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)

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre-IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.
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PMID:Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha. 186 53

Studies of the effect of short-term, intense treatment with thymic hormone on mitogen response, cytotoxicity to EL-4 lymphoma and natural killer cell (NK) activity was investigated Balb/c nude mice (about 12-16-week-old) were treated 5 times per week for 3 weeks with: Facteur Thymic Serique (FTS) and Thymopentin (TP5, Thymopoietin 32-36) at 1 microgram and 10 ng; TM4 1 ng (an enzyme resistant variant of FTS); Thymosin Fraction V (TF5), 10 and 1 microgram; and 0.1 ml saline, and killed 2 days after the last treatment. The animals were monitored for changes in weight, hematocrit, peripheral blood lymphocyte (PBL) and spleen mitogen response. Additional groups of nude mice were immunized with 1 x 10(7) 5000 R irradiated EL-4 cells 10 days before sacrifice and tested for the presence of cytotoxic T-lymphocytes (CTL). The results show that weight and hematocrit were similar among the groups. Treatment with FTS significantly elevated the number of PBL. Spleen stimulation in mice treated with 1 microgram TP5 was depressed to mitogen concanavalin A (ConA) and lipopolysaccharide (LPS) stimulation. The phytohemagglutinin (PHA) response was not different among the treatment groups. The PBL mitogen response to ConA and LPS was generally increased over saline control in the hormone treated groups but was not statistically significant. The PHA response was only slightly elevated. No CTL was generated in nude mice in any of the groups. However, there was a statistically significant general depression of NK activity in all of the hormone treated animals compared with saline. The results indicate that the basic differentiation defect of the T-cells of nude mice cannot be restored to full functional activity by short-term treatment.
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PMID:Effect of thymic hormone treatment on several immune functions of nude mice. 187 32

This study was aimed at evaluating the effect of histamine on tumor necrosis factor (TNF alpha) secretion by purified human blood monocytes. TNF alpha was measured by radioimmunoassay. Histamine caused a dose-dependent inhibition of lipopolysaccharide-induced TNF alpha production from human blood monocytes, averaging maximally 50% at 10(-5) M. Preincubation of mononuclear cells with an H2 antagonist (cimetidine), but not with an H1 antagonist (promethazine) prevented this inhibitory effect of histamine. In conclusion, histamine causes, in vitro, a depression of TNF alpha secretion by human monocytes through activation of H2 receptors.
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PMID:Effect of histamine on tumor necrosis factor production by human monocytes. 193 30

We evaluated cardiac function in an unanesthetized ovine model of hyperdynamic endotoxemia. The animals were instrumented for crystallographic dimension analysis of the left ventricle (LV) and measurement of LV, aortic, atrial, central venous, and pulmonary arterial pressures, and cardiac output. Seven sheep received 1.5 micrograms/kg of Escherichia coli endotoxin [lipopolysaccharide (LPS) LPS-P group] and were compared to a sham group. The sham group demonstrated no significant change in any of the variables. In the LPS-P group, the cardiac index increased (5.7 +/- 0.4 to 7.9 +/- 0.6 l.min-1.m-2) between 8 and 12 h after LPS. Concomitantly, the maximum elastance of LV end-systolic pressure-volume relations significantly decreased (2.88 +/- 0.27 mmHg/ml) compared with baseline (3.89 +/- 0.50 mmHg/ml). Other indexes of the LV contractility (maximum pressure development and ejection fraction) were also reduced. There was a simultaneous increase in the LV end-systolic and diastolic volumes. These findings confirm the hypothesis that there is a myocardial depression during LPS in the ovine model.
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PMID:Cardiac dysfunction after acute endotoxin administration in conscious sheep. 203 70

Expression of tumor necrosis factor (TNF alpha), tissue factor (TF), and interleukin 1-beta (IL-1 beta) mRNA was evaluated in monocytes isolated from patients infected with human immunodeficiency virus (HIV). There was a significant depression (66%) of the induced level of TF mRNA expression in response to lipopolysaccharide. Conversely, the response of TNF alpha and IL-1 beta, following LPS induction, was "normal." TF mRNA reduction was also observed to a lesser degree in AIDS-related complex patients (20%) but not in asymptomatic seropositives. TF is necessary for initiation of the coagulation protease cascade, leading to thrombin production and fibrin deposition, which play a role in inflammatory responses. Its selective reduction may be a factor in the diminished resistance to secondary infections observed in AIDS. Further, since the TF defect increases as patients progress toward AIDS, it may serve as a marker for disease progression.
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PMID:A selective defect in tissue factor mRNA expression in monocytes from AIDS patients. 229 2

