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)

The relationship between neutrophil polymorphonuclear leukocyte (PMN) locomotion and the exocytosis of neutrophil cytoplasmic granules was studied by assessing these processes in cells migrating through micropore filters and by measuring the effects of degranulating stimuli on PMN chemotaxis, orientation, adhesiveness, and ability to bind the chemoattractant f-Met-Leu-[3H]Phe. Studies of cells migrating through cellulose nitrate filters indicated that concentrations of f-Met-Leu-Phe optimal for exocytosis were greater than those optimal for chemotaxis and actually inhibited cell migration. In other studies incubation of PMNs with concentrations of secretagogues causing exocytosis of 30% or greater PMN lysozyme increased cell adhesiveness and inhibited chemotaxis. PMNs that had secreted more than 30% lysozyme appeared round, did not orient in a gradient of chemoattractant, and were capable of significantly less f-Met-Leu-[3H]Phe binding than were control cells. The decreased binding of f-Met-Leu-Phe was not associated with hydrolysis of chemotactic peptide by washed cells, although peptide hydrolysis was caused by cell products secreted extracellularly after vigorous exocytosis. In contrast, when only 10--15% cellular lysozyme was released f-Met-Leu-Phe binding was enhanced significantly and there was no depression of chemotaxis. The data indicate limited exocytosis of intracellular granule contents is associated with increased availability of PMN cehmotactic factor receptors. Vigorous exocytosis is associated with inactivation of chemotactic responsiveness related to increase cell adhesiveness, decreased PMN binding of chemotactic factors, and to hydrolysis of chemoattractants by factors secreted extracellularly.
 ...
PMID:Role of secretory events in modulating human neutrophil chemotaxis. 37 35

3H-leucine uptake by macrophages from swiss white and C57BL mice before and after M. leprae infection was studied. A depression in 3H-leucine uptake after infection was observed only in swiss white mice. 3H-leucine uptake was also studied in blood derived macrophages from normals, and LL and TT patients. A depression was obtained in 3H-leucine uptake after M. leprae infection in macrophages from LL patients.
 ...
PMID:The role of macrophages in leprosy as studied by protein synthesis of macrophages from resistant and susceptible hosts--a mouse and human study. 37 43

Perfusion of mouse pancreatic slices revealed that continuous exposition with cholecystokinin-pancreazymin (CCK-PZ) provokes an initially high peak of amylase secretion, which is followed by a slow decline in enzyme discharge. A return to the basal secretory level is noticed after about 45 min. Repeated pulse stimulations with CCK-PZ result in a more efficient stimulation of pancreatic amylase release, compared to a continuous stimulation. In the presence of CCK-PZ for 45 min, as well as during a post-stimulatory period of 45 min, a significant depression of L-(U-14C) leucine incorporation into amylase as well as total protein is recorded. In conclusion, in vitro incubated mouse pancreatic slices thus seem to be unable to increase their rate of protein synthesis during and after stimulation of secretion.
 ...
PMID:Effects of cholecystokinin-pancreozymin on amylase synthesis and secretion in the mouse pancreas. 42

1. The activation of human peripheral blood lymphocytes by phytohaemagglutinin in vitro was accompanied by striking increases in the concentrations of the natural polyamines putrescine, spermidine and spermine. 2. The enhanced accumulation of polyamines could be almost totally abolished by dl-alpha-difluoromethylornithine, a newly discovered irreversible inhibitor of l-ornithine decarboxylase (EC 4.1.1.17), or by methylglyoxal bis(guanylhydrazone) {1,1'-[(methylethanediylidene)dinitrilo]diguanidine}, an inhibitor of S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50). The inhibition of polyamine accumulation was associated with a marked suppression of DNA synthesis, which was partially or totally reversed by low concentrations of exogenous putrescine, spermidine, spermine and cadaverine and by higher concentrations of 1,3-diaminopropane. 3. In contrast with some earlier studies, we found that methylglyoxal bis(guanylhydrazone), at concentrations that were sufficient to prevent polyamine accumulation, also caused a clear inhibition of protein synthesis in the activated lymphocytes. Similar results were obtained with difluoromethylornithine. The decrease in protein synthesis caused by both compounds preceded the impairment of DNA synthesis. The inhibition of protein synthesis by difluoromethylornithine was fully reversed by exogenous putrescine, spermidine and spermine, and that caused by methylglyoxal bis(guanylhydrazone) by spermidine and spermine. In further support of the idea that the inhibition of protein synthesis by these compounds was related to the polyamine depletion, we found that difluoromethylornithine caused a dose-dependent decrease in the incorporation of [(14)C]leucine into lymphocyte proteins which closely correlated with the decreased concentrations of cellular spermidine. 4. Difluoromethylornithine and methylglyoxal bis(guanylhydrazone) also elicited a variable depression in the incorporation of [(3)H]uridine and [(14)C]adenine into total RNA. The apparent turnover of lymphocyte RNA remained essentially unchanged in spite of severe polyamine depletion brought about by difluoromethylornithine. 5. The present results, as well as confirming the anti-proliferative action of the inhibitors of polyamine biosynthesis, suggest that polyamine depletion may interfere with reactions at different levels of gene expression.
 ...
PMID:Suppression of the formation of polyamines and macromolecules by DL-alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) in phytohaemagglutinin-activated human lymphocytes. 43 70

