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)

Plasma taurine and serine decrease following trauma and in severe inflammatory disease. These changes may signify an increase in requirements for sulfur amino acids. We previously demonstrated that cysteine supplementation can restore the impaired ability of rats fed an 8% casein diet to increase hepatic zinc, glutathione (GSH) and protein concentrations in response to tumor necrosis factor alpha (TNF alpha). Here we examined whether serine or taurine produces a similar effect, because serine provides the carbon skeleton of cysteine and taurine is its major metabolite. After 7 d of receiving either a 20% casein diet supplemented with cysteine or an 8% casein diet supplemented with alanine, serine or taurine, rats received an intraperitoneal injection of human TNF alpha. Tumor necrosis factor caused no change in hepatic GSH but resulted in a lower GSH concentration in lung in rats fed the alanine-supplemented diet. Neither taurine nor serine increased liver GSH relative to that in rats fed alanine, but the depression in lung due to TNF injection was lessened. The absolute increase in ceruloplasmin in response to TNF was enhanced in rats fed the alanine-supplemented diet relative to those fed the 20% casein diet. Serine normalized this response. This observation--the effects of taurine and serine on lung GSH and a significant negative correlation between ceruloplasmin and liver and lung GSH concentration in rats fed TNF--suggests that supplemental serine and taurine may improve antioxidant defenses when dietary supplies of cysteine are low but do not influence cysteine availability for a normal response to TNF.
 ...
PMID:Taurine and serine supplementation modulates the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet. 137 44

The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis. Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure. The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days. Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0). These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis. 150 42

Spleen cells of Mycobacterium lepraemurium-infected mice were cultured on petri dishes coated with mycobacterial antigens, and antigen-reactive cells were isolated. Upon incubation in mitogen- or antigen-free culture medium, these cells released mediators capable of depressing the in vitro proliferative response of normal splenocytes to specific antigen and to concanavalin A and lipopolysaccharide. One of these mediators was identified with gamma interferon (IFN-gamma), mainly on the basis that treatment of supernatants with monoclonal anti-IFN-gamma antibodies markedly reduced the suppressive activity contained therein. Detectable levels of tumor necrosis factor alpha (TNF-alpha) and TNF-beta were present in spleen cell culture supernatants of infected mice. Moreover, low doses of recombinant TNF-alpha and TNF-beta were found to potentiate the suppressive activity of exogenous IFN-gamma. Soluble T-cell receptors beta were also detected in the culture supernatants. The elimination of these molecules with monoclonal anti-T-cell receptor beta (F23.1) antibodies immobilized on a plastic surface partially reversed the depression of the response to mycobacterial antigen but did not affect the response to mitogens. These results revealed the complex nature of suppressor mediators that are produced by mycobacterial antigen-reactive cells and that regulate the in vitro proliferative response.
 ...
PMID:A role for gamma interferon, tumor necrosis factors, and soluble T-cell receptors in the depressed blastogenic response of spleen cells of Mycobacterium lepraemurium-infected mice. 183 61

Iron increases the synthesis of the iron-storage protein, ferritin, largely by promoting translation of preexisting mRNAs for both the H and L ferritin isoforms (H, heavy, heart, acidic; L, light, liver, basic). We have recently cloned and sequenced a full-length cDNA to murine ferritin H and identified ferritin H as a gene induced by tumor necrosis factor alpha (TNF-alpha, cachectin). Using primary human myoblasts, we have now examined the relationship between TNF-alpha and iron in regulating ferritin. Four lines of evidence suggest that TNF-alpha regulates ferritin independently of iron. First, evaluation of mRNA showed that TNF-alpha increased ferritin H chain specifically, provoking no change in steady-state levels of ferritin L mRNA; iron, in contrast, increased the mRNA of both isoforms. Second, the increase in ferritin H protein synthesis observed during TNF-alpha treatment was dependent on an increase in ferritin H mRNA: actinomycin D blocked the TNF-alpha-induced changes in ferritin H but did not inhibit the translational induction of ferritin seen with iron treatment. Third, equal ferritin mRNA induction was observed in iron-loaded cells and in cells depleted of iron by a permeant chelator, 2,2'-dipyridyl. Fourth, ferritin H induction by TNF-alpha and iron was additive over the entire range of iron concentrations, even at TNF-alpha doses known to maximally stimulate ferritin H mRNA levels. Nonetheless, the role of iron in translational regulation of ferritin was retained in TNF-alpha-treated cells; effective biosynthesis of TNF-alpha-induced, H-subunit-predominant ferritin protein required iron and could be enhanced by treatment of the cells with additional iron or blocked by 2,2'-dipyridyl. Finally, we observed that the TNF-alpha-mediated increase in ferritin synthesis peaked at 8 hr and was followed by a decrease in both H and L isoferritin synthesis; the addition of iron, however, reversed the late-occurring depression in ferritin synthesis. This suggests that TNF-alpha-induced synthesis of H-rich ferritin may reduce the regulatory pool of intracellular iron, secondarily inhibiting iron-mediated translation of ferritin mRNA. We conclude that TNF-alpha acts independently of iron in its induction of ferritin H mRNA but requires the presence of iron for this effect to be fully expressed at the protein level.
 ...
PMID:Iron-independent induction of ferritin H chain by tumor necrosis factor. 205 77

