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)

Data on prenatal, labor and delivery, and postnatal medication exposure to neonates were collected. During an 11-week period, 100 neonates consecutively admitted to a hospital were studied. The pharmacist obtained a social and medication history from the mothers and reviewed maternal anesthesia records and the charts of the neonates. Fifteen definite and possible adverse medication reactions were detected in 13 neonates. The median number of different medications ingested prenatally was 4.7. The four most commonly ingested prenatal medications were vitamins (97%), iron preparations (90%), headache/pain/arthritis medications (68%) and antinausea/vomiting medications (40%). The most commonly used medications during labor and delivery were oxytocin (73%), meperidine (33%) and promazine (25%). The use of strong narcotics during this period produced neonatal respiratory depression in some cases. The four most commonly prescribed postnatal medications were vitamin K1 (100%), gentamicin (10%), ampicillin (8%) and Poly-Vi-Sol (6%). The maternal interview indicated that most mothers were unaware of the influence that many medications can play upon the fetus. It is recommended that the pharmacist conduct a maternal medication interview prior to labor and delivery.
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PMID:Neonatal medication surveillance by the pharmacist. 87 83

Poly(A+) mRNA was extracted from the post-mortem brain of schizophrenics (9 subjects), unipolar depressives (5 subjects) and controls (10 subjects) and used to direct the in vitro translation of radiolabelled protein in a cell-free reticulocyte-lysate system. Protein species were analysed on two-dimensional gels. Over 200 products were detected and, from these, 74 well-resolved species were chosen for further analysis. The optical density of each product was quantified by image analysis and normalised with respect to overall gel intensity. It was found that 7 novel, uncharacterised protein species, ranging from molecular weights (Mr) 17 kDa to 38 kDa and apparent isoelectric points (pI) 5.7-7.1, changed significantly in intensity in the psychotic groups compared to controls. One species changed only in the schizophrenia group (Mr = 26 kDa, pI = 5.8, 18% of control intensity) and 3 changed only in the depressive group (Mr = 38 kDa, pI = 6.2, 540% of control; Mr = 34 kDa, pI = 6.2, 6% of control; Mr = 17 kDa, pI = 5.7, 238% of control). Three further protein species were common to both psychotic groups (one species decreased in both schizophrenia and depression, Mr = 33 kDa, pI = 5.8; two species showed opposing intensity changes, decreasing in schizophrenia and increasing in depression, Mr = 35 kDa, pI = 7.1; Mr = 23 kDa, pI = 6.1). None of these changes was a function of post-mortem delay or mode of death. It is quite likely that such protein species reflect the abundance of specific mRNAs and target gene systems associated with the disease state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in brain gene expression in schizophrenic and depressed patients. 134 40

We have performed Phase I trials of two synthetic double-stranded polyribonucleotide complexes--poly(I,C)-LC, a complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxymethylcellulose, and poly(I,C)-L, which lacks carboxymethylcellulose--in patients with advanced cancer. With poly(I,C)-LC, several treatment schedules were investigated in an attempt to decrease toxicity and maximize interferon (IFN) induction. The best tolerated was an alternate-day schedule, with gradual dose escalation. Daily short infusions and continuous (24-h) infusions were tolerated less well. Maximum tolerated doses varied over a several hundredfold dose range. Toxicity consisted of fever, rigors, hypotension, and blood count depression. Two patients treated with poly(I,C)-L developed systemic allergic reactions, and antibodies to poly(I,C)-L and its components were detected in the serum of some patients treated with both compounds. IFN-alpha was induced in most patients at serum levels similar to those achieved after intramuscular administration of human IFN-alpha. Of 32 patients, one with renal cell carcinoma showed partial tumor regression. Poly(I,C) complexes are effective IFN inducers in humans, but their toxicity limits their use in cancer patients.
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PMID:Phase I trials of poly(I,C) complexes in advanced cancer. 241 62

Treatment of mice with the interferon inducer polyriboinosinic acid X polyribocytidylic acid [poly(IC)] results in the depression of several hepatic proteins. In this study we examined synthesis and degradation of the proteins of liver cell organelles in mice treated with poly(IC). Effects on synthesis were determined by using [14C]- and L-[3H]leucine incorporation into control and poly(IC)-treated mice, respectively. At selected times after poly(IC) treatment the 3H/14C ratio was established for preparations of nuclei, mitochondria, lysosomes, smooth endoplasmic reticulum, rough endoplasmic reticulum, and 105,000g supernatant (cytosol). Time-dependent alterations in de novo protein synthesis were greatest in lysosomal and rough endoplasmic reticular fractions; both were depressed 9 h after treatment. The effects of poly(IC) on protein degradation were determined with [14C]bicarbonate. Poly(IC) treatment decreased the time required for disappearance of 50% of 14C-labeled protein (t1/2) of smooth and rough endoplasmic reticula. Examination of endoplasmic reticulum marker enzymes showed depression of cytochromes P-450 and b5 from 9 h onward after poly(IC) administration. Tyrosine aminotransferase activity was elevated 6 h after treatment with poly(IC), and then depressed after 9 h. The other organelle marker enzymes were not affected significantly. We conclude that poly(IC) decreases the content of proteins of the hepatic endoplasmic reticulum, including certain cytochrome P-450 isozymes, by decreasing rates of protein synthesis and increasing rates of protein degradation.
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PMID:Depression of cytochrome P-450 and alterations of protein metabolism in mice treated with the interferon inducer polyriboinosinic acid X polyribocytidylic acid. 243 May 24

