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)

In these experiments, we tested in various in vivo assays the immune responses of inbred C3H/HeN(MTV-) (C3H-) mice during carcinogenesis by chronic exposure to UV irradiation. Although the UV-treated mice were unable to reject syngeneic UV-induced tumor transplants, they rejected H-2-incompatible tumor allografts and H-2-compatible skin allografts. The primary hemagglutinin response to sheep red blood cells was normal in these mice, as were the induction of a local graft-versus-host reaction with lymphoid cells from UV-irradiated donors and the induction of an inflammatory response to dimethyl sulfoxide in the footpads of UV-treated mice. An early transient depression of two reactions in UV-irradiated mice occurred: delayed hypersensitivity to dinitrochlorobenzene measured by footpad swelling and the graft-versus-host reaction in UV-irradiated recipients measured by the use of the popliteal lymph node weight gain assay. Both of these reactions returned to a normal level before the development of primary tumors. We conclude that the inability of UV-irradiated mice to reject syngeneic and autochthonous UV-induced tumors was not due to a generalized immunosuppressive effect of chronic UV irradiation.
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PMID:In vivo immune responses of mice during carcinogenesis by ultraviolet irradiation. 2 May 14

The present report is a continuation of our previous studies on the biochemical mechanisms of carcinogenesis; studying the nature of interactions taking place between Ethylnitrosourea and DNA, RNA and protein of various stages of their synthetic activity. As a model system we chose partially hepatectomized mice live 36 hrs after surgery. Synthetic macromolecule activity in the remaining liver segment was determined by means of 3H-thymidine, 3H-uridine and 3H-leucine. We observed complete depression of DNA synthetic activity (immediately after Ethylnitrosourea administration it remained depressed almost through out the whole period of our observations) while protein synthetic activity was highly elevated. Qualitative changes of soluble proteins which were analyzed by isoelectric fractionation on 5% polyacrylamide after previous 3H- and 14C-leucine incorporation, could not be detected. Our biochemical data are correlated with histological studies and with the tumour incidence following the Ethylnitrosourea treatment of partially hepatectomized mice in the course of long-term experiments. The results provide guideline for further analysis, which should be modified according to the information concerning Ethylnitrosourea carcinogenesis induced 36 hours after partial hepatectmoy.
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PMID:Macromolecular synthetic activity in mice regenerating liver after ethylnitrosourea injection. 15 33

Liver enlargement is frequently reported in studies on the short-term toxicity of chemicals. In many such studies no histological evidence of damage is present but biochemically there is often an increased microsomal enzyme activity (MEA) which is interpreted to represent a type of work hypertrophy. In a few instances, the MEA in the enlarged liver is either normal or less than normal. In such instances histochemical evidence of liver damage (depression of G-6-Pase and autophagy) is found. A compound which produced the latter changes is Ponceau MX. When administered for up to 21 months at a dose-level which produces biochemical and histochemical evidence of liver injury, a series of changes were observed consisting of progerssive diminution of MEA, areas of glycogen accumulation and centrilobular fatty change and these were followed first by nodular hyperplasia and then by frank carcinoma. The protective effect of increased MEA in carcinogenesis was shown by the reduction in tumour incidence on the administration of phenobarbitone simultaneously with acetylaminofluorene, 4-dimethyl aminoazo benzene and diethylnitrosamine. But no such protective effect is seen if the phenobarbitone is administered after treatment with these carcinogens. In fact the number of tumours is enhanced presumably due to preferential stimulation of the growth of malignant cells.
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PMID:Liver growth and tumorigenesis in rats. 28 28

When normal mice are exposed for short periods to ultraviolet light (UV), they support the progressive growth of transplanted syngeneic UV-induced tumors. Normal nonirradiated mice almost always reject these tumor implants. The UV-mediated suppression of the antitumor response can be adoptively transferred to normal syngeneic mice with lymphoid cells derived from short-term UV-irradiated donors. Transfer of the suppressive effect is dosage dependent and also appears to require the presence of viable T lymphocytes. Suppressive activity was observed in both the spleen and thymus of UV-irradiated donors. In the preceding paper we have established that UV irradiation does not cause a general depression of testable immune functions. Collectively these data suggest that short-term UV irradiation of mice leads to an increase in suppressor cell activity, thereby causing an inhibition in the host's ability to respond to an antigenic UV-induced tumor. The possible role of this phenomenon in the mechanism of UV carcinogenesis is discussed.
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PMID:Modification of immunological potential by ultraviolet radiation. II. Generation of suppressor cells in short-term UV-irradiated mice. 30 10

