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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well known that there are many independent and inter-related clinical and pathologic factors which influence the prognosis of patients with benign and malignant conditions. Lymphocyte level is an index of cell-mediated immunity which is important in host defense against cancer. But it is surprising that a simple test such as peripheral lymphocyte count could be correlated with clinical stages and survival results in patients with Hodgkin's disease, non-Hodgkin's lymphoma and non-lymphomatous solid tumors. Regarding the latter, lymphocyte count had prognostic values in patients with cancer of the bone, Ewing's sarcoma; breast; colon; kidney, neuroblastoma; uterine cervix, and other sites. In general, higher lymphocyte counts before therapy correlated with longer survival. Using newer immunologic techniques, T and B lymphocytes can be identified and the different subtypes of leukemia, immunodeficiency and lymphoproliferative diseases have been studied intensively. Chronic lymphocytic leukemia represents a proliferation of B cells, while the Sezary syndrome represents that of T lymphocytes. There is a qualitative and quantitative disturbance of Blymphocytes in patients with multiple myeloma. In Hodgkin's disease, there is hyperactivity of the B cells and functional defect of the T cells. Finally, the nodular non-Hodgkin's lymphoma resulted from neoplastic transformation of the B lymphocytes. In several nonmalignant autoimmune conditions, abnormality of T-cell or B-cell counts has been reported. For example, T cells were reported to be decreased in patients with ulcerative or granulomatous colitis and in patients with rheumatoid arthritis, However, it needs to be pointed out that, in 1973, Farid and associates (44) reported a significant increase in T and a proportionate reduction of B rosette in 17 patients with untreated Grave's disease and 16 with Hashimoto's thyroiditis as compared with 24 normal and eight goiter controls. In 1975, six publications later, they (143) had to announce a retraction because further studies by them and by other investigators could not repeat the earlier results. Despite variations and lack of standardization of the test systems, some consistent deviations of T-lymphocyte and B-lymphocyte counts have been reported. T lymphocytes were quantitatively decreased in patients with carcinoma of the brain, breast, head and neck, liver, lung and urologic organs and with malignant melanoma. In general, there is a marked decrease of T cells with increasing stage of disease and a return of T cells to normal level after successful therapy. Cellular immunity is depressed, often lasting for years after localized radiation therapy, whether or not the thymus is included in the treatment field...
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PMID:Peripheral lymphocyte count and suppopulations of T and B lymphocytes in benign and malignant diseases. 30 Jan 79

Recent evidence suggests that the human immunodeficiency virus type 1 (HIV) trans-activator gene (tat) has transforming properties and may be a causative factor in the development of certain types of cancers, in particular Kaposi's sarcoma (i.e., Vogel J. et al. Nature 335:606-611, 1988). To help elucidate the potential role or roles of the HIV tat gene in neoplastic transformation, cell lines were constructed that constitutively express a functional tat gene product. HeLa cells were coelectroporated with two plasmids, one containing the HIV tat gene in an expression cassette and another containing the dominant selectable marker gene xanthine guanine phosphoribosyltransferase (XGPRT). After XGPRT selection, single-cell clones that expressed a functional tat protein were identified by measuring chloramphenicol acetyltransferase (CAT) activity after electroporating a plasmid containing the CAT gene transcriptionally controlled by HIV trans-activation-responsive region (tar). Phenotypic alterations resulting from the expression of tat were then determined. Control cells and tat-expressing cells grew at similar rates in culture. However, when grown as tumors in nude mice, tat-expressing cells produced a lower percentage of tumors, and the tumors that were produced either regressed, stopped growing, or grew at a very reduced rate compared with cells not expressing tat. These differences may have resulted from a tat-associated reduction in neovascularization in the tumors. A comparison of total cellular proteins by two-dimensional polyacrylamide gel electrophoresis indicated only one reproducible alteration in a polypeptide of approximately 44 kDa and pl of approximately 6.2 associated with tat expression. These cells may be very useful in future in vitro and in vivo studies designed to examine the effects of HIV tat on endothelial and vascular smooth-muscle cells and the role of tat in the etiology of Kaposi's sarcoma.
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PMID:Alterations in tumor angiogenesis associated with stable expression of the HIV tat gene. 137 15

