Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first part of the paper outlines the actual situation of the recent investigations on the interpretative problem of the immunological deficits combined with enzymatic deficits. ADA deficit associated with combined immunodeficiency is an autosomal recessive form. Low enzyme levels, which is produced by a structural gene located on chromosome 20, were detected in chronic lymphatic leukemias where ADA decrease is correlated to low levels of T lymphocytes and the prevalence of an atypical B lymphocyte population. Particularly high levels of ADA were detected in acute lymphoblastic leukemias, in transplant rejection, in blastic crisis of chronic myeloid leukemia... NP deficit is associated with a T branch immunodeficiency, with high levels of inosine, guanosine, hypouricemia, hypochromic microcythemia and hematopoietic tissue megaloblastosis. This enzyme, with trimeric structure, whose structural gene is located on chromosome 14, shows a cytoplasmic location, and its maximum activity is to be found in T lymphocytes separated by rosetting. IGPT deficit is to be held responsible for the neurological Lesch-Nyhan syndrome. This deficit is associated with a depression of B lymphocyte function evaluated as response to the mitogens (PWM, Protein A) or as specific immunoglobulins production. At last the Authors report some personal investigations performed on hemolysates and lymphocytes of subjects with impaired immunity, as well as on some children at birth to establish the correlation between ADA and NP behaviour and immunosurveillance. Lastly, the data on the variations of the enzymatic and immunological parameters of subjects with immunodeficiency associated to enzymopenia after red cell transfusion are reported.
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PMID:[Immunodeficiencies and enzyme deficiencies]. 10 63

The natural killer activity of isolated mononuclear cell populations of acute myelocytic leukemia (AML) patients in remission and relapse was compared with that of mononuclear cells obtained from normal subjects. The target cells consisted of 51Cr-labeled blast cells of the K-562 cell line, which was originally obtained from a patient with chronic myelocytic leukemia in blast crisis. The natural killer activity of lymphocytes from AML patients in remission was similar to or higher than that of normal subjects. A marked depression in this function was associated with relapse, as well as with heavy combined chemotherapy. It is concluded that natural killer activity assessed in vitro is an accurate indicator of the clinical stage of AML patients.
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PMID:Natural killer activity in patients with acute myelocytic leukemia. 31 67

Sixteen Zambian Africans with chronic myeloid leukaemia are described. Clinical and haematological features were unremarkable except for the relative extreme youth of three patients (aged 18 years or less) and one patient with the aleukaemic form in whom the diagnosis was proved by marrow examination. Thirteen patients were treated with busulphan (Myleran), of whom 12 showed varying degrees of responsiveness, and one was completely resistant both to busulphan and cyclophosphamide. One patient became pregnant while receiving busulphan and another showed depression of spermatogenesis when investigated four years after start of treatment. The poor responsiveness of some Africans to busulphan is briefly speculated upon.
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PMID:Chronic myeloid leukaemia in Zambians. 105 59

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT-29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment.
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PMID:Regulation of de novo and salvage pathways in chemotherapy. 187 99

Fetal hemoglobin (Hb F) may increase in patients receiving chemotherapeutic drugs, a result of potential use in patients with symptomatic hemoglobinopathies. We examined Hb F in 13 patients with myeloproliferative disease (six polycythemia vera, five polycythemia vera with myeloid metaplasia, one agnogenic myeloid metaplasia, and one chronic myelogenous leukemia) who were treated with hydroxyurea. Four patients showed an increase in Hb F from less than 1% to between 5% and greater than 8% while on hydroxyurea, and a decline to less than 1% when the drug was discontinued. This group of "responders" received a higher average daily dose of hydroxyurea, which was administered continuously rather than intermittently, when compared to the "nonresponders." Mean corpuscular volumes (MCVs) rose in most patients, and i antigen remained elevated or decreased; neither parameter correlated with Hb F levels. Both responders and nonresponders had therapeutically desirable suppression of WBCs and platelets, and almost all had no depression of reticulocytes or Hb.
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PMID:The effect of hydroxyurea on hemoglobin F in patients with myeloproliferative syndromes. 241 68

In the present study plasma fibronectin levels were determined in patients with hematopoietic malignancy, particularly leukemias, in an effort to clarify their clinical implications. Among leukemia patients, those with AML, ALL, ATL or CLL had various plasma fibronectin levels that were higher in some cases, while lower in others, as compared to normal control values. An elevation of the fibronectin level was noted often in APL, while lower fibronectin values were observed in many instances of CML. In these types of leukemia, acute exacerbation as well as supervention of infection tended to be associated with lower than normal levels of fibronectin. An especially marked depression of fibronectin occurred, when leukemia was complicated by sepsis or DIC, in which a good parallel was noted between the progress of disease and the fibronectin level. In lymphoproliferative diseases, the fibronectin value varied widely, but low fibronectin levels were frequently associated with intercurrent infection or an extreme deterioration of the general physical conditions.
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PMID:Variation of plasma fibronectin levels in leukemia patients. 248 45

