PubMed Health⌕ Search

Biomedical subjects

Y Dobashi

Publications and source records attributed to Y Dobashi.

At least 55 records · Page 3Linked to original sources
PubMed1996

Upregulation of the APC gene product during neuronal differentiation of rat pheochromocytoma PC12 cells.

The adenomatous polyposis coli (APC) gene, the mutation of which is responsible for familial adenomatous polyposis and sporadic colorectal tumors, is highly expressed in the central nervous system. To elucidate the contribution of the APC protein to neuronal differentiation, changes in APC expression were examined during nerve growth factor (NGF)-induced differentiation of rat pheochromocytoma PC12 cells. The expression of APC gradually increased throughout the time course, in particular it increased markedly after 7 days of exposure to NGF. However, forced expression of APC did not induce neuronal differentiation of PC12 cells. These results suggest that the APC protein itself does not have the potential to induce neuronal differentiation, but rather is upregulated secondary to the differentiation of PC12 cells.

Adenomatous Polyposis Coli Protein↗
PubMed1996

Persistent activation of CDK4 during neuronal differentiation of rat pheochromocytoma PC12 cells.

It has been shown that suppression of cyclin-dependent kinase 4 (CDK4) expression or its kinase activity is a critical event for the differentiation of hematopoietic and myoblastic cells. To investigate the role of CDK4 during NGF-mediated neuronal differentiation of PC12 cells, we examined the changes in the expression and kinase activity of CDK4. Unexpectedly, both the expression of CDK4 and its kinase activity remained high throughout 10 days of exposure to NGF. Furthermore, constitutive overexpression of the human CDK4 did not inhibit the differentiation. These results suggest that suppression of CDK4 is not required for the NGF-induced neuronal differentiation of PC12 cells.

Animals↗
PubMed1996

DNA polymerase beta gene mutations in human bladder cancer.

We examined 24 human bladder cancer tissues for possible mutations in the entire coding region of the human DNA polymerase beta gene using polymerase chain reaction analysis, single-strand conformational polymorphism analysis of RNA, and sequence analysis. DNA polymerase beta gene mutations were observed in four of the 24 cases (16.7%) and included three missense point mutations and a single base insertion. The single base insertion was also observed in our previous study of human prostate cancer, suggesting that this region may be a hot spot for mutation of the DNA polymerase beta gene. No clinical or pathological association was found among the four cases that contained the mutation. Three of the four cases with DNA polymerase beta gene mutation had mutations of the p16 or RB genes or loss of heterozygosity of the p53 and APC gene loci. The results of the study presented here suggest that DNA polymerase beta gene mutations, in combination with mutations of tumor suppressor genes, may be involved in certain cases of human bladder cancer.

Base Sequence↗
PubMed1996

Giant epiphrenic diverticulum with achalasia occurring 20 years after Heller's operation.

We report a case of giant epiphrenic diverticulum in a 43-year-old woman who underwent Heller's myotomy because of achalasia 20 years earlier. She complained of heartburn and dysphagia from March of 1991 and was hospitalized in our institution. An upper gastrointestinal X-ray examination with contrast medium revealed a large hemispheric lesion (7.8 x 4.8 cm) occupying the right posterior wall of the lower thoracic and abdominal esophagus. Manometry revealed a motility disorder and high pressure of the lower esophageal sphincter due to achalasia. Therefore she was diagnosed as having a giant diverticulum with achalasia after Heller's operation. She underwent transhiatal esophagectomy and reconstruction with placement of a gastric tube on June 4, 1992. Pathology results on the resected specimen revealed a false diverticulum. She has been doing well for 4 years since the operation. It has been said that a complication of incomplete long myotomy causes pulsion diverticulum, but we could not find a case of epiphrenic diverticulum after myotomy for achalasia reported in the literature in the last 10 years.

Diverticulum, Esophageal↗
PubMed1996

[Tuberculous mediastinal lymphadenitis presenting as hoarseness].

A 70 year-old woman was admitted to our hospital complaining of hoarseness. Bronchoscopic examination revealed that the left vocal cord was fixed in the paramedian position, and therefore left recurrent nerve paralysis was suspected. Although a chest X-ray film showed no abnormal findings, a chest computed tomogram showed that pretracheal (#3) and subaortic (#5) lymph nodes were swollen (1 to 2 cm in diameter). An open biopsy was done. Histological examination of the resected mediastinal lymph nodes revealed an accumulation of Langhans giant cells and epithelioid cells in caseous necrosis. An acid-fast bacillus was seen after Ziehl-Neelsen staining. This was a rare case of mediastinal tuberculous lymphadenitis in which hoarseness was useful for early diagnosis. Fifty-three cases of tuberculous mediastinal lymphadenitis have been reported in Japan.

