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)

A total of 22 patients with advanced measurable colorectal carcinoma were treated with human lymphoblastoid interferon, 15 X 10(6) U/m2 im 3 times a week, in a trial designed to evaluate therapeutic activity, toxic effects, and biological response modification. One partial response (4.5% response rate) was observed which lasted 4 months. Sixty-eight percent of the patients required dose reduction for excessive toxicity, primarily constitutional symptoms. One patient developed phenobarbital toxicity, a previously undescribed side effect thought to be related to interferon-induced depression of hepatic microsomal enzymes required for drug metabolism. Treatment was associated with an increase in peripheral blood natural killer (NK) cell activity and the activity of an interferon-induced enzyme, 2'-5' oligoadenylate synthetase. The increase in NK cell activity was observed only in patients whose pretreatment NK cell activity was below normal. No induction of serum factors inducing differentiation of myeloid leukemic cell lines was documented. We conclude that human lymphoblastoid interferon, at the dose and schedule tested, has minimal antitumor activity as a single agent in advanced colorectal cancer and induces unacceptable toxicity in the majority of such patients. Recent literature suggesting a possible role for interferon alpha in combination with other drugs in the treatment of colorectal cancer is discussed.
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PMID:High-dose human lymphoblastoid interferon in metastatic colorectal cancer: clinical results and modification of biological responses. 379 Dec 67

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.
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PMID:[Antibody-dependent and natural cellular cytotoxicity in patients with dilated cardiomyopathy]. 379 51

The influence in vivo of immunosuppressive drugs (cyclosporine, azathioprine, and corticosteroids) on the production of various lymphokines (alpha and gamma interferon, interleukin 2), both in organ transplant recipients and in normal volunteers taking 100 mg hydrocortisone orally has been studied. To avoid interference with the rejection process or viral infection, patients were studied in a steady state with low maintenance immunosuppression consisting of prednisolone combined with azathioprine or with cyclosporine. In patients treated with both drug regimens, significant depression of production of the three lymphokines was found. Normal volunteers challenged with 100 mg hydrocortisone showed inhibition of production of interleukin 2 and alpha and gamma interferon in 4 hr, a time corresponding to the nadir of T cell lymphopenia, affecting the OKT4 subset preferentially. The percentage of OKT8 cells remained unchanged. Percentages of large granular lymphocytes increased, but their absolute number was not significantly modified. Changes in lymphocyte markers were fully reversible after 24 hr, but interleukin 2 production remained markedly depressed, showing that the redistribution patterns induced by corticosteroids on lymphocyte subsets may be dissociated from functional consequences.
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PMID:Influence of in vivo immunosuppressive drugs on production of lymphokines. 391 67

10 patients with disseminated colorectal cancer were treated either chronically or cyclically with human recombinant leukocyte A interferon (IFl-rA) for 3 months. During this period, leukocyte adherence inhibition (LAI), natural killer (NK) cell activity, concanavalin A-induced gamma-interferon production capacity (GIPCA) and phytohemagglutinin response were sequentially monitored. In both chronically and cyclically treated patients, IFl-rA therapy led to a 'short-lived' augmentation of NK cell activity. In the chronically treated patients, there was a further depression in the NK cell activity during the course of therapy. The outcome of LAI remained unaltered irrespective of the mode of IFl-rA therapy. There was an inverse correlation between GIPCA and phytohemagglutinin response.
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PMID:Leukocyte adherence inhibition, natural killer cell activity, gamma-interferon production capacity and phytohemagglutinin response in patients treated with recombinant leukocyte A interferon. 392 13

Experimental and more limited clinical studies have suggested that influenza vaccination may depress the oxidative hepatic metabolism of various drugs and lead to drug toxicity. The alleged mechanism is the formation of interferon and the resulting decrease in cytochrome P-450 available for drug oxidation. Because of the clinical and basic science implications of these reports, we undertook to study the effects of influenza vaccine on the metabolism of three commonly used drugs: chlordiazepoxide, theophylline, and lorazepam. Our healthy male subjects were studied just before and 1 and 7 days after vaccination. As expected, lorazepam metabolism, which proceeds by glucuronidation and not oxidation, was not altered by vaccination. Surprisingly, however, the oxidation of chlordiazepoxide was also not depressed by the vaccine. Theophylline oxidation, which proceeds primarily by microsomal oxidation (demethylation), was significantly decreased 1 day, but not 7 days, after vaccination. Serum alpha-interferon levels rose after vaccination for only about 8 hours, and levels of gamma-interferon rose to about 500 IU/ml at 24 hours, peaked at 72 hours, and returned to normal by 100 hours after dosing. It appeared that the higher the theophylline clearance before vaccination, the greater the degree of clearance depression after vaccination. Thus the inhibition of drug oxidation after influenza vaccination is selective and each drug should be studied individually. The degree of depression of theophylline clearance is small and transient and appears to be greater in subjects with higher prevaccination clearance.
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PMID:Effects of influenza virus vaccine on hepatic drug metabolism. 397 1

