Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the descriptive epidemiology of seizure disorder in 129 male residents of a Veterans Administration Nursing Home. Eighty-seven of the residents were institutionalized because of nonpsychiatric disorders (60 for chronic neurologic diseases, and 27 for other medical conditions). Forty-two were institutionalized because of a chronic psychosis (39 for schizophrenia, three for affective disorders). We determined for each resident an extensive clinical data base of 54 items including measures of hematologic, nutritional, metabolic and endocrine status, as well as continuing medications. In the nonpsychiatric group, 16 of the 87 men had a seizure disorder. In the psychiatric group, this proportion was only three of 42. The prevalence of epilepsy in the nonpsychiatric group was 20-40 times greater than in the aged-matched general population of men. In the nonpsychiatric group, the onset of seizures followed the onset of organic brain disease. Forty-five percent of seizure disorders occurred in men who had experienced a cerebrovascular accident, and 23% in men with other types of chronic brain disease. The seizures of the nonpsychiatric men had been observed to be generalized clonic-tonic in 45%, and partial complex in 22%. Ninety-four percent of the nonpsychiatric men with epilepsy received anticonvulsants, and none had experienced more than one seizure during the preceding year. Univariate statistical analysis of the 54 item data base showed that the occurrence of seizure disorder correlated inversely with age, blood urea nitrogen, serum creatinine and serum bilirubin, and directly with plasma testosterone, hemoglobin, use of anticonvulsants, and use of psychotherapeutic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Seizure disorder in the men of a Veterans Administration nursing home. 328 Jul 35

To examine the basic human brain proteins, we subjected 9 mmol/L urea extracts to non-equilibrium gel electrophoresis. The pattern observed differs distinctly from that with equilibrium gel electrophoresis. With this technique, the myelin proteins (myelin basic protein, proteolipids, and basic Wolfgram proteins) and many other unindentified major basic proteins can be demonstrated. The myelin basic proteins occur as two major polypeptides of different charge and slightly different molecular mass, indicating the action of at least two genes. The proteolipid proteins occur as a long series of charge isomers, suggesting multiple genes or extensive post-transcriptional modification. In one patient with schizophrenia, a charge-change mutation of the larger myelin basic protein (MBL) was observed and is termed "MBL-Duarte."
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PMID:Two-dimensional gel electrophoresis of human brain proteins. V. Non-equilibrium gel electrophoresis, with detection of a myelin basic protein mutation--MBL-Duarte. 617 63

Argininosuccinic aciduria (ASA-uria) is a rare inborn error of the urea cycle, in which there is massive excretion of argininosuccinic acid (ASA) in the urine together with elevated concentrations of ASA in the plasma and the CSF. The characteristic symptoms are either those of overwhelming metabolic disease in the newborn period, or variable psychomotor retardation. The present patient, the first Finnish one to be reported, was a 49-year-old woman. She was hospitalized at the age of 26 with a diagnosis schizophrenia and mental retardation. Her clinical symptoms consisted of ataxia, disturbance of coordination, clumsiness, intention treMor and a positive Romberg's sign. The laboratory findings were consistent with the mild, late-onset type of ASA-uria.
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PMID:Argininosuccinic aciduria in a Finnish woman presenting with psychosis and mental retardation. 713 86

The role of free radicals (FR) in the pathogenesis and in the progression of many diseases has been often discussed, but not widely investigated. However, the total antioxidant capacity in the serum seems to be of great evidence. Total antioxidant capacity was determined using oxygen absorbance capacity assay (ORAC) in serum of patients suffering from depression, schizophrenia, Alzheimer's disease (AD), anorexia nervosa, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Aids-encephalopathy, diabetic polyneuropathy (PNP), cardiomyopathy (CM), renal disease, and healthy individuals as controls (C). The results showed that the total antioxidant capacity in serum decreased significantly (p < 0.01) by 24, 20, 13, and 17% for anorexia nervosa, Aids-encephalopathy, PNP and CM respectively. In serum of patients with renal disease significantly elevated antioxidant capacity was found. The data indicated that increased oxidative stress can be involved in the pathogenesis or in the progression of PNP and CM. Decrease of serum antioxidant capacity in patients with anorexia nervosa and Aids-encephalopathy are probably due primarily to malnutrition and secondly to insufficient antioxidant and immune system. In renal disease, the accumulation of urea in serum seems to be responsible for high antioxidant capacity. In contrast, there were no changes in PD, AD, depression syndrome and schizophrenia.
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PMID:Serum antioxidant capacity in neurological, psychiatric, renal diseases and cardiomyopathy. 1211 62

