Search PubMed⌕ Search

Biomedical subjects

Y Miyoshi

Publications and source records attributed to Y Miyoshi.

At least 181 records · Page 10Linked to original sources
PubMed1992

Interstitial loss of the same region of 5q in multiple adenomas and a carcinoma derived from an adenomatous polyposis coli (APC) patient.

Accumulation of genetic alterations in oncogenes and tumor suppressor genes causes the transformation of a normal cell into a malignant cell. Recently, Fearon and Vogelstein (Cell 61:759-767, 1990) reported on a model for the genetic pathway in development of colorectal neoplasia. To investigate genetic alterations in colorectal carcinomas, we examined allelic losses on some chromosomes in adenomas and carcinomas derived from patients with adenomatous polyposis coli (APC). We found evidence for an interstitial deletion of 5q. Loss of heterozygosity (LOH) of 5q around the APC locus was observed in both adenoma and carcinoma in one case. The fact that the same region of chromosome 5 was lost in five adenomas and one carcinoma derived from the same patient suggests that a somatic interstitial deletion may be caused not by random mechanisms but by a specific mechanism.

Adenocarcinoma↗
PubMed1992

Screening for germ-line mutations in familial adenomatous polyposis patients: 61 new patients and a summary of 150 unrelated patients.

We report here the result of a screening for germ-line mutations in the adenomatous polyposis coli (APC) gene in 61 new familial adenomatous polyposis (FAP) patients as well as a summary of the results of 150 patients. Examination of the entire coding region of the APC gene, based on a ribonuclease protection assay coupled with the polymerase chain reaction (PCR), disclosed mutations that were considered to cause significant defects in the APC product in 97 of 150 unrelated FAP patients. Our findings revealed the following characteristics of the germ-line mutations of APC: 1) the great majority of the mutations were found to truncate the APC product; 2) almost all of the mutations were located within the first half of the coding region; 3) no correlation was observed between the locations of germ-line mutations and extracolonic manifestations in FAP patients; 4) more than 80% of base substitutions in the APC gene were from cytosine to other nucleotides, nearly one-third of which occurred at the GpG site. Our results provide information helpful to an understanding of the APC gene and will also contribute to presymptomatic diagnosis of members in FAP families.

Adenomatous Polyposis Coli↗
PubMed1992

A case of splenic vein occlusion caused by the intravenous tumor thrombus of nonfunctioning islet cell carcinoma.

We report herein a case of successfully treated advanced, nonfunctioning islet cell carcinoma associated with left-sided portal hypertension. The splenic vein was obstructed by a huge intravenous tumor thrombus developing from the main pancreatic tumor. Direct invasion to adjacent organs such as the spleen, colon, left kidney and stomach was also observed, although liver metastasis was not present. Radical resection was carried out with removal of these five involved organs and the patient is alive without recurrence more than 5 years after surgery.

Adenoma, Islet Cell↗
PubMed1992

Hepatic vascular and bile duct injury after ethanol injection therapy for hepatocellular carcinoma.

Three patients with serious hepatic vascular injury after percutaneous ethanol injection therapy for hepatocellular carcinoma (HCC) are described. In two cases, immediately after ethanol injection, liver function tests deteriorated and computed tomography (CT) showed a wedge-shaped low-density area due to liver infarction. In the other case, 1 year after ethanol injection, the intrahepatic bile duct in the right lobe was dilated and the right hepatic lobe atrophied. Endoscopic retrograde cholangiography showed stenosis of the main right hepatic duct. Since complications include both acute and delayed vascular injury after ethanol injection, patients should be followed for a long period after treatment.

Aged↗
PubMed1992

A point mutation of the T3 receptor beta 1 gene in a kindred of generalized resistance to thyroid hormone.