The elevation of culture temperatures of C6 cells that were persistently infected with the Lec strain of the subacute sclerosing panencephalitis (SSPE) virus (C6/SSPE) resulted in immediate selective inhibition of membrane (M) protein synthesis. This phenomenon was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total cytoplasmic lysates and immunoprecipitation with monoclonal antibody against the M protein in short-time labeling experiments. The synthesis of various viral mRNAs in the presence of actinomycin D decreased gradually at similar rates after a shift to 39 degrees C. No specific disappearance of the mRNA coding for the M protein was observed when viral RNAs isolated from the infected cells were compared before and after a shift up by Northern blot analysis. Results of pulse-chase experiments did not show any significant difference in M protein stability between 35 and 39 degrees C. This rapid block of M protein synthesis was observed not only in Vero cells that were lytically infected with plaque-purified clones from the Lec strain, clones isolated from C6/SSPE cells and the standard Edmonston strain of measles virus but also in CV1, MA160, and HeLa cells that were lytically infected with the Edmonston strain. Poly(A)+ RNAs that were extracted from C6/SSPE cells before and after a shift to 39 degrees C produced detectable phospho, nucleocapsid, and M proteins in cell-free translation systems at 32 degrees C. Even higher incubation temperatures did not demonstrate the selective depression of M protein synthesis described above in vitro. All these data indicate that M protein synthesis of measles virus is selectively suppressed at elevated temperatures because of an inability of the translation apparatus to interact with the M protein-encoded mRNA.
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PMID:Selective inhibition of translation of the mRNA coding for measles virus membrane protein at elevated temperatures. 380 92

Poly(I,C)-LC was administered in low (1 mg/m2) and intermediate (4 mg/m2) doses to cancer patients by intramuscular injection or intravenous infusion to evaluate the immunomodulatory effects. Natural killer cell (NK) activity was elevated slightly at the low dose and remained unchanged overall, but some depression was observed at the 4 mg/m2 intravenous dose. Monocyte function was elevated in all groups of patients, as was the interferon-induced enzyme 2'5'-oligo-A synthetase. These increases were observed at the 1 mg/m2 intramuscular dose, despite a lack of detectable circulating serum interferon (IFN). In regard to cell surface markers, poly(I,C)-LC induced an increase in OKT10-positive cells and a small but consistent trend toward increases in the ratio of Leu-3/Leu-2-positive cells. Lymphocyte proliferation in response to concanavalin A was depressed by poly(I,C)-LC administration. Although an optimum immunomodulatory dose and schedule was not determined, the data indicate that low doses produce significant changes in immune function and that induction of detectable levels of circulating interferon is not required for poly(I,C)-LC to have biological effects.
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PMID:Immunomodulatory effects of poly(I,C)-LC in cancer patients. 408 34

1. An electrophysiological and morphological study of sprouting and regeneration of motor nerves has been performed in the dually innervated pectoral muscle of Xenopus laevis. 2. Section of one of the nerves induced axon sprouting in the intact nerve. Synapse formation by the sprouting axons was slow since the intact nerve took more than 3 months to increase its field of innervation by 70%. The rate of axon regeneration was faster than that of axon sprouting since the cut nerve reinnervated its former territory in less than 1 month. 3. At early stages of synapse formation the sprouted or regenerated endings were poorly branched but any terminal branches were, as a rule, longer than normal. Signs of degeneration and replacement of endings have been observed. 4. Low levels of transmitter release persisted for several months in newly formed endings. This depression was more pronounced at the endings formed outside the normal field of innervation of the nerve. 5. Poly-innervated muscle fibres have been observed during reinnervation by regenerated or sprouted axons. Their number decreases gradually in the months that follow the beginning of reinnervation. Synaptic efficacy was lower at poly than at mono-innervated muscle fibres. At doubly innervated spots and at separated spots on the same fibre average end-plate potential (e.p.p.) amplitude was 1/3 and 2/3 respectively of that recorded at singly innervated fibres. 6. Electrophysiological and morphological data have been compared at individual doubly innervated end-plate sites. End-plate potential amplitude was positively correlated with the degree of ending development. 7. Sprouted endings remain functional after periods of reinnervation of 30 months, although signs of regression have been observed. These are probably mediated by spontaneous degeneration of the terminals and replacement by endings from the regenerating nerve.
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PMID:Interaction between motor axons from two different nerves reinnervating the pectoral muscle of Xenopus laevis. 626 4

