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)

Cyclodextrin glycosyltransferase (EC 2.4.1.19) from Bacillus circulans has been purified, crystallized and analyzed by X-ray diffraction. The enzyme is monomeric. SDS/polyacrylamide gel electrophoresis gave an Mr of 73,600(+/- 1000), corresponding to 670(+/- 10) amino acid residues. The structure of the crystalline enzyme has been elucidated at a resolution of 3.4 A, using multiple isomorphous replacement and solvent flattening for phase determination. The resulting electron density map allowed tracing of the polypeptide chain; 664 residue positions have been assigned. The chain fold has been subdivided into five domains. The N-terminal domain forms a (beta alpha)8-barrel, which contains the second domain of about 55 residues as an insert after the third beta-strand. The three remaining domains form almost exclusively beta-pleated sheet structures and consist of about 90, 80 and 95 residues. The chain fold of the three N-terminal domains of 492 residues resembles closely the two known structures of alpha-amylases. This geometric similarity corresponds to the observed amino acid sequence homology. On the basis of the sequence homology with alpha-amylases, the active center can be located. The fourth domain has an immunoglobulin fold and is far away from the active center, while the fifth domain participates in the formation of the broad depression at the active center. Accordingly, the cyclodextrin glycosyltransferase chain fold can be considered as an alpha-amylase chain fold with two additional domains.
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PMID:Three-dimensional structure of cyclodextrin glycosyltransferase from Bacillus circulans at 3.4 A resolution. 253 Dec 28

The three-dimensional structure of the native unliganded form of the Leu/Ile/Val-binding protein (Mr = 36,700), an essential component of the high-affinity active transport system for the branched aliphatic amino acids in Escherichia coli, has been determined and further refined to a crystallographic R-factor of 0.17 at 2.4 A resolution. The entire structure consists of 2710 non-hydrogen atoms from the complete sequence of 344 residues and 121 ordered water molecules. Bond lengths and angle distances in the refined model have root-mean-square deviations from ideal values of 0.05 A and 0.10 A, respectively. The overall shape of the protein is a prolate ellipsoid with dimensions of 35 A x 40 A x 70 A. The protein consists of two distinct globular domains linked by three short peptide segments which, though widely separated in the sequence, are proximal in the tertiary structure and form the base of the deep cleft between the two domains. Although each domain is built from polypeptide segments located in both the amino (N) and the carboxy (C) terminal halves, both domains exhibit very similar supersecondary structures, consisting of a central beta-sheet of seven strands flanked on either side by two or three helices. The two domains are far apart from each other, leaving the cleft wide open by about 18 A. The cleft has a depth of about 15 A and a base of about 14 A x 16 A. Refining independently the structure of native Leu/Ile/Val-binding protein crystals soaked in a solution containing L-leucine at 2.8 A resolution (R-factor = 0.15), we have been able to locate and characterize an initial, major portion of the substrate-binding site of the Leu/Ile/Val-binding protein. The binding of the L-leucine substrate does not alter the native crystal structure, and the L-leucine is lodged in a crevice on the wall of the N-domain, which is in the inter-domain cleft. The L-leucine is held in place primarily by hydrogen-bonding of its alpha-ammonium and alpha-carboxylate groups with main-chain peptide units and hydroxyl side-chain groups; there are no salt-linkages. The charges on the leucine zwitterion are stabilized by hydrogen-bond dipoles. The side-chain of the L-leucine substrate lies in a depression lined with non-polar residues, including Leu77, which confers specificity to the site by stacking with the side-chain of the leucine substrate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Periplasmic binding protein structure and function. Refined X-ray structures of the leucine/isoleucine/valine-binding protein and its complex with leucine. 264 82

