Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the results of treatment of Hodgkin's disease (HD) have improved considerably in the last decades, the disease remains fatal in a minority of patients. We have recently shown that numbers of activated cytotoxic T cells (CTLs), present in tumor biopsy specimens, differ considerably among individual HD patients. Because CTLs are the major effector cells in elimination of neoplastic cells, we investigated whether the number of activated CTLs is related to the clinical outcome of the individual patient with HD. Activated CTLs present in tumor biopsy specimens of patients with nodular sclerosis or mixed cellularity HD were identified by immunohistochemistry using an antibody directed against granzyme B (GrB), a major constituent of the cytotoxic granules of activated CTLs and natural killer cells, and an antibody directed against CD8. The presence of a high percentage of GrB+ lymphocytes was found to be an unfavorable prognostic marker. The large majority of GrB+ cells were also CD8+, indicating that these cells are activated CTLs. Prognosis was found to decrease with increasing percentages of GrB+ lymphocytes. Optimal discrimination between patients with good and poor prognosis was obtained when the threshold was set at 15% GrB+ cells; 6 of 10 patients with > or = 15% GrB+ lymphocytes died as a result of the disease, as compared with 6 of 70 patients with less than 15% GrB+ lymphocytes (P < .0001). In stage-2 patients, the percentage of GrB+ lymphocytes retained its predictive value in a multivariate analysis including histology, sex, age, erythrocyte sedimentation rate, and the presence of B symptoms as covariables. In addition, patients with > or = 15% GrB+ lymphocytes had a shortened progression-free survival time (P = .002). We conclude that a high percentage of activated CTLs present in biopsy material of HD patients is a strong indicator for an unfavorable clinical outcome.
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PMID:Activated cytotoxic T cells as prognostic marker in Hodgkin's disease. 922 92

CD40 is a 48 Kd integral membrane protein expressed by cells of B cells, origin, dentritic cells, monocytes, epithelial cells, endothelial cells and tumor cells including carcinomas, B cell lymphomas/leukemias and Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD). CD40 has been clustered as a member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily with the corresponding counterstructure, the CD40 ligand (L) being mainly expressed by activated CD4+ T cells, but also some activated CD8+ T cells, basophils, eosinophils, mast cells and stromal cells. CD40L shares significant amino acid homology with TNF particularly in its extracellular domain ("TNF homology region") and is therefore viewed as a member of the TNF ligand superfamily. Binding of CD40L+ T cells to CD40+ B cells is thought to play a major role in T cell-dependent B cell activation, B cell proliferation, Ig isotype switching, memory B cell formation and rescue of B cells from apoptotic death in germinal centers. Mutations of the CD40L gene have been associated with the X-linked hyper-IgM immunodeficiency syndrome, pointing to the critical role of the CD40/CD40L interaction in the T cell-B cell interplay. Accordingly, expression of CD40 by human lympho-hematopoietic tumors has been shown in most of the B cell neoplasias, H-RS cells and HD and some carcinomas. In contrast, CD40L+ tumor cells are almost invariably restricted to CD4+/CD8- T cell lymphomas. Overall, functional CD40/CD40L interactions appear to be critical for cellular activation signals during immune responses and neoplastic tumor cell growth. The understanding of the biology of CD40L has improved our diagnostic and therapeutic repertoire in the management of several human diseases, including CD40+ tumors.
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PMID:CD40/CD40 ligand interactions in normal, reactive and malignant lympho-hematopoietic tissues. 908 33

Immunophenotyping of cells by flow cytometry has become a routine test to diagnose pulmonary and mediastinal diseases. Peripheral blood, extravascular fluids, bronchoalveolar lavage (BAL) and suspension of single cells obtained by fine-needle aspiration can be used. Peripheral blood (MOAb for immunophenotyping of lymphocytes: CD14, CD45, CD3, CD19, CD4, CD8, CD16/56, HLA DR, CD38, CD25) is the material of choice for detection and monitoring of immunodeficiences. BAL (MOAb for immunophenotyping of lymphocytes: CD14, CD45, CD3, CD19, CD4, CD8, CD16/56, HLA DR) is used mainly for differential diagnosis of extrinsic allergic alveolitis (low CD4/CD8 ratio) and sarcoidosis (high CD4/CD8 ratio). The enumeration of alveolar macrophage subsets is an important tool to establish diagnosis of histiocytosis X (CD1a > 3%). Extravascular fluids, suspension of single cells and BAL are preferred materials for detection and classification of non-Hodgkin lymphomas (MOAb for immunophenotyping of lymphocytes: CD14, CD45, CD3, CD19, CD4, CD8, CD16/56, HLA DR, CD38, CD25, CD23, CD5, CDl1c, CD30, light chain immunoglobulins).
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PMID:[Flow cytometry for extensive thoracic diagnosis]. 920 29