A high frequency of lymphoma in human immunodeficiency virus-infected individuals has been reported since the outbreak of the acquired immunodeficiency syndrome (AIDS) epidemic in 1982. In the vast majority of cases, these lymphomas are highly aggressive B-cell, non-Hodgkin's lymphoma of intermediate or high grade of malignancy. AIDS-associated non-Hodgkin's lymphoma are histologically classified as small noncleaved cell lymphoma, large cell immunoblastic plasmacytoid lymphoma, or large noncleaved cell lymphoma. Host factors predisposing to lymphoma development in AIDS patients include decreased immunosurveillance as well as human immunodeficiency virus-induced chronic perturbation of the immune system leading to cytokine overproduction and increased B-cell stimulation. These alterations are associated with the development of multiple oligoclonal B-cell expansions, which are characterized by persistent generalized lymphadenopathy. The presence of Epstein-Barr virus within a persistent generalized lymphadenopathy clone further increases the risk of its neoplastic transformation. The appearance of non-Hodgkin's lymphoma is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal Epstein-Barr virus infection, c-myc rearrangements, Ras mutations, and p53 inactivation. The number and type of lesions varies among the different types of AIDS-non-Hodgkin's lymphoma, defining multiple alternative molecular pathways in AIDS-associated lymphomagenesis.
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PMID:Biologic aspects of human immunodeficiency virus-related lymphoma. 145 5

Autoimmune disease is generally felt to result from the interaction of genetic and environmental factors. In recent years, significant advances have been made in using recombinant DNA methods to analyze specific genetic factors and infectious agents. However, new techniques are needed that are more rapid, inexpensive, and suitable for small tissue biopsies obtained early in the course of disease. New methods of DNA amplification based on polymerase chain reaction (PCR) and Q beta-replicase (Q beta R) have recently been reported. These methods are briefly reviewed, and their potential applications to patients with autoimmune disease are presented. Several types of applications can be considered, including detection of: a) specific HLA-D alleles in order to predict prognosis and better utilize existing medications; b) bacterial, fungal, and spirochete infections in joint aspirates or synovial biopsies; c) human immunodeficiency virus (HIV) and other viruses (e.g., EBV, CMV) that may be associated with immune dysregulation in certain patients; and d) neoplastic transformation in blood or tissues by determining monoclonal gene rearrangements, karyotypic alterations or oncogene activation. It is likely that routine clinical laboratories will soon begin implementing DNA amplification methods in order to screen blood products for infectious agents (especially HIV and hepatitis B virus). Because these techniques will be readily available, rheumatologists/clinical immunologists should begin developing strategies that will allow them to use these methods in a cost-effective manner for diagnosis and monitoring treatment.
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PMID:Use of DNA amplification methods for clinical diagnosis in autoimmune diseases. 169 39

The spectrum of neoplastic disease seen in patients with the acquired immune deficiency syndrome (AIDS) is similar to that seen in several congenital and iatrogenic immunodeficiency states and provides a human model for studying neoplastic transformation in the immune compromised host. High grade lymphoid neoplasia, particularly of the central nervous system (CNS), as well as a virulent form of Kaposi's sarcoma (KS) and several types of squamous cell carcinomas, are appearing at an alarming rate in patients with AIDS. There is substantial serologic, pathologic and molecular evidence linking cytomegalovirus (CMV) to KS and Epstein-Barr virus (EBV) to squamous cell carcinoma and high-grade B-cell non-Hodgkin's lymphoma (NHL). The human T-cell lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV) may be responsible for the permissive immune deficient state allowing for opportunistic neoplasia and the aggressive biologic behavior and atypical anatomic distribution these neoplasms exhibit. The clinical features as well as potential etiopathogenetic mechanisms of these malignancies are reviewed.
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PMID:Cancers-associated with HIV infection. 332 37

