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J-M Luo H Yoshida S Komura N Ohishi L Pan K Shigeno I Hanamura K Miura S Iida R Ueda T Naoe Y Akao R Ohno K Ohnishi 《Leukemia》2003,17(1):1-8
The SH2 domain-containing inositol 5'-phosphatase (SHIP) is crucial in hematopoietic development. To evaluate the possible tumor suppressor role of the SHIP gene in myeloid leukemogenesis, we examined primary leukemia cells from 30 acute myeloid leukemia (AML) patients, together with eight myeloid leukemia cell lines. A somatic mutation at codon 684, replacing Val with Glu, was detected in one patient, lying within the signature motif 2, which is the phosphatase active site. The results of an in vitro inositol 5'-phosphatase assay revealed that the mutation reduced catalytic activity of SHIP. Leukemia cells with the mutation showed enhanced Akt phosphorylation following IL-3 stimulation. K562 cells transfected with the mutated SHIP-V684E cDNA showed a growth advantage even at lower serum concentrations and resistance to apoptosis induced by serum deprivation and exposure to etoposide. These results suggest a possible role of the mutated SHIP gene in the development of acute leukemia and chemotherapy resistance through the deregulation of the phosphatidylinositol-3,4,5-triphosphate (PI(3,4,5)P3)/Akt signaling pathway. This is the first report of a mutation in the SHIP gene in any given human cancer, and indicates the need for more attention to be paid to this gene with respect to cancer pathogenesis. 相似文献
95.
The expression of alternatively spliced mRNAs for amyloid precursor protein (APP) isoforms and their translation products were examined in the rat cerebral cortex 1, 3, 6, and 12 h and 1, 3, and 7 days (n = 4-5 in each group) after fluid-percussion brain injury. In situ hybridization studies demonstrated that the expression of APP695 mRNA decreased in and around the damaged area of the cerebral cortex exposed to fluid-percussion injury 1 h after the insult. On the other hand, APP751/770 mRNAs were increased in the regions surrounding the damaged cortical areas 1 day after the injury. An increase of immunoreactive APP was detected in the regions around the damaged cortical areas 3 h after traumatic injury and maintained for the following 3 days. The APP immunoreactivity in the damaged cortices declined to the level of sham-operated animals by post-experimental day 7. Using an anti-amyloid beta (Abeta) protein (17-24) antibody, no deposits of immunoreactive Abeta (17-24) were observed in any of the samples examined in these experiments. These results suggest that the induction of Kunitz-type protease inhibitor (KPI) domain-containing APP mRNAs and the increased accumulation of APP are involved in the physiological and neuropathological responses of brains under various neurodegenerative conditions, including head trauma. 相似文献
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Lung autopsies from four neonates with Ebstein's anomaly or tricuspid valve dysplasia and gross cardiomegaly were examined.
The mean cardiothoracic ratio was 92 ± 0.5%. The degrees of pulmonary hypoplasia and pulmonary artery muscularization were
assessed and were compared with those in lungs from four controls and four patients with diaphragmatic hernias. Lung and body
weight ratios and radial alveolar counts, which reflect pulmonary hypoplasia and immaturity, were significantly decreased
only in patients with diaphragmatic hernia. The thickness of the medial muscle layer in small pulmonary arteries was greater
in patients with diaphragmatic hernia; however, in patients with tricuspid valve disease, it was relatively small. Abnormal
vascular muscle extension was seen only in patients with diaphragmatic hernia. In the cases of tricuspid valve disease, although
cardiomegaly and lung compression were severe, lung hypoplasia and immaturity were not, and neither abnormal medial thickening
nor extension were found. Our results suggest that, at least in full-term infants with tricuspid valve disease, surgical relief
of lung compression may improve respiratory function, even if the cardiomegaly is severe. 相似文献
98.
Arai H Ishiguro K Ohno H Moriyama M Itoh N Okamura N Matsui T Morikawa Y Horikawa E Kohno H Sasaki H Imahori K 《Experimental neurology》2000,166(1):201-203
Cerebrospinal fluid (CSF) tau protein phosphorylated at both Thr231 and Ser235 sites (CSF/phospho-tau(231-235)) and total tau (CSF/total-tau) were quantified by sandwich ELISA in 20 patients with mild cognitive impairment (MCI) who eventually developed AD on follow-up as well as seven memory complainers with no objective memory loss. 13/20 (65%) of the MCI patients had high CSF/total-tau and detectable levels of CSF/phospho-tau(231-235), whereas these markers were low and under a detectable level in all of the memory complainers. Although either a total-tau, phospho-tau measurement or a combination of these can help in predicting if MCI will develop AD, our results suggest that the pathogenic steps of AD may be at the stage that finally leads to an accumulation of abnormally phosphorylated tau and neuron death, at least in some brain areas, when MCI patients present with the earliest detectable clinical symptoms of dementia. 相似文献
99.
Causes of nocturnal urinary frequency and reasons for its increase with age in healthy older men 总被引:1,自引:0,他引:1
PURPOSE: We investigate the causes of nocturnal urinary frequency and reasons for its increase with age. MATERIALS AND METHODS: All voided volumes and times were recorded for 3 days in 188 healthy older men without prostatic diseases during a mass screening program for prostatic diseases in Japan. Nocturnal urinary frequency for each night was defined as the frequency during sleep not counting the morning void. Relationships between nocturnal urinary frequency and functional bladder capacity, nocturnal bladder capacity, nocturnal urinary volume and sleep time were analyzed. Age related changes in functional and nocturnal bladder capacity, and nocturnal and diurnal urinary volume were evaluated. RESULTS: Multiple regression analysis demonstrated nocturnal bladder capacity and urinary volume to be significant independent determinants of nocturnal frequency. In age related analysis nocturnal bladder capacity and diurnal urinary volume decreased with age, while nocturnal urinary volume did not change. CONCLUSIONS: Nocturnal urinary volume and nocturnal bladder capacity were the significant determinants of nocturnal urinary frequency in healthy older men. The increase of nocturnal frequency with age was thought to be due to a decrease in nocturnal bladder capacity, since urinary volume did not change. In older men a decrease in water intake might influence age related changes in urinary volume. 相似文献
100.
Ohno T Ikebuchi E Henomatsu K Kasai K Nakagome K Iwanami A Hiramatsu K Hata A Fukuda M Honda M Miyauchi M 《Psychiatry research》2000,100(3):155-167
Social skill deficits in schizophrenia profoundly affect patients' life-long outcome, although the profile of the underlying cognitive dysfunction still remains a matter of debate. In the present study, we investigated the relationship between social skills and event-related potentials (ERPs) in an auditory selective attention task, in addition to the neurocognitive indices obtained from the degraded-stimulus continuous performance test (CPT) and clinical indices, such as Brief Psychiatric Rating Scale (BRPS) and global assessment of function (GAF) scores. Social skills were assessed using a Japanese version of the structured role play test. Fourteen persons with schizophrenia participated in the study. Non-verbal skills showed a positive correlation with GAF, the performance level, N1 and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Verbal communication skills showed a positive correlation with GAF, the performance level and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Processing skills showed a positive correlation with the performance level and N1 amplitude in the ERP task and a negative correlation with reaction time in the CPT. These findings suggested that the social skill deficits of persons with schizophrenia were related to the vigilance level and controlled stimulus detection processing. 相似文献