Aged↗
PubMed1995

Constitutive overexpression of CDK2 inhibits neuronal differentiation of rat pheochromocytoma PC12 cells.

Changes in the levels of cyclins A, D, and E, p21, and cyclin-dependent kinase 2 (CDK2) were examined in rat pheochromocytoma PC12 cells during neuronal differentiation induced by nerve growth factor (NGF). Expression of cyclin A decreased to an undetectable level after 5 days of exposure to NGF, while expression of CDK2 decreased gradually after day 3. In contrast, the levels of cyclins D1 and E increased gradually through day 10, yet the amount of cyclin E associated with CDK2 decreased concomitant with a decrease in the CDK2 protein level. p21 expression increased gradually after day 7, while the level of CDK2-associated p21 remained unchanged. When human cDNAs encoding cyclins and CDK2 were introduced into PC12 cells, only CDK2 overexpression inhibited NGF-induced differentiation. The cell lines overexpressing CDK2 showed stable and high levels of CDK2 kinase activity during differentiation, whereas parental and vector-transfected cell lines displayed a marked decline in CDK2 kinase activity 1 day after NGF treatment. In cell lines overexpressing cyclins A, D, and E, this reduction of the kinase activity was not apparent until day 3. These results suggest that down-regulation of CDK2 activity is a crucial event for the neuronal differentiation of PC12 cells.

Adrenal Gland Neoplasms↗
PubMed1995

Expression of transforming growth factor-beta 1 in human bladder cancer.

BACKGROUND: Elevated expression of transforming growth factor-beta 1 (TGF-beta 1) has been reported in several types of human cancer. However, the significance of TGF-beta 1 expression in clinical bladder cancer is not well known. METHODS: The levels of TGF-beta 1 expression were quantitated using a polymerase chain reaction-based method in tissue specimens obtained from 51 patients with bladder cancer. RESULTS: Transforming growth factor-beta 1 expression in bladder cancer was higher than that found in normal bladder epithelium (P < 0.01). Significantly higher levels of TGF-beta 1 transcripts were observed in low and intermediate grade (Grade 1 and 2) tumors than in high grade (Grade 3) tumors (P < 0.02). Superficial (pTa and pT1) tumors had higher levels of TGF-beta 1 than invasive (pT2 or higher) tumors (P < 0.05). CONCLUSIONS: These results suggest that enhanced expression of TGF-beta 1 is specific to low grade and stage bladder cancer. Transforming growth factor-beta 1 may play an important role in the early stages of human bladder cancer development, and TGF-beta 1 expression could provide a new relevant tumor marker for determining tumor progression in patients with bladder cancer.

Actins↗
PubMed1995

Tumor suppressor gene p53 mutations in human prostate cancer.

The genetic background underlying the growth and development of human prostatic cancer is not yet clear. Here we searched for possible mutations in the entire coding region of tumor suppressor gene p53 in primary human prostatic carcinomas, using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. We found p53 gene mutations in 4 of 21 cases (19%). DNA sequencing of the polymerase chain reaction products revealed missense point mutations that resulted in amino acid changes in exon 5 or 3 in three cases and single base deletions in exon 7 in two cases. One case contained both a missense point mutation and a single base deletion. Three of these four cases were pathologically diagnosed as poorly differentiated adenocarcinomas, and three of the four cases were clinically localized to stage C or D. None of seven noncancerous prostate tissues nor three well-differentiated adenocarcinoma tissues showed any mutations. The present results suggest that p53 gene mutation is involved in the late progression steps of human prostate carcinogenesis.

Adenocarcinoma↗
PubMed1995

Retinoblastoma gene mutations in primary human prostate cancer.

Structural alterations in the entire coding regions (exons 1 to 27) of the retinoblastoma (RB) gene in primary human prostate cancers were investigated, using polymerase chain reaction and single strand conformational polymorphism analysis of RNA. Of 25 samples obtained from patients, four (16.4%) were found to have RB alterations. DNA sequencing of the PCR products revealed point mutations resulting in single amino-acid substitutions of exons 6 and 19 in two cases, and base deletions of exons 8 and 17 in two cases. Two of four cases with RB mutations were moderately differentiated localized tumors and other two with RB mutations were poorly differentiated tumors with metastases. Our results suggest that RB gene mutation is involved in progression steps of prostate carcinogenesis.

Adenocarcinoma↗
PubMed1995

Polymorphisms in the human DNA polymerase beta gene.

Recently, evidence has accumulated that mutations in DNA repair genes might be associated with certain steps in carcinogenesis. The DNA polymerase beta gene is one of the DNA repair genes, and mutations in it have been detected in 83% of human colorectal cancers. To assess the involvement of polymerase beta gene mutations in the development of human prostate cancers, we performed sequence analyses of human DNA samples. Unexpectedly, we found six regions that were polymorphic. This information should be taken into consideration at the time of sequence analysis of the DNA polymerase beta gene.