Although supported by a number of experimental models, the assumption assigning a crucial role to the immune system in the antineoplastic defense mechanisms has not been convincingly demonstrated so far for human tumors. Should the theory be correct, severe functional impairment of the immune system would obviously result in the occurrence of tumors with abnormally high frequency. Registry holdings systematically collecting pertinent information on the malignancies developed in patients with primary immunodeficiency diseases or in organ transplant recipients maintained on therapeutically-induced immune depression, as well as the observation of tumors occurring in patients treated with immunosuppressive agents and of second malignancies arising after radio- and/or chemotherapy of the primary tumor consistently indicate that depressed immunity is usually associated with an increased incidence of cancer as compared with that expected in the general control populations. However, not all types of tumors are increased to the same extent, in that lymphoreticular neoplasias (especially non-Hodgkin's lymphomas), acute leukemias as second tumors and, among solid neoplasms, squamous cell carcinomas are those most frequently reported. These observations suggest that even deeply impaired tumoricidal immune mechanisms may facilitate the growth of certain tumors only, especially of those arising from the cells of the immune system itself, in remarkable contrast with their frequency in the general population. Oncogenesis may be favoured in various states of depressed immunity by a number of ways. Their elucidation might have bearing on the comprehension of the more general phenomenon of the neoplastic transformation.
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PMID:[Immunological deficiency syndromes, immunosuppression by drugs and occurrence of neoplasms: a casual association?]. 409 54

Peripheral blood T lymphocytes from 15 patients with gastric carcinoma and 6 normal healthy controls were evaluated for Interleukin-2 R gene expression. Total RNA was extracted from T cell-enriched fractions of patients as well as from control peripheral blood lymphocytes, with or without mitogenic stimulation. The presence of mRNA for IL-2 R alpha evaluated by Northern blot analysis revealed that unstimulated T cells expressed lower levels of IL-2 R mRNA than PHA stimulated T cells. Expression of both IL-2 R alpha transcripts (3.5 and 1.5 Kb) were either not detectable or only weakly detectable on T lymphocytes from patients even after mitogenic stimulation. In contrast, a significant rise in the expression of both IL-2 R alpha transcripts was observed on T cells from normal controls followed by mitogenic challenge. This paper reports on the defective IL-2 R alpha gene expression in gastric carcinoma patients, which may explain one of the causes of immunodeficiency associated with neoplastic transformation and progression.
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PMID:Defective interleukin-2 R gene expression in gastric carcinoma patients. 762 94

