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 interferons (IFN) act too slowly to arrest acute viral infections, but interferon-alpha (IFN alpha) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFN alpha have been identified. There are also 3 slightly different versions of the same single subtype, IFN alpha-2, made by recombinant DNA procedures in bacteria. IFN alpha preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFN alpha-2 than after IFN derived from human cells. Given intranasally, IFN alpha can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFN alpha has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFN alpha and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFN alpha are effective against Kaposi's sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFN alpha gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFN alpha. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFN alpha administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.
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PMID:The use of interferon-alpha in virus infections. 172 72

Quantification of human peripheral blood NK subsets has been made in a group of Kenyan adults and children with acute P. falciparum malaria. Results were compared with data obtained from three age- and sex-matched control cohorts: parasitaemic but asymptomatic children; aparasitaemic children and adults; and adult Caucasians with no previous history of malaria. Separated NK subsets were tested in vitro for cytotoxicity to erythrocytic schizonts of P. falciparum in the presence and absence of cytokines. There was a statistically significant quantitative and qualitative depression of the CD3-CD56+ subset in patients with acute malaria and this was accompanied by an expansion of the 'non-functional' CD3-CD57+CD16-CD56- subset. Both CD3-CD16+ and CD3-CD56+ NK cells from all patients and donors lysed schizonts, and this cytotoxicity was enhanced by the addition of recombinant interferon-alpha and/or IL-2, notably with the CD3-CD56+ subset. Interestingly, asymptomatic donors had the highest levels of CD3-CD56+ NK cells, which also demonstrated an enhanced response to cytokine stimulation. Cytotoxicity to schizonts was accompanied by the release of soluble NK cell lytic factors. Neomycin suppressed cytotoxicity in a dose-dependent manner, indicating that the lysis of schizonts by NK cells involves phospholipase C-mediated phosphoinositide metabolism. Our findings define a role for NK cells in immunity to malaria through the lysis of infected erythrocytes as a first-line defence against the parasite.
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PMID:Cytotoxicity of human natural killer (NK) cell subsets for Plasmodium falciparum erythrocytic schizonts: stimulation by cytokines and inhibition by neomycin. 183

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)
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PMID:Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma. 190 99

Bovine interferon-alpha I1 has extensive sequence and functional homology with the antiluteolytic protein, bovine trophoblast protein-1. Because of the possible use of interferon-alpha I1 as a drug that supplements embryonic secretion of bovine trophoblast protein-1, interferon-alpha I1 was tested for other biological actions that might affect its usefulness as a fertility-enhancing treatment. Experiments were performed to evaluate whether interferon-alpha I1 causes hyperthermia and an acute depression in circulating concentrations of progesterone. In four experiments, intramuscular administration of interferon-alpha I1 (range 1.25 to 20 mg) caused hyperthermia; average peak body temperatures of 40 to 40.4 degrees C occurred 2.5 to 6 h after injection. Temperatures returned to baseline 12 to 16 h later. The rise in rectal temperature could be reduced, but not totally alleviated, with concomitant administration of an inhibitor of prostaglandin synthesis. The maximal hyperthermic response was similar when interferon-alpha I1 was delivered via osmotic minipumps or through a series of intramuscular injections. The hyperthermic response decreased with repeated daily exposure to interferon-alpha I1. The increase in rectal temperatures was associated temporally with a decrease in serum progesterone. Effects of interferon-alpha I1 on body temperature and circulating progesterone could possibly limit its effectiveness in enhancing fertility.
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PMID:Effect of bovine interferon on acute changes in body temperature and serum progesterone concentrations in heifers. 209 65

We investigated the efficacy of interferon-alpha (IFN-alpha) treatment in 5 patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). Treatment with IFN-alpha yielded clinical improvement of gait, and sensory and/or sphincter disturbance in 4 out of the 5 HAM patients. IFN-alpha treatment did not bring about uniform changes in lymphocyte subsets or anti-HTLV-I antibody titer of peripheral blood. Although the stimulation indexes to phytohemagglutinin, concanavalin A, and pokeweed mitogen were decreased in the culture of the peripheral blood lymphocytes (PBL) in the 5 HAM patients before the treatment, the stimulation indexes to these mitogens were significantly increased except in 1 case after the IFN-alpha treatment. These changes were based primarily on the depression of the spontaneous proliferation of PBL without mitogen. These results appear to point out a very important phenomenon for the investigation of the pathogenesis of HAM.
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PMID:The efficacy of interferon-alpha treatment in human T-lymphotropic virus type-I-associated myelopathy. 227 19

