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)

Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B-lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) gamma and rIFN alpha in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5'-oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5'-oligoadenylate synthetase and dosage of rIFN gamma and rIFN alpha, respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN gamma and rIFN alpha can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN alpha and rIFN gamma might influence T-cell mediated antitumor activity.
 ...
PMID:Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial. 173 46

Spleen cells of Mycobacterium lepraemurium-infected mice were cultured on petri dishes coated with mycobacterial antigens, and antigen-reactive cells were isolated. Upon incubation in mitogen- or antigen-free culture medium, these cells released mediators capable of depressing the in vitro proliferative response of normal splenocytes to specific antigen and to concanavalin A and lipopolysaccharide. One of these mediators was identified with gamma interferon (IFN-gamma), mainly on the basis that treatment of supernatants with monoclonal anti-IFN-gamma antibodies markedly reduced the suppressive activity contained therein. Detectable levels of tumor necrosis factor alpha (TNF-alpha) and TNF-beta were present in spleen cell culture supernatants of infected mice. Moreover, low doses of recombinant TNF-alpha and TNF-beta were found to potentiate the suppressive activity of exogenous IFN-gamma. Soluble T-cell receptors beta were also detected in the culture supernatants. The elimination of these molecules with monoclonal anti-T-cell receptor beta (F23.1) antibodies immobilized on a plastic surface partially reversed the depression of the response to mycobacterial antigen but did not affect the response to mitogens. These results revealed the complex nature of suppressor mediators that are produced by mycobacterial antigen-reactive cells and that regulate the in vitro proliferative response.
 ...
PMID:A role for gamma interferon, tumor necrosis factors, and soluble T-cell receptors in the depressed blastogenic response of spleen cells of Mycobacterium lepraemurium-infected mice. 183 61

The effects of recombinant human alpha A interferon were studied in gnotobiotic calves challenged with respiratory syncytial virus (RSV). Gnotobiotic calves given doses of interferon by intramuscular injection over five days showed a marked, dose-related, rise in rectal temperature and depression of circulating leucocytes. Differential counts showed decreases in both lymphocytes and neutrophils. No significant pathological differences were found between treated and untreated calves, nor could any difference be demonstrated in the pattern of RSV infection.
 ...
PMID:Effects of recombinant human alpha A interferon in gnotobiotic calves challenged with respiratory syncytial virus. 185 59

Recombinant alpha-interferons are used as therapeutic agents in an increasing number of benign and malignant disorders. Long-term administration of recombinant alpha-interferon as a maintenance agent is associated with a small number of adverse side-effects which are responsible for patient intolerance of this drug. These include weight loss, alopecia and chronic fatigue, anorexia and depression syndrome. This latter syndrome needs to be distinguished from thyroid disease, which is documented in this report in a number of patients on recombinant alpha-interferon therapy.
 ...
PMID:Recombinant alpha-interferons, thyroid irradiation and thyroid disease. 190 80

A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma. 190 99

The relationship between depression of early protection against influenza virus infection and the decrease in the number of peripheral polymorphonuclear leukocytes in cyclophosphamide-treated mice was investigated by means of a novel synthetic compound, Y-19995 [2,4'-bis(1-methyl-2-dimethyl-aminoethoxyl)-3-benzoylpyridine dimaleate], which had been shown to exert a potent restorative effect on leukocytopenia in immunocompromised hosts. Following intranasal inoculation with influenza virus (1.5 x 10(3) plaque-forming units) into untreated mice, the pulmonary virus titer progressively increased during 3 days and decreased gradually from day 7 after infection. The treatment with cyclophosphamide 2 days before infection markedly enhanced the pulmonary virus multiplication from the early phase of infection, and the higher virus titer was maintained thereafter. When mice were given Y-19995 after cyclophosphamide treatment, virus titers from the early to late phases of infection were lower than those in untreated mice. The number of peripheral polymorphonuclear leukocytes in cyclophosphamide-treated mice rapidly decreased and returned to normal levels only 9 days after the treatment, while such leukocytopenia was prevented to some extent and the leukocyte count was restored completely up to 7 days by postcyclophosphamide treatment with Y-19995. Furthermore, the treatment with Y-19995 augmented the inactivation of virus by the polymorphonuclear leukocytes. However, the virus inactivation by alveolar macrophages was modified only slightly by Y-19995 treatment. In addition, Y-19995 treatment could potentiate antibody-dependent cell-mediated cytotoxicity of polymorphonuclear leukocytes against the virus-infected target cells, and the production of serum neutralizing antibody to influenza virus in untreated and cyclophosphamide-treated mice. Y-19995 revealed neither antiviral nor interferon-inducing activities.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Depression of early protection against influenza virus infection by cyclophosphamide and its restoration by Y-19995 [2,4'-bis(1-methyl-2-dimethyl-aminoethoxyl)-3-benzoylpyridine dimaleate]. 205 18

