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)

Insulin was adsorbed to a strongly acidic ion exchanger and incubated with pepsin. The digestion of the matrix-bound insulin was found to be restricted to the cleavage of the peptide bond between phenylalanine-B25 and tyrosine-B26. Factionation of the reaction products was achieved by gel filtrationon Sephadex G-50 at pH 8 where des-pentapeptide(B26-30)-insulin does not aggregate. Another way to purify this compound was ion-exchange chromatography, which was easy due to the loss of one positive charge on the modified insulin. Crystallization could be achieved in a phenol-containing buffer. Des-pentapeptide(B26-30)-insulin was found to be molecularly uniform by electrophoresis at pH 2.2 and 8.6, thin-layer chromatography, performic acid oxidation, end group analysis and amino acid analysis. The CD-spectrum indicated conformational changes compared to insulin. The biological activity was considerably reduced: fat cell assay 20%, blood sugar depression 30%.
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PMID:[B-chain shortening of matrix-bound insulin by pepsin, I:Preparation and properties of bovine des-pentapeptide(B26-30) insulin (suthor's transl)]. 24 Jul 71

In an open study dl-phenylalanine in doses from 75-200 mg/day was administered to 20 depressed patients for 20 days. Patients were classified according to the International Classification of Diseases (ICD). The AMP system, the Hamilton depression scale and the von Zerssen self rating questionnaire were used for documentation of psychopathological, neurologic and somatic changes. In addition a global clinical impression was agreed upon by experienced psychiatrists. At the end of the trial 12 patients (8 with complete, 4 with good response) could be discharged without any further treatment. 4 patients with partially untypical depressions experienced mild to moderate responses, whereas 4 patients did not respond at all to the phenylalanine administration. Depressive "core symptoms" as depressed mood, retardation and/or agitation were preferentially, anxiety and sleep disturbances moderately and hypochondriasis and compulsiveness were not influenced. It is concluded that dl-phenylalanine might have substantial antidepressant properties and that further more controlled investigations are warranted.
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PMID:Dl-phenylalanine in depressed patients: an open study. 33 27

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.
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PMID:Role of secretory events in modulating human neutrophil chemotaxis. 37 35

In a double-blind study, DL-phenylalanine (150--200 mg/24 h) or imipramine (150--200 mg/24 h) was administered to 40 depressed patients (20 patients in each group) for 30 days. Diagnoses were established according to the International Classification of Disease (ICD). The AMP system, the Hamilton Depression Scale and the Bf-S self rating questionnaire (von Zerssen et al., 1974) were used to document psychopathological, neurologic, and somatic changes. Twenty-seven patients (14 on imipramine, 13 on phenylalanine) completed the 30-day trial. No statistical difference could be found between these two drug treatment groups (Student's t-test) using the Hamilton Depression Scale and the Bf-S self rating questionnaire. Ratings for anxiety were significantly lower in the imipramine group on days 10 and 20, but not on day 30; in addition, sleep disturbances were more influenced by imipramine on days 1, 5, and 10, but not on days 20 and 30. Separate analysis of psychopathological syndromes as somatic depressive syndrome and retarded depressive syndrome did not show a group difference (0.05 level of significance using a two-way analysis of variance). It is concluded that DL-phenylalanine might have substantial antidepresant properties. However, certain methodological considerations still warrant a careful interpretation.
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PMID:DL-phenylalanine versus imipramine: a double-blind controlled study. 38

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.
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PMID:Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function. 44 62

Peptichemio (PTC) is a mixture of six synthetic peptides of m-L-phenylalanine mustard. It acts with both alkylating and antimetabolic effects, interfering with the synthesis of DNA, RNA, and proteins. PTC was administered iv to 18 previously untreated children with advanced neuroblastoma at a dose of 1-1.5 mg/kg/day for one to three cycles of 5-6 consecutive days each. Eleven of 12 patients (92%) experienced both objective and subjective improvement; complete remission was achieved in two of them. In spite of the high remission rate, the median duration of remission has been short (4 months) and the overall survival (median, 6 months) did not seem to be influenced by the use of PTC. The primary toxic effects were, in order of importance, bone marrow depression, phlebosclerosis, nausea and vomiting, and alopecia. Chronic use of PTC seems limited by two major factors: profound long-lasting thrombocytopenia and severe phlebosclerosis.
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PMID:Peptichemio in advanced neuroblastoma. 65 65