Fifteen patients with hairy cell leukemia (HCL) were treated with deoxycoformycin (pentostatin; dCF) (4 mg/m2 intravenous [IV] every week x 3) and recombinant interferon-alpha 2a (rIFN-alpha 2a) (3 x 10(6) units subcutaneously [SC] daily x 4 weeks) in alternating months for a total of 14 months. Eleven patients had undergone splenectomy; four had received prior systemic therapy with chlorambucil and/or steroids. All 15 are evaluable for toxicity and peripheral blood response, while 14 are assessable for bone marrow response. Toxicity was tolerable with grade 3 or 4 nausea and vomiting in three patients, neutropenic fevers in five, transient but significant depression in eight, and localized cutaneous herpes zoster in four. Circulating hairy cells were undetectable by the end of the first month in 10 of 13 patients, and by the end of the second month in the other three. Fourteen patients had bilateral bone marrow biopsies performed at baseline after 6 months of treatment, at the end of treatment (14 months), and at 6-month intervals during follow-up. Before treatment, all patients had hypercellular marrows with hairy cels replacing normal marrow elements; all showed at least a 95% clearing of their hairy cell infiltrate by 6 months of therapy. However, small collections of residual hairy cells could be detected intermittently on at least one side of bilateral samples in all patients. All patients have completed treatment with a median duration of follow-up off therapy of 27 months (range, 15 to 31 months). To date, all peripheral counts and serum soluble interleukin-2 receptor (sIL2R) levels remain stable, and no patient has had progression of the hairy cell infiltrate in the bone marrow. Although no patient achieved a pathologic complete response, alternating monthly cycles of dCF and rIFN-alpha 2a produced durable partial remissions (PRs) in all patients. Continued follow-up is required to determine the length of such remissions.
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PMID:Treatment of hairy cell leukemia with alternating cycles of pentostatin and recombinant leukocyte A interferon: results of a phase II study. 231 37

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.
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PMID:Coinhibition of viral interferon induction by benzo[a]pyrene in association with occupation-related particles. 235 Nov 30

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

Pigs were transported from several breeding facilities at the age of 10-12 weeks and regrouped in a fattening farm, specialized in breeding pigs for subsequent slaughter. Blood samples were obtained from the animals just before transport and daily for 17 days after installation in the fattening farm. On each occasion a group of ten animals (170 animals in total) was sampled. The levels of interferon-alpha (IFN-alpha) in serum were measured as antiviral activity in a cytopathic effect inhibition assay. Beginning at day 4 after installation, a significant proportion of sera contained IFN-alpha, with the highest incidence of IFN-alpha positive animals (25%) and IFN-alpha titers on days 5-10. This indicates a high frequency of viral infections in the animals. The in vitro ability of peripheral blood mononuclear leukocytes (PBMCs) to produce IFN-alpha after stimulation by glutaraldehyde-fixed pseudorabies virus-infected PK15 cells and their proliferative response to the T-cell mitogen leukoagglutinin (LA) was also monitored. There was a significant, but moderate decrease in the ability of PBMCs to produce IFN-alpha during the observation period. In contrast, the response to the mitogen LA decreased markedly during the first 5 days, and thereafter remained at the same low level. The proliferative response to LA was significantly lower for PBMCs from serum of IFN-alpha-positive than from IFN-alpha-negative animals. These impaired PBMC responses could indicate a stress-induced immune depression, possibly contributing to the high incidence of viral infections.
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PMID:Appearance of interferon-alpha in serum and signs of reduced immune function in pigs after transport and installation in a fattening farm. 262 98

Interferons (IFN) are known to modulate immune responses in an either stimulatory or inhibitory manner. Most of the knowledge about immunomodulatory activities of IFN comes from investigations of IFN effects on cells in vitro. This study examines the influence which long-term treatment with recombinant interferon-alpha 2 exerts on immune functions in cancer patients. Serial in vitro immune function studies of peripheral blood mononuclear cells were done to determine parameters of B-cell and T-cell functions as well as natural killer (NK)-cell activity. The authors detected profound suppression of in vitro immunoglobulin synthesis and lymphocyte proliferation as well as depression of NK-cell activity during IFN treatment. All suppressed immune functions normalized on discontinuation of IFN therapy. The authors conclude from these observations that, apart from their beneficial effects, IFN produce substantial immunosuppression.
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PMID:Immunosuppressive effects of recombinant interferon-alpha during long-term treatment of cancer patients. 270 71


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