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At least 91 records · Page 5Linked to original sources
PubMed1998

Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain.

Alzheimer's disease (AD) is a major dementing illness characterized by regional concentrations of senile plaques, neurofibrillary tangles, and extensive neuronal cell death. Although cell and synaptic loss is most directly linked to the severity of symptoms, the mechanisms leading to the neuronal death remain unclear. Based on evidence linking neuronal death during development to unexpected reappearance of cell cycle events, we investigated the brains of 12 neuropathologically verified cases of Alzheimer's disease and eight age-matched, disease-free controls for the presence of cell cycle proteins. Aberrant expression of cyclin D, cdk4, proliferating cell nuclear antigen, and cyclin B1 were identified in the hippocampus, subiculum, locus coeruleus, and dorsal raphe nuclei, but not inferotemporal cortex or cerebellum of AD cases. With only one exception, control subjects showed no significant expression of cell cycle markers in any of the six regions. We propose that disregulation of various components of the cell cycle is a significant contributor to regionally specific neuronal death in AD.

Aged↗
PubMedDate not supplied

The glycine peak in brain diseases.

Glycine is an excitatory amino acid, a neurotransmitter for the brain. A recent experimental study by a 9.3T laboratory spectrometer identified the peak of pure glycine at 3.52 ppm, and in a clinical case this peak was demonstrated at 3.50 ppm by a 1.5 T clinical scanner. This study was undertaken to investigate the brain diseases having the glycine peak. An experiment with a 1.5 T clinical MRI unit was performed. Two grams of pure glycine was dissolved in 200 cc of distilled water and the solution was frozen, and proton MR spectroscopy (TR=1500 ms, TE=20 ms) was obtained. Nine patients with various diseases studied by two-dimensional chemical shift spectroscopy (hybrid CSI) with TR=1500 ms, and TE=40 ms are included in the study. Ten normal cases were available for comparison. In the experiment with the clinical MRI unit, the glycine peak was centered at 3.50 ppm. The disease processes associated with distinct glycine peaks at 3.50 ppm included infarction, high-grade astrocytoma, megalencephalic leukoencephalopathy with cysts, Leigh's disease, adrenoleukodystrophy, congenital muscular dystrophy, Rasmussen's encephalitis, gliosis in neuronal migrational disorder, and hamartoma in tuberous sclerosis. None of the control cases displayed a glycine peak. In conclusion, glycine has a peak centered at 3.50 ppm in in vivo environments. It is distinct from the myoinositol peak. Detection of glycine in a wide variety of brain diseases ranging from infarction, tumor, leukoencephalopathies, infection to gliosis likely reflects presence of excitotoxic brain damage or a disturbance of neurotransmitting mechanisms in these conditions.

Adult↗
PubMed1993

Phosphoprotein phosphatase activities in Alzheimer disease brain.

Microtubule-associated protein tau is known to be hyperphosphorylated in Alzheimer disease brain and this abnormal hyperphosphorylation is associated with an inability of tau to promote the assembly of microtubule in the affected neurons. Our previous studies demonstrated that abnormally phosphorylated tau could be dephosphorylated after treatment with alkaline phosphatase, thereby suggesting that the abnormal phosphorylation of tau might in part be the result of a deficiency of the phosphoprotein phosphatase system in patients with Alzheimer disease. In the present study we used 32P-labeled phosphorylase kinase and poly(Glu, Tyr) 4:1 as substrates to measure phosphoprotein phosphatase activities in Alzheimer disease and control brains. The activities of phosphoseryl/phosphothreonyl-protein phosphatase types 1, 2A, 2B, and 2C and of phosphotyrosyl-protein phosphatase in frontal gray and white matters from 13 Alzheimer brains were determined and compared with those from 12 age-matched control brains. The activities of type 1 phosphatase and phosphotyrosyl phosphatase in gray matter and of type 2A phosphatase in both gray and white matters were significantly lower in Alzheimer disease brains than in controls. These findings suggest that the hyperphosphorylation of tau in Alzheimer disease brain could result from a protein dephosphorylation defect in vivo. The decrease in the phosphatase activities in Alzheimer disease might also be involved in the formation of beta-amyloid by augmenting the amyloidogenic pathway processing of beta-amyloid precursor protein.

