Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that the concentrations of 3', 5' cyclic adenosine monophosphate (cAMP) and 3', 5' cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF), brain, or both, are increased by melanotropic peptides and catechol amines, and by cholinergic agents. The present study measured the concentrations of cAMP, cGMP, and melanotropic activity in the CSF of normal patients and in 136 subjects with various neurologic diseases. In normal lumbar CSF, concentrations (ave +/- SD) were: cAMP, 21 +/- 8 mM; cGMP, 2.4 +/- 0.5 mM; melanotropic activity, 17 +/- 6 units/100 ml. Concentrations of cAMP, cGMP, and melanotropic activity did not differ significantly (P is less than .05) from normal in the following categories of adult and pediatric patients: back pain due to vertigo of unknown cause; cerebral atrophy; cerebral vascular disease; and brain tumor subdural hematoma not causing increased ventricular pressure. Nine children with retarded psychomotor development caused by diffuse brain disease (infection, trauma, hemorrhage, degenerative process, long-standing hydrocephalus with thinning of the cerebral mantle) had subnormal levels of cAMP and melanotropic activity. These two variables were significantly correlated in the entire series of CSF samples (r=+0.55, P is less than .005). cGMP was elevated in the ventricular fluid of adult and pediatric patients when the ventricular pressure was abnormally elevated. The nucleotide's level rose as high as 50 X normal when ventricular pressure exceeded 300 mm H2O. The concentration of ventricular cGMP was proportional to that of ventricular pressure (r=+0.76, P is less than .005). The correlation was similar regardless of the type of hydrocephalus (congenital or acquired, communicating or obstructive), the age of the patient, or the nature of the underlying disease.
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PMID:Observations on the cyclic nucleotide concentrations in human cerebrospinal fluid. 18 45

Oculo-palato-cerebral syndrome is an extremely rare disorder consisting of low birth weight, microcephaly, short stature, persistent hyperplastic primary vitreous, microphthalmia, large ears, small hands and feet, cleft palate, joint hypermobility, developmental delay, and cerebral atrophy. There has been one report of a consanguineous family with three affected children, suggesting autosomal recessive inheritance. We report on the second case of this disorder. Our patient, a 2-year-old boy, had growth delay, microcephaly, bilateral persistent hyperplastic primary vitreous with right microphthalmia, long ears with thickened helices, small hands and feet, highly arched palate, joint hypermobility, hypoplastic nails, frontal cerebral atrophy and thinning of the corpus callosum on brain magnetic resonance imaging, and mild developmental delay. He has much milder features than those seen in the previously reported cases.
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PMID:Oculo-palatal-cerebral syndrome: a second case. 1124 90

Defects in mitochondrial enzymes, such as pyruvate dehydrogenase and cytochrome oxidase, cause hereditary disorders which lead to modifications in cellular pH due to the accumulation of pyruvate and lactic acid. Mitochondrial diseases include severe neonatal diseases and less severe forms of adult diseases. We report the case of lactic acidosis in a newborn girl who was delivered at 36 weeks of gestation and who died 3 months after birth. Her family history revealed a relative with tetraparesis and mental retardation. Her clinical findings, such as tonic-clonic convulsions and accumulation of pyruvate and lactic acid in blood, urine and cerebrospinal fluid, were refractory to treatment and developed soon after birth. Ultrasound scans of the brain some days before death revealed cerebral atrophy with ventricular dilatation and thinning of the corpus callosum and septum pellucidum. The clinical diagnosis of metabolic lactic acidosis was confirmed by macroscopic, microscopic and ultrastructural findings seen at autopsy. On macroscopic examination, the heart was hypertrophic, and the brain was atrophic with ventricular dilatation and thinning of corpus callosum. Small cystic lesions were present in the basal ganglia. On microscopic examination, the latter were characterized by loss of neurons, gliosis and capillary proliferation. Ultrastructural examination of the heart and skeletal muscle showed lysis of myofibrils, mitochondrial pleomorphism and hyperplasia, and crystalline inclusion in mitochondria and in the matrix compartment. In reporting this case, we emphasize the importance of accurate postmortem examination and clinical data for the diagnosis of metabolic lactic acidosis.
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PMID:[An autopsy case of neonatal lactic acidosis]. 1129 18

We present a girl with proven nonketotic hyperglycinaemia. The pathological findings on MRI were brain atrophy with thinning of the corpus callosum and delayed myelination of the cerebral hemispheres, particularly the parietal lobes.
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PMID:MRI in nonketotic hyperglycinaemia: case report. 1159 34