Strains of Rhizobium leguminosarum biovar viciae specifically make an abundant protein (Rhi) in free-living culture but not in bacteroids. Genes needed for Rhi synthesis are on a Sym plasmid and here we show that one of these genes, rhiA, is the structural gene that specifies this polypeptide. Transcription of rhiA requires a regulatory gene, rhiR, located close to rhiA and to nod genes involved in nodulation. Mutations in rhiA or rhiR do not appear to affect symbiotic nitrogen fixation. Transcription of rhiA is repressed in cells grown in the presence of the flavanone hesperetin or the flavone apigenin, both of which are potent inducers of transcription of nod genes. This was deduced from the use of rhiA-lacZ fusions; however, when the Rhi polypeptide was detected in SDS gels, there was no apparent difference in the intensity of its staining in extracts obtained from cells grown with or without these flavanoid nod gene inducer molecules. However, a mutation in a nodulation gene, nolR, also closely linked to the nod and rhi genes, caused a severe depression in the amount of Rhi (as seen on gels) that was made in cells grown in the presence of inducer flavanoids.
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PMID:Transcription of rhiA, a gene on a Rhizobium leguminosarum bv. viciae Sym plasmid, requires rhiR and is repressed by flavanoids that induce nod genes. 271 20

Follow-up using immunological monitoring of 233 acute peritonitis patients revealed various immunological shifts occurring at all levels postoperatively, with the therapeutic methods being common. Depression of specific immune response mechanisms (T- and B-systems) along with disinhibited phylogenetically old forms of the common biological phenomenon non-specific immunity (phagocytosis) is believed to reflect the common adaptive mechanism activated in emergencies in patients with peritonitis. With high levels, the toxin median molecular mass polypeptide in the complicated postoperative course, the immunological impairment is more pronounced, while restoration of immunological responsiveness of the organism becomes protracted, resulting in reduction of the cellular homeostasis and metabolism reserved. Application of the extracorporeal detoxication-hemosorption promotes adaptation buildup and makes immunity functioning optimal.
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PMID:[Immunologic reactivity and sorption detoxication of patients with acute peritonitis]. 281 95

Type beta transforming growth factor (TGF-beta) is a unique polypeptide that has been isolated from a number of different tissues and can induce the phenotypic transformation of non-neoplastic fibroblasts as measured by the stimulation of their growth in soft agar. Recently, TGF-beta has been demonstrated to exert profound inhibitory effects on T and B lymphocyte proliferation. In this study, the effects of TGF-beta on natural killer (NK) cell function were investigated. After 20 hr of culture in the presence of TGF-beta, the NK activity of peripheral blood lymphocytes (PBL) was significantly reduced compared with PBL cultured in medium alone. Similarly, TGF-beta produced a significant depression in the cytolytic activity of highly enriched large granular lymphocytes (LGL). This effect of TGF-beta appeared to be mediated directly on the effector cells, because cultivation of the K562 target cells in TGF-beta did not affect target cell susceptibility to lysis. Binding studies with 125I-TGF-beta indicated that LGL possess approximately 1400 high-affinity (Kd = 1PM) receptors/cell, which represents a considerably higher affinity receptor for TGF-beta than that found on fibroblasts. Culturing of PBL and LGL in TGF-beta resulted in a marked blunting of the boosting of NK cytolysis by interferon-alpha but not by interleukin 2, which suggested that TGF-beta may down-regulate interferon-alpha receptors on NK cells. These results, indicate that in addition to inhibitory effects on T and B cells, TGF-beta also inhibits NK cell function. Although the in vivo role of TGF-beta is presently undefined, it may be an important immunoregulatory protein that has a negative influence on lymphocyte activation.
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PMID:Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. 287 Nov 7

Concentrations of the amines and amine metabolites dopamine (DA), noradrenaline (NA), adrenaline (A), serotonin (5-HT), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and of the peptides, vasopressin (AVP), vasoactive intestinal polypeptide (VIP), thyrotropin releasing hormone (TRH) and cholecystokinin (CCK) were measured in lumbar cerebrospinal fluid (CSF) in patients with depression and compared with that of controls. Diagnostic classifications were performed according to ICD-9 and the Newcastle Rating Scales for Depression. The severity of depression was measured by Bech-Rafaelsen melancholia scale. Significantly decreased concentrations of CSF-A and AVP were found in as well endogenous as in non-endogenous depression, whereas reduced levels of CSF-VIP were found only in the non-endogenous group. CSF-5-HT and DA were significantly increased in endogenously depressed patients. In these studies patients with non-endogenous depression were not included. No relationship between severity of depression and concentrations of neurotransmitters was found. For most of the neurotransmitters no correlation between concentrations measured at the lumbar and at the ventricular level seems to exist. This finding indicates that measurements on CSF collected from the lumbar sack not necessarily are indicative for concentrations measured at more central levels. Although several transmitter systems most likely are disturbed in depression, results from studies on lumbar CSF should be interpreted with precaution, until further information about origin and distribution of neurotransmitters in CSF has been obtained.
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PMID:Do concentrations of neurotransmitters in lumbar CSF reflect cerebral dysfunction in depression? 290 16