It is generally assumed that noises have a detrimental effect when the cochlear receptor is overloaded and, more specifically, when the cochlear microphonic (CM) fails to increase linearly with intensity. In order to investigate further the relations between the nonlinearity of CM and damage to the cochlea, a series of experiments was carried out on guinea pigs to relate the short-term CM depression following the presentation of noises or tones with the nonlinearity and the assymmetry. The asymmetrical non-linearity of CM was measured in tracing the input-out functions and also the wave-forms. Two other important tests of the asymmetrical nonlinearity were used: the measure of interference and of summating potential (SP DIF). The results show that the fatigability is greater when there is a large negative asymmetry or a large negative SP. Variations in asymmetry and in SP were observed among individuals. Other changes of symmetry were provoked by asphyxia or by introducing solutions of KCl in the perilymph. These changes were well correlated with the fatigability. These results are interpreted in a model of the cochlear transducer derived from the model of Davis. The assymetry of a flux of potassium ions between endolymph and the hair cells is assumed to be responsible for the alterations associated with cochlear fatigue and trauma.
 ...
PMID:Relations between cochlear fatigue and the asymmetrical nonlinearity of the cochlear microphonics. 736 35

Because HIV may alter the production of inflammatory factors produced by monocytes, the expression of tumor necrosis factor alpha (TNF-alpha), tissue factor (TF), interleukin (IL)-1 beta, and IL-6 was evaluated in 47 HIV-seropositive persons and seronegative control subjects. RNA was extracted from freshly isolated lipopolysaccharide (LPS)-stimulated or unstimulated monocytes. Cytokine and TF expression was quantitated by dot blot hybridization or a reverse transcription polymerase chain reaction (RT-PCR). A significant depression of TF mRNA was observed in LPS-stimulated monocytes (66% less in AIDS, 20% less in AIDS-related complex (ARC), and 0% less in asymptomatic patients), whereas normal responses were observed for TNF-alpha, IL-1 beta, and IL-6. When constitutive expression was measured in unstimulated monocytes by RT-PCR, a differential pattern was also observed. TNF-alpha and IL-1 beta were positive in 85% of asymptomatic persons, compared with only 27% of ARC and 42% of AIDS patients. Expression of IL-6 was observed in lower proportions, 27-30%, with no significant differences among disease states. All samples were negative for TF. Thus, the regulation of inflammatory molecules is differentially altered in individuals with HIV infection. TF is preferentially down-regulated, compared with TNF-alpha, IL-1 beta, and IL-6, in LPS-stimulated monocytes as patients progress to AIDS. TNF-alpha and IL-1 beta are preferentially up-regulated, compared with IL-6 and TF, in unstimulated monocytes in asymptomatic persons, with a loss of up-regulation as patients progress to AIDS.
 ...
PMID:Dysregulation of cytokine expression in monocytes from HIV-positive individuals. 808 6

We examined the effect of infusion of lipopolysaccharide (LPS) on serum tumor necrosis factor alpha (TNF alpha) concentration and clinical attitude in 2- 3-day-old colostrum-fed (CF) and colostrum-deprived (CD) foals. Eleven CF and 8 CD neonatal foals were given a bolus i.v. infusion of Escherichia coli O55:B5 lipopolysaccharide (0.5 microgram/kg of body weight) in sterile saline (0.9% NaCl) solution. Four CF and 2 CD foals were given saline solution alone. Serum IgG concentration and serum anti-LPS IgG(T) antibody titer were determined for each foal prior to infusion. A depression index was used to score clinical abnormalities. Serum TNF alpha concentration was estimated by use of an in vitro cytotoxicity bioassay that used WEHI 164 clone 13 cells as targets. The cytotoxic serum factor was identified as TNF alpha by immunoprecipitation with caprine antisera raised against the 15 NH2-terminal amino acids of human TNF alpha. Tumor necrosis factor alpha was not detected in any preinfusion serum samples nor in any samples from foals given saline solution alone. Serum TNF alpha concentration increased in all LPS-infused foals and peaked between 60 and 90 minutes after infusion. Serum TNF alpha concentrations, expressed as mean percentage of peak serum TNF alpha concentration, persisted longer in CD foals given LPS than in CF foals given LPS. All LPS-infused foals displayed clinical signs of endotoxemia, but mean depression index scores of the CF and CD foals given LPS were not significantly different at any time. Serum TNF alpha concentrations were correlated with depression index scores in both LPS-infused groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum tumor necrosis factor alpha concentrations and clinical abnormalities in colostrum-fed and colostrum-deprived neonatal foals given endotoxin. 823 25