Base Sequence↗
PubMed1995

Portal hypertension: influence on management.

In treating cases of portal hypertension, it is important to know the intramural, extramural, and communicating vascular structures of the esophagus and stomach using EUS. From these structures, suitable treatment for the esophagogastric varices can be selected and the efficacy of treatment can be evaluated.

Endoscopy, Digestive System↗
PubMed1995

Infrequent somatic mutations of the p16 and p15 genes in human bladder cancer: p16 mutations occur only in low-grade and superficial bladder cancers.

A recently identified gene, p16, located on chromosome 9p21, has been shown to be deleted and/or mutated in various types of human cancers. To investigate structural alterations of p16 and a neighboring gene, p15, we examined human bladder cancers for mutations in the entire coding region of these genes using polymerase chain reaction and single-strand conformational polymorphism analysis. Of 50 samples obtained from patients with bladder cancer, 3 (6%), all low-grade and superficial tumors, were found to have p16 gene alterations. The alterations included 1 missense mutation and 2 single-base deletions. We found no p15 gene mutations in these 50 bladder cancers. Our results suggested that p16 gene mutations, although they occurred at low frequency, are involved in some low-grade and early stage bladder cancers.

Base Sequence↗
PubMed1994

DNA polymerase beta gene mutation in human prostate cancer.

DNA polymerase beta is a nuclear protein essential to DNA repair in mammalian cells. A high frequency of mutations in this gene has been reported in colorectal cancers. To clarify the tumorigenesis steps of human prostate cancers in the molecular basis, we examined the entire coding region of the human DNA polymerase beta gene in human prostate cancer tissues using polymerase chain reaction, single-strand conformational polymorphism analysis of RNA, and sequencing analysis. Consequently, we detected DNA polymerase beta gene mutations in 2 of 12 cases (17%). The first case is an A to G transition at nucleotide 893, resulting in a substitution of the amino acid from tyrosine to cysteine. In the second case, we found an A to G transition at nucleotide 305, a T deletion at nucleotide 569, and an A insertion into the 6 repeats of A from nucleotide 612 to 617. This T deletion shifted the subsequent reading frame and resulted in the premature termination at codon 163 instead of 336. The two cases were advanced grade and stage. Present results suggest that polymerase beta gene mutations, although they occurred at relatively low frequency, are involved in certain cases of human prostate carcinogenesis.

Adenocarcinoma↗
PubMed1994

An approach to the hepatic hilus with marked fibrosis: a surgical technique for reconstruction of the bile duct with a benign stricture.

It is very difficult to approach the hepatic hilus safely in patients with common and/or hepatic bile duct strictures in which normal tissue has been replaced by scarred tissue with firm fibrous adhesions. In this report, we describe how eight patients with benign strictures of the bile duct underwent an operation which involved dividing the superior mesenteric and portal veins from the lower margin of the pancreas in a dorsal direction using a finger in a tunneling technique. The common bile duct, which was buried in scar tissue, was then explored, while the common and/or proper hepatic arteries in the hepatoduodenal ligament were confirmed, after transsection at the superior margin of the pancreas. Biliary reconstruction was successfully performed after resection of the constricted bile duct in all the patients, none of whom have experienced recurrence from 6 months to 5 years after the operation.

Aged↗
PubMed1994

Stepwise participation of p53 gene mutation during dedifferentiation of human thyroid carcinomas.

The spectrum of p53 gene mutations was investigated in thyroid carcinomas with respect to histopathological classification. In all histological subtypes of thyroid carcinoma that had previously revealed positivity in immunohistochemical staining for p53 protein, single-stranded conformation polymorphism analysis and direct sequencing were performed to detect point mutations between exons 5 and 8. In well differentiated papillary and follicular carcinomas, in which we had already known that 11.1 and 14.3% of the cases, respectively, revealed p53 overexpression as determined by immunohistochemistry, genetic aberrations were undetectable. In poorly differentiated carcinoma, in which 40.9% had revealed overexpression, two of six cases revealed point mutations at codon 244 in exon 7 and at codon 278 in exon 8. In undifferentiated carcinoma, in which 63.6% had revealed overexpression, four of six cases examined showed point mutations at codon 157 in exon 5, at codon 248 in exon 7, and at codon 273 and a two-base insertion between codons 266 and 267 in exon 8. These results strongly suggest the crucial role of p53 gene aberration and protein overexpression in a biologically aggressive subtype, possibly as a stepwise participation in the process of tumor dedifferentiation in human thyroid carcinomas.

Amino Acid Sequence↗