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)

The branched-chain protein amino acids isoleucine, valine and leucine can provide precursors for synthesis of complex polyketide secondary metabolites in streptomycetes; therefore the regulation of their own synthesis is of interest. DNA sequences upstream of ilvBNC, ilvD, leuA, leuB, ilvE and leuCD in Streptomyces coelicolor A3(2) have been obtained in this laboratory or as part of the S. coelicolor genome sequencing project. Upstream of ilvB and leuA, typical features of classical attenuator systems can be discerned, in particular hypothetical short ORFs with runs of Ile/Val/Leu and Leu codons, respectively. No such features are apparent upstream of other genes or gene clusters present. All five upstream regions were fused to xylE (encoding catechol dioxygenase, CO) as a reporter gene in the SCP2*-based low-copy-number vector pIJ2839. All wild-type regions showed strong depression of CO activity in the presence of all three branched-chain amino acids whether or not the attenuation features were present. By site-directed mutagenesis, the Ile/Val/Leu and Leu triplets in the putative attenuator peptides for ilvB and leuA were replaced by ones for other amino acids. In the case of ilvB, this had no effect at all; for leuA, the wild-type regulatory phenotype persisted in at least some experiments. It was concluded that (i) an unknown regulatory mechanism must be operating in the ilv/leu system of S. coelicolor A3(2) in place of classical attenuation; and (ii) it is unsafe to infer the functioning of a regulatory mechanism from sequence homologies alone.
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PMID:End-product control of expression of branched-chain amino acid biosynthesis genes in Streptomyces coelicolor A3(2): paradoxical relationships between DNA sequence and regulatory phenotype. 1051 90

The influence of an increase or a decrease in the stimulation frequency on tension development during a tetanus was studied in motor units of the rat medial gastrocnemius muscle. These effects were tested in one tetanus evoked at two frequencies of stimulation, a lower immediately followed by a higher one or the reverse. For all fast motor units it was observed that after the first part of a tetanus at a lower frequency of stimulation the tension of the following part, of the better fused contraction, was depressed. This effect was called a tetanic depression. When the lower stimulation frequency was followed by the higher one, the depression was visible in some motor units only whereas in the remaining units a potentiation of the second part of the tetanus was visible. The tetanic depression was larger in fast resistant than in fast fatigable motor units. In slow motor units tetanic depression was not observed. The tetanic depression is a phenomenon which can influence the production of contractile tension by fast motor units.
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PMID:Tetanic depression: a phenomenon influencing the production of tension in fast-twitch motor units in rat medial gastrocnemius. 1151 9

Selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenergic reuptake inhibitors (SNaRIs) and noradrenergic and specific serotoninergic antidepressant (NaSSA) are widely used in the treatment of depression. An increase in antidepressant intoxications led to the development of reliable analytical methods for their analysis. A new determination procedure for these compounds (milnacipran, venlafaxine, desmethylvenlafaxine, mirtazapine, desmethylmirtazapine, citalopram, desmethylcitalopram, fluvoxamine, paroxetine, sertraline and fluoxetine) was developed by micellar electrokinetic capillary chromatography (MEKC) with diode array detection (DAD). Separation and determination were optimised on an uncoated fused-silica capillary (600 mm, 75 microm I.D.). The migration buffer consisted of 20 mM sodium borate, pH 8.55, with 20 mM SDS and 15% isopropanol, at an operating voltage of 25 kV. The column temperature was maintained at 40 degrees C. Injection in the capillary was performed in the hydrodynamic mode (0.5 p.s.i., 15 s). In these conditions, the migration time of the antidepressants was less than 11 min. In most cases, calibration curves were established for 30 - 2000 ng/ml (r > 0.995). The limit of detection and the limit of quantification were ranged between 10 and 20 and between 20 and 30 ng/ml, respectively, for all the molecules. This method allowed the determination of some of these compounds in biological fluids (blood, urine) in post-mortem cases. Samples (1 ml) were extracted with diethyl ether (5 ml) at pH 9.6 and reconstituted in diluted migration buffer. Similar results were obtained by a HPLC-DAD determination, performed as a reference method. These results suggest that this MEKC method can be useful for the determination of new antidepressants in post-mortem cases.
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PMID:Separation of new antidepressants and their metabolites by micellar electrokinetic capillary chromatography. 1201 66

