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)

The authors report cognitive functions of a 13-year-old boy with a cavernous angioma occupying the posterior left parahippocampal gyrus (PHG) and part of the left fusiform gyrus but not hippocampus. Neuropsychological examinations soon after the removal of the tumor showed selective deficits in semantic memory function, as evaluated by the Category Fluency Task and the Wechsler Memory Scale-Revised, while visual memory, attention, and IQ were not affected. These observations suggest the involvement of the PHG in the processing of semantic memory and provide an insight into the neural substrates underlying the distinct cognitive deficits in some of the psychiatric diseases such as schizophrenia.
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PMID:Verbal memory deficits in a preadolescent case of lesions of the left parahippocampal gyrus associated with a benign tumor. 1644 96

Sigma receptors are classified into sigma(1) and sigma(2) subtypes. These subtypes display a different tissue distribution and a distinct physiological and pharmacological profile in the central and peripheral nervous system. The characterization of these subtypes and the discovery of new specific sigma receptor ligands demonstrated that sigma receptors are novel targets for the therapeutic treatment of neuropsychiatric diseases (schizophrenia, depression, and cognition), brain ischemia, and cocaine addiction. Furthermore, imaging of sigma(1) receptors in the human brain using specific PET radioligands has started. In addition, the two sigma receptor subtypes are also expressed on tumor cells, where they could be of prognostic relevance. The ability of sigma(2) receptor agonists to inhibit tumor cell proliferation through mechanisms that might involve apoptosis, intracellular Ca(2+), and sphingolipids has promoted the development of sigma(2) receptor agonists as novel therapeutic drugs for treating cancer. Consequently, sigma(2) receptor ligands have been demonstrated to be potentially useful tumor imaging ligands. In this article, we focus on the sigma receptor ligands as therapeutic agents and as radiopharmaceuticals.
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PMID:Sigma receptor ligands: possible application as therapeutic drugs and as radiopharmaceuticals. 1707 84

TGFBR2 gene is a tumor suppressor gene located at chromosome 3p22, and the locus is reported to be linked with schizophrenia susceptibility. According to the previous studies, a reduced incidence of cancer is observed in schizophrenic patients compared with the general population and tumor suppressor genes may be associated with schizophrenia. We measured the mRNA expression of TGFBR2 gene in the peripheral leukocytes from 19 medication-free schizophrenics and 25 medication-free major depressive patients compared with age- and sex-matched control subjects using a quantitative real-time PCR method. We also followed up the TGFBR2 mRNA expression levels from 13 schizophrenics after several weeks - antipsychotic treatments. The TGFBR2 mRNA levels of medication free schizophrenics were significantly higher than those of control subjects and decreased to almost the same level as controls after antipsychotic treatment. On the other hand, the TGFBR2 mRNA levels of medication-free major depressive patients were not significantly different from controls. In genetic studies, we failed to find any association between the TGFBR2 gene and schizophrenia with 10 SNPs of TGFBR2 gene in Japanese subjects (279 subjects each) and there was no significant difference with haplotype analysis, either. Our results suggest that the TGFBR2 gene itself does not link to schizophrenia but that the TGFBR2 mRNA levels in the peripheral leukocytes may be a potential state marker for schizophrenia.
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PMID:TGFBR2 gene expression and genetic association with schizophrenia. 1756 Jun 8

