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)

Fifteen patients with chronic hepatitis B were treated with adenine arabinoside (Ara-A) or human leukocyte interferon (HLI). Cellular immune response to hepatitis B virus surface antigen and antigens prepared from herpes simplex virus, varicella zoster virus, and cytomegalovirus was measured by a lymphocyte blast transformation assay and an assay for interferon production. Measurements were made before, during, and after antiviral treatment. Unlike patients convalescing from acute hepatitis B, only 2 of 15 patients with chronic hepatitis B had significant blast transformation to hepatitis B surface antigen. One such response occurred during the pretreatment period of HLI therapy, and the other was in a patient undergoing low-dose (<10(5) U/kg per day) HLI therapy. Mononuclear cell cultures were tested for interferon production in the presence of hepatitis B surface antigen. Cells from only 1 of 15 patients produced detectable levels of interferon. In contrast, all of these patients had normal cellular immune responses to herpesvirus antigens. Transformation responses to herpes antigens decreased three- to fivefold after patients were treated with >10(5) U of HLI per kg per day. Antiviral therapy with <10(5) U of HLI per kg per day or Ara-A did not produce a detectable depression of transformation response. Ara-A produced marked lymphocytopenia and a marked lymphocyte fragility after 5 or more days of therapy. In vitro Ara-A was toxic to lymphocytes at concentrations as low as 0.5 mug/ml. These changes in lymphocyte parameters may affect the outcome of antiviral therapy.
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PMID:Effects of interferon and adenine arabinoside treatment of hepatitis B virus infection on cellular immune responses. 53 59

Twenty-two patients with Stages Ia to IVa cutaneous T cell lymphoma were entered into a controlled trial of interferon alfa-2a (Roferon-A). Patients initially received either 3 million IU interferon alfa-2a, or their dosage was escalated to 36 million IU intramuscularly daily for a 10-week induction period. At the end of induction, 14/22 (64%) of patients had an objective antitumor response: three patients had a complete response, ten patients had a partial response (greater than or equal to 50% resolution of clinical disease), and one patient had a minor response. Responders included those with Stages Ia to IVa cutaneous T cell lymphoma, and remissions have lasted at least 4 to 27.5 months. Three patients progressed from a partial to complete response with further treatment, for an overall complete response rate of 27%. Acute flu-like side effects were generally minor and transient. Malaise/fatigue, depression, anorexia, and weight loss were common chronic dose-related side effects and the most frequent reasons for dose reduction or discontinuation of drug. Leukopenia was the most common laboratory side effect and was also dose-related. Recombinant human leukocyte interferon alfa-2a is an effective and well-tolerated single-agent therapy for early and advanced cutaneous T cell lymphoma.
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PMID:Interferon alfa-2a in the treatment of cutaneous T cell lymphoma. 278 39

A total of 20 patients with advanced colorectal cancer received recombinant leukocyte interferon-alpha A (rIFN alpha A) either chronically (group I: twice a week up to 20 X 10(6) IU/m2 i.m.) or cyclically (group II: 1-4 periods of 8 consecutive days up to 20 X 10(6) IU/m2 i.m. daily at 20-days intervals) over a period of 12 weeks. There was 1 partial response, 1 mixed response and 1 patient with stable disease, whilst 17 patients had progressive disease. Median survival was 15.5 months. Survival was significantly shorter when the extent of hepatic disease was greater than 25% (P = 0.05), extrahepatic disease was extensive (P less than 0.005), alkaline phosphatase level was greater than 2 X normal (P less than 0.02), or performance status was less than 100% (P less than 0.001). Toxicity consisting mainly of fever, fatigue, anorexia and weight loss was serious in group I and minimal in group II. Administration of rIFN alpha A led to a "short lived" augmentation of natural killer (NK) cell activity. In the cyclically treated group this was a recurrent phenomenon whereas a marked lasting depression of NK cell activity was seen in chronically treated patients. Interferon-gamma production capacity was significantly stimulated during rIFN alpha A therapy. The differences in toxicity and immunostimulatory effects between the two schedules may be of importance in the design of further studies.
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PMID:Clinical and immunological evaluation of 20 patients with advanced colorectal cancer treated with high dose recombinant leukocyte interferon-alpha A (rIFN alpha A). 363 19

