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1.
The tumor suppressor gene PTEN on chromosome 10q23.3 regulates the Akt signaling pathway and modulates cell growth and apoptosis. The PTEN gene is mutated in 20–40% of glioblastomas. In this study, we assessed whether loss of PTEN expression is also caused epigenetically. Methylation-specific PCR revealed that CpG islands of the PTEN promoter were methylated in 27 of 77 (35%) glioblastomas and in 4 of 11 (36%) glioblastoma cell lines. Only two glioblastomas showed loss of PTEN immunoreactivity in the entire biopsy; both had a missense PTEN mutation and LOH at the PTEN locus, but lacked PTEN methylation. In biopsy specimens with focal loss of PTEN expression, DNA samples extracted from microdissected foci showed PTEN methylation only in areas with loss of PTEN expression. These results suggest that PTEN methylation occurs frequently in glioblastomas and may be associated with focal loss of PTEN expression. However, the correlation between PTEN methylation, PTEN mutations, LOH at the PTEN locus, and loss of PTEN protein expression was inconsistent. Possible reasons for discrepancies between gene status and protein expression include differences in the biological effect of specific PTEN mutations and the possibility that the processed PTEN pseudogene on 9p21 is expressed in glioblastomas and co-reacts with the PTEN antibody. 相似文献
2.
We assessed alterations in the EGFR/PTEN/PI3K pathway in 107 primary (de novo) glioblastomas and 32 secondary glioblastomas
that progressed from low-grade or anaplastic astrocytomas. SSCP followed by DNA sequencing in exons 9 and 20 of the PIK3CA gene revealed missense mutations in 5/107 (5%) primary and 1/32 (3%) secondary glioblastomas. Quantitative real-time PCR
showed PIK3CA amplification (>3 copy numbers) in 14/107 (13%) primary and 3/32 (9%) secondary glioblastomas. Only one glioblastoma showed
both PIK3CA mutation and amplification. Taken together with previously published data on EGFR amplification and PTEN mutations, at least one alteration in the EGFR, PTEN, or PIK3CA genes was detected in 63% of primary glioblastomas, which was significantly more frequent than in secondary glioblastomas
(31%; P < 0.001). Furthermore, this signaling pathway was altered by either PTEN mutations or PIK3CA amplification in 10 of 12 (83%) malignant glioma cell lines analyzed. These results suggest that the EGFR/PTEN/PI3K pathway
is frequently altered in glioblastomas and is a promising target for therapy, in particular for primary glioblastomas. 相似文献
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Aminollah Bahaoddini Hassan Farrashbandi Mostafa Saadat 《Journal of molecular neuroscience : MN》2009,38(2):173-177
Several antipsychotic agents are known to prolong the QT interval in a dose-dependent manner. The antipsychotic drugs are
substrates of the phase I of biotransformation enzymes of cytochrome P450. In order to find the possible influence of polymorphism
of GSTT1 (a member of class theta glutathione S-transferase) on rate-corrected QT interval (QTc) of schizophrenia patients, the present study was done. Forty-three schizophrenia
in-patients participated in the study. The patients were diagnosed as chronic schizophrenia according to structured clinical
interview using SCID-I (clinician version) to confirm and document DSM-IV diagnosis. Measurements of QT and RR intervals were
recorded using a magnifying grid on lead II. The QTc was calculated according to Bazett’s formula. Polymerase chain reaction-based
method was used in order to determine the GSTT1 genotypes. Based on the fitted model of multiple linear regression analysis, QTc decreased in persons with positive GSTT1 genotype in comparison with the null genotype (β = −0.328, t = −2.346, p = 0.024). Active genotype of GSTT1 decreased the QTc. Also, QTc was significantly associated with smoking status; it was decreased in smokers compared with
nonsmokers (β = −0.372, t = −2.372, p = 0.014). 相似文献
5.
Background
The Spontaneously Hypertensive Rat (SHR) shows a number of behaviours that closely parallel those seen in children with attention-deficit hyperactivity disorder. These include motor hyperactivity, excessive responses under a fixed-interval/extinction schedule, difficulty in acquiring operant tasks and increased sensitivity to immediate behavioural reinforcement. As in children with ADHD, the behavioural and cognitive deficits in the SHR are responsive to stimulants, including d-amphetamine and d,l-methylphenidate. The non-hyperactive Wistar Kyoto (WKY) rat strain is often used as a control in behavioural studies of the SHR, and WKY itself has been suggested to be a useful animal model of depression. Numerous studies have shown that dopaminergic neurotransmission is altered between the two strains. Human genetic studies have found associations between several dopaminergic genes and both ADHD and depression. 相似文献6.