A patient with a history of schizophrenia was brought to the emergency department with extensive self-inflicted soft tissue injuries. Primary polydipsia was evident on admission, because he had a maximally dilute urine, a urine flow rate of 10 ml/min, and hyponatraemia (100 mmol/l). During an imaginary consultation with Professor McCance in which he applied basic principles of integrative physiology and a deductive analysis in quantitative terms, other reasons for the polyuric state were considered. Moreover, based on the very low value for the concentration of urea in plasma (< 0.7 mmol/l, BUN 1 mg /dl), the goals of therapy to prevent osmotic demyelination became evident. Applying this simple approach, a more comprehensive and accurate differential diagnosis, and a plan for therapy to avoid serious complications was compiled.
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PMID:An integrative physiological approach to polyuria and hyponatraemia: a 'double-take' on the diagnosis and therapy in a patient with schizophrenia. 1288 96

Phencyclidine (PCP) administration elicits positive and negative symptoms that resemble those of schizophrenia and is widely accepted as a model for the study of this human disorder. Group II metabotropic glutamate receptor (mGluR) agonists have been reported to reduce the behavioral and neurochemical effects of PCP. The peptide neurotransmitter, N-acetylaspartylglutamate (NAAG), is a selective group II agonist. We synthesized and characterized a urea-based NAAG analogue, ZJ43. This novel compound is a potent inhibitor of enzymes, glutamate carboxypeptidase II (K(i) = 0.8 nM) and III (K(i) = 23 nM) that deactivate NAAG following synaptic release. ZJ43 (100 microM) does not directly interact with NMDA receptors or metabotropic glutamate receptors. Administration of ZJ43 significantly reduced PCP-induced motor activation, falling while walking, stereotypic circling behavior, and head movements. To test the hypothesis that this effect of ZJ43 was mediated by increasing the activation of mGluR3 via increased levels of extracellular NAAG, the group II mGluR selective antagonist LY341495 was co-administered with ZJ43 prior to PCP treatment. This antagonist completely reversed the effects of ZJ43. Additionally, LY341495 alone increased PCP-induced motor activity and head movements suggesting that normal levels of NAAG act to moderate the effect of PCP on motor activation via a group II mGluR. These data support the view that NAAG peptidase inhibitors may represent a new therapeutic approach to some of the components of schizophrenia that are modeled by PCP.
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PMID:NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR. 1514 Jan 87

Several lines of evidence suggest a link between the alpha7 neuronal nicotinic acetylcholine receptor (nAChR) and brain disorders including schizophrenia, Alzheimer's disease, and traumatic brain injury. The present work describes a novel molecule, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596), which acts as a powerful positive allosteric modulator of the alpha7 nAChR. Discovered in a high-throughput screen, PNU-120596 increased agonist-evoked calcium flux mediated by an engineered variant of the human alpha7 nAChR. Electrophysiology studies confirmed that PNU-120596 increased peak agonist-evoked currents mediated by wild-type receptors and also demonstrated a pronounced prolongation of the evoked response in the continued presence of agonist. In contrast, PNU-120596 produced no detectable change in currents mediated by alpha4beta2, alpha3beta4, and alpha9alpha10 nAChRs. PNU-120596 increased the channel mean open time of alpha7 nAChRs but had no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increased the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect was suppressed by TTX, suggesting that PNU-120596 modulated the function of alpha7 nAChRs located on the somatodendritic membrane of hippocampal interneurons. Accordingly, PNU-120596 greatly enhanced the ACh-evoked inward currents in these interneurons. Systemic administration of PNU-120596 to rats improved the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. Together, these results suggest that PNU-120596 represents a new class of molecule that enhances alpha7 nAChR function and thus has the potential to treat psychiatric and neurological disorders.
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PMID:A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. 1585 66

