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)

Natural killer (NK) activity and natural killer cytotoxic factors (NKCF) were found to be depressed in large granular lymphocytes (LGL) from the peripheral blood and lymph node lymphocytes (LNL) from untreated non-Hodgkin's lymphoma (NHL) patients. The LGL number was also reduced in NHL patients as compared to the normal subjects. The depression in all the activities mentioned above showed a correlation with the clinical status of the patients. Exogenous interferon-alpha (IFN-alpha) treatment of the effector cells could augment the NK activity to a comparable extent in normal as well as patient's LNL. The results indicate that the production of interferon may be affected in cases of NHL and therefore it would be worthwhile to test the tolerance and efficacy of IFN-alpha in these patients.
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PMID:Natural killer activity and NK cytotoxic factors in peripheral blood and lymph node cells from non-Hodgkin's lymphoma patients. 261 73

alpha-Interferon has antitumor activity in a variety of malignancies but is frequently associated with unacceptable toxic side-effects. The routine use of agents potentially capable of reducing these side-effects has not been recommended out of concern for possible reductions in the therapeutic activity of interferon. We conducted a prospective randomized trial of alpha-interferon given with or without indomethacin to patients with malignant melanoma to determine what effect, if any, indomethacin might have on the toxic, immunomodulatory, and therapeutic properties of interferon in this disease. 53 patients were stratified according to performance status and randomized to receive alpha 2b-interferon, 20 million units per m2 i.v., 5 days per week for 4 weeks followed by 10 million units per m2 s.c. three times per week, either with or without indomethacin, 25 mg orally three times a day. The overall major response rate was 13% (three complete responders and three partial responders among 47 evaluable patients) and was the same on both arms. The mean maximal temperature elevation induced by interferon was significantly reduced (from 102.1 to 100.7, P = 0.0002) by indomethacin, but the incidence and severity of interferon-related fatigue, reduction in performance status, headache, depression, confusion, elevations in liver function tests, and myelosuppression were no different in either arm of the study. Indomethacin did not reduce the frequency of dose reductions for toxic side-effects and did not permit the administration of higher interferon doses. Peripheral blood natural killer activity was significantly enhanced in patients during maintenance therapy whether or not they received indomethacin. Indomethacin appeared to inhibit augmentation of natural killer activity during high dose induction therapy. Immunological changes did not correlate with response status. We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma without interfering with its therapeutic or chronic immunomodulatory activities. Since fever is rarely the dose-limiting toxicity of interferon, indomethacin is of marginal benefit to patients with malignant melanoma receiving interferon at the doses outlined in this study.
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PMID:Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. 264 94

The present report describes a comparative study in dwarf goats on human IFN-alpha 2a (0.5 x 10(6) IU kg-1 body weight IM), poly I: poly C (an interferon inducer; 30 micrograms kg-1 b.w. IV), and Escherichia coli endotoxin (an I1-1 inducer; 0.1 micrograms kg-1 b.w. IV). Although IFNs are considered to be species specific, human IFN-alpha 2a was very potent in dwarf goats. All 3 stimuli induced the 'acute phase response'. Among the varied physiological alterations, which together produce this response, are fever and depression, inhibition of gastric function, tachycardia, a decrease in serum alkaline phosphatase activity, leukopenia, lymphopenia and neutropenia followed by neutrophilic leukocytosis, hypoferraemia and hypozincaemia. The results suggest that, apart from I1-1, IFN-alpha also seems to mediate the systemic 'acute phase response' to certain exogenous stimuli.
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PMID:Comparative observations of fever and associated clinical, haematological and blood biochemical changes after parenteral administration of poly I: poly C, interferon-alpha 2a and Escherichia coli endotoxin in goats. 265 64

With progress in cellular immunology and the development of hybridoma technology, the idea of manipulating host-tumor immune interactions to improve the prognosis of brain tumors has aroused renewed interest. Although no brain tumor-specific antigens have been found, and in spite of the wide antigenic heterogeneity of brain tumor cells, some monoclonal antibodies possessing restricted specificity have been isolated and their potential clinical applications investigated. One of the most pronounced changes in the cellular immune responses of brain tumor patients is a profound depression of the T4-helper lymphocytes. Clinical and laboratory trials are under way to assess the ability of lymphokines, such as gamma-interferon or interleukin-2, to restore immunologic competence in these patients and potentiate a specific anti-tumor immunologic response. Recent work suggests that the endothelium-astrocyte complex may have a pivotal role in assisting the escape of brain tumors from the host's immunologic responses, since it is responsible for the intracerebral sequestration of antigens and local anti-tumor responses. In this review, the data on the antigenic properties of central nervous system tumors and the host's humoral and cellular immune responses to them are analyzed and potential immunologic therapies are discussed.
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PMID:Immunology of central nervous system tumors. 268 42