Mutations of the thyroid hormone receptor (TR) beta 1 gene have recently been detected in several unrelated families with generalized resistance to thyroid hormone (GRTH). We now report a novel point mutation in the TR beta 1 gene in a case of a Korean-Japanese kindred. The intracellular localization and the amount of TR proteins were considered to be normal by the immunocytochemical study of cultured skin fibroblasts from the patients using anti-T3 receptor antibody. The cDNA of the T3-binding domain of the TR beta 1 gene, synthesized from the total RNA of the patients' fibroblasts, was amplified by the polymerase chain reaction, and was sequenced. A point mutation, A to G, in one allele at 1612 resulting in an amino acid substitution from lysine 438 to glutamic acid was detected. The same mutation was identified in one allele in each of the affected members. In vitro translation products of the mutant TR beta 1 gene showed decreased T3-binding activity. These data suggest that a TR mutation is predominantly responsible for GRTH, irrespective of ethnic background.

Adolescent↗
PubMed1992

Does the type of anomalous arrangement of pancreaticobiliary ducts influence the surgery and prognosis of choledochal cyst?

A new classification of the anomalous arrangement of pancreaticobiliary ducts (APBD) has been proposed following amendments and modificiations of the previous one. Fifty-one cases of choledochal cyst complicated with APBD were extensively examined and analyzed for clear visualization of the APBD system to make a standard classification. APBD were classified broadly into three types: type I, type II, and type III with their subtypes. Type I of APBD was seen in 18 (35.3%), type II in 11 (21.6%) and type III in 22 (43.1%) cases, respectively. A radical operation, including complete excision of the dilated biliary duct followed by reconstruction of the biliary tract was the surgical treatment of choice, because the reflux of the pancreatic juice into the biliary tract is prevented. However, a dilated common channel or accessory pancreatic duct, according to the new Komi type Ib, IIb, and IIIc3 of APBD, could be the cause of relapsing pancreatitis leading to chronic pancreatitis, due to the formation of a protein plug or pancreatic calculus in the dilated duct, even after this radical operation. In two complicated cases of type IIIc3 of APBD in choledochal cyst, we performed a pylorus-preserving pancreatoduodenectomy as one of the operative methods of choice. Long-term follow-up, more than decades, is essential to evaluate the results of surgical procedure for choledochal cyst, especially in those complicated cases with type Ib, IIb, and IIIc3 of APBD according to the new Komi's classification.

Adolescent↗
PubMed1992

Immunohistochemical study of p53 expression in microwave-fixed, paraffin-embedded sections of colorectal carcinoma and adenoma.

Expression of p53, a tumor-suppressor gene product, was studied immunohistochemically in microwave-fixed, paraffin-embedded sections of 84 colorectal carcinomas and 44 adenomas. Using a monoclonal antibody (PAb1801), nuclear p53 was detected successfully in 51 of 84 (60.7%) cases of carcinomas, and no stain for p53 was demonstrated in the adjacent normal mucosa. The results in the microwave-fixed, paraffin-embedded sections correlated with those in the frozen sections. The incidence of p53 expression in colorectal carcinomas was high in the cases with distant metastasis, but it was not affected by clinicopathologic features such as tumor size or depth of invasion. In colorectal adenomas, only 4 of 44 (9%) adenomas expressed p53. This expression of p53, however, was restricted to only a few glands within tubular adenomas with mild dysplasia. Thus, p53 protein was expressed preferably by malignant tumors of the colorectum. The present study demonstrated the usefulness of microwave fixation to preserve p53. The immunohistochemical detection of p53 in microwave-fixed, paraffin-embedded sections of colorectal carcinoma and adenoma can provide valuable information about the mechanism of carcinogenesis in colorectal epithelium.

Adenoma↗
PubMed1992

Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene.

