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)

Acute administration of Aroclor-1254 (500 mg/kg) or 3,4,5,3',4',5'-hexabromobiphenyl (HBB) (2-6 mg/kg) IP, profoundly inhibited the plaque forming response to subsequent challenge with sheep erythrocytes in Ah locus positive (C57Bl/6N or B6C3F1N) mice. These studies showed: the immunotoxicity results paralleled enzyme induction results insofar as HBB was approximately 100 times more potent than Aroclor 1254; neither Aroclor nor HBB treatment caused significant induction in the Ah locus negative DBA/2N mice; when B6C3F1 mice were challenged with sheep red blood cells (SRBC) 6 or 16 weeks post Aroclor 1254 treatment, substantial recovery of a PFC response was observed; when these compounds were administered to older (76-week-old) (B6C3F1 mice, severe depression of a PFC response was observed. In contrast to its profound depression of a PFC response, Aroclor-1254 (up to 1250 mg/kg) caused slight increases in lymphocyte proliferation induced by either T or B cell mitogens. A single 500 mg/kg dose of Aroclor-1254 also suppressed the ability of recipient B6C3F1 animals to reject a challenge with either the syngenic fibrosarcoma (PYB6) or the gram negative pathogen (Listeria monocytogenes).
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PMID:Induction of immunotoxicity in mice by polyhalogenated biphenyls. 309 83

Infection of mice with a temperature-sensitive mutant of Salmonella typhimurium C5TS allowed the survival of genetically susceptible mice. The ability to mount a delayed-type hypersensitivity (DTH) response to sheep erythrocytes during infection with C5TS was studied in various inbred mouse strains, recombinant inbred strains derived from C57BL/6 (susceptible) and A/J (resistant) mice, and C3H congenic mice. Suppression of the DTH response to sheep erythrocytes was found in mice that carried the Itys allele, the H-2b haplotype, or both. These genes are known to increase susceptibility to S. typhimurium infection. In contrast, no DTH response suppression was observed in mouse strains that carried other genes that increased susceptibility to S. typhimurium, e.g., DBA/2 and C3H/HeJ. Apart from a transient suppression in A/J mice, the DTH responses of resistant mice (A/J and CBA) were normal or increased. The DTH response to sheep erythrocytes could be restored in immunodepressed mice by increasing the immunizing dose, suggesting the possible role of activated macrophages in depression of the DTH response.
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PMID:Genetic control of Salmonella typhimurium-induced depression of delayed-type hypersensitivity to sheep erythrocytes in mice. 312 86

Dimethylnitrosamine (DMN) exposure altered the cell-mediated immune response of B6C3F1 adult female mice as assessed by several immunological assays. Following 14 daily exposures (i.p.) to 1.5, 3.0, or 5.0 mg DMN/kg, mice exhibited a depression in their lymphoproliferative response to the T-cell mitogens concanavalin A and phytohemagglutinin, and in their mixed lymphocyte response to mitomycin-treated DBA-2 spleen cells. The delayed hypersensitivity response (DHR) to keyhole limpet hemocyanin (KLH), as measured by vascular permeability changes, was decreased by over 50% at the 5.0-mg/kg dose. When the DHR to KLH was measured by an influx of endogenously 125I-iododeoxyuridine (IUdR)-labelled monocytes, there was a 300% increase in the response of the 5.0-mg-DMN/kg group. Adoptive transfer studies using exogenously radiolabelled (51Cr) bone marrow cells from either vehicle- or DMN-treated (5 mg/kg) donors indicated a greater than 60% reduction in the DHR to KLH in DMN-treated mice (5.0 mg/kg level) regardless of the donor treatment. Animals exposed to DMN exhibited a decreased susceptibility to Listeria monocytogenes. The dichotomy in the results of the KLH DHR measured by monocyte influx and the increased resistance to the bacterial challenge were interpreted to reflect an effect on bone marrow. The numbers of granulocyte/monocyte stem cells were increased in a dose-related fashion in bone marrow from DMN-treated mice. The results indicate that DMN-treatment impairs cell-mediated immunity while increasing the number of bone marrow cells differentiating to form granulocytes or monocytes with an apparent enhancement in functional activity.
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PMID:Effects of N-nitrosodimethylamine on cell-mediated immunity. 315 99

