translocations in T cells. Relatively little is known about translocations in circulating B lymphocytes in normal individuals, but A-T siblings have been shown to have clonal chromosome rearrangements of both B and T cells, simultaneously, although in these siblings the T-cell clones occupied all the T-cell compartment and the B-cell clones were small. An important inference from these facts is that the A-T defect preferentially affects immune system gene recombination in T cells rather than B cells. Recent evidence suggests that the V(D)J recombination machinery is not identical or is not regulated identically in T- and B-cell progenitors. This finding is consistent with the hypothesis that V(D)J rejoining in the majority, at least, of A-T patients may be preferentially deficient in T cells compared with B cells giving rise to the greatly increased number of translocations and T-cell tumors. Carbonari et al proposed that the recombination defect in A-T cells affected both Ig isotype switching and TCR rearrangeme
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PMID:Leukemia and lymphoma in ataxia telangiectasia. 855 63

While there is a clear association between several types of immunodeficiency-related lymphomas and Epstein-Barr virus (EBV), the association of EBV infection in AIDS-related lymphoma in Brazil, where the incidence of AIDS is high, has remained unknown. The authors report their findings from an analysis of tissue samples from 24 cases of AIDS-related lymphoma in Brazil. The samples were analyzed for morphologic classification, immunophenotype, and EBV association. 20 cases were classified as non-Hodgkin's lymphoma, while 4 were Hodgkin's disease. 11 non-Hodgkin's lymphomas were classified as diffuse large cell type, 5 as small, non-cleaved cell, Burkitt-type, and 4 as large cell immunoblastic non-Hodgkin's lymphoma. 18 cases were of B-cell phenotype; one was a T-cell lymphoma and one was classified as null. EBV was demonstrated in the tumor cells of 11 of the 20 non-Hodgkin's lymphoma cases and in 3 of the 4 cases of non-Hodgkin's disease.
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PMID:AIDS-related lymphoma in Brazil. Histopathology, immunophenotype, and association with Epstein-Barr virus. 860 50

Hodgkin's disease (HD) has been linked to an increase risk of second malignant neoplasms (SMN), especially non-Hodgkin's lymphoma (NHL) and acute nonlymphoblastic leukaemia (ANLL). The mutagenic property of cytotoxic therapy as well as defective immunity have been implicated as playing a major role in the development of SMN in patients previously treated for HD. We report a case of a 14-year-old girl with HD who developed two different second malignancies within a latent period of 28 months following HD diagnosis. The patient presented initially with bilateral cervical and supraclavicular as well as mediastinal and paraaortic lymphadenopathy. She was staged as IIIA, nodular sclerosing type HD, and was given eight alternative cycles of MOPP-ABVD followed by "mantle" field radiotherapy to a total dose of 3.3 Gy plus 0.4 Gy to the upper mediastinum. Within 8 months following the completion of therapy, a period of myelodysplasia and progressive severe immune deficiency, considered as a result of initial treatment, occurred. Eighteen months after HD diagnosis while the patient was continuously neutropenic and heavily immunocompromised, a peripheral T-cell lymphoma of the angiocentric immunoproliferative lesion type (AIL) Grade III, appeared in both lungs within and beyond the radiation field, with no evidence of HD in biopsy specimens. After institution of a new chemotherapy regimen (L17M), a satisfactory response regarding NHL lesions was noted. However, 10 months later the myelodysplastic syndrome (MDS) accompanied by complex chromosomal abnormalities evoluted to frank ANLL with a rapid fatal course. This case supports the hypothesis that combined modality treatment accompanied by severe immunodeficiency may result in the development of multiple second malignancies even within a very short latent period, especially in a subgroup of HD patients who may be particularly increased risk of second cancers.
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PMID:Secondary malignancies in a child with Hodgkin's disease: T-cell lymphoma and myelodysplastic syndrome evolving into acute nonlymphoblastic leukaemia. 861 70

Multiple biopsies taken from 76 European human immunodeficiency virus (HIV)-negative patients with primary cutaneous T-cell lymphoproliferations, including mycosis fungoides (MF), pleomorphic T-cell lymphoma (PMTCL), anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis (LyP) were investigated for the presence of Epstein-Barr virus (EBV) through a combined approach. Polymerase chain reaction (PCR) was employed for EBV-DNA detection, in situ hybridization (ISH) for cellular localization of EBV-encoded nuclear RNAs (EBER1 and EBER2) and immediate early Bam H-fragment; lower frame (BHLF) RNA, and immunohistology (IH) for the identification of EBV-encoded latent membrane protein 1 (LMP1) and of nuclear antigen (EBNA) 2 expression. EBV-DNA was detectable by PCR in 15 of 76 cases (19.7%). EBER-ISH combined with IH identified a variable, usually very low, number of infected neoplastic cells in only seven of the 15 EBV-DNA-harbouring cases. This discrepancy between the results obtained with PCR and ISH is apparently caused by the low number of the infected cells per tissue section. The PMTCL entity produced the greatest number of positive cases, whilst ALCL and LyP cases were almost constantly devoid of the virus. BHLF transcripts were not detectable in any case, nor did any of the EBER-positive cells show an LMP1 or EBNA2 expression. These data show that primary cutaneous T-cell lymphoproliferations display an infrequent association with a latent EBV infection and that the pathogenic role of the virus in the positive cases remains obscure as the virus frequently infects only a minority of the atypical cells.
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PMID:Low incidence of Epstein-Barr virus presence in primary cutaneous T-cell lymphoproliferations. 874 41