We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8alphaalpha homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4-, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.
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PMID:Long-term depletion of naive T cells in patients treated for Hodgkin's disease. 934 51

Diagnosis of Hodgkin's disease (HD) is quite difficult in the patient with seropositivity for human T cell lymphotropic virus I (HTLV-I). Herein, two cases of Epstein-Barr virus (EBV)-associated HD, which occurred in males with seropositivity for anti-HTLV-I, are reported. One patient is alive and was diagnosed as having interfollicular HD with CD20+CD15-CD30-CD3-CD4-CD8-CD45RO-Read-Sternberg (R-S) cells. Positivity for EBV-encoded RNA 1 (EBER-1) and latent membrane protein 1 (LMP-1) was shown on follicular germinal center cells and R-S cells. In that case, neither T cell receptor (TCR) beta chain rearrangement nor integration of the HTLV-I provirus was demonstrated in the lymph nodes, although atyical lymphocytes (2%) were found in the peripheral blood. The other case pursued an aggressive clinical course and the patient was diagnosed as having an adult T cell leukemia/lymphoma (ATLL) because of the presence of anti-HTLV-I antibody, lymph node swelling, and the appearance of flower-like cells in the peripheral blood. However, an autopsy revealed no obvious ATLL cell infiltration in any of the organs examined. Multiple granulomatous lesions were found in the bone marrow, liver, kidneys, spleen, and lymph nodes. Reassessment of lymph node lesions in biopsies and granulomatous lesions in autopsy samples demonstrated that both lesions contained CD15+CD30+CD3-CD4-CD8-CD20-CD45RO-EBER-1+L MP-1+R-S cells, and they were considered to be a composite lymphoma of HD and ATLL. These two cases therefore suggest that EBV-associated HD can develop in patients with seropositivity for HTLV-I.
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PMID:Epstein-Barr virus-associated Hodgkin's disease in HTLV-I seropositive patients: a report of two cases. 958 68

One hundred seventy-four patients with progressive or advanced chronic lymphocytic leukemia (CLL) have received initial therapy with fludarabine as a single agent or fludarabine combined with prednisone. The overall response rate was 78% and the median survival was 63 months. No difference in response rate or survival was noted in the 71 patients receiving fludarabine as a single agent compared with the 103 patients who received prednisone in addition. The median time to progression of responders was 31 months and the overall median survival was 74 months. Patients over the age of 70 years had shorter survivals. Patients with advanced stage disease (Rai III and IV) had a somewhat shorter survival than earlier stage patients. More than half the patients who relapsed after fludarabine therapy responded to salvage treatment, usually with fludarabine-based regimens. Second remissions were more common in patients who had achieved a complete remission on their initial treatment. The CD4 and CD8 T-lymphocyte subpopulations decreased to levels in the range of 150 to 200/microL after the first 3 courses of treatment. Although recovery towards normal levels was slow, the incidence of infections was low in patients in remission (1 episode of infection for every 3.33 patient years at risk) and decreased with time off treatment. There was no association of infections or febrile episodes with the use of corticosteroids or the CD4 count at the end of treatment and a poor correlation with the increase in CD4 counts during remission. Infectious episodes were less common in patients who had a complete response compared with partial responders. Richter's transformation occurred in 9 patients and Hodgkin's disease occurred in 4 patients. Five other patients died from other second malignancies. Fludarabine appears to be an effective initial induction therapy with a reasonable safety profile for patients with CLL.
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PMID:Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. 969 4