Kishi T Ikeda M Kitajima T Yamanouchi Y Kinoshita Y Kawashima K Okochi T Inada T Ozaki N Iwata N 《Journal of neural transmission (Vienna, Austria : 1996)》2008,115(10):1457-1461
Several lines of evidence suggest that nicotinic cholinergic dysfunction may contribute to the cognitive impairments in schizophrenia.
The majority of high affinity nicotine binding sites in the human brain have been implicated in heteropentameric alpha4 and
beta2 subunits of neuronal nicotinic acetylcholine receptors; therefore, these two neuronal nicotinic acetylcholine receptors
genes (CHRNA4 and CHRNB2) are considered to be attractive candidate genes for the pathophysiology of schizophrenia. To represent these two genes in
a gene-wide manner, we first evaluated the linkage disequilibrium structure using our own control samples. Thirteen SNPs (7
SNPs for CHRNA4 and 5 SNPs for CHRNB2) were selected as tagging SNPs. Using these tagging SNPs, we then conducted genetic association analysis of case-control
samples (738 schizophrenia and 753 controls) in the Japanese population. No significant association was detected in the allele/genotype-wise
or haplotype-wise analysis. Our results suggest that CHRNA4 and CHRNB2 do not play a major role in Japanese schizophrenia. 相似文献
7.
Jainn-Jim Lin Chang-Teng Wu Shao-Hsuan Hsia Kuang-Lin Lin Cheng-Hsun Chiu 《Child's nervous system》2009,25(6):723-725
Introduction
Pseudomonas aeruginosa (PS) infection is serious in children and can cause malignant external otitis, endophthalmitis, endocarditis, meningitis,
pneumonia, and septicemia (Huang et al. Pediatr Infect Dis J 1). The treatment of Pseudomonas infection requires prompt medical evaluation and appropriate antibiotic treatment.
Case report We report the case of a 6-month-old boy with an unusual presentation of acute obstructive hydrocephalus owing to Pseudomonas meningitis. Treatment with optimal antibiotic begun immediately after the pathogen was recognized and continued for 4 weeks.
The patient received prompt surgical intervention for the complication of acute obstructive hydrocephalus.
Conclusion The early stage of obstructive hydrocephalus caused by community-acquired Pseudomonas is rare and should be immediately detected. 相似文献
8.
Buss C Schuelter U Hesse J Moser D Phillips DI Hellhammer D Meyer J 《Journal of neural transmission (Vienna, Austria : 1996)》2007,114(5):563-569
Summary. Corticosteroid-binding globulin (SERPINA6) deficiency is an extremely rare hereditary disorder characterized by reduced corticosteroid-binding
capacity with normal or low plasma corticosteroid-binding globulin concentration, and normal or low basal cortisol levels
associated with hypo-/hypertension and muscle fatigue. Here, we present a patient with severe muscle fatigue, normal blood
pressure, and abnormal high saliva cortisol levels following a standardized stress test. This patient was found heterozygous
for a de novo 367 asparagine-encoding variant of the corticosteroid-binding globulin gene, previously described as “transcortin Lyon”.
Both parents were homozygous for the (“wildtype”) 367 aspartate-encoding allele. To the best of our knowledge, this case represents
the first de novo mutation reported for corticosteroid-binding globulin deficiency, implicating a pathogenic role of variants of SERPINA6 in some cases of muscle fatigue. 相似文献
9.
We applied multiple ligation-dependent probe amplification (MLPA) to patients from three families with characteristic dopa-responsive dystonia (DRD) but no base change in the gene GCH1. We found a complete deletion of GCH1 in affected members of family 1, and partial deletions in affected individuals of family 2 (exons 4-6) and of family 3 (exons 2-6). The findings were confirmed by quantitative real-time PCR. Our investigations demonstrate the utility of MLPA for routine deletion analysis of GCH1 in DRD patients with no sequence changes in this gene. 相似文献
10.
Abstract.