Brain atrophy as determined by quantitative MRI can be used to characterize disease progression in multiple sclerosis. Many studies have addressed white matter (WM) alterations leading to atrophy, while changes of the cerebral cortex have been studied to a lesser extent. In vivo, the cerebral cortex has been difficult to study due to its complex structure and regional variability. Measurement of cerebral cortex thickness at different disease stages may provide new insights into grey matter (GM) pathology. In the present investigation, we evaluated in vivo cortical thickness and its relationship to disability, disease duration, WM T2 hyper-intense and T1 hypo-intense lesion volumes. High-resolution MRI brain scans were obtained in 20 patients with clinically definite multiple sclerosis and 15 age-matched normal subjects. A novel method of automated surface reconstruction yielded measurements of the cortical thickness for each subject's entire brain and computed cross-subject statistics based on the cortical anatomy. Statistical thickness difference maps were generated by performing t-tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between cortical thickness and clinical variables. The mean overall thickness of the cortical ribbon was reduced in multiple sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients). In patients, we found significant main effects for disability, disease duration, T2 and T1 lesion volumes. The visualization of statistical difference maps of the cortical GM thickness on inflated brains across the cortical surface revealed a distinct distribution of significant focal thinning of the cerebral cortex in addition to the diffuse cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)] brain regions was observed, even early in the course of the disease or in patients with mild disability. Patients with longstanding disease or severe disability, however, presented additionally with focal thinning of the motor cortex area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)]. We conclude that in vivo measurement of cortical thickness is feasible in patients suffering from multiple sclerosis. The data provide new insight into the cortical pathology in multiple sclerosis patients, revealing focal cortical thinning beside an overall reduction of the cortical thickness with disease progression.
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PMID:Focal thinning of the cerebral cortex in multiple sclerosis. 1286 Jul 46

We report an autopsy case of a 51-year-old man clinically diagnosed with a complicated type of hereditary spastic paraplegia. His sister showed similar manifestations. Gait disturbance was manifested at 14 years of age. Subsequently, slowly progressive spastic tetraplegia developed with mental deterioration, neuropathy and amyotrophy. Marked cerebral atrophy with thin corpus callosum was shown by cranial MRI. Autopsy revealed a severely atrophic brain with extreme thinning of the whole corpus callosum. Microscopically, neurodegeneration was found in the corticospinal tract, thalamus, cerebral white matter and substantia nigra, as well as in the anterior horn and posterior column of the spinal cord. The remaining neurons contained large amounts of lipofuscin and eosinophilic granules. Unique to this patient was the severe gliosis in the cerebral white matter and substantia nigra, suggesting that sufficient development had been established when the degenerative process occurred. The predominant feature of the present case is the neurodegeneration process rather than hypoplasia.
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PMID:Autopsy case of hereditary spastic paraplegia with thin corpus callosum showing severe gliosis in the cerebral white matter. 1638 84

Magnetic resonance imaging (MRI) measures of brain atrophy are often considered to be a marker of axonal loss in multiple sclerosis (MS) but evidence is limited. Optic neuritis is a common manifestation of MS and results in optic nerve atrophy. Retinal nerve fibre layer (RNFL) imaging is a non-invasive way of detecting axonal loss following optic neuritis. We hypothesise that if the optic nerve atrophy that develops following optic neuritis is contributed to by axonal loss, it will correlate with thinning of the RNFL. Twenty-five patients were studied at least 1 year after a single unilateral attack of optic neuritis without recurrence, with a selection bias towards incomplete recovery. They had MR quantification of optic nerve cross-sectional area and optic nerve lesion length, as well as optical coherence tomography (OCT) measurement of mean RNFL thickness and macular volume, quantitative visual testing, and visual evoked potentials (VEPs). Fifteen controls were also studied. Significant optic nerve atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33% versus controls), and macular volume loss occurred in patients' affected eyes when compared with patients' unaffected eyes and healthy controls. The optic nerve atrophy was correlated with the RNFL thinning, macular volume loss, visual acuity, visual field mean deviation, and whole field VEP amplitude but not latency. These findings suggest that axonal loss contributes to optic nerve atrophy following a single attack of optic neuritis. By inference, axonal loss due to other post-inflammatory brain lesions is likely to contribute to the global MRI measure of brain atrophy in multiple sclerosis.
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PMID:Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy. 1644 3