The effects of polyinosinic, polycytidylic acid [poly(I) X poly(C)] on the activation and RNA metabolism in murine peritoneal macrophages (M phi) elicited by proteose-peptone (pM phi) was investigated. Poly(I) X poly(C) triggered the cytolytic activity of pM phi and augmented their glucose oxidation. In contrast, a profound depression of [3H]uridine incorporation into RNA was observed in poly(I) X poly(C)-activated pM phi. The degree of depression of RNA labeling paralleled the dose of poly(I) X poly(C) used to activate the pM phi and the expression of tumoricidal activity. This decrease in [3H]uridine incorporation into M phi RNA could not be accounted for by decreased permeability of the activated M phi to [3H]uridine, or by instability of the labeled RNA. Moreover, analysis of the specific activity of the intracellular uridine triphosphate (UTP) pool and studies on the labeling of M phi RNA with [32P] orthophosphate indicated that the decreased RNA labeling was not due to changes in the specific activity of UTP. We concluded that poly(I) X poly(C)-activated pM phi exhibit a depressed rate of RNA synthesis. We suggest that the rate of RNA synthesis may be investigated as a potential new indicator for M phi activation.
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PMID:RNA synthesis in activated macrophages I. Poly(I) X poly(C)-induced triggering of cytolytic activity is associated with decrease in RNA synthesis. 666 87

Poly(A(+)) RNA was extracted from the temporal lobe (TL) of medically intractable epileptic patients which underwent surgical TL resection. Injection of this mRNA into Xenopus oocytes led to the expression of ionotropic receptors for gamma-aminobutyric acid (GABA), kainate (KAI) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Membrane currents elicited by GABA inverted polarity at -15 mV, close to the oocyte's chloride equilibrium potential, were inhibited by bicuculline, and were potentiated by pentobarbital and flunitrazepam. These basic characteristics were also displayed by GABA currents elicited in oocytes injected with mRNAs isolated from human TL glioma (TLG) or from mouse TL. However, the GABA receptors expressed by the epileptic TL mRNA exhibited some unusual properties, consisting in a rapid current run-down after repetitive GABA applications and a large EC(50) (125 microM). AMPA alone evoked very small or nil currents, whereas KAI induced larger currents. Nevertheless, upon cyclothiazide treatment, AMPA elicited substantial currents that, like the KAI currents, were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore, the glutamate receptor 5 (GluR5) agonist, ATPA, failed to evoke an obvious current although both RT-PCR and Western blot analyses showed GluR5 expression in the epileptic TL. Oocytes injected with mouse TL or human TLG mRNAs generated KAI and AMPA currents similar to those evoked in oocytes injected with epileptic TL mRNA but, in contrast to these, the mouse TL and human TLG oocytes were also responsive to ATPA. Our findings are in accord with the concept that both a depression of GABA inhibition and a dysfunction of the KAI-receptor system maintain a high neuronal excitability that results in epileptic seizures.
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PMID:Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy. 1240 14

This study was aimed to determine whether administration of an inhibitor of caspase-3 protects hepatocellular function in rats with hemorrhagic shock and whether caspases are important pharmacological targets in attenuating liver injury induced by hemorrhagic shock and resuscitation. Male adult rats were subjected to hemorrhagic shock by bleeding to a mean arterial blood pressure of 35-40 mmHg for 1 h and were then resuscitation with 60% shed blood and lactated Ringers solution. A subgroup of animals was injected i.v. with 2 mg/kg caspase inhibitor, Z-DEVD-FMK, prior to blood withdrawal. Fas ligand expression was markedly elevated and caspase-3 activity increased by 3-fold in hemorrhagic untreated rats. The increase in caspase-3 activity was prevented by administration of Z-DEVD-FMK prior to shock and resuscitation. Poly (adenosine diphosphate ribose) polymerase proteolysis was reduced in rats treated with the caspase-3 inhibitor compared with hemorrhagic untreated animals. Plasma aspartate aminotransferase and alanine aminotransferase values showed a significant increase at 6 h of shock in untreated animals (+360% and +515% as compared with sham-operated animals, respectively). Administration of the caspase-3 inhibitor did not prevent the increase in plasma transaminases. The cytosolic concentration of thiobarbituric acid-reactive substances (TBARS) and the oxidized:reduced glutathione ratio increased in the animals with hemorrhagic shock (+94% and +170%, respectively). These parameters were not significantly modified by pretreatment with Z-DEVD-FMK. It appears that caspase inhibition does not attenuate hepatocellular depression and liver injury induced by hemorrhagic shock and resuscitation.
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PMID:Caspase inhibition does not protect against liver damage in hemorrhagic shock. 1255 41


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