Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytotoxic T-lymphocytes (CTL's) harvested from mixed splenic lymphocyte cultures (DBA/2 + C57BL) were tested for their ability to lyse allogeneic P815 mastocytoma cells under various tumor-like assay conditions, with or without previous exposure to ionizing radiation or hyperthermia (43 degrees). There was little or no decrease of immune cytolysis when CTL's were assayed by 51Cr release under tumor-like conditions (plateau-phase target cells, low pH, or anoxia) or after irradiation, but cytolytic activity was greatly reduced when CTL's were exposed to heat; 45 min of hyperthermic treatment decreased activity by greater than or equal to 99% while reducing the apparent cell viability (as indicated by trypan blue exclusion) by only 30%. When the P815 target cells rather than the CTL's were exposed to heat their susceptibility to immune lysis was not affected even after treatment times that were lethal to the tumor cells. Despite the dissimilar heat sensitivities of CTL and P815 cells, the dose-response curves for inhibition of protein synthesis by heat, as indicated by [3H]leucine incorporation, were similar for both cell types: neither the depression of protein synthesis in heated CTL's nor the decreased cytolytic ability of these cells was reversed within 3 hr. When irradiated or heated P815 cells were incubated with CTL's, the resulting survival curves were always additive, indicating that neither irradiation nor heat treatment affected the susceptibility of the tumor cells to immune attack. The extreme heat sensitivity of cytotoxic T-lymphocytes raises important questions about the possible effects of hyperthermic treatment on the immune competence of cancer patients.
 ...
PMID:Effects of Tumor-like assay conditions, lonizing radiation, and hyperthermia on immune lysis of tumor cells by cytotoxic T-lymphocytes. 0 45

Both in vitro and in vivo murine cytomegalovirus (MCMV) infection depressed the responses of lymphocytes to both B and T cell mitogens. The possibilities that macrophages or nonspecific T cell inhibition of B cells might account for the depressed responses were eliminated. In vitro data suggested that B cell responses are more susceptible to this depression than T cell responses. The possibility that the depression of T cell responses is not a direct effect of viral infection of lymphocytes is discussed. To investigate further the interaction between B and T lymphocytes and MCMV, mice with B and T cell deficiences were studied. A comparison of the susceptibility of athymic Nu/Nu mice and T cell competent Nu/+ littermates to MCMV showed that the LD50 for Nu/Nu mice is 10-fold lower than that for Nu/+ mice, but Nu/+ mice given an LD50 of virus died much sooner after infection than Nu/Nu mice given an LD50. Pathogenic mechanisms responsible for death may be different in these two groups of mice. Similarly the MCMV LD50 for B cell-deficient mice (treated with goat anti-mouse IgM serum) was 10-fold lower than the LD50 for mice treated with normal goat serum, but given an LD50 of virus, the latter died sooner after infection than the former. In contrast, there was little difference between the LD50 or time of death after MCMV infection of CBA x DBA F1 male mice (which are deficient in their response to thymic independent antigens) and their normal littermates, the CBA x DBA F1 female mice.
 ...
PMID:Effect of murine cytomegalovirus on the in vitro responses of T and B cells to mitogens. 17 97

Spleen cells removed from C57Bl/6J mice bearing a methylcholanthrene-induced fibrosarcoma (MC-16) demonstrate suppressed responsiveness of phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) induced mitogenesis as compared to non-tumorous mice. A similar depression of PHA-induced mitogenesis was observed with spleen cells from C3H/HeJ mice bearing syngeneic mammary adenocarcinomas (C3HBA). The administration of indomethacin, a non-competitive irreversible prostaglandin (Pg) synthesis inhibitor, (75 or 100 mug/mouse, IP) on an alternate day basis to groups of tumor-bearing mice of both strains, significantly enhanced immune cell responsiveness to mitogenic stimulation. The addition of indomethacin (10 mug/ml) to cultures of spleen cells from these tumor-bearing mice, as well as to DBA/1J mice bearing the Cloudman S-91 melanoma, enhanced spleen-cell responsiveness to mitogen-induced DNA synthesis by as much as 156%. Indomethacin administration in vivo or in vitro had no significant effect on mitogen-induced DNA synthesis of spleen cells from non-tumor-bearing animals. It is hypothesized that tumors, or tumor-cell antigens, increase Pg production of a population of spleen cells, and that the increased Pg content of the spleen may be important in controlling immune responsiveness in mice.
 ...
PMID:Indomethacin enhancement of spleen-cell responsiveness to mitogen stimulation in tumorous mice. 18 13

