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

In situ hybridization (ISH) to detect and to quantitate viral nucleic acid sequences in cryopreserved central nervous system (CNS) tissue is a reliable, valid and sensitive molecular technique. On the other hand, utilization of formaldehyde fixed paraffin embedded (FFPE) tissue to improve cytomorphology requires fundamental changes in the procedure since it is necessary to cleave the elaborate protein network cross-linked by formaldehyde using elevated concentrations of proteinases in order to permit diffusion of complementary DNA probes to the targets (genomic viral nucleic acid sequences and/or viral mRNA). Adversely, this procedure hydrolyzed the proteinaceous glues generally used to fix tissue to glass slides resulting in loss of tissue sections during the ISH protocol. This report describes the application of a novel procedure utilizing a silano-organic compound to covalently bond to glass slides FFPE sections as well as cryopreserved tissue sections and cultured cells with and without virus infections. This covalent bonding procedure has permitted optimization of the ISH procedure for virus detection and quantification, especially for exploratory studies of specificity and wash stringency in relation to the Tm of the hybridized product. Progressive multifocal leucoencephalopathy (PML) caused by an opportunistic papovavirus (JC) was chosen because of the ready availability of tissue, stability of papovavirus nucleic acids, and specificity of 3H- and 35S-radiolabeled JC cloned DNA probes. Further, this laboratory is utilizing the optimized sensitive procedure to search for several virus etiologies in human diseases such as multiple sclerosis, temporal lobe epilepsy, Alzheimer's disease, schizophrenia, and Parkinson's disease, as well as normal aging.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quest for a reliable, valid, and sensitive in situ hybridization procedure to detect viral nucleic acids in the central nervous system. 329 27

Rats administered intracerebroventricular (IVT) injections of 3-Carboxy-1,2,3,4-tetrahydroisoquinoline (I) or 6,7-Dihydroxy-1,2,3,4-tetrahydroisoquinoline (II), the condensation products of formaldehyde with phenylalanine and dopamine, respectively, were evaluated in the open field and shuttle box situation. In the open field, 45 min after the acute administration of I, several repetitive purposeless responses and other manifestations such as teeth chattering, wet dog shakes and stiffness of the tail were observed; however, no quantitative effects were detected in the behavioral parameters recorded. Further studies were performed utilizing the shuttle box situation with drugs I and II. They produced an increase in the number of escapes and latency of shocks when measured 45 min after IVT administration (10 mg/ml and 1 mg/ml, respectively; 20 microliters). Our data suggest that the studied compounds induce qualitative alterations as well as changes in shuttle avoidance behavior in the rat when measured 45 min after administered. The effects were found to be dose and time dependent, being reversible when measured 24 and 48 hours after administration of the drugs. The present results open the possibility that the in vivo formation of tetrahydroisoquinolines could be involved in some mental pathologies, such as schizophrenia, as has been previously suggested.
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PMID:Behavioral alterations induced by formaldehyde-derived tetrahydroisoquinolines. 724 42

A biochemical hypothesis concerning the etiology of schizophrenia is presented. This hypothesis postulates the presence of a genetically determined lesion in the disposition of one-carbon units leading to elevated levels of formaldehyde, i.e hyperformaldehydism. The relationships between this hypothesis and the existing major biochemical hypotheses of schizophrenia regarding dopamine and transmethylation are discussed.
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PMID:Hyperformaldehydism: a unifying hypothesis for the major biochemical theories of schizophrenia. 740 42

Neuroimaging studies of cerebellar atrophy in schizophrenia have yielded contradictory results. In computer-tomography (CT) studies, cerebellar atrophy was found in up to 40% of schizophrenic patients. However, several recent magnetic resonance imaging (MRI) studies could not replicate these early findings; in addition, contradictory observations of enlargement of vermal structures were reported. In contrast to the number of CT and MRI studies, there are only a few neuropathological reports on this subject. In a post-mortem study we analyzed the midsagittal vermal area of formaldehyde-fixed cerebella of 12 deceased schizophrenic patients and 12 age- and gender-matched control subjects by using morphometrical methods. Statistical analysis using ANOVA revealed no significant group effects, but there were interactions with gender and cerebellar brain weight. In view of the present results, the common concept of cerebellar atrophy in schizophrenic patients appears premature. Gender effects and secondary processes (e.g., relevant alcohol or drug abuse) cannot be excluded as possible factors causing decrease of vermal areas in schizophrenic patients.
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PMID:Cerebellar vermis area in schizophrenic patients - a post-mortem study. 1070 82

D-Serine is a co-agonist at the NMDA receptor glycine-binding site. Early studies have emphasized a glial localization for D-serine. However the nature of the glial cells has not been fully resolved, because previous D-serine antibodies needed glutaraldehyde-fixation, precluding co-localization with fixation-sensitive antigens. We have raised a new D-serine antibody optimized for formaldehyde-fixation. Light and electron microscopic observations indicated that D-serine was concentrated into vesicle-like compartments in astrocytes and radial glial cells, rather than being distributed uniformly in the cytoplasm. In aged animals, patches of cortex and hippocampus were devoid of immunolabeling for D-serine, suggesting that impaired glial modulation of forebrain glutamatergic signaling might occur. Dual immunofluorescence labeling for glutamate and D-serine revealed D-serine in a subset of glutamatergic neurons, particularly in brainstem regions and in the olfactory bulbs. Microglia also contain D-serine. We suggest that some D-serine may be derived from the periphery. Collectively, our data suggest that the cellular compartmentation and distribution of D-serine may be more complex and extensive than previously thought and may have significant implications for our understanding of the role of D-serine in disease states including hypoxia and schizophrenia.
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PMID:Immunocytochemical analysis of D-serine distribution in the mammalian brain reveals novel anatomical compartmentalizations in glia and neurons. 1634 69