Marrow cells of a patient with CDA, type III, were (1) incubated with 3H-thymidine for 0.5 h and studied using a combination of Feulgen microspectrophotometry and light microscope autoradiography and (2) incubated with 3H-thymidine, 3H-uridine or 3H-leucine for 1 h and studied using the technique of electron microscope autoradiography. The data revealed multiple abnormalities in the proliferation of erythroblasts but no abnormality in the distribution of neutrophil promyelocytes and myelocytes in the different stages of interphase. Some mononucleate erythroblasts had DNA contents of 4-20c and the multinucleate erythroblasts had total DNA contents of 2-40c. In about 40% of the multinucleate erythroblasts, only some of the nuclei within the same cell incorporated 3H-thymidine and the electron microscope autoradiographic studies revealed that the nuclei which failed to synthesize DNA virtually always showed abnormalities in the electron-density of the heterochromatin or euchromatin or a Swiss-cheese appearance of the heterochromatin. Furthermore, in some multinucleate cells but not in others, the ultrastructurally abnormal nuclei showed a marked depression of RNA synthesis when compared with the normal-looking nuclei within the same cell. An occasional binucleate, multinucleate and giant mononucleate erythroblast showed ultrastructural changes suggestive of advanced degeneration and such cells, which showed a marked depression of RNA and protein synthesis, appeared to be phagocytosed by macrophages.
 ...
PMID:Some aspects of the biology of multinucleate and giant mononucleate erythroblasts in a patient with CDA, type III. 43 98

The importance of adhesion in regulating locomotion and accumulation of polymorphonuclear leukocytes (PMN) has remained vague. We found that the chemotaxis of human PMN resuspended in heat-inactivated plasma was maximal toward 1-10 nM N-formyl-met-leu-phe (f-Met-Leu-Phe), but fell below random motility toward >/= 100 nM. This impressive decrease of motility was paralleled by increased cell adherence on Petri dishes being minimal at 1 nM and maximal at >10 nM f-Met-Leu-Phe (6+/-1 and 37+/-2% [SE] adherent cells, respectively). Checked by phase-contrast microscopy, cells under stimulated adhesion lost the typical bipolar shape of moving PMN and became immobilized and highly flattened. PMN, preexposed to 250 nM f-Met-Leu-Phe and tested after washing, retained increased adhesiveness and showed extremely low random and chemotactic motility. In contrast, preexposure to 1 nM f-Met-Leu-Phe had no effect on chemotaxis. Supporting the concept that immobilizing hyperadhesiveness does not correspond to a general functional hyporesponsiveness of PMN, no depression of the initial ingestion rate was observed in the presence of 250 nM f-Met-Leu-Phe. Moreover, a close correlation was found between the induction of PMN adhesiveness and the stimulation of the hexose monophosphate pathway activity as well as of lysomal enzyme release (r >/= 0.98). Thus, "chemotactic deactivation" and "high-dose inhibition of chemotaxis" by N-formyl peptides is the consequence of increased cell adhesiveness. This phenomenon provides a mechanism for cell trapping at the inflammatory site. Conversely, if operative in circulating blood, e.g., in septicemia, it may impair PMN emigration to such sites.
 ...
PMID:Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function. 44 62

Lysine supplementation of the growth medium of a wild type strain of the yeast Saccharomycopsis lipolytica specifically results in saccharopine dehydrogenase repression. Starvation of the strain for histidine triggers a general depression of various histidine, leucine, arginine and lysine biosynthetic enzymes, including saccharopine dehydrogenase. These two types of control, specific and general, act independently on saccharopine dehydrogenase expression, since mutants which fail to respond to the specific control still are sensitive to the general one. These mutants were first selected as unable to catabolize lysine, suggesting that a link may exist between saccharopine dehydrogenase specific regulation and activity of the catabolic pathway.
 ...
PMID:General and lysin specific control of saccharopine dehydrogenase levels in the yeast Saccharomycopsis lipolytica. 48 78