A porcine strain of Pasteurella multocida (serotype D:3) produced a toxin causing turbinate atrophy (TA) in pigs. The toxin (TAT), processed on a high performance liquid chromatography size exclusion column, eluted as a single peak (molecular weight of about 160,000) containing trace amounts of endotoxin (lipopolysaccharide, LPS; protein:LPS, 85:1). The eluted fraction migrated on sodium dodecyl sulfate polyacrylamide gels as a single band. It could be prevented from dissociating into two prominent polypeptides by addition of a protease inhibitor. A single dose (2.0 to 79.0 micrograms/kg) of TAT given to pigs intravenously was lethal. Doses from 0.02 to 1.0 microgram/kg caused transient clinical signs of porcine systemic toxicosis with reduced appetite, generalized weakness, depression, lethargy, weight loss, and in some instances, death. Intradermal doses of TAT (greater than or equal to 0.1 microgram/site) produced hemorrhagic areas within four hours. Systemically, TAT causes bilateral TA, lymphopenia, liver dysfunctions, and possible renal impairment. Affinity of TAT for cells of epithelial origin was demonstrated in mice given 125I-TAT. In vitro, TAT stimulated DNA and protein syntheses of peripheral blood lymphocytes and suppressed syntheses in turbinate and kidney cell cultures without being cytolytic. Biological effects of TAT were eliminated by exposure to either heat, trypsin or anti-TAT antibody.
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PMID:Host response to Pasteurella multocida turbinate atrophy toxin in swine. 230 67

In experiments designed to examine the adverse effects of chronic liposome administration in vivo on the mononuclear phagocyte system (reticuloendothelial system), the presence of drug entrapped in the liposomes may increase the level of reticuloendothelial impairment. We have compared the effects on the mononuclear phagocyte system in mice of chronic administration of empty liposomes with the effects of liposomes containing the anti-leishmanial drug meglumine antimoniate. We have also examined the effect on the mononuclear phagocyte system of continued injections of liposomes containing lipid A, a component of bacterial lipopolysaccharide, which is responsible for macrophage activation. Ten intravenous injections of multilamellar liposomes composed of dipalmitoylphosphatidylcholine and cholesterol (1:0.75 M ratio) were given to ICR mice over a 25-day period. Two individual groups of mice received endotoxin-free liposomes in which meglumine antimoniate was either present or absent. One addition group received liposomes containing lipid A derived from Escherichia coli lipopolysaccharide. A control group received sterile saline injections. In each group, a depression of the phagocytic index, as measured by reduction of uptake of particulate carbon, was observed among some of the individual animals 24 h after the first injection. In many mice a marked splenomegaly was observed. A depressed phagocytic index and splenomegaly were most marked for mice receiving lipid A liposomes. However, there was a large individual variability among mice receiving these preparations and some mice in each group had normal spleen size and a nearly normal phagocytic index. Tissue distribution of liposomes containing [14C]dipalmitoylphosphatidylcholine as a phospholipid marker was examined in all groups in mice 24 h after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects on the murine mononuclear phagocyte system of chronic administration of liposomes containing cytotoxic drug or lipid A compared with empty liposomes. 243 31

Experiments were conducted to determine the influence of immunologic stress on methionine and lysine requirements of growing chicks. Immunologic stress was elicited by injection of either Escherichia coli lipopolysaccharide or heat-killed Staphylococcus aureus every other day for 6 d. In the first experiment, diets were formulated to provide methionine levels of 0.30, 0.50 and 0.70%. In the second experiment, diets contained 0.75, 0.90 or 1.2% lysine. In chicks fed amino acid-sufficient diets, those chicks injected with immunogens had slower growth, lower feed intake and poorer efficiency of feed utilization than those injected with saline. The decreases due to immunogens were diminished in chicks fed amino acid-deficient diets. The methionine requirements of saline- and immunogen-injected chicks were above 0.5% and between 0.3 and 0.5%, respectively; the lysine requirements were greater than 0.95% and between 0.7 and 0.95%, respectively. Thus immunogen injection decreased methionine and lysine requirements, probably because of a decreased need of amino acids for growth and tissue accretion. Immunogen-induced depression in serum zinc and increase in serum copper levels were ameliorated by lysine or methionine deficiencies. Compared with saline-injected chicks, immunogen-injected chicks had significantly higher serum interleukin-1 (IL-1) activity by 53% when fed the methionine-sufficient diet, but they did not have significantly greater IL-1 levels when fed the methionine-deficient diet. These observations indicate that the diminished expression of immunologic stress in amino acid-deficient chicks is due to an impaired immune response.
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PMID:Decreased amino acid requirements of growing chicks due to immunologic stress. 245 41

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.
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PMID:Regulation of rabbit acute phase protein biosynthesis by monokines. 246 85

The effect of prenatal exposure to cyclophosphamide on postnatal somatic development and the function of the immune system was studied in random-bred ICR mice. In a dose of 1.2 mg (i.e. an average of 23.5 mg/kg pregnant female body weight), cyclophosphamide administered on the 16th day of gestation (a vaginal plug = day 1) caused both prenatal and postnatal retardation of growth. In the 3rd, 5th and 8th postnatal week, increased proliferation of the splenocytes of the experimental mice was observed in vitro, with changes in the intensity of their activation by Concanavalin A and lipopolysaccharide. In the 3rd week their capacity for activation by lipopolysaccharide was markedly lower than their activation by Concanavalin A and phytohaemagglutinin. No differences were observed between proliferation and activation of the splenocytes of the offspring of the control and the experimental mice at the age of 16 weeks. After depression at three weeks, the delayed type hypersensitivity reaction showed a tendency to increase; in the offspring of the experimental mice the haemagglutinin titre against sheep RBC was raised during the whole period of the investigation. At 16 weeks, the activity of peritoneal macrophages was likewise elevated.
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PMID:Effects of prenatally administered cyclophosphamide on postnatal immunocompetence in mice. 260 86


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