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)

This study investigated the defective natural killer (NK) cell activity in two patients with the Chediak-Higashi syndrome (CHS) using both a standard 51-chromium release microcytoxicity and a single cell-in-agarose assay against K562 and Molt-4 target cells. CHS patients were deficient in overall maximum NK capacity, but had normal percentages of potentially cytotoxic target bindng cells. the relative number of TBC that could kill bound targets (i.e., "active" NK cells) was significantly depressed in CHS patients when compared with normal controls. The diminished CHS active NK cells that were present, however, were capable of recycling and lysing multiple target cells during the assay period. In vitro interferon (INF) treatment of normal and CHS effector cells did not alter target cell binding, but did increase the maximum NK capacity, percentage of active NK cells and the maximum recycling capacity, as well as the rate of lysis. These studies indicate that the depression of NK activity in patients with CHS is secondary to a deficiency of active NK cells. The CHS active NK cells that are present, however, are capable of normal target lysis and recycling. Potentially cytotoxic pre-NK cells, which can bind but not kill target cells, can be activated by in vitro IFN to develop lytic activity. Thus, IFN treatment may be of potential benefit to the immune surveillance network of CHS patients by activating a population of pre-NK cells to express their cytotoxic potential.
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PMID:Deficiency of active natural killer cells in the Chediak-Higashi syndrome. Localization of the defect using a single cell cytotoxicity assay. 617 15

Direct determinations indicate that some types of interferon increase the duration of hexobarbital-induced sleep time and decrease acetaminophen toxicity. Pretreatment of mice with cloned human leukocyte interferon subtype A, IFN-alpha A, did not increase hexobarbital sleep time but pretreatment with mouse interferon or a hybrid human leukocyte interferon, IFN-alpha AD (Bgl), increased the duration of the effect of the barbiturate. Hybrid IFN-alpha AD (Bgl) also decreased the lethality of acetaminophen. These findings are predictable based on reports of hepatic cytochrome P450 depression resulting from treatment with some interferons.
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PMID:Influence of various purified interferons on effects of drugs in mice. 618 63

Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T4 (inducer) T-cell subset could be demonstrated as a sequence of events: decreased fluorescence intensity of the T4 inducer cells (day 2 of culture), decreased percentages of T4 cells as demonstrated by cell cytofluorometry (days 3-6 of culture), and decreased 3H-thymidine incorporation of purified T4 cells and decreased numbers of T4 cells harvested from IFN MLRs (days 5-6 of culture). In contrast, it was shown that the T8 (cytotoxic/suppressor) subset in MLRs was either not affected or slightly stimulated by the addition of IFN. The depression of the T4 cells by IFN was accompanied by a decrease in the number of activated T cells expressing Ia antigens. On the other hand, IFN MLRs contained greater numbers of cells expressing the T10 differentiation antigen. In experiments with purified T-cell subsets the IFN effect was exerted directly on the T4 cells and not mediated by either T8 suppressor cells or monocytes. These findings are discussed in relation to other immunoregulatory effects of IFN-alpha.
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PMID:Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures. 622 62

Patients with a variety of malignancies were treated in phase I clinical trials of recombinant leukocyte A interferon (IFL-rA) schedules consisting of either twice-daily doses for 28 days (48 patients) or three times weekly for 28 days (86 patients). Extensive monitoring of several immune functions was done on these patients, with rigorously standardized assays and determination of inherent variability of function for each individual. The assays performed were natural killer (NK) cell cytotoxicity, monocyte cytostatic activity, lymphoproliferative responses to concanavalin A (con A) and mixed leukocyte culture, and an analysis of changes in leukocyte populations as determined using a panel of monoclonal antibodies and flow cytometry. No appreciable increase in NK activity was observed on any of the treatment regimens, and an unexpected observation was the depression of activity in a substantial proportion (30%) of patients. In contrast, monocyte function, as measured in an assay of growth inhibition of tumor target cells, was found to be elevated in 70% of the patients. Lymphoproliferative responses were depressed in most patients in response to both con A and the mixed leukocyte culture. Cell surface marker studies revealed an increase in the percentage of OKT10 positive cells in the majority of patients studied and a transient increase in cells reacting with the antibody MO2. The data have been analyzed in terms of their relationship to dose and schedule of administration, and the depression of NK activity was shown to be greatest at the highest doses and more frequent schedule of administration.
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PMID:Effects of recombinant interferon-alpha on immune function in cancer patients. 635 23

Recombinant gamma-interferon (rec gamma-IFN) caused potent inhibition of collagen synthesis by cultured confluent human diploid fibroblasts in a dose-dependent manner. Gel electrophoresis of the newly synthesized proteins from the culture media of rec gamma-IFN-treated fibroblasts demonstrated a selective depression of procollagen without a significant change in non-collagenous proteins. Dot blot hybridization to a Type I procollagen cDNA probe showed that the inhibition of collagen production was accompanied by a decrease in the levels of collagen mRNA. These results indicate that rec gamma-IFN is capable of exerting transcriptional modulation of collagen biosynthesis and suggest that it may play an important role in regulation of normal and pathologic fibrogenesis.
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PMID:Transcriptional control of human diploid fibroblast collagen synthesis by gamma-interferon. 643 19