Chlorodiazepoxide (CDP) produces stimulation of the locomotor activity of CD-1 and DBA/2 mice. This effect is strongly pronounced at the commencement of the testing session, and it is followed by a decline of the locomotor activity. The drugs impairing noradrenergic transmission: reserpine, clonidine and alpha-methyltyrosine, depressed or abolished the stimulatory effect of CDP; clonidine, in addition antagonized the subsequent decline of the locomotor activity in CDP-treated mice. Mice receiving reserpine subchronically (in the dose of 0.5 mg/kg daily for 3 days) displayed either motor depression or hypermotility. In approx. 50% of subchronically reserpinized mice CDP produced a strong hypermotility, lasting for at least 1 hr. It can be concluded that a noradrenergic mechanism is involved in the stimulatory effect of CDP on exploratory locomotor activity in mice, and that there exist two distinct subpopulations within the CD-1 strain, reacting differently to chronic reserpine treatment.
 ...
PMID:Stimulatory effect of chlordiazepoxide on locomotor activity in mice: importance of noradrenergic transmission. 22 33

The erythropoietic stem cell compartment was studied in Friend-virus (polycythemic strain, FV-P) infected DBA/2 and NMRI mice with the CFUE and BFUE technique. Early after infection there was a depression in CFUE number in bone marrow and spleen, followed by an increase of the CFUE concentration, earlier and more pronounced in the spleen than in the marrow. Three days after FV-P infection an erythropoietin (Ep) independent CFUE population started to grow and replaced the normal Ep-dependent population within 8 to 12 days. The shift to Ep independency was not gradual. CFUE colonies of FV-P infected bone marrow cells were two to three times larger than control colonies after three days in vitro incubation. BFUE colonies increased in number during the first days of infection, but were totally lost after more than ten days. After velocity sedimentation of bone marrow cells of FV-P infected animals, however, the BFUE containing fractions showed normal BFUE colony growth and normal Ep sensitivity. In unfractionated bone marrow cell cultures BFUE colony growth could be observed later than ten days post infection when the cultures were refed with medium. It was therefore concluded that the loss of BFUE colony growth after FV-P infection was an in vitro artefact due to inadequate culture conditions.
 ...
PMID:Erythroid stem cells in Friend-virus infected mice. 65 22

Gene differences may alter an individual's response to foreign compounds by affecting their absorption, binding, distribution, excretion, biotransformation, or drug-drug interactions. Genetic differences in the metabolism of xenobiotics among inbred strains of various laboratory animals and model systems are reviewed. The inbred mouse has been studied most extensively. Genetic differences in toxicity are shown to be caused by various environmental pollutants in several inbred strains of mice and in siblings of the (C57BL/6N)(DBA/2N)F1 X DBA/2N backcross, in which the phenotypes "aromatic hydrocarbon responsiveness" or "nonresponsiveness" had been predetermined. This trait of "responsiveness"--which refers to the capacity for induction of cytochrome P1450 and numerous monooxygenase activities by certain aromatic compounds--segregates almost exclusively as a single gene among offspring of this backcross. All nonresponsive mice ingesting benzo/a/pyrene (about 125 mg/kg per day) die within 4 weeks, whereas the survival of responsive mice receiving the chemical orally is not significantly different from that of control mice; the apparent cause of early death in these experiments in toxic depression of the bone marrow. The life span of animals exposed to certain environmental pollutants can therefore be markedly influenced by a single gene or a very small number of genes. The same genetic trait can be either beneficial or detrimental to the animal, depending on whether detoxification or metabolic potentiation occurs. There also may exist genetic differences in man's susceptibility to toxicity or cancer caused by the numerous foreign compounds in his environment.
 ...
PMID:Importance of genetic factors influencing the metabolism of foreign compounds. 81 76