Two endonuclease activities in rat liver for damaged DNA were assayed. Double-stranded, covalently closed DNA from phage PM2 was damaged by either ultraviolet irradiation or by heating at acid pH, and used as substrate for endonucleases specific for ultraviolet DNA damage and for DNA apurinic sites, respectively. The levels of both enzyme activities in livers of normal rats were compared to levels in livers of rats fed N-2-acetylaminofluorene. At critical stages of the carcinogenic regimen levels of both endonuclease activities were normal. This, together with other data, suggests that depression of excision-repair of DNA damage does not take place during experimental carcinogenesis.
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PMID:Normal endonuclease activities for damaged DNA during hepatocarcinogenesis. 88 9

Effects of cyclopentenone inhalation were examined in a 78-week study with 420 hamsters evenly distributed over two inhalation chambers, one for exposure to air and the other for exposure to the test substance. Cyclopentenone was dosed at a level of 18 ppm (seven hr/day, five days/week) during the first 52 weeks, and at a level of 27 ppm during the last 26 weeks of the study. During the first 52 weeks, part of the animals in both chambers fortnightly received an intratracheal instillation of benzo(a)pyrene (BP) or diethylnitrosamine (DENA) in saline or saline alone. Exposure to cyclopentenone caused slight growth depression in both sexes, and slightly increased relative liver weights and enhanced development of renal amyloidosis in females only. There was no evidence of cyclopentenonne possessing carcinogenic activity or being a co-factor in respiratory tract carcinogenesis.
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PMID:Repeated exposure to cyclopentenone vapour: long-term study in Syrian golden hamsters. 102 May 35

Reports of complications due to estrogen-progestagen combinations are summarized. Common minor symptoms include nausea, abdominal distress, headache, depression, and weight gain. Some of these are directly due to the pill, but others are not; for instance, depression may result from pyrodoxine deficiency, but psychodynamic factors explain the problem in others. Effects on the reproductive organs include secondary amenorrhea in about 2 of every 1000 women; structural and functional changes of the ovaries, uterus, and cervix; increase in incidence of yeast vulvovaginitis; and inhibition of lactation. Most changes in laboratory values of various constituents of blood and other body fluids reflect changes in hepatic function. Thromboembolic diseases, hypertension, and hypertriglyceridemia are rare but more serious conditions for which the pill may be responsible in some cases. Contribution of the pill to carcinogenesis and fetal abnormalities has not been proven.
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PMID:Clinical complications of oral contraceptives. 109 Jan 18

Patients with sickle cell anemia were treated with daily doses of hydroxyurea, to assess pharmacokinetics, toxicity, and increase in fetal hemoglobin (Hb) production in response to the drug. Plasma hydroxyurea clearances were not a useful guide to maximum tolerated doses of the drug. The mean daily single oral dose that could be maintained for at least 16 weeks was 21 mg/kg (range, 10 to 35 mg/kg). Among 32 patients, last HbF levels were 1.9% to 26.3% (mean, 14.9%) with increases in HbF over initial values of 1.4% to 20.2% (mean, 11.2%). The most significant predictors of last HbF were last plasma hydroxyurea level, initial white blood count and initial HbF concentration. Last HbF was not related to beta globin haplotype or alpha globin gene number. No serious toxicity was encountered. Clinically significant bone marrow depression was avoided, and chromosome abnormalities after 2 years of treatment were no greater than those observed before treatment. The period of observation has been too short to evaluate the risk of carcinogenesis. Patient's red cells developed striking macrocytosis. Median red cell Hb concentrations did not change. Hb concentrations increased, on average 1.2 g/dL, but serum erythropoietin levels increased. Patients' body weights increased, and some returned to work or school, but no conclusions regarding therapeutic efficacy could be drawn from this uncontrolled open-label study.
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PMID:Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. 137 2