The effects of lyotropic (swelling) anions (Cl(-), Br(-), NO(3)(-) and I(-)) on contractile properties of fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles were investigated in vitro at 20 degrees C and 35 degrees C. Isolated muscles bathed in anionic Tyrode solution were stimulated directly and isometric single twitches and fused tetanic contractions were recorded. In a Cl(-)Tyrode solution a decrease of the bathing temperature led to a cold potentiation of the twitch tension (P(t)) in EDL muscles, however, to a cold depression in SOL muscles, in both muscles combined with a prolongation of contraction (CT) and half relaxation (HRT) times. The extent and order of the potentiating effect of lyotropic anions on the P(t), CT and HRT in EDL and SOL were quite similar and increased in the order: Cl(-)< Br(-)< NO(3)(-)< I(-). Since the lyotropic anions did not influence tetanic tensions, the twitch-tetanus ratio (TTR) was increased in NO(3)(-) and I(-)solutions. All effects of the anions were rapidly and completely reversed in both muscles when the test solution was replaced by the normal one. The temperature decrease caused no significant alteration in the potentiation capacity of the anions or in the kinetics of their action and reversibility.
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PMID:Actions of lyotropic anions on the mechanical properties of fast and slow twitch rat muscles at different temperatures. 1262 17

Species status is stated for Hyalomma anatolicum and H. excavatum, based on numerous material from the territory of their distribution. The differentiation of species is recovered for all stages of the life cycle. Diagnosis of Hyalomma anatolicum. Female: small tick--length of scutum commonly less than 2 mm; width of scutum commonly less than 1.9 mm; color of scutum, gnathosoma and coxae light, yellowish- or reddish-brown; whitish enameled pigment on scutum absent; posterolateral ledges of scutum weakly expressed or absent; cervical and lateral grooves more shallow (than in H. excavatum) (fig. 1); setae of scutum, alloscutum, sternal setae and ventromedian setae of second article of palpae more tapering to the apex, narrow rounded or acute (fig. 2, 1, 2, 5, 8). Male: small tick--length of conscutum, as a rule, less than 4 mm; width of scutum, as a rule, less than 2.3 mm; shape of conscutum marrow oval (fig. 3), widest in the midlevel; color of conscutum, anal shields, gnathosoma and coxae light, yellowish- or reddish-brown; whitish enameled pigment on conscutum absent; caudal depression with less dense and more large punctuations (than in H. excavatum); ridges lateral to caudal field less high and sharp (than in H. excavatum); posteromedian groove separated from parma by contiguous punctuations or smooth non high area; setae of conscutum conus-like, more sharpening (fig. 4, 1-3); posterior dorsal margin of gnathosoma straight or slightly concave (fig. 4, 8); segments of leg IV not swallowed. Nymph: large tick (see description). Scutum more narrow. Dorsal tale of spiracular plates clear expressed, marginal perforations distant from margin of spiracular plates at the base of tale (fig. 5, 3); anterolateral side of basis capituli approximately equal to half of gnathosoma width; ventrally lateral projections of gnathosoma situated in posterior half of capitulum base (fig. 5, 4, 5). Hypostome more longer and narrow (fig. 5, 5). Larva: large tick (see description). Diagnosis of Hyalomma excavatum. Female: large tick--length of scutum commonly more than 2 mm; width of scutum commonly more than 1.9 mm; color of scutum, gnathosoma and coxae dark, reddish- or black-brown; whitish enameled pigment commonly present; posterolateral ledges of scutum clearly expressed; cervical and lateral grooves more dipper (than in H. anatolicum) (fig. 7). Setae of scutum, alloscutum, sternal setae and ventromedian setae of second article of palpae more stick-like, more widely obtuse (fig. 8, 1-5). Male: large tick--length of conscutum more than 4 mm; width of scutum more than 2.3 mm; shape of conscutum wide oval (fig. 9), widest in posterior half of length; color of conscutum, anal shields, gnathosoma and coxae dark, reddish- or black-brown; whitish enameled pigment often present; caudal depression with more dense and more small punctuations (than in H. anatolicum); ridges lateral to caudal field more high and sharp (than in H. anatolicum); posteromedian groove separated from parma by strong elevations fused with paraparmal festoons; setae of conscutum more obtuse, often stick-like (fig. 10, 1, 2); posterior dorsal margin of gnathosoma straight or lightly concave. (fig. 10, 3); segments of leg IV swallowed. Nymph: small tick (see description). Scutum more wide. Dorsal tale of spiracular plates weakly expressed, marginal perforations not distant from margin of spiracular plates at the base of tale (fig. 11, 3); anterolateral side of basis capituli clearly shorter than half of gnathosoma width; ventrally lateral projections situated in the middle of or anterior half of capitulum base (fig. 11, 4, 5). Hypostome more shorter and wider (fig. 5, 5). Larva: small tick (see description). Established taxonomical independence of H. anatolicum and H. excavatum is confirmed by several criteria: external morphology (see diagnoses); morphometrical data (see diagnoses and fig. 12, 13); size inversion: larva and nymph of H. anatolicum are large, but females and males are small; while H. excavatum vise versa--larva and nymph are small, but adults--large; host specialization of immature stages: larvae and nymphs of H. anatolicum, as rule, parasitize larger mammals (cattle, camels), while immature stages of H. excavatum parasitize smaller mammals (rodents, hares); presence of sympatry areas: almost entire area of H. excavatum include in area of H. anatolicum and cattle help to mix its populations.
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PMID:[Differentiation of closely related species Hyalomma anatolicum and H. excavatum (Acari: Ixodidae) based on a study of all life cycle stages, throughout entire geographical range]. 1451 5