We have performed genetic screening on the skeletal muscle chloride channel gene (CLCN1) in Taiwanese population. A total of four patients with myotonia congenita (MC) together with 106 normal individuals were examined. All 23 exons of the CLCN1 gene were analysed by direct sequencing of PCR products to detect the nucleotide changes. Five mutations and three polymorphisms were identified in this study. Among these, three missense mutations (S471F, P575S, D644G) and one polymorphism (T736I) are novel and could be unique to the Taiwanese. In addition, a previously documented recessive G482R mutation was identified in a heterozygous patient and his nonsymptomatic father, indicating that this mutation might indeed function recessively or dominantly with incomplete penetrance. In conclusion, this is the first report of MC in Taiwan with proven CLCN1 gene mutations and showing high molecular heterogeneity in Taiwanese MC patients. 相似文献
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Harshitha S.M. Sibin M.K. Chetan G.K. Dhananjaya I. Bhat 《Journal of molecular neuroscience : MN》2018,66(3):378-382
Lumbar disc degeneration (LDD) is a multifactorial disorder caused by genetic and environmental factors. Polymorphisms in several structural and inflammatory genes like collagens, aggrecan, matrix metalloproteinases are associated with the risk of disc degeneration. In this study, we analyzed the role of a few important single nucleotide polymorphisms in cartilage intermediate layer protein (CILP), collagen 9A2 (COL9A2) and matrix metalloproteinase 3 (MMP3) genes in LDD from an Indian population. Two hundred patients with LDD and 200 healthy controls were recruited for the study. Genotyping was performed by allelic discrimination assay. The rs2073711 polymorphism (CILP gene - GG genotype) was associated with reduced risk of LDD in the Indian population (OR?=?0.43, p?=?0.016). The rs591058 polymorphism (MMP3 gene - TT genotype) is found to be associated with lower risk among women (OR?=?0.34, p?=?0.041). No significant association was found between COL9A2 polymorphism rs7533552 and the risk of LDD. We conclude that the CILP gene polymorphism (rs2073711) is associated with a lower risk of LDD, the MMP3 (rs591058) gene polymorphism is associated with LDD among women, and the TT genotype confers a lower risk of LDD. 相似文献
14.
Sato J Shimazu D Yamamoto N Nishikawa T 《Journal of neural transmission (Vienna, Austria : 1996)》2008,115(9):1355-1365
SAP97 gene encodes the synaptic scaffolding PDZ proteins that interact with the L: -alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionate (AMPA), kainate and N-methyl-D: -aspartate (NMDA) type glutamate receptors. Because the disturbed glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia, we investigated association between the SAP97 gene and schizophrenia. We genotyped 23 SNPs capturing the known common haplotype variations of the gene in a sample comprising 229 schizophrenic patients and 214 matched controls. In a single marker analysis, ten SNPs displayed nominally significant (P < 0.05) association with schizophrenia, although the P values of these SNPs were non-significant after the Bonferroni correction. We also compared haplotype estimates based on case-control genotypes and observed significant association of eight-two- and three- SNP haplotypes with schizophrenia following permutation-based correction. Further examination of the above series of SNPs or haplotypes in each gender revealed significant associations between some of these SNPs or haplotypes and the disorder only in males. The present findings suggest that the SAP97 gene may be a susceptibility factor in male schizophrenics and that the modification of the glutamate receptors-SAP97 signaling pathway could be involved in the disease pathophysiology. 相似文献
15.
Lladó A Sánchez-Valle R Reñé R Ezquerra M Rey MJ Tolosa E Ferrer I Molinuevo JL 《Journal of neural transmission (Vienna, Austria : 1996)》2007,114(8):1051-1054
Summary We describe a new mutation in the PGRN gene (A303AfsX57) associated with late-onset frontotemporal dementia and with “cat’s eye” shaped intranuclear and cytoplasmatic
ubiquitin immunoreactive inclusions in the neuropathological exam. The A303AfsX57 mutation is consistent with a nucleotide
deletion in exon 8 (c908delC). This deletion causes a frameshift at codon 303 that introduces a premature termination codon
(A303AfsX57). 相似文献
16.
Raefski AS Carone BR Kaur A Krueger W O'Neill MJ 《Journal of molecular neuroscience : MN》2007,32(2):111-119
Certain neurobehavioral deficiencies associated with Turner Syndrome have been attributed to brain volumetric abnormalities,
particularly of the amygdala. Haplo-insufficiency of a non-dosage compensated gene or genes on the X chromosome has been hypothesized
to be the cause of the neuroanatomical defect. We examined gene expression levels of 6,628 genes in developing amygdalae of
late-stage embryos of a mouse model for Turner Syndrome. In total, 161 genes show significant differences in expression level
between TS and normal female amygdala. In silico pathway analysis of both X-linked and autosomal mis-regulated genes suggests that modulation of Wnt signaling is a critical factor in the normal growth and development of the amygdala.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
17.