We compared the hormonal and epidemiological aspects of ovarian cancer patients in search of the etiology of this neoplasia. Case-control studies of Japanese women with and without cancer were conducted in parallel, with regard to both the excretion of 14 urinary steroids and the pertinent physical and physiological parameters. The results obtained are as follows: 1) premenopausal ovarian cancer patients before and after radical ovariectomy and postmenopausal-postoperative patients were associated with a specified steroid deviation profile characterized by a combination of general depression of androgens, progestins and corticosteroids with sole rescue of tetrahydrocortisol (THF) in urine. 2) The deviation profile of postmenopausal-preoperative cancer patients was distinguished from the 3 partner profiles by its preservation of normalcy in the excretions of androgen and progestin in urine. 3) Ovarian cancer patients were associated with growth retardation, when compared with urban healthy controls and patients with either breast cancer or endometrial cancer by the age-matching method. Ovarian cancer patients were also less fertile than age-matched normal controls, and were as infertile as age-matched patients with either breast cancer or endometrial cancer. 4) Epidemiological evidence was presented to suggest that the incidence of ovarian cancer in Japan was increasing in parallel with the recent increase of social tension in Japan. The possible relevance of the hormonal characteristics of ovarian cancer patients to both the epidemiological characteristics of the same cancer patients and the genesis of this neoplasia is discussed in the light of the 2-step carcinogenesis theory.
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PMID:Relation between the hormonal and epidemiological aspects of ovarian cancer patients in Japan. 144 27

Tricyclic antidepressants, such as amitriptyline (Elavil), and the nontricyclic agent, fluoxetine (Prozac), bind to growth-regulatory intracellular histamine receptors, associated with anti-estrogen binding sites in microsomes and nuclei. The prototype anti-estrogen binding site/intracellular histamine receptor ligand, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl, inhibits normal cell proliferation in vitro but stimulates tumor growth in vivo. Because of their structural similarity to N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl, we carried out studies to determine whether amitriptyline and fluoxetine stimulate tumor growth and/or development in rodents at concentrations relevant to the treatment of human depression (equivalent human dose range, approximately 100-150 mg/day for amitriptyline and approximately 20-80 mg/day for fluoxetine). All experiments were performed blinded. In studies of growth stimulation of transplantable syngeneic tumors, groups of mice were inoculated s.c. with C-3 fibrosarcoma cells or given i.v. or s.c. injections of B16f10 melanoma cells, followed 24 h later by daily i.p. injections of saline, amitriptyline, or fluoxetine. Tumor latency (fibrosarcoma), aggregate tumor weight (s.c. injected melanoma), or time to death from pulmonary metastasis (i.v. injected melanoma) was determined; drug-induced stimulation of DNA synthesis in C-3 fibrosarcoma cells in vitro was correlated with tumor growth acceleration in vivo. In a mammary carcinogenesis model, the effects of chronic saline, amitriptyline, or fluoxetine administration on the rate and frequency of development of mammary tumors in rats fed dimethylbenzanthracene (DMBA) were compared. Eight of 20 amitriptyline- or fluoxetine-treated mice developed fibrosarcoma tumors by day 5, as compared to none of 20 saline controls (P less than 0.002). Similarly, 20 of 21 DMBA-treated rats receiving the antidepressant drugs developed 33 mammary tumors by week 15 as compared to 5 tumors in 4 of 7 DMBA-treated rats receiving saline (P less than 0.001). For both models, tumor latency decreased 30-40% and, in the DMBA model, tumor frequency increased greater than 2-fold in the antidepressant-treated rats as compared to controls. Stimulation of fibrosarcoma growth in vivo correlated with a corresponding bell-shaped drug-induced increase in DNA synthesis in vitro. While the median time to death from pulmonary metastases did not differ among groups given i.v. injections of melanoma cells, a significant (P less than 0.01) stimulation of growth of s.c. injected melanoma was observed in mice receiving the antidepressants.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. 161 49


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