Extensive studies have demonstrated that Epstein-Barr virus (EBV) is associated with Burkitt's lymphoma, immunodeficiency related lymphoma, Hodgkin's disease and T-cell lymphoma. In order to investigate whether an association exists between EBV and B-cell lymphoma in patients without overt immunodeficiency, we examined 127 B-cell lymphomas without overt immunodeficiency for expression of EBV-encoded small RNA (EBER-1) using RNA/RNA in situ hybridization. EBER-1 expression was found in nuclei of tumor cells in 8 of 127 cases (6.3%) of B-cell lymphomas. This result is similar to that of studies in Europe and the United States (about 5%). The low frequency of EBV in B-cell lymphomas suggests that EBV does not pay an important role in the pathogenesis of B-cell lymphomas without overt immunodeficiency.
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PMID:[A study of the association between EBV and B-cell lymphoma]. 876 30

A strong association was found to exist between patterns of lymphoid malignancies and socioeconomic status. B-cell lymphomas and T-acute lymphoblastic leukemia are much more prevalent in developing countries where the chances of acquiring infections especially at a younger age are high. B-cell precursor acute lymphatic leukemia, however, are much more prevalent in the Western world. Many infectious agents are associated with lymphatic malignancies. Epstein-Barr virus is involved in African Burkitt's lymphoma, human immunodeficiency virus-related Burkitt's lymphoma, lymphoproliferative syndrome post-transplantation, and Hodgkin's disease. Other infectious agents which may play a role in lymphoproliferative disorders are human immunodeficiency virus in acquired immune deficiency syndrome-associated lymphoma, human T-lymphotropic virus in adult T-cell lymphoma, Helicobacter pylori in mucosa-associated lymphoid tissue lymphoma, theileriosis in lymphoproliferative syndrome in cattle, Avian leukosis virus in chicken bursal lymphoma, and possibly a bacterial infection in immunoproliferative small intestine disease, potentially reversed by antibiotic therapy. The association between infectious agents and hematologic malignancies may be explained by the creation of large populations of activated cells followed by higher occurrences of 'genetic accidents'. This theory may be reinforced in at least some malignancies with the existence of viral proteins which either have complex relationships with key cellular gene products like p53 and Rb which have roles in cell cycle control, or share common motifs with bc1-2, therefore operating as anti-apoptotic elements. Whenever these genes are deranged, cell deoxysibonucleic acid repair or apoptosis are no longer possible, thereby creating a state of genome instability, increased acquisition of mistakes, and increased chances for malignant transformation.
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PMID:Infectious agents and environmental factors in lymphoid malignancies. 881 40

Lymphoid neoplasia is a complex area comprising multiple diseases with varied pathology, treatment, and outcome. The non-Hodgkin's lymphomas are reviewed here. Non-Hodgkin's lymphomas, collectively, represent the sixth most common cancer in the United States as well as the sixth most common cause of cancer deaths. The overall incidence of non-Hodgkin's lymphoma has risen steadily over the past four decades. Although some of this is attributable to human immunodeficiency virus (HIV)-associated lymphoma, HIV-associated disease accounts for only a small part of the increase in lymphoma. As our knowledge of normal as well as neoplastic lymphoid development has expanded on the basis of histopathology as well as adjunct cellular and molecular techniques, multiple classifications have been proposed to take these into account. The clinical relevance to our understanding of non-Hodgkin's lymphoma is the concept that various lymphoid cancers are counterparts of stages of normal lymphoid development. Stages of lymphoid development in terms of cell surface markers and immunoglobulin gene rearrangements have been well characterized. These are particularly applicable to the early B-cell development, which is antigen-independent and occurs in the bone marrow. Diseases correlating with these stages are largely acute lymphocytic and lymphoblastic leukemia/lymphoma and high-grade lymphomas, such as Burkitt's lymphomas. Much has been learned recently about subsequent antigen-dependent B-cell development in secondary lymphoid organs to improve our understanding of the corresponding stages of B-cell neoplasia. Many of these stages correlate with more recently described entities such as mantle cell and marginal zone lymphomas. Histologic study remains crucial in determining the subtype of NHLs, whereas immunohistochemistry, surface phenotype, and molecular studies are useful in selected cases. Although some lymphoma classifications may be better in terms of understanding the lymphoma biology, the working formulation remains useful to guide clinical decision making. Lymphomas classified as low grade are considered incurable with standard therapy when diagnosed, as is usual, at advanced stages. Different subtypes may have different median survivals, but the goal has typically been palliation, whereas experimental approaches are clearly needed. Intermediate and high-grade lymphomas are potentially curable with aggressive combination chemotherapy. Recent evidence suggests that CHOP chemotherapy is as effective as more complex regimens. Still, 40% to 50% of patients are cured. Prognostic factor analysis has allowed separation of subgroups with much better survival in whom CHOP is adequate versus those with much poorer survival in whom experimental approaches are rational. Additional subtypes of lymphomas have been described and characterized since the working formulation was developed, including mucosa-associated lymphoid tissue tumors (MALT-oma), mantle zone lymphoma, anaplastic large cell lymphoma and AILD-like T-cell lymphoma. Approaches to these entities are still being optimized. Newer approaches, including high-dose therapy with stem cell support, biologic agents, and newer chemotherapeutic agents are discussed, as are special situations such as localized lymphoma of certain sites and lymphoma in immunosuppressed patients.
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PMID:Non-Hodgkin's lymphoma. 891 70

