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

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.
 ...
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

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.
 ...
PMID:Immunohistological assessment of bone marrow biopsies from patients with hairy cell leukemia: changes following treatment with alpha-2-interferon and deoxycoformycin. 278 47

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.
 ...
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.
 ...
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

Natural killer (NK) activity against cells of the K-562 line was significantly depressed in 12 of 18 children (66%) with untreated acute lymphocytic leukemia (ALL). No suppression of allogeneic NK activity was observed with sera of the patients, regardless of the level of NK depression. The ability of peripheral blood lymphocytes (PBLs) to suppress allogeneic NK activity was tested in two ALL patients - one with no detectable NK activity, and one with high NK activity. No NK-suppressive activity was found with PBLs of the areactive patient; PBLs of the reactive patients exhibited some suppressive activity, but only at a particular suppressor-to-effector cell ratio. Leukemic blasts were resistant to killing by autologous NK cells stimulated by IFN, as well as to killing by allogeneic, IFN-stimulated PBLs. Leukemic blasts of an ALL patient inhibited lysis of K-562 cells in an 18-h, but not in a 4-h NK assay. The inhibition could partly be reversed by pretreatment of ALL cells with alpha interferon, suggesting that the blasts might inhibit the lysis of K-562 targets in a competitive manner. Disturbed function and/or regulation of NK cells may influence attempts at NK cell activation by lymphokines.
 ...
PMID:Defects of natural killer cell activity in children with untreated acute lymphocytic leukemia. 316 91

Serial in vitro immune function studies of peripheral blood mononuclear cells (PBMC) were carried out during the long-term treatment with recombinant interferon-alpha 2 (IFN-alpha 2) in a patient with hairy-cell leukemia (HCL). Parameters of B- and T-cell functions as well as NK-cell activity were determined. Treatment with IFN-alpha 2 is associated with temporary and long-term depression of some immune functions, but can also normalize immune responses: in vitro-induced immunoglobulin synthesis, which was normal at diagnosis, was inhibited during the first weeks of IFN therapy but subsequently rose to normal levels. Lymphocyte proliferative responses to mitogens and antigens that were markedly reduced pretherapeutically were further depressed by IFN treatment but, with the exception of pokeweed mitogen (PWM)-induced responses, normalized completely by the 15th to 17th week of treatment. Cocultivation of PBMC with monocytes from normal individuals enhanced depressed lymphocyte proliferative responses. NK-cell activity, which was low at diagnosis, did not rise to the normal range during IFN treatment, but rapidly normalized when IFN therapy was stopped. A discussion is presented on the implications of the alteration of immune functions by treatment with IFN.
 ...
PMID:Modulation of immune functions by long-term treatment with recombinant interferon-alpha 2 in a patient with hairy-cell leukemia. 325 51

Pharmacokinetic studies of five biological response modifiers (BRMs) show diverse regulator functions on effector cell responses and a capacity to cause the secretion of specific soluble factors. Of the five BRMs tested, MVE-2, Poly ICLC, OK-432, and alpha beta IFN were capable of stimulating both natural killer (NK) cell and macrophage (M phi) tumoricidal activity, whereas BM 41-332 augmented only NK cells. Following one treatment with the aforementioned BRMs, M phi activity remained elevated for a longer period (10-14 days) than did NK cell activity (6-9 days). Of particular interest, multiple treatment with BRMs led to a downregulation of NK cell activity (hyporesponsiveness). Three soluble secretory products were induced by these BRMs (colony stimulating factor, CSF; prostaglandin E, PGE; and interferon, IFN). Treatment with MVE-2 and Poly ICLC led to a significant increase in bone marrow cellularity and GM-CFV-C. Results of studies with the cyclo-oxygense-inhibited indomethacin indicate that CSF and PGE are produced and/or secreted by different cellular mechanisms. The depression of effector cells (NK, bone marrow, and GM-CFU-C), as the result of cyto-reductive treatment with cyclophosphamide, could be reversed by treatment with MVE-2. A significantly earlier time to recovery of these effector cells was achieved following MVE-treatment. When MVE-2 was used as an adjuvant to initial tumor cyto-reductive chemotherapy, more successful antitumor response was achieved, indicating that MVE-2 functioned to elevate a substantial effector cell response as well as reconstituting bone marrow cellularity.
 ...
PMID:Biological response modifiers: regulators of the cellular immune system and adjuvants in antitumor therapy. 348 34

Two patients with AIDS and histologically confirmed Kaposi's sarcoma were treated with 3 X 10(6) U/m2 interferon alpha 2C (rIFN alpha 2C) subcutaneously three times a week. In both cases remissions (7 weeks and more than 9 months) of the tumour lesions were achieved and in one case pretherapeutic moderate thrombocytopenia improved. The positive serum antibody titres to HTLV III-virus showed no conversion. Except for fever (below 39 degrees C) during the first two weeks of IFN treatment in both patients, therapy-requiring hypotonia, mild depression, leucopenia (WHO grade 1) and thrombocytopenia (WHO grade 2) in one patient, no side effects were observed. All the above-mentioned features were reversible after termination of treatment. Further studies to optimize the dosage of rIFN alpha 2C and its time schedule in the treatment of Kaposi's sarcoma in patients with AIDS are recommended.
 ...
PMID:[Interferon alpha 2C in the treatment of 2 patients with AIDS-associated Kaposi sarcoma]. 357 87

A study was made of the functional activity of natural killer cells (NK-cells), antibody dependent cellular cytotoxicity of killer cells (K-cells) and the effect of interferon (alpha-IFN) in vitro on function of these cells in a group of donors and patients with dilated cardiomyopathy (DCMP) as well as in patients with chronic coronary heart disease (CHD) and myocardial infarction (MI). Patients with DCMP might be divided into 3 groups according to the nature of NK- and K-cell functional activity: in a grave and rapid DCMP course the functional activity of NK- and K-cells was sharply decreased, a favorable course of disease was characterized by normal or raised values of their cytotoxicity. Patients with a severe type of DCMP revealed profound depression of lymphocyte killer activity.
 ...
PMID:[Antibody-dependent and natural cellular cytotoxicity in patients with dilated cardiomyopathy]. 379 51

Recent animal studies have demonstrated the importance of cancer surveillance in determining susceptibility to UV-induced cancers. On the other hand, even subcarcinogenic UV doses have been shown to suppress cancer surveillance immune mechanisms in experimental animals. To find out if photochemotherapy may compromise human cancer surveillance mechanisms, natural killer (NK) cell activity was monitored during PUVA treatment for up to 38 irradiations in dermatological patients. A significant depression of basal NK activity was seen during the first 4 to 24 irradiations in psoriatic patients. Thereafter, an increase toward starting values was seen in assays performed at high effector to target (E:T) ratios, but not at low ones. The maximal (interferon-boosted) NK activity, however, remained unchanged during the therapy, due to an increased sensitivity to IFN augmentation. The results are interpreted as a redistribution in the proportions of immature and mature NK cells. Thus, no serious effects of PUVA treatment on human natural resistance against cancer could be demonstrated, but longer follow up studies are recommended.
 ...
PMID:Influence of whole-body PUVA treatments on human peripheral blood NK cell activity. 608 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>