Patients having a depressive disorder vary widely in their therapeutic responsiveness to a selective serotonin reuptake inhibitor (SSRI), but there are no clinical predictors of treatment outcome. Studies using dichotic listening, electrophysiologic and neuroimaging measures suggest that pretreatment differences among depressed patients in functional brain asymmetry are related to responsiveness to antidepressants. Two new studies replicate differences in dichotic listening asymmetry between fluoxetine responders and nonresponders, and demonstrate the importance of gender in this context. Right-handed outpatients who met DSM-IV criteria for major depression, dysthymia, or depression not otherwise specified were tested on dichotic fused-words and complex tones tests before completing 12 weeks of fluoxetine treatment. Perceptual asymmetry (PA) scores were compared for 75 patients (38 women) who responded to treatment and 39 patients (14 women) who were nonresponders. Normative data were also obtained for 101 healthy adults (61 women). Patients who responded to fluoxetine differed from nonresponders and healthy adults in favoring left- over right-hemisphere processing of dichotic stimuli, and this difference was dependent on gender and test. Heightened left-hemisphere advantage for dichotic words in responders was present among women but not men, whereas reduced right-hemisphere advantage for dichotic tones in responders was present among men but not women. Pretreatment PA was also predictive of change in depression severity following treatment. Responder vs nonresponder differences for verbal dichotic listening in women and nonverbal dichotic listening in men are discussed in terms of differences in cognitive function, hemispheric organization, and neurotransmitter function.
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PMID:Dichotic listening tests of functional brain asymmetry predict response to fluoxetine in depressed women and men. 1523 92

General anesthetics have marked effects on synaptic transmission, but the mechanisms of their presynaptic actions are unclear. We used quantitative laser-scanning fluorescence microscopy to analyze the effects of the volatile anesthetic isoflurane on synaptic vesicle cycling in cultured neonatal rat hippocampal neurons monitored using either transfection of a pH-sensitive form of green fluorescent protein fused to the luminal domain of VAMP (vesicle-associated membrane protein), (synapto-pHluorin) or vesicle loading with the fluorescent dye FM 1-43. Isoflurane reversibly inhibited action potential-evoked exocytosis over a range of concentrations, with little effect on vesicle pool size. In contrast, exocytosis evoked by depolarization in response to an elevated extracellular concentration of KCl, which is insensitive to the selective Na+ channel blocker tetrodotoxin, was relatively insensitive to isoflurane. Inhibition of exocytosis by isoflurane was resistant to bicuculline, indicating that this presynaptic effect is not caused by the well known GABA(A) receptor modulation by volatile anesthetics. Depression of exocytosis was mimicked by a reduction in stimulus frequency, suggesting a reduction in action potential initiation, conduction, or coupling to Ca2+ channel activation. There was no evidence for a direct effect on endocytosis. The effects of isoflurane on synaptic transmission are thus caused primarily by inhibition of action potential-evoked synaptic vesicle exocytosis at a site upstream of Ca2+ entry and exocytosis, possibly as a result of Na+ channel blockade and/or K+ channel activation, with the possibility of lesser contributions from Ca2+ channel blockade and/or soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated vesicle fusion.
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PMID:The general anesthetic isoflurane depresses synaptic vesicle exocytosis. 1572 62