Two polyomaviruses, JC virus (JCV) and BK virus (BKV), affect humans. JCV is the causative agent of progressive multifocal leukoencephalopathy (PML), and detection of JCV in the central nervous system (CNS) is a prerequisite for confirmation of the disease. BKV is generally not associated with neurological disease, but involvement of BKV in patients with CNS disorders has been reported. In the present study polyomavirus DNA was detected by a nested PCR at a sensitivity corresponding to the detection of 10 copies of JCV DNA in 10 microliters of cerebrospinal fluid (CSF). CSF samples from 212 patients with neurological symptoms and immunodeficiencies were investigated for the presence of polyomavirus DNA. Of 128 human immunodeficiency virus (HIV)-infected patients, 14 (11%) had JCV DNA in their CSF, and all 14 patients had clinical PML. BKV DNA was detected in one HIV-infected patient with neurological symptoms not compatible with PML. Among 84 HIV-negative patients, 6 (7%) had detectable JCV DNA in their CSF, confirming PML in patients with clinical conditions of T-cell lymphoma, chronic lymphatic leukemia, status postliver transplantation, congenital immunodeficiency, sarcoidosis, and immunodeficiency of unknown origin. The specificity of the PCR was confirmed by a clinical follow-up study which showed full agreement between the detection of JCV DNA in CSF and clinically manifest PML. The described PCR is a rapid, reproducible, and easily performed assay.
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PMID:Analysis of PCR as a tool for detection of JC virus DNA in cerebrospinal fluid for diagnosis of progressive multifocal leukoencephalopathy. 894 Apr 24

We examined 81 cases of primary gastrointestinal lymphomas in Korea, including 64 gastric lymphomas and 17 intestinal lymphomas, for EBV expression by EBER-1 in situ hybridization (ISH) and EBNA-1 PCR. In EBER-1 positive cases, we performed immunohistochemistry for latent membrane protein-1 (LMP-1) and EBV diffuse early antigen (EA(D)) to compare EBV latent gene expression and lytic process. EBER-1 was detected in 15 of 81 cases of lymphomas. EBER-1 expression showed three different patterns on tumour cells; diffuse 4/81 (5%), localized 4/81 (8%), and a few scattered pattern 7/81 (9%). We regarded diffuse pattern and localized pattern as EBER-1 positive group (8/81: 10%). Diffuse pattern of EBER-1 was shown in all three T-cell lymphomas and one B-cell lymphoma. A localized pattern was seen all in B-cell lymphomas. The EBER-1 expression was 11% in the stomach (7/64) and 6% in the intestine (1/17). Five of the eight EBER-1 positive gastric lymphomas were histologically diffuse large B-cell lymphomas, and the other three were peripheral T-cell lymphoma, unspecified, one angiocentric lymphoma, and one intestinal T-cell lymphoma by REAL classification. Eight MALT type gastric B-cell lymphomas showed no EBV association. EBV nuclear antigen (EBNA-1) was detected in 15 of 45 resected cases (33%) by PCR. EBER-1 positive cases were all EBNA-1 positive. Twelve EBNA-positive/EBER-negative cases consisted of seven cases showing a few scattered EBER-1 positive lymphocytes. LMP-1 and diffuse early antigen (EA(D)) was detected in five and three cases, respectively. Although follow-up information in our series was incomplete, it seemed that there was no significant difference in their staging or prognosis between EBER-positive cases and EBER-negative group. It is concluded that EBV is associated with some lymphomas among Koreans without overt pre-existing immunodeficiency, especially in T-cell lymphomas.
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PMID:Epstein-Barr virus-associated primary gastrointestinal lymphoma in non-immunocompromised patients in Korea. 908 52


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