A histological and immunohistological analysis of lymph nodes after allogeneic bone marrow transplantation (BMT) was performed to investigate the microarchitecture of the lymphatic tissue and the phenotype of the recovering lymphoid cells. The study included four patients with chronic myeloid leukaemia who had died between 0.5 and 12 months after transplantation. The study yielded the following results: 1. All lymph nodes, irrespective of length of the survival period, exhibited severe atrophy of the lymphoreticular tissue with marked depletion of lymphocytes and dilatation of the sinuses. The number of lymphoid cells increased considerably with time after transplantation. 2. The main constituents of the recovering immune system were mature T lymphocytes (CD4+ and CD8+ cells in nearly equal numbers) and macrophages. The earliest signs of recovery of the immune system could already be detected 0.5 month after BMT. 3. Extreme paucity of B lymphocytes was a prominent finding in all lymph nodes studied. True lymphatic follicles and germinal centres were never detected. 4. Polytypic plasma cells were seen in low or moderate numbers mainly in the lymph node sinuses, while neither marked plasmacytic hyperplasia nor even a monotypic pattern were found. 5. Immune-accessory reticulum cells were detected only in the lymph nodes of the patient who survived 12 months. 6. Natural killer cells occurred only in low numbers irrespective of the duration of survival after BMT. Altogether, the histopathological lymph node findings clearly reflect the marked long-standing depression of the immune responses seen after allogeneic bone marrow transplantation. Since three of the four patients had shown signs of acute or chronic graft-versus-host disease, the histological findings presumably do not fully reflect the normal reconstitution of the immune system, but may have been modified by phenomena related to graft-versus-host disease.
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PMID:Lymph node morphology after allogeneic bone marrow transplantation for chronic myeloid leukemia: a histological and immunohistological study focusing on the phenotype of the recovering lymphoid cells. 329 90

In a retrospective analysis of 199 cases of myeloproliferative diseases a concomitant plasma cell dyscrasia was found in three out of 46 patients with idiopathic myelofibrosis. Chronic myeloid leukemia, polycythemia vera or unclassifiable myeloproliferative disorders were in no case associated with monoclonal gammopathy. One patient with idiopathic myelofibrosis had primarily coexistent IgG-lambda paraproteinemia and increasing osteolytic lesions; histologic evidence of multiple myeloma, however, was insufficient. In the second patient the interval between diagnosis of idiopathic myelofibrosis and IgG-kappa paraproteinemia was 11 years. After a stable period of 9 years' duration the paraprotein level rapidly increased, associated with depression of normal background immunoglobulins and progressive bone marrow failure. The exact nature of this patient's malignant plasma cell dyscrasia remained uncertain. In the third case benign monoclonal gammopathy of the IgM-lambda type was diagnosed 13 years after idiopathic myelofibrosis. A review of the literature confirms a remarkably high incidence of monoclonal gammopathies in idiopathic myelofibrosis. Benign monoclonal gammopathy seems to occur in at least 8% of the patients while only a few cases of concomitant multiple myeloma have been reported. It may be speculated that plasma cell dyscrasias in idiopathic myelofibrosis reflect involvement of the lymphoid lineage in the neoplastic stem cell disorder.
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PMID:Frequent association of idiopathic myelofibrosis with plasma cell dyscrasias. 335 2

Mitoxantrone, a new anthracenedione, was administered to thirty-nine patients with relapsed and refractory acute leukemia and to 12 patients with blastic crisis of chronic myelogenous leukemia between August 1981 and September 1984. Eleven patients were not evaluable and 40 were analysed. There were 24 males and 16 females with a median age of 37 yrs (range 6-73 yrs). Three of these were less than 15 yrs and 7 more than 60 yrs. The initial dose employed was 1.9 mg/m2/day X 5. Although eventually a starting dose of 12.3 mg/m2/day X 5 was used, about one half of cases were given more than 5 mg/m2/day X 5 by i.v. bolus. Among 25 patients with acute non-lymphocytic leukemia, there were 4 complete and 6 partial remissions. Among 7 patients with acute lymphocytic leukemia there was one complete remission and one partial remission. All patients except one who attained remissions had received prior anthracyclines. One of 8 patients with blastic crisis of chronic myelogenous leukemia had a partial remission. The durations of complete remission were 1, 1, 5+, 13+ and 17 weeks, respectively. Side-effects showed expected bone marrow depression. Mucositis occurred in ten patients. Gastrointestinal symptoms were noted in approximately 50%, but were mostly mild. Mild alopecia occurred occasionally. The trials were too short to allow evaluation of possible cardiac toxicity. These data indicate that mitoxantrone is non-toxic but hematological and a promising single drug for use in treating relapsed and refractory acute leukemia and suggest that further study would be worthwhile in order to identify its role in the first-line therapy of acute leukemia.
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PMID:[Phase II trial of mitoxantrone in patients with relapsed and refractory acute leukemia]. 346 30


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