We examined somatic mutations of the adenomatous polyposis coli (APC) gene in 63 colorectal tumors (16 adenomas and 47 carcinomas) developed in familial adenomatous polyposis (FAP) and non-FAP patients. In addition to loss of heterozygosity (LOH) at the APC locus in 30 tumors, 43 other somatic mutations were detected. Twenty-one of them were point mutations; 16 nonsense and two missense mutations, and three occurred in introns at the splicing site. Twenty-two tumors had frameshift mutations due to deletion or insertion; nineteen of them were deletions of one to 31 bp and three were a 1-bp insertion. One tumor had a 1-bp deletion in an intron near the splicing site. Hence, 41 (95%) of 43 mutations resulted in truncation of the APC protein. Over 60% of the somatic mutations in the APC gene were clustered within a small region of exon 15, designated as MCR (mutation cluster region), which accounted for less than 10% of the coding region. Combining these data and the results of LOH, more than 80% of tumors (14 adenomas and 39 carcinomas) had at least one mutation in the APC gene, of which more than 60% (9 adenomas and 23 carcinomas) had two mutations. These results strongly suggest that somatic mutations of the APC gene are associated with development of a great majority of colorectal tumors.

Adenoma↗
PubMed1992

Insertion/deletion polymorphism and other restriction fragment length polymorphisms in the MCC gene.

The MCC gene is a candidate as a tumor suppressor gene for colorectal neoplasms. Further, MCC is tightly linked to the familial adenomatous polyposis (FAP) locus by linkage and physical analysis. Hence, restriction fragment length polymorphisms (RFLPs) of this gene might be very useful for presymptomatic diagnosis of individuals in families segregating mutant alleles of the APC gene. Here we report the identification of five polymorphic systems in MCC gene (both cDNA and genomic), one of which is an insertion/deletion polymorphism that is detectable by a polymerase chain reaction method. These five RFLP systems should be useful for linkage studies in FAP and for examining loss of heterozygosity at this locus in colonic polyps and tumors.

Adenomatous Polyposis Coli↗
PubMed1992

Endothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery.

ATP-sensitive K+ channels with a conductance of 30 pS in smooth muscle cells of porcine coronary artery were found to be highly active in the intact cell-attached patch configuration when the pipette contained a physiological concentration of Ca2+ (greater than 10(-4) M). In the inside-out configuration, these channels were activated by extracellular Ca2+ and blocked by cytosolic ATP and glibenclamide. Endothelin applied to the pipette specifically blocked these channels in a concentration-dependent manner in the cell-attached configuration (half-maximal inhibition, 1.3 x 10(-9) M). A K+ channel opener, nicorandil, activated these channels even in the presence of 10(-8) M endothelin. In the whole-cell current-clamp method, the cell membrane was depolarized by endothelin and then repolarized by nicorandil. The membrane depolarization is closely related to contraction of smooth muscle cells. These results suggest that the ATP-sensitive K+ channels are important in controlling the vascular tone of the coronary artery and that endothelin can increase vascular tone by blocking these channels.

Adenosine Triphosphate↗
PubMed1992

Mutations of the APC (adenomatous polyposis coli) gene in FAP (familial polyposis coli) patients and in sporadic colorectal tumors.

We have isolated several genes on chromosome 5q21 region tightly linked to hereditary familial polyposis coli (FAP) and Gardner's syndrome (GS). Two of these genes (MCC and APC) were found to be somatically altered by point mutation, deletion or insertion in tumors of sporadic colorectal cancer patients. One (APC) of them was also found mutations in the germ line of both APC and GS patients. The identification of these genes has significant implications for understanding the pathogenesis of colorectal neoplasia and for the diagnosis and counseling of individuals with inherited predispositions to colorectal cancer.

Adenomatous Polyposis Coli↗
PubMed1992

Unusual cases of benign stricture of the biliary tract.

Three patients, i.e., two adults and one child, with unusual benign stricture of the extrahepatic biliary duct are reported. Case 1 is a 63-year-old male with obstructive jaundice caused by a sclerotic vascular ring formed by the right hepatic artery and its branch. Case 2 is an 18-year-old male with obstructive jaundice due to stricture of the common bile duct caused by compression of enlarged collateral varicose veins, so-called cavernous transformation following extrahepatic obstruction of the portal vein. Case 3 is a 19-month-old boy complicated with biliary obstruction resulting from ischemic changes of the biliary duct at 10 months after extended right hepatectomy for mesenchymal hamartoma of the liver. The definitive diagnosis was made on the basis of imaging evaluations and the surgical findings. They have been free of jaundice and have shown an uneventful clinical course after the surgical interventions.