Eight previously treated and four untreated patients with B cell chronic lymphocytic leukemia (CLL) received 20 X 10(6) U/m2 recombinant leukocyte interferon clone A (rIFN-alpha A) intramuscularly three times a week for 8 weeks. None of the eight patients who had received prior chemotherapy exhibited objective evidence of tumor regression. Two of the four previously untreated patients responded with transient (90%) decreases in absolute lymphocyte counts lasting for 2 and 7 months. Toxicity was moderate, with all patients experiencing a flu-like syndrome requiring a 50% dose reduction. Half of the patients exhibited anorexia, weight loss, and a drop in performance status. The two responders had normal serum immunoglobulin levels prior to treatment, whereas 80% of non-responders had depressed levels. Treatment with rIFN-alpha A was associated with a depression of nonspecific and specific humoral immunity in assays employing cryopreserved autologous pretherapy CLL cells. No consistent effects were demonstrable in cytolytic assays with purified peripheral blood T cells as effector cells, including one that utilized autologous CLL target cells. rIFN-alpha A has limited antitumor activity in B cell CLL which is restricted to untreated patients with an early stage of disease. With the assays employed it was not possible to demonstrate that rIFN-alpha A could augment autologous antitumor immunity.
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PMID:Recombinant leukocyte A interferon in B-cell chronic lymphocytic leukemia: in vivo effects on autologous antitumor immunity. 387 30

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

In vitro and in vivo studies utilizing a combination of leukocyte interferon-alpha (IFN) and chlorambucil (CLB) were done to investigate possible synergism between a biological response modifier and a chemotherapy drug. In vitro studies utilized a human myeloid leukemia cell line (K-562) pretreated with IFN and then exposed to CLB. The combination resulted in significant depression of cell growth compared with use of IFN or CLB alone. In vivo studies involved eight heavily pretreated patients given 6 million units IFN for 5 days followed by oral CLB (16 mg/m2) for 5 days repeated every 4 weeks. Three myeloma patients had reduction in immunoglobulins and experienced clinical responses. Three of four patients with Hodgkin's disease responded after relatively short periods of treatment. One patient with a diffuse lymphocytic lymphoma had a complete unmaintained remission lasting 6 months. Toxicity was minimal, with mild fever, nausea, and vomiting. These preliminary studies suggest that IFN may be a biological response modifier when used in combination with a cytotoxic agent.
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PMID:Leukocyte interferon as a possible biological response modifier in lymphoproliferative disorders resistant to standard therapy. 651 61

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

Over a 60-week period, a patient with multiple warts received a total of 281 x 10(6) units of human leukocyte interferon (IFN-alpha) by intramuscular (IM) or intralesional (IL) injections. Circulating IFN was significantly higher following IM administration than after IL administration. These pharmacokinetics did not change. The patient's body temperature was always significantly elevated after administration of IFN. However, hyporeactivity to the febrile response developed when the interval between repeated injections of IFN was less than six days. The lymphocyte count was significantly decreased within 5-7 h after administration of IFN and had returned to normal by 24 hours, whereas total WBC, platelet, and monocyte counts were not altered. There was a depression of specific lymphocyte proliferative response to herpes simplex virus after multiple daily injections, but not after prolonged therapy. Circulating natural killer (NK) levels were not elevated during the first two months of IFN therapy. After the patient had received about 100 x 10(6) units of IFN, however, the NK cell level became elevated and remained elevated upon cessation of treatment. NK activity was stimulated by in vitro incubation of peripheral mononuclear cells with 1000 units of IFN during the initial phase of treatment. A decline of in vitro stimulation of NK activity by interferon developed during two subsequent periods of treatment with mean daily doses of 2.46 and 1.07 x 10(6) units of IFN. Long-term therapy in our patient with an average of 4.7 x 10(6) units of IFN/week was well tolerated, did not irreversibly affect platelet or white cell counts or nonspecific or virus-specific cell mediated immune responses, and enhanced circulating NK levels.
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PMID:Effect of prolonged administration of interferon-alpha on pharmacokinetics, fever, lymphocyte proliferative response, and NK cell activity. 711 6


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