Effects of alpha-human atrial natriuretic polypeptide (alpha-HANP) on electrical and mechanical properties of smooth muscle cells of the guinea-pig and rabbit renal arteries and of the guinea-pig mesenteric artery were investigated. alpha-HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea-pig and rabbit renal arteries. In the guinea-pig mesenteric and renal arteries, alpha-HANP (up to 10 nM) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) of excitatory junction potentials nor on action potentials. In the guinea-pig renal artery, alpha-HANP (up to 10 nM) had no effect on the depolarization induced by noradrenaline (NA) (up to 10 microM) but markedly inhibited NA-induced contraction. alpha-HANP (10 nM) slightly inhibited the K-induced contraction. In the rabbit renal artery, alpha-HANP (10 nM) inhibited the NA-induced contraction and to a lesser extent the K-induced contraction. In the rabbit renal artery, the effects of alpha-HANP on the release of Ca from the cellular storage by two applications of NA, and its re-storage, were investigated in Ca-free solution containing 2 mM-EGTA. When 5 nM-alpha-HANP was applied before and during the first application of 0.5 microM-NA, the contraction was markedly inhibited but the contraction to a second application of 10 microM-NA was potentiated. If the first dose of NA was 10 microM the effect was very small. Under the same experimental procedures, nitroglycerine (10 microM) showed almost the same effects as alpha-HANP on the NA-induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca-free solution, alpha-HANP (5 nM) and nitroglycerine (10 microM) inhibited both contractions to the same extent. In the rabbit renal artery, applications of alpha-HANP or nitroglycerine increased the amount of guanosine 3',5'-phosphate (cyclic GMP) in a dose-dependent manner. However, a much higher concentration of nitroglycerine was required (2 X 10(3) times). In the rabbit renal artery, hydrolysis of phosphatidyl inositol 4,5-bisphosphate (PI-P2) activated by 0.5 microM-NA was inhibited by alpha-HANP, in a dose-dependent manner, but activation by 10 microM-NA was not inhibited by alpha-HANP (up to 100 nM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism of vasodilation induced by alpha-human atrial natriuretic polypeptide in rabbit and guinea-pig renal arteries. 302 29

Ehrlichia risticii has a close antigenic relationship to E. sennetsu. Sera of ponies experimentally infected with E. risticii, the etiologic agent of Potomac horse fever, consistently reacted with E. sennetsu, a human pathogen, in indirect fluorescent-antibody (IFA) testing, while human E. sennetsu convalescent serum reacted with E. risticii by IFA testing and immunoferritin labeling of cells infected in vitro. Two ponies injected intravenously with live E. sennetsu did no develop clinical illness. Subsequent injection with live E. sennetsu did not develop clinical illness. Subsequent injection with live E. risticii also did not induce any disease, in contrast to two control ponies given E. risticii without prior exposure to E. sennetsu. Both controls developed fever, anorexia, depression, dehydration, and diarrhea, which are typical clinical signs of Potomac horse fever, and had characteristic lesions of enteritis and lymph node histiocytosis at postmortem examination. E. sennetsu-exposed ponies had normal gastrointestinal morphologies and lymph node hyperplasia. Ponies primed with E. sennetsu before E. risticii challenge developed high titers of immunoglobulin G antibody which reacted against both E. sennetsu and E. risticii antigens by IFA testing. The most prominent antigenic polypeptide in Western (immuno-) blot analysis of sera collected from ponies primed with E. sennetsu before subsequent challenge with E. risticii was present in lysates of both Ehrlichia species and had an apparent molecular mass of 44 kilodaltons. This band was not prominent in Western blots performed with sera of ponies injected with E. risticii alone. Thus, injection of E. sennetsu protects ponies from clinical and pathological manifestations of the disease induced by injection with E. risticii. Immunologic cross-reactivity of the two organisms with IFA testing and strong immunologic recognition by ponies of the 44-kilodalton antigen common to the two organisms may be related to the development of protective immunity against E. risticii.
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PMID:Clinical, histopathological, and immunological responses of ponies to Ehrlichia sennetsu and subsequent Ehrlichia risticii challenge. 316 93