Twenty-three years after an injection of Thorotrast, profound depression of humoral and cellular immunity associated with extensive marrow plasmocytosis developed in a man aged 75 years. Twelve months of chemotherapy with L-phenylalanine mustard, resulted in hematologic remission. Radioautograph of his marrow showed signs of alpha-radiation; whole body counting revealed a significant thorium burden. One year after chemotherapy was stopped, and two years after initial presentation, aleukemic acute granulocytic leukemia led to his death. The role of thorium in the etiology of possibly two successive hematopoietic neoplasms is discussed.
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PMID:Nonsecretory plasma cell dyscrasia followed by acute granulocytic leukemia 25 years after Thorotrast administration. 81 53

Delta 9-Tetrahydrocannabinol (THC) elicited a dose-dependent (3.2-24 muM) response for form/movement, cellular growth and division in log growth phase and division-synchronized Tetrahymena pyriformis GL. Progressive dose-dependent action of THC on division delays in division-synchronized cell cultures was correlated with a concomitant reduction of division maxima and the percent of cells that completed division I. THC depressed the incorporation of 5-3H-uridine, 2-14C-thymidine and L-3-14C-phenylalanine into RNA, DNA and protein macromolecules respectively of division-synchronized Tetrahymena during division I. The depression of incorporation of 5-3H-uridine into nucleic acid macromolecules was correlated with a reduction of exogenous precursor in the cellular pool. The specific activity of radiolabeled mRNA and nascent polypeptides of polyribosomal fractions from synchronized cells was reduced by THC treatment. THC caused an inhibition of the incorporation of 5-3H-uridine into ribosomal RNA (17S and 25S RNA) and ribosomal precursor RNA (35S RNA) of synchronized cells.
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PMID:Action of delta 9-tetrahydrocannabinol on cell division and macromolecular synthesis in division-synchronized protozoa. 81 44

The mechanism of action of a carboxypeptidase inhibitor from potatoes has been probed by studying its interaction with derivatives of carboxypeptidase A containing modified residues at the active site. Arsanilazocarboxypeptidase A, a derivative containing a chromophore attached to tyrosine 248, exhibits a circular dichroism spectrum which is sensitive to the presence of ligands at the active site (Kagan, H.M., and Vallee, B.L. (1969), Biochemistry 8, 4223). Since the spectral change attending binding of the carboxypeptidase inhibitor to arsanilazocarboxypeptidase A is similar to that produced by small substrates and inhibitors, the enzyme-inhibitor interaction also involves the enzyme active site. Catalytic activity is not required for inhibitor binding. Complexes of the inhibitor with apocarboxypeptidase A anc carboxypeptidase A which was inactivated by treatment with the affinity label, N-bromoacetyl-N-methyl-L-phenylalanine, are demonstrated by gel filtration experiments. Morever, competitive binding studies reveal that the latter derivative, in which the binding pocket is presumably blocked by reagent, binds inhibitor nearly as strongly as does the native enzyme, and differences in free energy of association being only 0.4 kcal/mol of a total binding energy of - 11 kcal/mol. A model is proposed to account for both the tight binding of inhibitor to the N-bromoacetyl-N-methyl-L-phenylalanine derivative and the involvement of the active site of arsanilazocarboxypeptidase A. It is suggested that the inhibitor fits into a shallow depression at the active site of the enzyme but does not penetrate into the binding pocket.
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PMID:Carboxypeptidase inhibitor from potatoes. Interaction with derivatives of carboxypeptidase A. 93 26

There was rapid efflux of L-leucine, L-phenylalanine, and alpha-methyl-D-glucoside after infection of Salmonella typhimurium with the clear plaque mutant C1 of phage P22. The efflux was similar to that observed with cyanide or arsenate treatment except that there was partial recovery in the case of phage infection and almost complete recovery under the condition of lysogeny. There was no efflux after infection with the temperature-sensitive mutant ts16C1 at nonpermissive temperature. Superinfection of superinfection exclusion negative lysogen (sie A minus sie B minus) with C1 led to efflux, whereas the efflux was much less on superinfection of sie A+ Sie B+ lysogen. These results indicate that an effective injection process is enough to cause depression in the cellular transport processes.
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PMID:Transport in bacteriophage P22-infected Salmonella typhimurium. 109 32


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