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 reactivity of peripheral blood lymphocytes from patients with advanced malignancy was assessed by mitogen-induced stimulation of protein synthesis as measured by 3H-leucine incorporation. It was confirmed that the lymphocyte response of patients was depressed. Furthermore, the lymphocytes of 15 out of 27 cancer patients, selected because of their low responses, inhibited the reactivity of normal lymphocytes in co-cultures. The lymphocytes from one patient with Hodgkin's disease were also inhibitory. In contrast, lymphocytes from healthy subjects, patients with chronic lymphocytic leukaemia, lymphosarcoma or multiple myeloma caused no suppression. Experiments with purified cell populations from patients with carcinoma indicated that purified T cells responded to mitogens while unseparated lymphocytes failed to respond and that the inhibitory activity was due to adherent cells, presumably monocytes. There was no evidence for B-cell-mediated suppression. However, in two cases inhibition was caused by isolated T cells of the patients and not by adherent cells. These experiments suggested that one mechanism for the depression of cell-mediated immunity seen in patients with advanced cancer may be the nonspecific suppresssion of certain T-cell functions by circulating monocytes.
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PMID:Depressed in vitro peripheral blood lymphocyte response to mitogens in cancer patients: the role of suppressor cells. 30 Nov 22

A 49-year-old man is described with morphologic T cell chronic lymphocytic leukemia, whose clinical course, however, progressively deteriorated with central nervous system involvement, resistance to treatment and death within eight months. In addition to widespread organ invasion by leukemic cells there was depression of cellular immunity. The leukemic lymphocytes showed an aberrant response to mitogens, and despite undetectable Ia-like surface antigens were able to stimulate allogeneic cells in the mixed leucocyte reaction. From this and similar cases reviewed herein, it appears that the syndrome of small T-lymphocyte leukemia of the adult is a rapidly aggressive and resistant disease with characteristic clinical and laboratory findings.
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PMID:Small lymphocyte T-cell leukemia in the adult. 31 Mar 37

A monospecific rabbit antibody to human plasma P component was used in a quantitative immunoelectrophoretic system. The assay readily detected levels as low as 0.3 microgram/ml, the equivalent of 0.008 U/ml of a normal plasma pool. he average coefficient of variation of duplicate determinations from five sets of nine dilution points of normal plasma was 6.6%. Among normal individuals, groups of 50 adults, 24 children, and 43 term and preterm newborns were each significantly different (p less than 0.001) and the level was positively correlated with age. Three fetal samples of approximately 20 weeks' gestation were near the lower limit of detection of the assay. P component levels in selected groups of patients demonstrated a 1.5 fold elevation of the mean level in 15 patients with high erythrocyte sedimentation rates, no difference in the mean level of 23 patients on warfarin or 16 patients with plasma cell dyscrasia or chronic lymphocytic leukemia, and a depression of the mean level to one fourth of normal in 14 patients with alcoholic liver disease. Among the latter, the prolongation of the prothrombin time was correlated with the depression of P component (p less than 0.05). Conditioned media, even after 10-fold concentration, and lysed cell fractions of cultured adult fibroblasts, B and T lymphocytes, and endothelial and smooth muscle cells failed to demonstrate P component. Circulating levels of P component increase during growth and development to adult life and the hepatocyte is the most likely site of synthesis. Although homologous in structure, C-reactive protein levels are distinguished by their marked response to inflammation and their elevation in most of the patients with hepatocellular damage.
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PMID:Human plasma P component (protein AP): changes during growth and development and evidence for hepatocellular synthesis. 42 72