The hydatidosis is an endemic illness in regions of the Middle Orient, Mediterranean, south of America, north Africa and the Australia. The preferential localization of cyst hydatic is the liver (48%), the lung (36%) and in 6% of cases it localizes in unaccustomed place as the brain. Intracerebral localization is relatively rare, its impact is 1 to 5% of all cases of hydatidose. This localization is the child's appendage with a masculine predominance. The cyst hydatic intracranien is often lone, of localization usually supratentorielle, sometimes infratentorielle. Symptoms are especially the diffuse headache associated to various neurological signs in relation with sits of the tumor. The psychiatrics symptoms depends on its localization, sides, intracranial hypertension, and the previous personality. In 15 to 20% of cases these tumors can appear in the beginning of their evolution by the isolated psychiatric symptoms. We report the case of two patients that have been hospitalized first in the Academic Psychiatric Unit of Marrakech for isolates psychiatric disorders and whose scanning revealed the presence of cerebral hydatic cyst and that required a surgical intervention in neurosurgery. Case 1 - Patient 29 years old, bachelor, uneducated, leaving in country outside, fermar, in permanent contact with dogs. No particular medical history. The patient has been brought by his family to the psychiatric emergencies after behavior disorders. The beginning of his symptomatology was one year ago by behavior disorders: instability, violence, isolation, and a corporo-sartorial carelessness. His symptomatology worsened and the patient became very aggressive. In psychiatric unit, he was disregarded, sad, anguished, indifferent to his state, very dissonant, completely detached, depersonalized. He brought back some visual and auditory hallucinations with attitude of monitoring. He was raving with delirium of persecution, of ideas of reference and delirium of bewithment. He was unconscious of his disorders. The patient has first been put under classical neuroleptic 9 mg/day of Haloperidol and 200 mg/day of chlorpromazine. The diagnosis of schizophrenia has been kept according to criteria of DSM IV. The PANSS (Positive and Negative Syndrome Scale) was to 137 (score on a positive scale was to 34, score on a negative scale was to 35 and the general psychopathologie scale was to 58). One week after his hospitalization, he developed headache with subconfusion, a cerebral scanning has been made in emergency and showed a voluminous cyst in oval foramen compressing the mesencephalon strongly. The cyst was well limited, hypodense, not taking the contrast, and without intracerebral oedema, the diagnosis of cerebral hydatic cyst has been made. The complementary exploration didn't show any other localizations, and biologic exam results didn't show any particular anomalies. The patient has been operated in neurosurgery. The immediate evolution was favorable with disappearance of confusion and absence of complications. The patient was lost of view. Six months after, the patient has been readmitted to the psychiatric emergency. He dropped his neuroleptic treatment. He was aggressive, raving, hallucinated and depersonalized. The global score to the PANSS was 63. He has been put back under neuroleptics. Three weeks after improvement and passage of the PANSS to 30, the patient went out. We couldn't have a cerebral scanner of control because the patient had no medical assurance and no money for cerebral scanner. Case 2 - Patient aged of 53 years, father of four children, uneducated, native and resident of Marrakech, confectioner as profession. He is in contact with dogs since 12 years. He has been brought to the psychiatric emergencies by his family after an agitation. The history of his illness seemed to go back at eight months ago, by the progressive apparition of an instability, sleep disorders, hostility, associated with an emotional lability. To the interview he was agitated and had a delirium of persecution. He was convinced that his wife and his children plotted against him. He had sad mood. He was anguished and had auditory and visual hallucinations. The patient was not confused but it had a hypoproxie, an fixing amnesia, a disorders of judgment and a light left hemiparesia. Cerebral scanner revealed three cerebral cyst. The first measuring 42 x 40 mm, sitting at the level parietal right, to the contact of the occipital horn, dragging his/her/its amputation and an effect of mass on ventricle homolateral, the median line and ventricle controlateral. The two other, at the level of the center semi oval, behind the first, measuring 23 mm and 15 mm on the big axis. The patient has been addressed in neurosurgery. He had a completeray exploration to search other localizations. The thoracic x-ray showed 2 pulmonary cyts. The abdominal scan and imagery by magnetic resonance showed liver cyst, peri-heart cyst and mediastinal cyst. The patient has been operated for these three cysts with good recuperation on the psychiatric and neurological symptoms. He has been addressed in heart surgery for the heart localization. The hydatidose is an endemic illness in Morocco and constitute a public health problem. The cerebral localization is rare and appear by signs of cerebral hypertension and signs of focusing. The psychiatric demonstrations are rare but preserve a major interest, by the therapeutic measure specificity that they impose. Of course, the surgical ablation of the tumor can be sufficient to attenuate the psychiatric symptoms but the recourse to a specific treatment can prove to be necessary to act on the precise targets. We are conscious of the methodological difficulties that present these 2 cases but there are unfortunately due to the financial difficulties of our patients.
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PMID:[Cerebral hydatic cyst and psychiatric disorders. Two cases]. 1767 18