Twenty-two patients with Stages Ia to IVa cutaneous T cell lymphoma were entered into a controlled trial of interferon alfa-2a (Roferon-A). Patients initially received either 3 million IU interferon alfa-2a, or their dosage was escalated to 36 million IU intramuscularly daily for a 10-week induction period. At the end of induction, 14/22 (64%) of patients had an objective antitumor response: three patients had a complete response, ten patients had a partial response (greater than or equal to 50% resolution of clinical disease), and one patient had a minor response. Responders included those with Stages Ia to IVa cutaneous T cell lymphoma, and remissions have lasted at least 4 to 27.5 months. Three patients progressed from a partial to complete response with further treatment, for an overall complete response rate of 27%. Acute flu-like side effects were generally minor and transient. Malaise/fatigue, depression, anorexia, and weight loss were common chronic dose-related side effects and the most frequent reasons for dose reduction or discontinuation of drug. Leukopenia was the most common laboratory side effect and was also dose-related. Recombinant human leukocyte interferon alfa-2a is an effective and well-tolerated single-agent therapy for early and advanced cutaneous T cell lymphoma.
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PMID:Interferon alfa-2a in the treatment of cutaneous T cell lymphoma. 278 39

Thirteen patients with metastatic malignant melanoma received interferon alpha-2a (Roferon-A) and vinblastine. The interferon dosage was increased from 3 x 10(6) IU to 9 x 10(6) IU daily in 10 weeks and thereafter 9 x 10(6) IU was administered three times weekly intramuscularly. Vinblastine (0.075-0.15 mg/kg) was given every third week intravenously. One of the ten evaluable patients had partial remission (PR) (11%) for 10 months. The diseases was stabilized (NC) in three patients (30%) for 3, 6 and 9 months. Progression (PD) occurred in six patients. The treatment time varied from 5 weeks to 44 weeks. The median survival time from the beginning of this combination treatment was 5 months. The most common side-effects were fever, fatigue, loss of taste, weight loss and neutropenia. The mitogen response to phytohemagglutinin and purified protein derivative of tuberculin decreased in all patients. The response to concanavalin A decreased less and began to increase again in the patients with PR and NC. The natural killer cell activity in PD patients decreased more than in the patients with PR and NC. The ratio of T4/T8-positive cells was restored in PR + NC patients but rose in PD patients indicating a difference in the immunomodulatory effect of the combination or of the advanced disease itself on T-cell function in PD patients. This combination of daily interferon and vinblastine did not prove to be effective in melanoma. The depression of immunological functions, which was more marked in patients with PD, might indicate that vinblastine in this combination counteracts the immunostimulatory effect of interferon.
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PMID:Combined interferon and vinblastine treatment of advanced melanoma: evaluation of the treatment results and the effects of the treatment on immunological functions. 278 56

Forty-six bone marrow biopsies from twelve hairy cell leukemia (HCL) patients, treated with either interferon(IFN)-alpha-2 (n = 8) or 2'deoxycoformycin(DCF) (n = 4), were examined using cryostat sections and an immunoperoxidase technique. Using this sensitive method we were able to demonstrate residual hairy cell (HC) infiltration in five cases, in which evaluation with conventional staining techniques on plastic embedded biopsies revealed complete remission. The amount of HCs in these five samples ranged from 1 to 7% (mean: 3%) of bone marrow cells. Consecutive biopsies in individual HCL patients revealed no changes of the immunological phenotype (CD19, CD22, CD25, CD10, CD11c, FMC7, HLA-DR, surface immunoglobulins) during IFN and DCF treatment. Within the infiltrated bone marrow a considerable number of "reactive" T lymphocytes was identified with prevalence of the T-helper (CD4+) subtype in untreated cases, whereas T-suppressor/cytotoxic (CD8+) cells were within the normal range. IFN treatment resulted in a reduction of CD4+ T lymphocytes (p less than 0.02). Minor alterations of CD8+ T lymphocytes and NK cells (HNK-1 + lymphoid cells) were found in bone marrow during IFN treatment. In DCF-treated patients bone marrow T lymphocytes were markedly reduced below the values of normal bone marrow. This DCF-induced T-cell depression might be related to the clinical observation of persistent cellular immune dysfunctions in HCL patients despite a DCF-induced remission.
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PMID:Immunohistological assessment of bone marrow biopsies from patients with hairy cell leukemia: changes following treatment with alpha-2-interferon and deoxycoformycin. 278 47