Sixty-six parents of adolescents (mean age, 14.8 years), who attended special education classes and who were diagnosed as having attention deficit and hyperactivity disorder/learning disabilities (ADHD/LD), were interviewed. The comorbidity of the ADHD group included emotional lability and/or depression, 70%; oppositional defiant disorder (ODD), 67%; obsessive-compulsive disorder (OCD), 44%; addiction to buying, 44%; and aggressiveness, 62%. Twenty-one percent were either involved in the past or presently using drugs. Nine percent had attempted suicide. According to their parents, the main characteristic of these adolescents was low self-image. Parents enumerated five negative characteristics: impulsiveness; nervousness; angered easily ('short fused'); aggressiveness with cursing and outbursts; and impaired sociability with impoliteness.
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PMID:Attention deficit and hyperactivity disorder/learning disabilities (ADHD/LD): parental characterization and perception. 1579 57

The phosphorylation of ionotropic glutamate receptors (iGluRs) by protein kinases plays a crucial role in synaptic plasticity. In the cerebellum, protein kinase C (PKC) activation is required for the induction of long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Although delta2 glutamate receptors (GluRdelta2), expressed predominantly in Purkinje cells, are essential for cerebellar LTD, little is known about the mechanism by which GluRdelta2 participates in LTD or its relationship with PKC activation pathways. We found that a PKC activator, phorbol ester, induced postsynaptic LTD in Purkinje cells in mouse cerebellar slice preparations without significantly changing the presynaptic properties. Under this condition, the GluRdelta2 prepared from the cerebellar slices was significantly phosphorylated. Indeed, the C-terminus of the GluRdelta2 fused with glutathione-S-transferase (GST) was directly phosphorylated by purified PKC at a specific serine residue. In addition, two-dimensional phosphopeptide mapping analysis indicated that the major phosphorylation site of the GST-fusion protein containing the C-terminus of GluRdelta2 was identical to that of GluRdelta2 prepared from cerebellar slices. Therefore, GluRdelta2 is phosphorylated by PKC in vitro and by an LTD-inducing stimulus in slice preparations. Because this region of GluRdelta2 is known to associate with certain intracellular molecules, the PKC phosphorylation status of the C-terminus of GluRdelta2 may be involved in new signaling pathways during LTD.
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PMID:Induction of long-term depression and phosphorylation of the delta2 glutamate receptor by protein kinase C in cerebellar slices. 1619 24

The glutamate receptor delta2 subunit (GluRdelta2) is selectively expressed in cerebellar Purkinje neurons (PNs) and is involved in the long-term depression (LTD). However, little is known about the mechanism of its action. Acute expression of the wild-type GluRdelta2 in the GluRdelta2-deficient PN rescued the induction of LTD, suggesting the direct role of GluRdelta2 in LTD. To identify the critical region of GluRdelta2 necessary for LTD, we constructed and expressed various mutant GluRdelta2 proteins in the GluRdelta2-deficient PNs. The mutant GluRdelta2 possessing the membrane-proximal 21 aa residues in the C-terminal cytoplasmic region rescued the induction of LTD, whereas the mutant with membrane-proximal 13 aa failed. In addition, overexpression of 865 approximately 871 aa of GluRdelta2 (corresponding to membrane-proximal 14-20 aa) fused to EGFP (enhanced green fluorescent protein) suppressed LTD in a wild-type PN. These results suggest that 865 approximately 871 aa of GluRdelta2 play an essential role in LTD. We next identified protein interacting with C kinase 1 (PICK1) as a molecule interacting with the membrane-proximal C-terminal region of GluRdelta2 by yeast two-hybrid screening. PICK1 plays an essential role in LTD. It colocalized with GluRdelta2 at spines of PNs, and immunoprecipitation assays showed that GluRdelta2 bound to PICK1 mainly through 865-871 aa. These results indicate that 865-871 aa of GluRdelta2 are essential for both LTD and interaction with PICK1, and suggest that interaction between GluRdelta2 and PICK1 might be critical for the induction of LTD.
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PMID:Membrane-proximal region of glutamate receptor delta2 subunit is critical for long-term depression and interaction with protein interacting with C kinase 1 in a cerebellar Purkinje neuron. 1659 15


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