Adult↗
PubMed1996

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 1)--report on clinical usefulness in diagnosis of various brain diseases].

Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. The safety and clinical effectiveness of 123I-IMZ SPECT in the diagnosis of brain diseases were evaluated in 655 patients with various brain diseases, such as epilepsy, cerebrovascular diseases, degenerative diseases and mental disorders relating to BZR. This was a Phase 3 study conducted as a multicenter trial at 52 collaborating institutions. There was no significant adverse reactions in the clinical symptoms or abnormal laboratory test values. The investigators judged 123I-IMZ SPECT to be effective in 95% of 638 analyzed cases. The injected dose did not correlate with the image quality or the clinical effectiveness of 123I-IMZ SPECT, suggesting that these items depend largely on the characteristics of the apparatus used, the disease or pathology of the patients, rather than the dose. We conclude that 123I-IMZ imaging is safe and provides effective information based on BZR binding which is useful in the diagnosis of various brain diseases.

Adolescent↗
PubMed1992

Safety and Efficacy of ECT in Depressed Patients with Organic Brain Disease: Review of a Clinical Experience.

We performed a retrospective review of 5 years of experience with electroconvulsive therapy (ECT) in patients with organic brain lesions. On 26 of 27 occasions, patients with organic brain disease and a concurrent depressive disorder obtained a good affective response to a course of ECT. Patients with diffuse or multifocal brain disease were vulnerable to ECT-induced delirium; however, this was severe enough to compel discontinuation of ECT on only one occasion. We conclude that ECT is an effective treatment for depression in patients with concurrent neurological disease, although patients with degenerative brain disease or diffuse encephalopathy may be especially prone to ECT-induced delirium.

Journal Article↗
PubMed2006

An online database for brain disease research.

BACKGROUND: The Stanley Medical Research Institute online genomics database (SMRIDB) is a comprehensive web-based system for understanding the genetic effects of human brain disease (i.e. bipolar, schizophrenia, and depression). This database contains fully annotated clinical metadata and gene expression patterns generated within 12 controlled studies across 6 different microarray platforms. DESCRIPTION: A thorough collection of gene expression summaries are provided, inclusive of patient demographics, disease subclasses, regulated biological pathways, and functional classifications. CONCLUSION: The combination of database content, structure, and query speed offers researchers an efficient tool for data mining of brain disease complete with information such as: cross-platform comparisons, biomarkers elucidation for target discovery, and lifestyle/demographic associations to brain diseases.

Bipolar Disorder↗
PubMed2004

Proteomics: a new approach to investigate oxidative stress in Alzheimer's disease brain.

In Alzheimer's disease (AD) brain oxidative stress is observed indexed by several markers, among which are protein carbonyls and 3-nitrotyrosine, markers for protein oxidation. We hypothesized that identity of these oxidatively modified proteins would lead to greater understanding of some of the potential molecular mechanisms involved in neurodegeneration in this dementing disorder. Proteomics is an emerging method for identification of proteins, and its application to neurodegenerative disorders, especially AD, is just beginning. Posttranslational modification of brain proteins, particularly that due of oxidation of proteins, provides an effective means of screening a subset of proteins within the brain proteome that likely reflects the extensive oxidative stress under which the AD brain exists, and this new methodology provides insights into mechanisms of neurodegeneration in and new therapeutic targets for AD. In this review, the use of proteomics to identify specifically oxidized proteins in AD brain is presented, from which new insights into mechanisms of neurodegeneration and synapse loss in this dementing disorder that is associated with oxidative stress have emerged.

Alzheimer Disease↗
PubMed2005

Marble brain disease in two Saudi Arabian siblings.

Marble brain disease, also known as Guibaud-Vainsel syndrome, is a syndrome consisting primarily of renal tubular acidosis, cerebral calcification and osteopetrosis. The majority of reports originate from the Middle East. It is an autosomal recessive condition owing to carbonic anhydrase type II deficiency in renal and brain cells with a variant form of osteopetrosis. We report two siblings with this condition from Saudi Arabia. Both cases improved in both somatic growth and mental development after commencing treatment for renal tubular acidosis in the form of alkaline therapy and potassium supplementation.