Ultrastructural morphometric and biochemical studies were conducted on hepatic mitochondria from control rats and rats treated in vivo with arsenate to examine changes in interrelationships between mitochondrial structure and biochemical functions. Morphometric analysis disclosed an over-all 1.2-fold increase in the relative mitochondrial volume density and 1.4-fold increase in the surface density of the inner mitochondrial membrane of arsenate-exposed rats. These structural changes were associated with a 1.5-fold increase in 14C-leucine incorporation into all mitochondrial proteins, which was primarily associated with the acid-insoluble membranous fraction. Mitochondria from arsenate-treated rats showed a marked disruption of normal conformational behavior with depression of nicotinamide adenine dinucleotide (NAD)-linked substrate oxidation and a resulting in vivo increase in the mitochondrial [NAD] to [NADH] ratio. Observed changes in mitochondrial membranes from arsenate exposure also resulted in 1.5- to 2-fold increases in the specific activities of the membrane marker enzymes monoamine oxidase, cytochrome oxidase, and Mg2+-ATPase. Activity of malate dehydrogenase, which is localized in the mitochondrial matrix, was unchanged. The results of this study demonstrate a positive quantitative in vivo correlation between mitochondrial structure and function and indicate a marked dependency upon membrane integrity for normal maintenance of the specific biologic activities performed by this organelle in vivo.
 ...
PMID:Studies of hepatic mitochondrial structure and function: morphometric and biochemical evaluation of in vivo perturbation by arsenate. 49 44

1. 1,3-Diaminopropane and some of its derivatives are potent inhibitors of ornithine decarboxylase (EC 4.1.1.17) in Ehrlich ascites cells grown in suspension culture. Among the amine derivatives tested, 1,3-diamino-2-propanol most effectively prevented any accumulation of spermidine and spermine in ascites cells when the proliferation was stimulated by diluting the cells with fresh medium. 2. The effectiveness of diaminopropanol in abolishing polyamine accumulation was primarily based on a rapid decay of ornithine decarboxylase activity following the exposure of the cells to the drug. 3. The mechanism of action of diaminopropanol on ornithine decarboxylase apparently involved a formation of macromolecular inhibitors or 'antizymes' to the enzyme. 4. Even though the inhibitory effect of 1,3-diaminopropane on polyamine accumulation approached that of diaminopropanol, the former compound only marginally inhibited the incorporation of [3H]thymidine into DNA and that of [14C]leucine into protein, in contrast to the marked depression of macromolecular synthesis produced by diaminopropanol. The apparent dissociation of polyamine depletion brought about by 1,3-diaminopropane from an antiproliferative action was apparently due to the fact that diaminopropane, unlike diaminopropanol, was partially capable of taking over the function of natural polyamines. 5. The inhibition of DNA and protein synthesis as well as the prevention of increase in cell number by diaminopropanol was closely associated with polyamine depletion and was fully comparable, as regards timing and magnitude, with that achieved with difluoromethylornithine. The antiproliferative effect of diaminopropanol, however, was only partly reversed by a simultaneous addition of putrescine (or spermidine) into the culture medium. The lack of a complete reversal of the action of diaminopropanol on cell growth by natural polyamines was apparently due to the fact that it was remarkably difficult or even impossible to increase intracellular polyamine concentrations by exogenous polyamines in the presence of diaminopropanol. Nevertheless, the diaminopropanol-induced arrest of growth was reversible as judged by a rapid increase in ornithine decarboxylase activity followed by restoration of DNA synthesis.
 ...
PMID:Inhibition of polyamine accumulation and cell proliferation by derivatives of diaminopropane in Ehrlich ascites cells grown in culture. 49 23

The effects of ethanol withdrawal were determined on cell free brain protein synthesis in physically dependent rats. Following the development of physical dependence, ethanol abstinence for 24 h resulted in decreased protein synthesis in cerebral tissue. The observed inhibition of [14C]leucine incorporation into protein was found to be reversible after 7 days of ethanol withdrawal. Although the ribosomes from control, ethanol-treated and ethanol-withdrawn animals were highly responsive to polyuridylic acid stimulation, the ribosomes from the control group consistently exhibited higher activity. The determination of protein content of the ribosomal fraction showed a significant increase following ethanol administration and was further enhanced by ethanol abstinence. The results suggest that ethanol-induced changes at the ribosomal level may result in defective association of mRNA causing depression of brain protein synthesis.
 ...
PMID:Alterations in cell free brain protein synthesis following ethanol withdrawal in physically dependent rats. 55 14


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