The effects of direct intratumoral inoculation with Vibrio cholerae neuraminidase and inoculation of tumor-bearing mice with tumor cells incubated with neuraminidase in vitro were studied in C57BL/6 X DBA/2 F1 mice bearing s.c.-transplanted, methylcholanthrene-induced pulmonary squamous cell or Lewis lung carcinomas. The growth of the squamous cell tumor was more greatly inhibited by both treatments than was the Lewis lung tumor. In the squamous cell tumor-bearing mice, both modes of neuraminidase treatment depressed tumor growth by approximately 80%. However, 20% of the mice in the group treated with the neuraminidase-incubated squamous cell vaccine and 10% of those treated intratumorally underwent total tumor regression and developed specific immunity to the squamous cell tumor. although the growth rate of the Lewis lung tumor was suppressed by both types of treatment, the direct intratumoral neuraminidase treatment group underwent a greater depression in tumor growth (73 versus 42%). A possible explanation of the different results of the two treatments in squamous cell and Lewis lung tumor systems may be based on tumor etiology and cellular composition.
 ...
PMID:Effectiveness of neuraminidase in experimental immunotherapy of two murine pulmonary carcinomas. 83 Apr 25

Daily (five times/week) administration of 0.25-2 mg methotrexate (MTX)/kg to 5- to 6-week-old male C57BL/6, DBA/2, and C3H mice for 12-18 months was well tolerated, apart from minimal cellular suppression in the lymphoid tissues, testes, and skin. Larger doses of MTX (3-6 mg/kg) given to 5- to 6-week-old mice produced well-known acute to subacute hematopoietic and gastrointestinal damage that leads to early death. These young mice did not develop other lesions that were described in humans after long-term MTX administration, nor was the toxicity cumulative. A large difference was observed in the ability of mice of different ages to withstand the toxic effects of MTX; 16-week-old mice were able to survive daily doses of 3-6 mg/kg up to 18 months. Histologic studies of these mice showed a more pronounced cellular depression of the lymphoid tissues, testes, and skin. Osteoporosis was also observed in these older mice that tolerated the drug for 10 months or longer, thus providing a laboratory animal model for further study of this MTX-induced lesion.
 ...
PMID:Chronic toxicity of methotrexate in mice. 83 65

Mice of the high-ethanol selecting C57BL/6j strain consume significantly larger amounts of 10% solution of 1,2-propanediol and 1-propanol than the low-ethanol selecting DBA/2j strain. Both strains uniformly avoid a 10% solution of 1,3-propanediol and 2-propanol. Open field activity was tested 30 min after an IP injection of 3 different equimolar doses of each alcohol. An increase in activity was produced in the DBA/2j strain by high (0.003 ml/mg) and middle (0.0015 ml/lg) doses of 1,2-propanediol and by a low dose (0.0005 ml/mg) of 2-propanol. The C57BL/6j strain were unaffected by these doses. High doses of 2-propanol produced sleep in both strains with the DBA/2j strain sleeping significantly longer, and 1,3-propanediol produced depression in both strains. Death resulted in all animals following injections at the high (0.002 mg/gm) and medium (0.001 ml/gm) doses of 1-propanol while the low dose (0.0005 ml/gm) produced slight depression.
 ...
PMID:Selection of C3 alcohols by high and low ethanol selecting mouse strains and the effects on open field activity. 95 31

An increase in prostaglandins (PGs) of the E series has been demonstrated in Moloney sarcoma virus (MSV)-induced leg tumors of 6-week-old BALB/c male mice. The level of the hormone has been shown to increase with the tumor diameter and decrease with tumor regression. At the peak of tumor size the tibial bones of the mice were considerably deformed, suggesting osteoclastic activity. The systemic calcium level was not elevated, indicating possible release of calcium into the local tumorous area. In mice treated with indomethacin the tumors failed to develop and PG levels were markedly lower. Tibial bones of treated mice were similar in appearance to those of control, non-tumorous mice. PG levels of DBA/1J mice bearing extensive Cloudaman S91 melanomas were not elevated and no bone deformation was seen. When contrasted with studies of immuno-depressed mice the results suggest that indomethacin acted in conjunction with and possibly to restore the PG-induced depression of the immune system in preventing tumor development. It is also hypothesized that indomethacin, by suppressing the PG-mediated calcium release from bone, could be operative in inhibiting tumor growth.
 ...
PMID:Prostaglandin synthesis inhibition: effect on bone changes and sarcoma tumor induction in balb/c mice. 114 Aug 69


1 2 3 4 5 6 7 8 9 10 Next >>