Kahle PJ 《Acta neuropathologica》2008,116(1):87-95
Point mutations and genomic multiplications in the α-synuclein (αSYN) gene cause autosomal-dominant Parkinson’s disease. Moreover,
αSYN fibrils are the major component of Lewy bodies, the neuropathological hallmarks of Parkinson’s disease and dementia with
Lewy bodies as well as of glial cytoplasmic inclusions in multiple system atrophy. These diseases are collectively referred
to as α-synucleinopathies. Cellular mechanisms regulating αSYN fibril formation and toxicity are intensely studied in vitro,
and in cell culture and diverse animal models. Specific neuropathology was achieved in transgenic mouse models using several
promoters to express human wild-type and mutant αSYN in brain regions affected by the various α-synucleinopathies. Somatodendritic
accumulation of the transgenic αSYN with neuritic distortions was a common finding. The nigrostriatal dopaminergic projections
were surprisingly resistant to α-synucleinopathy in transgenic mice, although they tended to be more vulnerable to neurotoxins.
In a few mouse models, αSYN aggregated in an age-dependent manner into genuine fibrillar amyloid. Brain region selective αSYN
neuropathology correlated with specific behavioral impairments, such as locomotor dysfunction and cognitive decline. Thus,
the αSYN fibrillization process is tightly linked to neuropathology. The role and thus therapeutic potential of post-translational
modifications (ubiquitinylation, oxidation, phosphorylation, truncation) and modifier genes on αSYN neuropathology can now
be assessed in valid transgenic mouse models of α-synucleinopathies. 相似文献
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Jing Zhang Xingwang Li Yang Wang Jue Ji Fengping Yang Guoyin Feng Peng Wan Klaus Lindpaintner Lin He Guang He 《Journal of neural transmission (Vienna, Austria : 1996)》2009,116(3):357-361
Bipolar disorder is known to be subject to maternal transmission. Mitochondrial DNA has been suggested as playing a role in the illness. NDUFV2, located on 18p11.31-p11.2, encodes an important subunit of mitochondrial NADH (complex I). Previous studies have reported the association of NDUFV2 with bipolar disorder in the Japanese and Caucasian populations. Whether it is also a susceptible gene in the Chinese population is unknown. To study the role of NDUFV2 in bipolar disorder in the Chinese population, 506 unrelated bipolar patients and 507 unrelated controls of Chinese Han origin were recruited. Six SNPs (rs11661859, rs6506640, rs1156044, rs4148965, rs906807, rs977581) were genotyped using either TaqMan® technology or direct sequencing. The haplotype consisting of rs6506640 (?342G > A) and rs906807 (86C > T) was found to be associated with bipolar disorder (global p = 0.012 before corrected, p = 0.030 after 10,000 permutations; individual p (A–T of rs6506640–rs906807) = 0.014 after 100,000 permutations (p = 0.0065 before corrected). The genotype frequency of rs906807 differed between bipolar female patients and female controls (p = 0.012, uncorrected). No other individual associations of SNPs with bipolar were detected. Our study indicated that the regions spanning from the promoter to the exon 2 may contain susceptible polymorphisms which predispose to bipolar disorder. 相似文献
20.
Richards M Iijima Y Shizuno T Kamegaya Y Hori H Omori M Arima K Saitoh O Kunugi H 《Journal of neural transmission (Vienna, Austria : 1996)》2008,115(9):1347-1354
Previous studies suggested that genetic variations in the 5' region of Epsin 4, a gene encoding enthoprotin on chromosome 5q33, are associated with schizophrenia. However, conflicting results have also been reported. We examined the possible association in a Japanese sample of 354 patients and 365 controls. Seventeen polymorphisms of Epsin 4 [3 microsatellites and 14 single nucleotide polymorphisms (SNPs)] were selected. A microsatellite marker (D5S1403) demonstrated a significant difference in the allele frequency between patients and controls (uncorrected P = 0.04). However, there was no significant difference in the genotype or allele frequency between the two groups for the other microsatellites or SNPs. Haplotype-based analysis provided no evidence for an association. The positive result at D5S1403 no longer reached statistical significance when multiple testing was taken into consideration. Our results suggest that the examined region of Epsin 4 does not have a major influence on susceptibility to schizophrenia in Japanese. 相似文献