Gap junctions (GJs) are composed of proteins that form a channel connecting the cytoplasm of adjacent cells. Connexins were initially considered to be the only proteins capable of GJ formation. Another family of GJ proteins (innexins) were first found in invertebrates and were proposed to be renamed pannexins after their orthologs were discovered in vertebrates. The lack of both connexins and pannexins in the genomes of some metazoans suggests that other, still undiscovered GJ proteins exist. In vertebrates, connexins and pannexins co-exist. Here we discuss whether vertebrate pannexins have a nonredundant role in animal physiology. Pannexin channels appear to be suited for ATP and calcium signaling and play a role in the maintenance of calcium homeostasis by mechanisms implicating both GJ and nonjunctional function. Suggested roles in the ischemic death of neurons, schizophrenia, inflammation and tumor suppression have drawn much attention to exploring the molecular properties and cellular functions of pannexins.
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PMID:Pannexins and gap junction protein diversity. 1798 31

A 38-year-old man with a history of schizophrenia presented with pain and swelling of his testicles, with the right side worse than the left. Physical examination was remarkable for a very firm, large, right-sided scrotal mass. Testicular ultrasound was suspicious for neoplasm or abscess. On the pelvic computed tomography (CT) scan, which was obtained as part of a metastatic cancer work-up, two metallic foreign bodies were identified in the pelvis. On further questioning, the patient admitted to ingesting the nails 2 days prior, in a suicide attempt. We review the evaluation of unilateral scrotal pain and swelling, and incidental foreign body ingestion.
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PMID:A right scrotal abscess and foreign body ingestion in a schizophrenic patient. 1815 84

The incidence of cancer in patients with schizophrenia has been reported to be lower that in the general population. On the other hand, it is well established that patients with schizophrenia have a hyper-dopaminergic system and dopamine has the ability to inhibit tumor angiogenesis. Therefore, in order to investigate the molecular mechanisms responsible for the lower cancer risk in schizophrenic patients, we used a mouse model of schizophrenia, which shows hyper-dopaminergic transmission in the nerve terminals of dopaminergic neurons. Here, we hypothesized that tumor growth was reduced in a mouse model of schizophrenia, lacking the dopamine transporter (DAT), and investigated tumor growth and angiogenesis in DAT knockout mice. The subcutaneous tumor in mice inoculated with cancer cells was smaller in DAT-/- mice than in the wild type (p < 0.05); however, the level of plasma dopamine in DAT-/- mice was lower than that of control littermates. Using human umbilical vascular endothelial cells (HUVEC), we examined dopamine signaling through dopamine D(1) receptor (D(1)R) and D(2)R. Dopamine stimulation slightly decreased the surface expression of vascular endothelial growth factor receptor-2 (VEGF-R2) but induced the phosphorylation of VEGF-R2 through Src in HUVEC. In addition, DAT-/- mice had less D(1)R. Both pharmacological and genetic interruption of D(1)R showed inhibited tumor growth. These results suggest that modulation of the dopaminergic system may contribute to cancer therapy.
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PMID:Reduced tumor growth in a mouse model of schizophrenia, lacking the dopamine transporter. 1847 Sep 12

Human endogenous retroviruses HERV-W families have been identified from monozygotic twin pairs with schizophrenia and patients with multiple sclerosis. Identification of retroviral RNA in the cerebrospinal fluids and brains of individuals with schizophrenia indicated that the transcriptional activation of the HERV-W elements within the central nervous system could be associated with the brain diseases. Here, we examined the expression of the HERV-W env gene in tumor/normal adjacent tissues and various areas of brain tissues. In silico expression data indicated that 14 complete HERV-W families from human chromosomes 1, 2, 4, 7, 8, 11, 13, 15, and Y are randomly expressed in various cancer tissues. HERV-W env transcripts did not show significant differences among the human tumor/normal adjacent tissues (colon, liver, uterus, breast, and stomach). Quantitative real-time RT-PCR analysis indicated that strong expression of the HERV-W env gene was detected in the cerebral cortex and pons of the human brain.
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PMID:Quantitative expression of the HERV-W env gene in human tissues. 1860 68