Fifty patients with lymphocytic lymphoma and chronic lymphocytic leukemia underwent splenectomy for various combinations of anemia, thrombocytopenia, and leukopenia. All of these patients had advanced lymphoproliferative disease, and most had infiltration of bone marrow by neoplastic cells. Good response in all hematologic parameters was obtained in 27 of 48 evaluable patients. An additional 13 patients responded in one or two parameters; there were only 8 complete failures. The over-all surgical mortality was 8%. The median duration of response was 4 months, and the mean, 7 months. Increased tolerance to further antitumor therapy and a decreased transfusion requirement were seen among responding patients. Those patients with anemia who had evidence of shortened erythrocyte survival and splenic sequestration of 51Cr-labelled erythrocytes uniformly responded with rises in hemoglobin. However, half of the patients with negative splenic sequestration also showed improvement of anemia. Preoperative diagnostic studies failed to predict favorable responses of patients with thrombocytopenia or leukopenia. The classical criteria for the diagnosis of hypersplenism are not applicable in many cases of neoplastic lymphoproliferative disease; splenectomy could have been considered "contraindicated" in most of the patients in this series. We conclude that splenectomy is worth undertaking in patients with lymphoproliferative disease complicated by hematologic depression regardless of marrow findings or the results of other diagnostic studies.
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PMID:Splenectomy for hematologic depression in lymphocytic lymphoma and leukemia. 117 72

Forty-three patients with disseminated refractory malignancies each received an individually specified combination of either Adriamycin (n = 24) or mitomycin-C (n = 19) conjugated to a cocktail of murine monoclonal antibodies (mAb). Cancers were typed with both immunohistochemistry and flow cytometry using a panel of antibodies. Cocktails of up to six antibodies were selected based on total binding of greater than 80% of the malignant cells in the biopsy specimen. These mAb cocktails were then drug conjugated, safety tested, and administered intravenously. The Adriamycin immunoconjugates were well tolerated in 22/24 patients, with 17/24 having significant side effects. Fever, chills, pruritus, and skin rash were by far the most common transitory reactions. All were well controlled with premedication. A total of up to 1 g Adriamycin and 5 g mAb were administered to each patient. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. Similar findings were noted among 19 patients treated with mitomycin-C conjugates. Thrombocytopenia at a 60-mg dose of mitomycin-C in this schedule was dose limiting. Serological evidence suggested that the development of an immunoglobulin M antibody specific against the mouse mAb had the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C-treated patients. Selected patients were retreated. One patient with chronic lymphocytic leukemia was treated on three occasions with regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions, and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors. Drug-induced colitis was seen at higher doses with some binding of these conjugates to normal colon epithelium. This study demonstrated the feasibility of preparing individually specified drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery to the tumor in vivo was accomplished. There was limited antigenic drift among various biopsies within the same patient over time. The major technical hurdle continues to be the selection of effective drug conjugation methods to optimally bind drugs to mAbs for targeted cancer therapy.
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PMID:Custom-tailored drug immunoconjugates in cancer therapy. 176 66

Antiplatelet antibodies were studied in patients with chronic lymphatic leukemia (CLL) using ELISA for detection of serum antibodies and RIA for determination of antibodies associated with platelet surface. Serum antibodies were identified in 1 out of 6 CLL patients with the platelet count 100,000-200,000 per microliter and in 7 out of 54 CLL patients with the platelet count lower than 100,000. Platelet-associated antibodies were not detected in patients with the normal platelet count, but were revealed in 14 out of 25 patients with the platelet count 100,000-200,000 per microliter and in 21 of 27 patients with the platelet count lower than 100,000 per microliter. The presence of a group of thrombocytopenic patients lacking serum or platelet-associated antibodies suggested that the development of thrombocytopenia in CLL could be mediated not only by antibodies but also by other pathogenic mechanisms, i.e. by the depression of megakaryocytes in bone marrow. Increase of the platelet count after steroid and cytostatic treatment in CLL patients correlated with decrease of antiplatelet antibodies. In splenectomized CLL patients, the increase of the platelet count and disappearance of hemorrhage occurred in patients with the low level as well as with the high level of antibodies after the operation.
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PMID:[Antithrombocyte antibodies in the serum and on the surface of the thrombocytes in patients with chronic lymphoproliferative diseases]. 178 1