The goal of our study was to assess whether the human immunodeficiency virus (HIV) coat protein gp120 induces functional alterations in astrocytes and microglia, known for their reactivity and involvement in most types of brain pathology. We hypothesized that gp120-induced anomalies in glial functions, if present, might be mediated by changes in the levels of intracellular messengers important for signal transduction, such as cAMP. Acute (10 min) exposure of cultured rat cortical astrocytes or microglia to 100 pM gp120 caused only a modest (50-60%), though statistically significant, elevation in cAMP levels, which was antagonized by the beta-adrenergic receptor antagonist propranolol. More importantly, the protein substantially depressed [by 30% (astrocytes) and 50% (microglia)] the large increase in cAMP induced by the beta-adrenergic agonist isoproterenol (10 nM), without affecting that induced by direct adenylate cyclase stimulation by forskolin. Qualitatively similar results were obtained using a glial fibrillary acidic protein (GFAP)-positive human glioma cell line. The depression of the beta-adrenergic response had functional consequences in both astrocytes and microglia. In astrocytes we studied the phosphorylation of the two major cytoskeletal proteins, vimentin and GFAP, which is normally stimulated by isoproterenol, and found that gp120 partially (40-50%) prevented such stimulation. In microglial cells, which are the major producers of inflammatory cytokines within the brain, gp120 partially antagonized the negative beta-adrenergic modulation of lipopolysaccharide (10 ng/ml)-induced production of tumor necrosis factor alpha. Our results suggest that, by interfering with the beta-adrenergic regulation of astrocytes and microglia, gp120 may alter astroglial "reactivity" and upset the delicate cytokine network responsible for the defense against viral and opportunistic infections.
 ...
PMID:Human immunodeficiency virus coat protein gp120 inhibits the beta-adrenergic regulation of astroglial and microglial functions. 838 71

The production of the cytokines interferon gamma (IFN gamma), interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) was investigated in the mitogen-stimulated whole blood cell culture media from 51 patients with urinary bladder carcinomas, 52 patients with renal carcinomas, 31 patients with prostatic carcinomas and 360 healthy controls. The cytokines were measured 4 days after induction by a sensitive enzymo-immunological assay. In the blood cell culture supernatants of the patients with urinary bladder carcinomas significant lower levels of IFN gamma (P < or = 0.001), IL-2 (P < or = 0.01) and TNF alpha (P < or = 0.05) were found as compared to the controls. Blood cells of patients with renal carcinomas had lower production of IFN gamma (P < or = 0.01), IL-2 (P < or = 0.001) and IL-1 alpha (P < or = 0.01), whereas the values of the total group of patients with prostatic carcinomas were not significantly different from those of the controls. Lymphocyte and monocyte counts were almost identical in the control and all tumor patient groups. When the patients with renal carcinomas and prostatic carcinomas were analyzed according to their different clinical stages we could show a gradual depression of the IFN-gamma levels, which was related to tumor burden.
 ...
PMID:Impaired cytokine production in whole blood cell cultures of patients with urological carcinomas. 849 65

We evaluated the long-lasting effects of systemic high-dose recombinant interferon alpha-2a (rIFNA) in relapsing-remitting (RR) MS after discontinuing treatment in a single-blind randomized placebo-controlled trial with 20 RR clinically definite MS patients using either nine million IU intramuscular rIFNA (n = 12) or placebo (n = 8) every other day for 6 months. Follow-up continued for a further 6 months without IFN treatment. In rIFNA-treated patients, main outcome measures, significantly different from placebo during treatment, returned, after discontinuing treatment, to values similar to placebo or baseline. Active MRI lesions per patient increased from 0.08 +/- 0.08 to 1.2 +/- 0.4 (p < 0.02), number of patients with clinical MRI signs of disease activity from 2 of 12 to 8 to 12 (P < 0.04), lymphocyte IFN gamma production from 3.0 +/- 0.7 to 12.4 +/- 2.2 IU/mL (p < 0.01), lymphocyte tumor necrosis factor alpha production from 5.8 +/- 0.9 to 18.9 +/- 6.3 pg/mL (p < 0.05). All side effects of rIFNA treatment disappeared after discontinuing the drug. The reduction of clinical MRI signs of disease activity and the immunologic effects were temporary and restricted to the period of rIFNA administration. The depression of many immunologic and clinical MRI responses during drug administration and their simultaneous return to baseline after discontinuing the drug strongly argue all observed changes were related to drug administration.
 ...
PMID:Interferon alpha-2a treatment of relapsing-remitting multiple sclerosis: disease activity resumes after stopping treatment. 871 65


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