3,7-Dimethyl-1-propargylxanthine (DMPX), a caffeine analog that exhibits in vitro selectivity for A2-adenosine receptors, compared to A1-adenosine receptors, has now been investigated with respect to in vivo potency and selectivity. DMPX potently and selectively blocked the actions of the potent A2 adenosine agonist, 5'-N-ethylcarboxamidoadenosine (NECA), in DBA/2 mice, compared to blockade of the same responses elicited by the selective A1-adenosine agonist, N6-cyclohexyladenosine (CHA). DMPX was 57-fold more potent versus NECA-induced hypothermia than versus CHA-induced hypothermia and 11-fold more potent versus NECA-induced behavioral depression than versus CHA-induced behavioral depression. The hypothermia is mediated by peripheral receptors, based on blockade by 8-(p-sulfophenyl)theophylline (PSPT), while the behavioral depression is centrally mediated, based on lack of blockade by PSPT. DMPX was 28- and 15-fold more potent than caffeine in blocking peripheral and central NECA-responses, respectively. DMPX was equipotent with caffeine versus CHA-induced hypothermia and 2.5-fold more potent than caffeine versus CHA-induced behavioral depression. The motor stimulating potency of DMPX (ED50 10 mumol/kg) was slightly greater than caffeine.
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PMID:3,7-Dimethyl-1-propargylxanthine: a potent and selective in vivo antagonist of adenosine analogs. 319 54

Subcutaneous administration of the enkephalin analogue FK33-824 (FK) elicited a dose-related decrease in rectal temperature and respiratory rate in male ddY strain mice. Naloxone and 3 days' implantation of morphine pellet decreased the effects of FK, suggesting the involvement of opioid receptors and cross-tolerance with morphine to both effects of FK. A positive correlation was found between the FK-induced decrease in rectal temperature and that in respiratory rate among the 6 strains of inbred mice including BALB/c, C3H, A/J, CBA, C57BL/6 and DBA/2. The degree of hypothermia elicited by FK was different among strains, whereas marginal strain difference was seen in the respiratory depression induced by FK. The strain difference in the FK responses may be due to the difference in the opioid receptor subtypes in the brain.
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PMID:Effects of the enkephalin analogue FK33-824 on rectal temperature and respiratory rate in male mice. 322 53

The potentials of octachlorostyrene (OCS) and hexachlorobenzene (HCB) to induce liver microsomal ethoxyphenoxazone deethylation (an indicator of induction of 3-methylcholanthrene and beta-naphthoflavone-like cytochrome P-450 monoxygenase activity) and cause porphyria in male C57BL/6 and C57BL/10 mice and female F344 rats were compared. Ethoxyphenoxazone deethylation was induced much more by HCB than by OCS in both of these strains of mice (although neither OCS nor HCB greatly induced deethylation in the DBA/2 strain). In rats ethoxyphenoxazone deethylase was induced 26-fold by HCB but only four-fold by OCS, whereas dealkylation of pentoxyphenoxazone (an indicator of phenobarbital-like induction) increased 43- and 36-fold, respectively. Both chemicals were poor inducers of dealkylation of pentoxyphenoxazone in mice. When fed HCB continuously but not when given OCS, C57BL/6 and C57BL/10 mice (both after pretreatment with iron) and F344 rats developed porphyria with a depression of hepatic uroporphyrinogen decarboxylase activity. The results illustrate that in these species OCS and HCB cannot be considered as equally efficient agents for inducing ethoxyphenoxazone deethylation or causing porphyria. If these effects are mediated through binding to the aromatic hydrocarbon responsiveness (Ah) receptor, HCB would appear to have a much greater affinity than OCS despite the face that neither chemical possesses a structure currently considered to be necessary for efficient binding.
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PMID:Distinction between octachlorostyrene and hexachlorobenzene in their potentials to induce ethoxyphenoxazone deethylase and cause porphyria in rats and mice. 327 68