The cardiotoxic actions of Kenyan green mamba (Dendroaspis angusticeps) venom have been investigated using primary myocardial cell cultures isolated from neonatal rat hearts. The cardiotoxic actions of the whole venom and its fractionated components were evaluated on the basis of leakage of lactate dehydrogenase (LDH), changes in morphology, cell membrane lysis, decreases in viability and inhibition of spontaneous beating activity. The whole venom caused time- and concentration-dependent arrest of myocardial contraction, leakage of LDH, extensive disruption of cell monolayer, and decreases in viability. The venom was separated into 6 (DaI to DaVI) fractions by gel permeation chromatography on Sephadex G-50. Spontaneous beating activity was abolished by DaI to DaVI at high concentrations, while at lower doses they induced progressive depression of beating frequency after a 3-h treatment period. DaI to DaIV caused significant leakage of LDH, morphological damage, and decreases in viability after a 6-h incubation period. The most cardiotoxic fraction (DaIV), which also contains about 54% of the total protein of the whole venom, was fractionated into 18 polypeptides (Da1 to Da18) by ion exchange chromatography on Bio-Rex 70. On the basis of their ability to abolish myocardial contractility, release LDH, alter cellular structure, lyse cell membranes and reduce viability, the 18 fractions have been divided into 4 arbitrary subgroups of cytotoxins: cardiotoxins, Da1 to Da3; cardiotoxin-like polypeptides, Da4 to Da12, Da14; less active membrane lytic polypeptides, Da13, Da15 to Da17; and membrane lytic polypeptide, Da18. Marked synergistic cell membrane lysis occurred in myocardial cell cultures treated simultaneously with 2 cardiotoxin-like polypeptides, Da7 and Da11. It is suggested that the additive and synergistic cardiotoxic effects of high molecular weight cytotoxic proteins (DaI to DaIII), very low molecular weight cholinomimetic substances (DaV to DaVI) and the 4 subgroups of cardiotoxins may directly contribute to the pronounced cardiovascular problems observed in victims of green mamba bites.
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PMID:Cardiotoxicity of Kenyan green mamba (Dendroaspis angusticeps) venom and its fractionated components in primary cultures of rat myocardial cells. 318 32

Subjecting primary cultures of bovine brain microvessel endothelial cells to thermal stress (heat shock) results in: (1) an inhibition of further tight junction assembly, (2) the disappearance and/or disassembly of tight junctions, (3) a 30-fold increase in the number of plasmic fracture (PF)-face intramembrane particles, and (4) the new and/or enhanced synthesis of at least three heat-shock polypeptides (HSPs) with molecular masses of approximately 100,000, 90,000 and 70,000. Endothelial cells which are heat-shocked and allowed to recover at 37 degrees C exhibit, within the first 2 h, a marked depression in the synthesis of HSPs and the new and/or enhanced synthesis of a 47,000 dalton "recovery" polypeptide. In later periods of recovery (2-4 h), the synthesis of this polypeptide is even more pronounced and is accompanied by the new and/or enhanced synthesis of a polypeptide(s) with a molecular mass of 35 to 37,000. The appearance of these "recovery protein(s)" in the endothelial cells is concomitant with a decrease in the number of PF-face intramembrane particles and the resumption of tight junction assembly. Results of this study suggest that some of the HSPs synthesized by thermally-stressed cultures of brain endothelial cells may activate or be directly involved in a mechanism(s) to ensure survival of these cells by decreasing membrane fluidity and stabilizing the plasma membrane of these cells. Moreover, our results also suggest that the recovery of these cells from the stress of heat shock is accompanied by the synthesis of "recovery" proteins which, in some manner, may be directly involved in, or necessary for, rapidly reversing the membrane-stabilizing effect of heat shock by promoting membrane fluidity and the apparent amplified synthesis and assembly and/or reassembly of tight junctions.
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PMID:The effect of heat shock on primary cultures of brain capillary endothelium: inhibition of assembly of zonulae occludentes and the synthesis of heat-shock proteins. 339 88


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