In our efforts to further pursue one of the most selective dopamine D(3)-receptor antagonists reported to date, we now describe the synthesis and SAR of novel and highly selective dopamine D(3) antagonists based on a 1H-pyridin-2-one or on a urea scaffold. The most potent compounds exhibited K(i) values toward the D(3) receptor in the nano- to subnanomolar range and high selectivity versus the related D(2) dopamine receptor. Thus, 1H-pyridin-2-one 7b displays oral bioavailability (F=37%) as well as brain penetration (brain plasma ratio 3.7) in rat. Within the urea series, an excellent D(3) versus D(2) selectivity (>100-fold) could be achieved by removal of one NH group (compound 6), although bioavailability (rat) was suboptimal (F<10%). These data significantly enhance our understanding of the D(3) pharmacophore and are expected to lead to novel approaches for the treatment of schizophrenia.
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PMID:Synthesis and SAR of highly potent and selective dopamine D3-receptor antagonists: variations on the 1H-pyrimidin-2-one theme. 1643 27

Neuroleptic malignant syndrome is a rare but potentially lethal, rare reaction to neuroleptics which is characterized by altered levels of consciousness, extrapyramidal effects, autonomic instability, hyperthermia, and elevated serum creatine phosphokinase levels. The most serious complication of neuroleptic malignant syndrome is acute renal failure. We investigated six cases of neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure due to rhabdomyolysis and effect of hemodialysis or hemodiafiltration. The patients were five males and one female with a mean age of 43.5 yr. All of the patients, who developed acute renal failure induced from rhabdomyolysis, had previously received butyrophenone (haloperidol), phenothiazine, benzamide, iminomide, benzisoxazole, antidepressants, and hypnotics (benzodiazepine and barbiturate) for the treatment of schizophrenia. The clinical manifestations of neuroleptic malignant syndrome were characterized by altered consciousness, muscle rigidity and weakness, fever, and excessive perspiration. The peak laboratory data were blood urea nitrogen 102 +/- 26 (mean +/- SD) mg/dL, serum creatinine 9.1 +/- 2.1 mg/dL, serum creatine phosphokinase 229,720 +/- 289,940 IU/L, and all of them developed oliguric acute renal failure. Dantrolene sodium administration was given to five cases and hemodialysis or hemodiafiltration was performed in all of them. The serum creatinine level after hemodialysis or hemodiafiltration was 1.4 +/- 1.0 mg/dL. All patients were successfully cured of acute renal failure by hemodialysis or hemodiafiltration. As a result, myoglobulinemic acute renal failure associated with neuroleptic malignant syndrome was successfully treated by hemodialysis or hemodiafiltration.
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PMID:Successful treatment of six patients with neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure. 1652 19

Surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) enables the sensitive, high-throughput protein profiling of complex biological mixtures. In combination with bioinformatics, this technology has the potential to identify combinations of spectral peaks that can differentiate individuals with a particular disease from normal controls. SELDI-TOF-MS was used to screen postmortem tissue derived from the dorsolateral prefrontal cortex of individuals with schizophrenia (n = 34) and matched controls (n = 35), obtained from the Stanley Foundation Neuropathology Consortium. Tissue samples were homogenized in urea buffer, applied to four different chip arrays which possess different chromatographic surfaces, and analyzed using the Ciphergen ProteinChip Biomarkers System (Model PBS II). Protein expression profiles of the schizophrenia and control groups were compared and analyzed using the Ciphergen Express (CE) and Biomarker Patterns Software (BPS) package. We detected several protein peaks whose intensities differed between the schizophrenia and control groups to a highly significant degree. A combination of these peaks was capable of distinguishing between schizophrenia and controls with a sensitivity and specificity of about 70%. The classification model that distinguished schizophrenia from controls was complex, suggesting that the biochemical abnormalities underlying schizophrenia are heterogeneous. Our results suggest that SELDI-TOF-MS has the potential for distinguishing individuals with schizophrenia from normal controls and may eventually lead to a better understanding of the classification, diagnosis and pathogenesis of this disorder.
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PMID:Protein expression profiling of postmortem brain in schizophrenia. 1662 32


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