Previous studies have shown that the progressive growth of the M-1 fibrosarcoma in DBA/2J mice is associated with the activation of suppressor cells which inhibit both mitogen-induced proliferative responses and antibody synthesis. In this study, we have analyzed the effect of tumor growth on NK cell activity. Mice in the advanced stages of tumor growth did have a significant depression in NK activity, and this depression could not be overcome by the injection of the interferon inducer, polyinosinic-polycytidylic acid (Poly I:C). The decline in NK activity was associated with the presence in the spleens of suppressor cells capable of inhibiting the NK activity of spleen cells from Poly I:C-treated syngeneic mice. In order to characterize the suppressor cells, we used a combination of negative selection procedures and kinetic analysis. These studies demonstrated that the spleens of tumor-bearing mice contained two distinct populations of suppressor cells which were not evident in normal mice. One population was non-adherent to nylon wool, Thy-1-, non-phagocytic, did not bind target cells, and had a non-competitive mechanism of suppression. The second population was adherent, Thy-1-, phagocytic, and had a competitive mechanism of suppression. In addition, the spleens of both normal and tumor-bearing mice contained an adherent, non-competitive suppressor cell population which was enriched following negative selection procedures removing T cells or phagocytic cells.
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PMID:Kinetic analysis of the inhibition of natural killer (NK) activity by multiple populations of tumor-activated suppressor cells. 287 55

Mononuclear leukocytes from human immunodeficiency virus (HIV)-seronegative and -seropositive homosexual men lysed HIV-infected U937 cells to a significantly greater degree than uninfected U937 cells. Depletion of cell subsets with monoclonal antibodies and complement indicated that the effector cells were primarily of the CD16+ phenotype. Acid-stable alpha interferon (IFN-alpha) production induced by the HIV-infected cells correlated with, although was not an absolute requisite for, preferential lysis of the infected targets. The activity of these CD16+, natural killer (NK) cells decreased in relation to the duration of HIV infection and the presence of acquired immunodeficiency syndrome. Pretreatment of peripheral blood mononuclear cells from HIV-seronegative subjects, but not HIV-seropositive men, with IFN-alpha or recombinant interleukin-2 enhanced lysis of both uninfected and HIV-infected U937 cells. These results suggest that IFN-alpha-associated, NK-like mechanisms are active in the cytotoxic response against HIV-infected cells and that HIV infection results in an early and progressive depression of such responses. Prospective investigations may be useful in determining the role of this NK cell response in the natural history and pathogenesis of HIV infection and the efficacy of therapeutic modalities.
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PMID:Association of alpha interferon production with natural killer cell lysis of U937 cells infected with human immunodeficiency virus. 291 35

A novel analogue of human alpha-interferon (IFN-alpha CON1) was tested for its ability to modify the hepatic cytochrome P-450-dependent mixed-function oxidase system in the hamster. This cloned interferon was derived by selecting the most frequently observed amino acid sequences at each position in the known human alpha-interferon subtypes. IFN-alpha CON1 had a biphasic effect on cytochrome P-450 and related drug biotransformation in the hamster causing an initial increase followed by a significant depression. IFN-alpha CON1 also had a biphasic effect on cytochrome P-450 in the lung, adrenal and spleen but only a depressant effect in the kidney. This effect was not due to morphological damage and followed the species specificity for this type of interferon. Both the increase and the decrease in cytochrome P-450 could be prevented by the administration of the protein synthesis inhibitor puromycin. Various isozymes of cytochrome P-450 induced by phenobarbital, beta-napthaflavone and clofibrate were also depressed by this interferon. The results presented in this report suggest that IFN-alpha CON1 interferon will likely depress drug biotransformation in humans because the antiviral effects and the "anti-cytochrome P-450" effect of interferons cannot be separated, and this interferon has antiviral properties in both hamster and human cells. Clinically relevant drug interactions may be common during the concomitant use of this interferon and other drugs that are metabolized by cytochrome P-450.
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PMID:Induction and depression of cytochrome P-450-dependent mixed-function oxidase by a cloned consensus alpha-interferon (IFN-alpha CON1) in the hamster. 291 6


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