Direct radioimmune assay (RIA) have been developed for detection of antibodies associated wild platelet membrane. Platelets from 12 patients with idiopathic thrombocytopenic purpura (ITP) and 27 patients with chronic lymphocytic leukemia (CLL) (platelet count (100,000 in 1 microliters) have been tested. Antibodies on platelets surface have been detected in all 12 patients with ITP and in 21 patients with CLL. In 6 CLL patients the number of immunoglobulins associated with platelets surface does not increase control level. It is possible, that in some CLL patients development of thrombocytopenia is mediated not only by platelet associated antibodies but by other mechanisms, one of which can be linked with the depression of megakaryocytes growth in bone marrow. Direct RIA for measurement of antibodies on platelet surface detect antiplatelet antibodies with higher frequency than indirect enzyme-linked-immunosorbent-assay (ELISA), developed earlier for assessment of antiplatelet antibodies in serum. Increase of platelet count in CLL patients after steroid and cytostatic treatment correlated with the decrease of platelet surface associated antibodies.
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PMID:[Determination of antiplatelet antibodies on the surface of platelets by direct radioimmune method in patients with different types of immune thrombocytopenia]. 189 96

Based on earlier clinical and preclinical investigations, we designed two different pilot trials for patients with nodular lymphoma or chronic lymphocytic leukemia. These studies evaluated the use of either 41.8 degrees C whole body hyperthermia (WBH), or the nonmyelosuppressive chemotherapeutic drug, lonidamine (LON), as an adjunct to total body irradiation (TBI) (12.5 cGy twice a week, every other week for a planned total dose of 150 cGy). Whole body hyperthermia was initiated approximately 10 min after total body irradiation; lonidamine was administered orally (420 mg/m2) on a daily basis. Although entry to the studies was nonrandomized, the two patient populations were accrued during the same time frame and were comparable in terms of histology, stage of disease, performance status, and prior therapy. Of 8 patients entered on the TBI/WBH study, we observed 3 complete responses (CR), 4 partial responses (PR), and 1 improvement (i.e., a 48% decrease in tumor burden). Of 10 patients entered in the TBI/LON study, there was 1 CR and 4 PR. For the TBI/WBH study, myelosuppression was not treatment-limiting; there were no instances of infection or bleeding and platelet support was never required. The median survival time for the TBI/WBH study is 52.5 months based on Kaplan Meir estimates. Two patients remain in a CR. The median time to treatment failure (MTTF) is 9.4 months (90% confidence interval = 7-15.4 months). In the TBI/LON study, 50% of patients receiving TBI required treatment modification due to platelet-count depression during therapy, but there were no instances of infection or bleeding. Frequently observed LON-related toxicities included myalgias, testicular pain, photophobia and ototoxicity. For the TBI/LON study, median survival is 7.6 months; MTTF was 2.4 months. In analyzing the results of these pilot studies, our subjective clinical impressions lead to the hypothesis that WBH protected against TBI-induced thrombocytopenia during therapy, whereas LON had no effect on TBI-induced myelosuppression. This speculation was tested and confirmed in a series of in vitro and in vivo experiments.
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PMID:Adjunctive therapy (whole body hyperthermia versus lonidamine) to total body irradiation for the treatment of favorable B-cell neoplasms: a report of two pilot clinical trials and laboratory investigations. 218 81

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

Forty-three patients with disseminated refractory malignancies each received an individually-specified combination of either Adriamycin (24 patients) or mitomycin-C (19 patients) conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously. Seventeen out of twenty-four patients had reactions to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic depression. Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C patients. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors and colon with likely drug induced colitis seen after colon binding. This study demonstrates the feasibility and illustrates technical considerations in preparing drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery was accomplished. The major technical hurdle appears to be the selection of effective conjugation methods that can be used to optimally bind drugs to monoclonal antibodies for targeted cancer therapy.
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PMID:Individually specified drug immunoconjugates in cancer treatment. 250 30


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