The effects of cocaine on Y-maze activity and heart rate have been examined in four inbred strains of mouse (BALB, C57BL, C3H and DBA). In addition, brain [3H]-cocaine concentrations were measured at the time of maximal response to cocaine. Cocaine produced a dose-related increase in Y-maze cross activity in C3H, DBA and C57BL, with C3H mice being considerably more sensitive than DBA or C57BL. Cocaine was without effect on Y-maze cross activity in BALB mice. Cocaine produced a biphasic effect on rearing activity in C3H mice, a dose related depression in BALB mice, and was without effect on C57BL and DBA mice. At the highest dose studied (15 mg/kg), cocaine produced a small decrease in heart rate in C3H mice. Strain differences in behavior were maximal 15 minutes after a dose of 5 mg/kg, IP. At this dose and time interval, brain [3H]-cocaine concentrations were not significantly different among the four strains of mice. The results suggest a genetically-determined difference in CNS sensitivity to cocaine.
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PMID:An analysis of cocaine effects on locomotor activities and heart rate in four inbred mouse strains. 335 21

Positive therapeutic effects of interferons (IFNs) in combination with other therapies will depend on defining modalities, doses, and timing of treatment in the setting of varied tumor burdens. When 10(4) P388 leukemia cells were inoculated i.p. on day 0 in BALB/c x DBA/2 F1 mice, all mice died within 18 days if left untreated. Murine IFN-alpha/beta (5 x 10(5) units) injected daily i.p. on days 5-9 resulted in 20% increase in life span (ILS) (P less than 0.0001). Cyclophosphamide (CY) (100, 33, or 15 mg/kg) was injected i.p. once 2 days before start (day 3), simultaneously with start (day 5), or 2 days after cessation of IFN treatment (day 11). When 100 mg/kg CY alone were injected on day 3 or 5, all mice survived more than 90 days and were considered cured. When IFN was given after this curative dose of CY, more tumor deaths occurred; up to 100% of the mice died when 100 mg/kg CY on day 3 were combined with IFN on days 5-9. Increased mortality with the combination was not due to added toxicity of CY and IFN since the mice developed abdominal tumors and ascites. Mice not inoculated with tumor cells and treated similarly suffered only a transient weight loss, had only moderate white count depression, and did not die. When IFN was injected before CY on days 1-5 (instead of days 5-9), IFN did not alter the effectiveness of CY (100 mg/kg on day 5). In contrast to these results, when CY (100 mg/kg) was administered on day 11, after IFN (days 5-9), an augmented survival occurred with 119% ILS and 40% cures (CY alone on day 11 resulted in 69% ILS but no cures). In addition, when CY at a lower dose of 15 mg/kg was injected in combination with IFN, survival was consistently augmented by IFN; e.g., CY alone on day 3 caused 40% ILS and with IFN (days 5-9) 60% ILS (P less than 0.0001). Qualitatively similar findings were obtained when P388 leukemia cells were inoculated s.c. and the drugs delivered i.p. Inhibition by IFN of antitumor effects of a second alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea, was also identified. Thus, IFN-alpha/beta potentiated suboptimal CY effects for P388 leukemia, had neutral effects when injected before CY treatment, and inhibited antitumor activity of curative CY or nitrosourea schedules.
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PMID:Schedule-dependent variations in the response of murine P388 leukemia to cyclophosphamide in combination with interferons-alpha/beta. 335