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a new category of treatment-responsive encephalitis associated with "anti-NMDAR antibodies", which are antibodies to the NR1/NR2 heteromers of NMDAR. The antibodies are detected in the CSF/serum of young women with ovarian teratoma, who typically develop schizophrenia-like psychiatric symptoms, usually preceded by fever, headache, or viral infection-like illness. After reaching the peak of psychosis, most patients developed seizures followed by an unresponsive/catatonic state, decreased level of consciousness, central hypoventilation frequently requiring mechanical ventilation, orofacial-limb dyskinesias, and autonomic symptoms. Brain MRI is usually unremarkable but focal enhancement or medial temporal lobe abnormalities can be observed. The CSF reveals nonspecific changes. EEG often reveals diffuse delta slowing without paroxysmal discharges, despite frequent bouts of seizures. This is a highly characteristic syndrome evolving in 5 stages, namely, the prodromal phase, psychotic phase, unresponsive phase, hyperkinetic phase, and gradual recovery phase. The hyperkinetic phase is the most prolonged and crucial. This disorder is usually severe and can be fatal, but it is potentially reversible. Once patients overcome the hyperkinetic phase, gradual improvement is expected with in months and full recovery can also be expected over 3 or more years. Ovarian teratoma-associated limbic encephalitis (OTLE) was first reported in 1997 when this syndrome was reported independently in 1 Japanese girl and 1 woman, both of whom improved following tumor resection. In 2005, Dalmau and his research group first demonstrated antibodies to novel neuronal cell membrane antigens in 4 women with OTLE in a non-permeabilized culture of hippocampal neurons. Two years later, they identified conformal extracellular epitopes present in the NR1/NR2B heteromers of NMDAR, which are expressed in the hippocampus/forebrain. The target extracellular epitopes are not detectable by immunoblotting, and should not be confused with the linear epitopes of NR2B subunits (also known as epsilon2). The antibodies disappear with clinical improvement, suggesting their pathogenic role. Autopsies revealed IgG deposits in the hippocampus, extensive microgliosis, rare T-cell infiltrates, and neuronal degeneration predominantly involving, but not restricted to, the hippocampus. The nervous tissues of the tumors exhibit not only strong expression of the NR2B subunits but also reactivity with the patients' antibodies. The pathogenesis remains unknown; however, this disorder is considered to be an antibody-mediated encephalitis. Based on the current NMDAR hypofunction hypothesis of schizophrenia, we speculate that the antibodies may cause inhibition rather than stimulation of NMDARs in presynaptic GABAergic interneurons, causing a reduction in GABA release. This results in disinhibition of postsynaptic glutamatergic transmission, excessive release of glutamate in the prefrontal/subcortical structures, and glutamate and dopamine dysregulation that might contribute to development of schizophrenia-like psychosis and bizarre dyskinesias. The antibodies were initially found only in young women with teratoma in the ovaries. However, recent studies show that this disorder can occur even in the absence of teratoma in up to 35% of patients, and even boys and adult men had been affected. Although recovery occurs without the need for tumor removal, the severity and extended duration of symptoms support tumor removal. Combined therapy including tumor resection and immunotherapy is recommended. In this review, we also discuss the relationship between anti-NMDAR encephalitis and related disorders, including acute diffuse lymphocytic meningoencephalitis and acute juvenile female non-herpetic encephalitis (AJFNHE).
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PMID:[Anti-nMDA receptor encephalitis--clinical manifestations and pathophysiology]. 1880 39

DNA methylation is the best-studied epigenetic modification, and in mammals it describes the conversion of cytosine to 5-methylcytosine in the context of CpG dinucleotides. In recent years, it has become evident that epigenetic mechanisms are severely disrupted in human neoplasia, and evidence suggests that alterations of DNA methylation patterns may be an integral mechanism in the etiology of other diseases such as bipolar disorder and schizophrenia. The main effect of altered DNA methylation is the disruption of normal patterns of gene expression through genomic instability and hypermethylation of CpG islands, which together could lead to uncontrolled cell proliferation. DNA methylation can be reversed through pharmacological intervention via the systemic administration of DNA methylation inhibitors. Thus, the ability to accurately quantify DNA methylation levels in genomic sequences is a prerequisite to assess not only treatment efficacy, but also the effect of the DNA methylation inhibitors on bystander tissues. Several methods are currently available for the analysis of DNA methylation. Nonetheless, accurate and reproducible quantification of DNA methylation remains challenging. Here, we describe Bio-COBRA, a modified protocol for combined bisulfite restriction analysis (COBRA) that incorporates an electrophoresis step in microfluidics chips. Microfluidics technology involves the handling of small amounts of liquid in miniaturized systems. Bio-COBRA provides a platform for the rapid and quantitative assessment of DNA methylation patterns in large sample sets. Its sensitivity and reproducibility also make it an excellent tool for the analysis of DNA methylation in clinical samples.
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PMID:Bio-COBRA: absolute quantification of DNA methylation in electrofluidics chips. 1898 20


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