The cystine/glutamate exchanger (xCT) provides intracellular cyst(e)ine for production of glutathione, a major cellular antioxidant. Using xCT overexpression and underexpression, we present evidence that xCT-dependent glutathione production modulates both neuroprotection from oxidative stress and cell proliferation. In embryonic and adult rat brain, xCT protein was enriched at the CSF-brain barrier (i.e., meninges) and also expressed in the cortex, hippocampus, striatum, and cerebellum. To examine the neuroprotective role of xCT, various non-neuronal cell types (astrocytes, meningeal cells, and peripheral fibroblasts) were cocultured with immature cortical neurons and exposed to oxidative glutamate toxicity, a model involving glutathione depletion. Cultured meningeal cells, which naturally maintain high xCT expression, were more neuroprotective than astrocytes. Selective xCT overexpression in astrocytes was sufficient to enhance glutathione synthesis/release and confer potent glutathione-dependent neuroprotection from oxidative stress. Moreover, normally nonprotective fibroblasts could be re-engineered to be neuroprotective with ectopic xCT overexpression indicating that xCT is a key step in the pathway to glutathione synthesis. Conversely, astrocytes and meningeal cells derived from sut/sut mice (xCT loss-of-function mutants) showed greatly reduced proliferation in culture attributable to increased oxidative stress and thiol deficiency, because growth could be rescued by the thiol-donor beta-mercaptoethanol. Strikingly, sut/sut mice developed brain atrophy by early adulthood, exhibiting ventricular enlargement, thinning of the cortex, and shrinkage of the striatum. Our results indicate that xCT can provide neuroprotection by enhancing glutathione export from non-neuronal cells such as astrocytes and meningeal cells. Furthermore, xCT is critical for cell proliferation during development in vitro and possibly in vivo.
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PMID:Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. 1703 36

Alzheimer's disease and frontotemporal dementia (FTD) can be difficult to differentiate clinically because of overlapping symptoms. Distinguishing the two dementias based on volumetric measurements of brain atrophy with MRI has been only partially successful. Whether MRI measurements of cortical thinning improve the differentiation between Alzheimer's disease and FTD is unclear. In this study, we measured cortical thickness using a set of automated tools (Freesurfer) to reconstruct the brain's cortical surface from T1-weighted structural MRI data in 22 patients with Alzheimer's disease, 19 patients with FTD and 23 cognitively normal subjects. The goals were to detect the characteristic patterns of cortical thinning in these two types of dementia, to test the relationship between cortical thickness and cognitive impairment, to determine if measurement of cortical thickness is better than that of cortical volume for differentiating between these dementias and normal ageing and improving the classification of Alzheimer's disease and FTD based on neuropsychological scores alone. Compared to cognitively normal subjects, Alzheimer's disease patients had a thinner cortex primarily in bilateral, frontal, parietal, temporal and occipital lobes (P < 0.001), while FTD patients had a thinner cortex in bilateral, frontal and temporal regions and some thinning in inferior parietal regions and the posterior cingulate (P < 0.001). Compared to FTD patients, Alzheimer's disease patients had a thinner cortex (P < 0.001) in parts of bilateral parietal and precuneus regions. Cognitive impairment was negatively correlated with cortical thickness of frontal, parietal and temporal lobes in Alzheimer's disease, while similar correlations were not significant in FTD. Measurement of cortical thickness was similar to that of cortical volume in differentiating between normal ageing, Alzheimer's disease and FTD. Furthermore, cortical thickness measurements significantly improved the classification between Alzheimer's disease and FTD based on neuropsychological scores alone, including the Mini-Mental State Examination and a modified version of the Trail-Making Test. In conclusion, the characteristic patterns of cortical thinning in Alzheimer's disease and FTD suggest that cortical thickness may be a useful surrogate marker for these types of dementia.
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PMID:Different regional patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia. 1735 26

Prenatal viral infection has been associated with development of schizophrenia and autism. Our laboratory has previously shown that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) administration of influenza virus. We hypothesized that late second trimester infection (E18) in mice may lead to a different pattern of brain gene expression and structural defects in the developing offspring. C57BL6J mice were infected on E18 with a sublethal dose of human influenza virus or sham-infected using vehicle solution. Male offsping of the infected mice were collected at P0, P14, P35 and P56, their brains removed and prefrontal cortex, hippocampus and cerebellum dissected and flash frozen. Microarray, qRT-PCR, DTI and MRI scanning, western blotting and neurochemical analysis were performed to detect differences in gene expression and brain atrophy. Expression of several genes associated with schizophrenia or autism including Sema3a, Trfr2 and Vldlr were found to be altered as were protein levels of Foxp2. E18 infection of C57BL6J mice with a sublethal dose of human influenza virus led to significant gene alterations in frontal, hippocampal and cerebellar cortices of developing mouse progeny. Brain imaging revealed significant atrophy in several brain areas and white matter thinning in corpus callosum. Finally, neurochemical analysis revealed significantly altered levels of serotonin (P14, P35), 5-Hydroxyindoleacetic acid (P14) and taurine (P35). We propose that maternal infection in mouse provides an heuristic animal model for studying the environmental contributions to genesis of schizophrenia and autism, two important examples of neurodevelopmental disorders.
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PMID:Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. 1824 90


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