Acidosis, Renal Tubular↗
PubMed1995

Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain.

Microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated in affected neurons of Alzheimer disease brain. This hyperphosphorylated tau can be dephosphorylated at some of the abnormal phosphorylated sites by purified protein phosphatase-1, 2A, and 2B in vitro. In the present study, we have developed an assay to measure protein phosphatase activity toward tau-1 sites (Ser199/Ser202) using the hyperphosphorylated tau isolated from Alzheimer disease brain as substrate. Using this assay, we have identified that in normal brain, protein phosphatase-2A and 2B and, to a lesser extent, 1 are involved in the dephosphorylation of tau. The Km values of dephosphorylation of the hyperphosphorylated tau by protein phosphatase-2A and 2B are similar. The tau phosphatase activity is decreased by approximately 30% in brain of Alzheimer disease patients compared with those of age-matched controls. These findings suggest that a defect of protein phosphatase could be the cause of the abnormal hyperphosphorylation of tau in Alzheimer disease.

Aged↗
PubMed1993

In vivo and in vitro tissue scanning studies in alcoholic brain disease.

X ray CT and MRI can identify brain lesions in organic syndromes attributed to chronic alcoholism. Cortical atrophy which improves with abstinence can also be identified. Magnetic resonance relaxation times are altered and may provide a means of monitoring improvement or deterioration in response to abstinence or continued drinking. Altered relaxation times may be due to altered free-to-bound ratios of water and may act as a marker for biochemical change in alcoholic brain disease.

Alcoholism↗
PubMed1986

Molecular size distribution of somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with degenerative brain disease.

The molecular size distribution of somatostatin-like immunoreactivity (SLI) in the cerebrospinal fluid (CSF) of patients with brain disease was investigated by separation with a Sephadex G-25 superfine column and subsequent radioimmunoassay of the eluate. Marked heterogeneity of SLI in the CSF of control subjects as well as in demented patients, was observed. Controls and schizophrenics exhibited an SLI distribution pattern consisting mainly of two pronounced peaks: the first eluting with the void volume of the column; the second being compatible with a peptide of N-terminally extended somatostatin-14. SLI from the CSF of patients with senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID) and normal pressure hydrocephalus (NPH) showed the same two peaks found in controls and schizophrenics; and in addition, a third peak co-eluting with somatostatin-14. However, this peak was more pronounced in patients with SDAT and MID than in patients with NPH. Re-chromatography of G-25 sf void volume immunoreactivity afforded two fractions of an apparent molecular weight of about 10,000 daltons and 15,500 daltons, respectively.

Adult↗
PubMed1996

Embryonic genes expressed in Alzheimer's disease brains.

Alzheimer's disease (AD)-specific or characteristic gene expression was explored by the identification of cDNA clones by means of differential screening for embryonic brain cDNA library with 32P-labeled cDNA probes prepared from mRNA of AD and normal human brains. To isolate neuronal genes in degenerating neurons, we used rat embryonic cDNA library at stage day 15 when glial cells developed poorly in the brain. Seventeen embryonic genes were identified as embryonic alpha-tubulin, embryonic beta-tubulin, hnRNP, protein L-isoaspartyl methyltransferase (PIMT), ferritin heavy chain, type IV collagen, actin-binding protein cofilin, profilin and nine novel sequences designated as A1-9. We characterized these genes by Northern blot analysis, RNase protection assay and immunohistochemical studies, showing that PIMT and a novel gene designated as A5 showed the transcriptional up-regulation in AD brains. In addition, the immunohistochemical studies showed PIMT, type IV collagen, and cofilin were associated with neurofibrillary tangles in degenerating neurons, brain vessels in affected regions, and synaptosomal structures in AD brains, respectively. The catalogue presented here also showed the involvement of cytoskeletal proteins, cytoskeleton-associated proteins, and an iron-storage protein, suggesting the presence of regenerating activity and the abnormal metabolisms in affected neurons of AD brains.

Alzheimer Disease↗