In the mouse, the concurrent evaluation of micronuclei frequencies in peripheral blood polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) permits an assessment of both recently-induced and chronically-accumulated bone-marrow damage. This assay system was used to evaluate on a weekly basis the effect of exposure duration (1-13 weeks, 6 h per day) and exposure regimen (Regimen 1:5 exposure days per week; Regimen 2:3 exposure days per week) on the ability of 300 ppm benzene to induce genotoxic damage in the bone marrow of male and female DBA/2 mice. In addition, an analysis of the percentage of PCE in peripheral blood was used to evaluate benzene-induced alterations in the rate of erythropoiesis. Exposure to benzene induced a marked increase in the frequency of micronucleated PCE (MN-PCE), an effect which was considerably greater in male mice than in female mice. In both sexes, the induction of MN-PCE was independent of exposure regiment and of exposure duration. Exposure to benzene also resulted in an exposure duration-dependent increase in the frequency of MN-NCE. The frequency of MN-NCE increased more slowly in female than in male mice and, within each sex, more slowly in Regimen 2 animals. Apparent steady-state conditions for MN-NCE frequencies were attained by about the fifth week of exposure in female mice exposed by either regimen and in male mice exposed by Regimen 2. Steady-state conditions for MN-NCE frequencies in male mice exposed to benzene by Regimen 1 did not occur during the duration of the study. An analysis of %PCE data revealed an initial severe depression in the rate of erythropoiesis in both sexes, with the return in the production of PCE to control levels being dependent on both sex and exposure regimen. Suppression of PCE production occurred throughout the course of the study in Regimen 2 males, while the percentage of PCE returned to control levels sporadically after 5 weeks in Regimen 1 males and within 5 weeks in females, regardless of regimen. Thus, while the sex-dependent induction of genotoxic damage by multiple exposures to benzene over a 13-week period was independent of exposure regimen and duration, the induction of cytotoxic damage was both sex- and regimen-dependent. The most severe depression of erythropoiesis occurred in male DBA/2 mice exposed to benzene by the more intermittent regimen (i.e., 3 days/week versus 5 days/week).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effect of exposure regimen and duration on benzene-induced bone-marrow damage in mice. I. Sex comparison in DBA/2 mice. 340 35

In a companion paper (Luke et al., 1988), the effect of exposure duration and regimen on benzene induced-bone marrow damage was evaluated in male and female DBA/2 mice using the peripheral blood micronucleus assay. To assess the general applicability of the findings obtained for DBA/2 mice to other strains, similar studies were conducted using B6C3F1 and C57B1/6 male mice. An analysis of peripheral blood smears taken weekly from these mice exposed to 300 ppm benzene for 13 weeks (6 h per day) for either 5 days per week (Regimen 1) or for 3 days per week (Regimen 2) revealed: (i) a highly significant increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCE), the magnitude of which was strain specific (DBA/2 greater than C57B1/6 = B6C3F1), but independent of exposure regimen and, except for Regimen 2 B6C3F1 mice, of exposure duration. In male B6C3F1 mice, MN-PCE frequencies increased slightly with increasing exposure duration; (ii) a strain- (C57B1/6 = B6C3F1 greater than DBA/2) and regimen- (Regimen 1 greater than Regimen 2) dependent increase across time in the frequency of micronucleated normochromatic erythrocytes (MN-NCE). Apparent steady-state conditions for MN-NCE frequencies were attained by about 5 weeks of exposure in male mice of all three strains exposed to benzene by Regimen 2. Steady-state conditions for MN-NCE frequencies in male mice exposed to benzene by Regimen 1 did not occur during the duration of the study, with strain-dependent differences in the kinetics of MN-NCE accumulation being present; and (iii) in all 3 strains, an initial severe depression in the rate of erythropoiesis, the return of which to normal levels was both strain- (C57B1/6 = B6C3F1 greater than DBA/2) and regimen- (Regimen 1 greater than Regimen 2) dependent. These data indicate that the induction of genotoxic and cytotoxic damage in the bone marrow of male mice exposed to benzene for 13 weeks can be highly dependent on strain, exposure regimen and exposure duration but that under no circumstance did the level of genotoxic damage induced by benzene decrease under multiple exposure conditions.
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PMID:The effect of exposure regimen and duration on benzene-induced bone marrow damage in mice. II. Strain comparisons involving B6C3F1, C57B1/6 and DBA/2 male mice. 340 36


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