A transient depression of HBV serologic markers has been reported for some chronically infected patients treated with human interferons. To determine a molecular basis for these observations, a human, HBV-carrying, hepatocellular carcinoma cell line (PLC/PRF/5) was treated with human alpha, beta, or gamma interferons. Administration of these interferons resulted in a marked depression of HBV surface antigen (HG-sAg) levels in the culture medium. This inhibition was transient, with media levels of HBsAg rising substantially within 48 hours following the termination of interferon treatment. Cell growth rates were not affected by alpha interferon treatment, indicating that overall cell protein synthesis was not substantially altered. Although all three classes of interferons were effective in lowering HBsAg levels in the culture medium, intracellular levels of HBsAg-specific RNA were unaffected. These results suggest that the transient depression of HBV serologic markers in interferon-treated patients may be a consequence of the failure to disrupt the intracellular pools of HBV RNA in the liver.
 ...
PMID:Direct modulation of HBV surface antigen in a human, HBsAg-producing hepatocellular carcinoma cell line by alpha, beta, or gamma interferons. 217 72

Escalating doses of recombinant interferon alfa-2a (Roferon-A), administered intramuscularly three times weekly, combined with psoralen plus ultraviolet light irradiation (PUVA), were tested in a phase I trial for the therapy of patients with cutaneous T-cell lymphomas (CTCL). Interferon doses were escalated in groups of three patients from 6 million to 30 million IUs three times weekly. Disease stages ranged from IB to IVB. Eighty percent of the patients entered in this trial had failed at least one prior therapy. Complete remissions were obtained in 12 of 15 patients, and partial responses were seen in two of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 13 months (range, 3-15+). All patients who responded have been maintained on therapy. The dose-limiting toxic effects were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). These side effects were reversible with a decrement in dose or discontinuation of the interferon. No patient tolerated 30 million IU of the interferon for extended periods; the maximally tolerated dose was 18 million IU. Interferon plus PUVA appears to be a highly effective regimen for the treatment of patients with CTCL. Phase II studies investigating this combination, using 18 million IU of interferon alfa-2a three times weekly, should be undertaken to expand these findings, and to attempt to reduce the toxic effects associated with this therapy.
 ...
PMID:Interferon alfa-2a combined with phototherapy in the treatment of cutaneous T-cell lymphoma. 229 50

Treatment of mice with interferon and interferon inducers causes down regulation of a number of hepatic proteins. In a previous publication it was demonstrated that these treatments depress hepatic protein synthesis and increase protein degradation, particularly of the endoplasmic reticulum Gooderham NJ and Mannering GJ, Arch Biochem Biophys 250: 418-425, 1986. In the present study the effects of polyriboinosinic acid.polyribocytidylic acid (poly IC) treatment on mouse hepatic RNA levels and the translation of this RNA in a cell-free system were examined. Poly IC treatment of mice increased hepatic poly (A+) RNA levels. The translation of isolated poly(A+)RNA was evaluated at various intervals after the administration of poly IC. Translation was marginally increased at 3-6 hr after treatment and depressed after 12-18 hr. Antibodies were employed to examine the effects of poly IC treatment on specific polypeptides in order to evaluate the in vitro translation of mRNAs for tyrosine aminotransferase and albumin; translation of these proteins was biphasic with pronounced depression. These studies indicate that in vivo interferon may regulate gene expression by altering levels of hepatic proteins via increased transcription and decreased translation.
 ...
PMID:In vitro translational activity of messenger-RNA isolated from mice treated with the interferon inducer, polyriboinosinic acid.polyribocytidylic acid. 231 Apr 11

Benzo[a]pyrene (B[a]P) in combination with coal, asbestos, or metal particles was studied for its inhibitory effects on interferon-alpha/beta induction by influenza virus in rhesus monkey kidney (LLC-MK2) cell monolayers. B[a]P per se had no adverse effect on the induction process. However, when cell cultures were pretreated with B[a]P that was bioactivated by rat liver S9 homogenate, from 52 to 65% inhibition of interferon induction occurred. Significantly greater (P less than 0.05) depression (coinhibition) of viral interferon induction (greater than 83%) resulted when bioactivated B[a]P was incorporated with coal particles representative of coal rank (anthracite, bituminous, lignite, peat). Coinhibition affected by bioactivated B[a]P was coal rank-independent but any interferon inhibitory activity affected by coal particles per se was coal rank-dependent. When metals (aluminum, aluminum oxide, ferric oxide, nickel, or chromium) or asbestos fibers (chrysotile, crocidolite, anthophyllite, or amosite) were individually mixed with bioactivated B[a]P, coinhibition of cellular interferon synthesis also resulted which was significantly greater (P less than 0.05) than that manifested by bioactivated B[a]P or particles per se. Coinhibition of interferon induction by silicates (Min-U-Sil, DQ-12, hypersthene, or wollastonite) and the bioactivated hydrocarbon was not in evidence although some silicates alone partially inhibited the induction process. Viral interferon induction was inhibited in a dose-response manner by B[a]P (+/- S9) in combination with selected particles. The adsorption of B[a]P to all types of particles was no more than 5.98 micrograms B[a]P/mg of particles and, moreover, less than 0.5% by weight. These findings provide further evidence that bioactivated B[a]P and occupation-related particles act together to coinhibit a biological defense mechanism, the interferon induction phase of the interferon system.
 ...
PMID:Coinhibition of viral interferon induction by benzo[a]pyrene in association with occupation-related particles. 235 Nov 30


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