Adolescent↗
PubMed1992

[Complex chromosome aberrations between no. 17 and no. 21 in acute myelo-megakaryocytic leukemia: a case report].

A 10 month-old boy presented with fever. He was diagnosed as having acute myelo-megakaryocytic leukemia by electron microscopic cytochemical examination. In spite of aggressive chemotherapy, complete remission could not be achieved and he died seventeen months after the diagnosis was made. G-band karyotypes of the bone marrow cells revealed 45, XY, -17, -21, + dir tan dup (17;21) (17pter----cen----17q25::17q21----17q25;21q11 ----21qter). Furthermore, the same chromosomal aberrations were detected in the cells which were tetraploid and octaploid. Although, neoplastic changes in the progenitor cells immediately before differentiating to CFU-Meg and CFU-GM, are suggested there is a possibility of clonal evolution.

Chromosome Aberrations↗
PubMed1992

[Clinical and molecular biological study of Ph positive acute leukemia: comparison with blast crisis of chronic myelogenous leukemia and Ph negative acute lymphoblastic leukemia].

Eight cases of Philadelphia positive acute leukemia (Ph+AL) were compared with 13 cases of Ph+ chronic myelogenous leukemia in blast crisis (BC) and 10 cases of Ph negative acute lymphoblastic leukemia (Ph-ALL) based on the clinical and molecular biological findings. Distinguishing clinical features were a high leukocyte count (median; 147.9 x 10(3)/microliters) for Ph+AL, and a high incidence of tumor formation and basophilia for BC. A cytogenetic study demonstrated the disappearance or marked reduction of Ph+ metaphases in Ph+AL in remission, while Ph+ cells persisted in BC. The major bcr gene was not rearranged in 4 Ph+AL cases, whereas it was found rearranged in 4 other cases of Ph+ AL and 6 cases of BC. Reverse transcriptase polymerase chain reaction technique demonstrated the presence of minor bcr/abl mRNA in the former three cases, and major bcr/abl mRNA in the latter 4 cases. Remission rates were 63% for Ph+AL, 38% for BC, and 100% for Ph-ALL, and the 50% survival were 12, 5 and 29 months, respectively. It was concluded that Ph+AL can be differentiated from BC by a marked reduction of Ph+ cells at remission, and that the prognosis of Ph+AL is better than BC, but worse than Ph-ALL.

Adolescent↗
PubMed1991

Angiotensin II blocks ATP-sensitive K+ channels in porcine coronary artery smooth muscle cells.

ATP-sensitive K+ channels with small conductance (30 pS in symmetrical K(+)-rich solutions) in porcine coronary artery smooth muscle cells were highly active at physiological concentrations of Ca2+ (greater than 10(-4) M) even in the presence of physiological ATP levels, suggesting that these channels contribute to the generation of the resting membrane potential in vascular smooth muscle cells and their modulation is important in controlling vasomotor tone. Angiotensin II, applied from outside the membrane, blocked these channels in a concentration-dependent manner. This would be expected to cause depolarization and result in vasoconstriction.

Adenosine Triphosphate↗
PubMed1991

Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.

Previous studies suggested that one or more genes on chromosome 5q21 are responsible for the inheritance of familial adenomatous polyposis (FAP) and Gardner's syndrome (GS), and contribute to tumor development in patients with noninherited forms of colorectal cancer. Two genes on 5q21 that are tightly linked to FAP (MCC and APC) were found to be somatically altered in tumors from sporadic colorectal cancer patients. One of the genes (APC) was also found to be altered by point mutation in the germ line of FAP and GS patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS. The identification of these genes should aid in understanding the pathogenesis of colorectal neoplasia and in the diagnosis and counseling of patients with inherited predispositions to colorectal cancer.

Adenomatous Polyposis Coli↗