Immunologic parameters were studied in 54 patients with myeloma multiplex (MM), acute leukosis (AL), non-Hodgkin's disease (NHD) before and after in vitro exposure of these patients' blood to weak constant magnetic field (CMF) and CMF in combination with variable magnetic field (VMF). Blood irradiation with CMF over 60 min in AL and MM patients brought about in some cases enhancement of the expression of +CD3, +CD4 and CD8 together with augmentation of the immunoregulatory index. At the same time phagocytic activity of leucocytes got increased as did digesting capability and index of completeness of phagocytosis, i.e. exposure to CMF prevents a blockade of receptors for neutrophilic complement, increases their phagocytic activity and antibody-dependent cellular cytotoxicity. In studying immunocompetent cells of NHD patients' blood, T-helpers were found out to be moderately decreased, with T-suppressors to a greater extent so. Study of CMF and VMF effects on MM and AL patients' blood has shown an immunocorrective action thereof though to a lesser extent so.
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PMID:[The effect in vitro of permanent and variable magnetic fields on immunocompetent blood cells from patients with hemoblastoses and non-Hodgkin's malignant lymphoma]. 969 91

We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.
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PMID:A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature. 1043 11

The defects in lymphocyte apoptosis that underlie the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of the CD95 (Fas) gene. In this report, we present the histopathological and immunophenotypic features seen in the lymph nodes (n = 16), peripheral blood (n = 10), bone marrow (n = 2), spleen (n = 3), and liver (n = 2) from 10 patients with ALPS. Lymph nodes showed marked paracortical hyperplasia. Interfollicular areas were expanded and populated by T cell receptor-alphabeta CD3+ CD4-CD8- (double-negative, DN) T cells that were negative for CD45RO. CD45RA+ T cells were increased in all cases studied. The paracortical infiltrate was a result of both reduced apoptosis and increased proliferation, as measured by in situ detection of DNA fragmentation and staining with MIB-1, respectively. The paracortical proliferation may be extensive enough to suggest a diagnosis of malignant lymphoma. Many of the paracortical lymphocytes expressed markers associated with cytotoxicity, such as perforin, TIA-1, and CD57. CD25 was negative. In addition, most lymph nodes exhibited florid follicular hyperplasia, often with focal progressive transformation of germinal centers; in some cases, follicular involution was seen. A polyclonal plasmacytosis also was present. The spleens were markedly enlarged, more than 10 times normal size. There was expansion of both white pulp and red pulp, with increased DN T cells. DN T cells also were observed in liver biopsies exhibiting portal triaditis. In the peripheral blood, the T cells showed increased expression of HLA-DR and CD57 but not CD25. CD45RA+ T cells were increased in the four cases studied. Polyclonal B cell lymphocytosis with expansion of CD5+ B cells was a characteristic finding. Taken together, the histopathological and immunophenotypic findings, particularly in lymph nodes and peripheral blood, are sufficiently distinctive to suggest a diagnosis of ALPS. Of note, two affected family members of one proband developed lymphoma (T-cell-rich B-cell lymphoma and nodular lymphocyte predominance Hodgkin's disease, respectively).
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PMID:Pathological findings in human autoimmune lymphoproliferative syndrome. 981 46

High levels of soluble lymphocyte antigens have been described in a large number of tumors and, particularly, in hematopoietic neoplasms. As previously reported, many antitumor immune responses are IL-2 dependent: clinical observations indicate that a worse survival in advanced tumor patients is related with a decrease of soluble IL-2 levels. A soluble form of CD8 has been described: as found in Hodgkin's disease and acute lymphoblastic leukemia, sCD8 levels have a prognostic value. To explain the significance of these soluble molecules in solid tumors, we a) determinated sIL-2R and sCD8 in 84 patients; b) correlated the expression of p55 chain of IL-2R and CD8 antigen on the cell-surface of peripheral lymphocytes to sIL-2R and sCD8 levels; c) analyzed endogenous IL-2R levels in patients with lung cancer. An increase of sIL-2R was found in 82% of cases, while high levels of sCD8 were observed in 32%; no correlation was observed between sIL-2R and the expression of p55 on the surface of peripheral lymphocytes: IL-2 levels in patients with NSCLC were significatively reduced, when compared to healthy controls, with an inverse relationship between endogenous IL-2 concentration and sIL-2R levels. Whatever may be the physiopathological mechanism of the increase of sIL-2 observed in solid tumors, this rise may contribute to the immunodepression correlated to neoplastic disease. Therefore, higher levels of sIL-2R/IL-2 ratio has a negative biologic prognostic significance. We think that determinating CD8 antigen in the serum can offer a more sensitive and specific measurement of activation of suppressor/cytotoxic T-lymphocytes.
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PMID:Soluble interleukin-2 receptor and soluble CD8 antigen levels in serum from patients with solid tumors. 985 47


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