Retroviruses vary widely in their ability to cause neoplastic transformation or immunodeficiency, and may even lack pathogenicity, but all retroviruses require cytoplasmic expression of intron-containing mRNA. In the cytoplasm, the primary viral transcript has two essential roles as mRNA template for protein synthesis and as genomic RNA for packaging into progeny virions. Cellular proteins are used by the virus to modulate synthesis, processing, and translation of the viral RNA. To subvert the normal RNA processing cascade and achieve nuclear export of intron-containing viral RNA, retroviruses utilize structured RNA elements and viral or cellular protein partners. These nuclear interactions determine the cytoplasmic fate of viral RNAs by facilitating RNA stability, nuclear export, translational efficiency, and even assembly of progeny virions. The HIV Rev responsive element (RRE) and Rev protein have been a informative paradigm for dissection of the process of eukaryotic RNA nuclear export. Rev is an adapter protein that bridges RRE-containing RNA and the CRM1 nuclear export receptor, which delivers intron-containing RNA to a nuclear export pathway typically used for 5s rRNA and protein transport. This review summarizes data indicating that Rev/RRE also targets cytoplasmic transcripts to the cytoskeletal polysomes and activates their translational efficiency. The interesting parallel is discussed that genetically simpler retroviruses lack a Rev-like protein and recruit cellular proteins to distinct RNA elements that modulate post-transcriptional gene expression through different export pathways. These pathways include the global mRNA export pathway mediated by Tap, and Tap- and CRM1-independent pathways. The CRM1-independent nuclear export pathway accessed by the spleen necrosis virus post-transcriptional control element is functionally linked to RU5-mediated translational enhancement in the cytoplasm. The simple retroviral post-transcriptional control elements also modulate RNA splicing efficiency, stability, assembly of virions, and subsequent viral egress from the cell. Thus, multiple layers of post-transcriptional control are executed by these retroviral RNA elements, which serve as a compact platform for interaction with nuclear and possibly cytoplasmic protein partners. Further characterization of the cellular partners and their regulation will be an important step to full understanding of nuclear-cytoplasmic connections that hardwire post-transcriptional gene expression in eukaryotic cells.
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PMID:Retroviral RNA elements integrate components of post-transcriptional gene expression. 1172 75

DC-SIGNR is a human immunodeficiency virus (HIV)-binding C-type lectin that is expressed on endothelium in the hepatic sinusoids, lymph node sinuses and placenta. Like closely related DC-SIGN, DC-SIGNR can bind both ICAM-3 and HIV and can potentiate HIV infection of T lymphocytes in trans. In the present study we have investigated reasons underlying the restricted distribution of DC-SIGNR and have examined DC-SIGNR expression in relation to HIV entry receptors. We show that DC-SIGNR expression does not depend on endothelial cell specialization or on activation state. DC-SIGNR-positive endothelium continues to express DC-SIGNR in conditions of hyperplasia, whereas the molecule is lost after neoplastic transformation, most likely as a result of changes in the microenvironment of the endothelial cells. We have further shown that CCR5, but not CD4, is coexpressed with DC-SIGNR on hepatic sinusoidal and placental capillary endothelial cells. However, CD4-positive CCR5-positive cells, such as hepatic Kupffer cells, placental Hofbauer cells, and CD4-positive T lymphocytes in lymph nodes, can be found adjacent to DC-SIGNR-positive endothelium. Therefore, DC-SIGNR may be able to mediate HIV infection of these cells in trans. Finally, we demonstrate that DC-SIGN and DC-SIGNR can be coexpressed on lymph node sinus endothelial cells, which may lead to modulation of the function of both molecules.
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PMID:Expression of human immunodeficiency virus (HIV)-binding lectin DC-SIGNR: Consequences for HIV infection and immunity. 1215 66

Within a system that operatively allows a progressive infection of T-lymphocytes by human immunodeficiency virus (HIV) in a manner that also entails depletion of the T-helper subset with directly resulting severe immunodeficiency, there might also be implicated a form of modulation of effects conducive to neoplastic transformation based on peculiar consequences of lesions induced by HIV integration within the cell genome. It might, in addition, be valid to consider Epstein Barr virus (EBV) as a cause of both B-lymphocyte infection and also of the creation of a whole population of atypical T-lymphocytes as seen in infectious mononucleosis, to constitute a close parallel analogy to HIV; in this manner it might be suggestive also of a series of analogous reactive lymphocytic changes also in AIDS; such a phenomenon might perhaps help account for the emergence in some AIDS patients of a primary Central Nervous System Lymphoma that is virtually always of B-cell derivation, analogous to Burkitt's lymphoma that is also of B-cell origin. In addition, the occurrence of T-cell rich B-cell lymphoma would appear perhaps to constitute a series of phenomena that intricately implicate both B-lymphocyte and T-lymphocyte participation in the genesis even of lymphomatous states as a category.
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PMID:Possible close analogy between HIV and EBV infection and, respectively, induced lymphomas. 1269 17


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