A synthetic mutant of beta-interferon, produced by recombinant DNA technology, was prepared with serine substituted for the naturally occurring cysteine at amino acid 17. This molecule, after purification to homogeneity, was evaluated in 23 patients with cancer for tolerated doses, safety, and pharmacokinetics. Each patient was begun on twice weekly administration, one dose i.m., then an identical dose i.v. Doses, escalated weekly, were tolerated by 9 of 12 patients at 100 X 10(6) units i.m., 11 of 14 patients at 100 X 10(6) units i.v., and 8 of 10 patients receiving i.v. doses of 200 X 10(6) units. Fever (greater than or equal to 38.9 degrees C), the commonest cause for ceasing dose escalation, occurred in 11 of 13 patients who developed limiting i.v. toxicity and 6 of 11 who developed limiting i.m. toxicity. Patients who did not have progressive cancer after completion of dose escalation received five consecutive daily doses at their maximum tolerated single dose by each route, i.m. and i.v. These two 5-day treatments were given without difficulty. All patients treated with 300 X 10(6) units or less, i.m. (n = 13) or i.v. (n = 10), were able to receive five daily doses without limiting toxicity. Peak serum titers occurred immediately after i.v. administration and declined in an exponential manner thereafter. Despite absence of measurable titers in serum after i.m. injection, fever and significant (P less than 0.05) depression of WBC and platelet counts, serum calcium, and serum cholesterol occurred (prestudy to maximum tolerated dose). An immunoglobulin antibody to beta-interferon, detected by enzyme-linked immunoabsorbent assay, developed in 17 of 23 patients. Neutralizing activity (titer 10(2] was found in only 1 of 23 patients. No immune-mediated sequelae (symptomatic or renal) were identified. Further Phase I and II trials with this molecule will determine whether it will prove to have a better therapeutic index or different spectrum of therapeutic activity from alpha-interferon or gamma-interferon.
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PMID:Phase I evaluation of a synthetic mutant of beta-interferon. 405 62

Poly(I,C)-LC was administered in low (1 mg/m2) and intermediate (4 mg/m2) doses to cancer patients by intramuscular injection or intravenous infusion to evaluate the immunomodulatory effects. Natural killer cell (NK) activity was elevated slightly at the low dose and remained unchanged overall, but some depression was observed at the 4 mg/m2 intravenous dose. Monocyte function was elevated in all groups of patients, as was the interferon-induced enzyme 2'5'-oligo-A synthetase. These increases were observed at the 1 mg/m2 intramuscular dose, despite a lack of detectable circulating serum interferon (IFN). In regard to cell surface markers, poly(I,C)-LC induced an increase in OKT10-positive cells and a small but consistent trend toward increases in the ratio of Leu-3/Leu-2-positive cells. Lymphocyte proliferation in response to concanavalin A was depressed by poly(I,C)-LC administration. Although an optimum immunomodulatory dose and schedule was not determined, the data indicate that low doses produce significant changes in immune function and that induction of detectable levels of circulating interferon is not required for poly(I,C)-LC to have biological effects.
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PMID:Immunomodulatory effects of poly(I,C)-LC in cancer patients. 408 34

Gordon, Irving (University of Southern California, Los Angeles), Sara S. Chenault, Douglas Stevenson, and Jean D. Acton. Effect of interferon on polymerization of single-stranded and double-stranded mengovirus ribonucleic acid. J. Bacteriol. 91:1230-1238. 1966.-The effect of interferon on actinomycin-resistant mengovirus ribonucleic acid (RNA) replication in L cells was investigated to determine whether defective or partially polymerized RNA products were made and whether synthesis of any specific class of virus RNA was prevented. RNA labeled with uridine-C(14) was extracted in hot and cold phenol and analyzed by zonal sucrose density centrifugation. Both single- and double-stranded infectious RNA peaks were identified. Interferon treatment caused almost complete depression of uridine-C(14) incorporation throughout linear sucrose gradients except in the 4S region, and no infectivity was detectable in any fraction. These inhibitory effects are attributable to the action of interferon, because they were reversed when cultures were treated with actinomycin D simultaneously with interferon. The results, with those of other investigators, indicate that the step at which interferon interrupts virus multiplication is between the events immediately after uncoating and the formation of template "minus" strands; under the conditions of our experiments, no partially polymerized virus RNA products were made.
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PMID:Effect of interferon on polymerization of single-stranded and double-stranded mengovirus ribonucleic acid. 428 47

Effects of altered gaseous environments (parabarosis) on interferon production in mice were studied, with Newcastle disease virus (NDV) as the inducer. Increased levels of interferon in lung tissue were observed when mice were exposed to 11% O(2) in N(2) for 3 days before and after, or only after, injection of NDV. However, serum interferon levels remained unchanged. Exposure of mice to 77% O(2) for up to 7 days did not affect the response to interferon induction as assayed in lungs or sera. Interferon levels were significantly depressed in mice exposed to a simulated depth of 213 ft in seawater [with normal partial pressure of O(2) (pO(2)) in N(2)] for 2 or 4 weeks. Whereas definite depression of interferon was also observed in mice maintained at a simulated altitude of 37,000 ft (with normal pO(2)) for 2 weeks, those maintained at the same condition for 4 weeks showed a normal level of interferon. The results obtained with hypoxia are compatible with other reports on the influence of O(2) tension on viral infection. The factors responsible for alterations observed in interferon level in mice kept in normal pO(2), but under altered pressure, have not yet been identified.
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PMID:Production of interferon in mice: effect of altered gaseous environments. 568 5

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.
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PMID:Influence of whole-body PUVA treatments on human peripheral blood NK cell activity. 608 64


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