The percentage of peripheral blood lymphocytes (PBLs) which formed rosettes with sheep erythrocytes declined from 62 +/- 2% to 29 +/- 4% (p = 0.001) when PBLs were incubated 18 h at 37 degrees C. In the presence of alpha interferon (IFN-alpha), a dose-dependent increase occurred in the percentage of sheep erythrocyte-binding PBL at the end of incubation compared with PBL incubated without IFN-alpha. Change in the number of sheep erythrocyte "receptors" (SER) probably did not account for the observed modulation of rosetting capacity, since the frequency and density of an SER-associated determinant (T11, as defined by immunofluorescence flow cytometry using the monoclonal antibody OKT11A) was unaffected by incubation with or without IFN-alpha. Treatment of PBL, control or IFN-alpha-treated, with neuraminidase (0.4 u/ml), restored rosetting capacity to levels characteristic of freshly prepared PBL. Neuraminidase did not affect rosetting or T11 expression by freshly prepared PBL, nor did it affect T11 expression on PBL cultured with or without IFN-alpha. We thus postulated that steric interference with SER function by sialic acid residues might result from de novo protein synthesis and glycosylation at the cell surface. Inhibition of either protein glycosylation by tunicamycin or protein synthesis by cycloheximide prevented the incubation-induced depression of rosetting capacity. IFN-alpha may modulate functional expression of SER and other surface receptors by altering cell-surface glycoprotein composition and distribution.
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PMID:Effects of interferon alpha on the sheep erythrocyte "receptor" of human lymphocytes. 650 43

Peripheral blood natural killer (NK) cell cytotoxicity of 24 cancer patients was studied prior to and after single and multiple injections of various doses of human leukocyte recombinant interferon-alpha clone A (IFN-alpha rA). The NK cell cytotoxicity of all cancer patients declined consistently 4 and 8 hours after a single injection of IFN-alpha rA. Twenty-four hours after the injection of IFN-alpha rA, NK cell cytotoxicity of patients with low NK cell phenotype (NK-LR) was significantly augmented, whereas that of patients with medium (NK-MR) or high (NK-HR) NK phenotype was depressed. After multiple injections of IFN-alpha rA, depression of NK cell cytotoxicity was observed in a number of NK-MR and NK-HR patients, but in some patients with NK-LR phenotype, further potentiation was observed. No direct correlation between the NK cell augmentation and serum IFN levels was detected. In in vitro studies, IFN-alpha rA, when added to cultures of target and effector cells of normal individuals in a dose of 10(3) U/ml, was efficient in augmenting NK cell cytotoxicity. NK cell cytotoxicity of cancer patients could also be augmented by the IFN-alpha rA preparation; however, this augmentation occurred only prior to in vivo IFN-alpha rA therapy. After IFN-alpha rA in vivo therapy, their NK cells became refractory to further in vitro IFN-alpha rA treatment.
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PMID:Analysis of natural killer cell cytotoxicity of cancer patients treated with recombinant interferon. 658 Apr 90

Human leukocyte interferon (IFN alpha) was administered to 15 patients with epithelial ovarian carcinoma after previous chemotherapy or therapeutic irradiation. One objective response was observed. Three patients had possible stable disease for up to 6 months, including two patients who were re-explored 6 months after commencing IFN alpha and one patient who was observed to have a less than 50% reduction in her tumor diameters. Three of seven patients demonstrated clinical responses to subsequent chemotherapy, indicating an absence of resistance to subsequent chemotherapy. Toxicity included the relatively mild symptoms of anorexia, lassitude, and diarrhea. Malabsorption was observed in one patient. Platelet depression and abnormal enzyme liver functions were also observed more frequently following IFN alpha. No life-threatening toxicity was observed.
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PMID:Leukocyte interferon (IFN alpha) in patients with epithelial ovarian carcinoma. 664 31

We have studied the peripheral blood natural killer (NK) cell cytotoxicity of 32 cancer patients prior to and after single and multiple injections of various doses of human recombinant leukocyte interferon clone A (IFN-alpha rA). Consistent decline in NK-cell cytotoxicity of all cancer patients was observed 4 and 8 h after a single injection of IFN-alpha rA. Twenty-four hours after the injection, NK-cell cytotoxicity of patients with low NK cell phenotype (NK-LR) was significantly augmented, whereas that of most patients with medium (NK-MR) or high (NK-HR) NK phenotype was depressed. After multiple IFN-alpha rA injections, depression of NK-cell cytotoxicity was observed in a number of NK-MR and NK-HR patients, whereas in some patients with NK-LR phenotype, elevated NK-cell levels were observed. No direct correlation between NK-cell augmentation and serum IFN levels was detected. In vitro studies demonstrated that NK-cell cytotoxicity of normal donors was augmented by IFN-alpha rA (10(3) U/ml). Augmentation of NK cells was also observed in cancer patients after in vitro addition of IFN-alpha rA, but only prior to and not after in vivo IFN-alpha rA therapy.
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PMID:Regulation of human natural killer cell cytotoxicity by recombinant leukocyte interferon clone A. 664 51

The antitumor effect of human leukocyte interferon was investigated on ten patients with malignant brain tumor. In eight cases of primary tumor, IFN alone was administered when their recurrent sign was evident. A dose of 3 X 10(6) IU or 1 X 10(6) IU of IFN was injected intramuscularly two or three times a week in high-dose group, while a dose of 5 X 10(4) IU once a week in low-dose group. No remarkable side effects including bone marrow depression were noted. Natural killer activity was enhanced and immunologic skin reaction manifested. Partial remission of more than 50% decrease of tumor volume calculated on CT scan was seen in two cases in the low-dose group for about 3-6 months. Complete remission could not be obtained by IFN alone. Our pilot study has shown that IFN alone will not be effective against progressive malignant brain tumors by general administration. Further investigation should be carried out to improve the use of IFN therapy in malignant brain tumor.
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PMID:Effect of human leukocyte interferon on malignant brain tumors. 683 90


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