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Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 163 records · Page 9Linked to original sources

Mutations of p53 in morphologically non-neoplastic mucosa of long-standing ulcerative colitis.

Two cases of ulcerative colitis (UC)-associated carcinoma or dysplasia and morphologically non-neoplastic mucosa with p53 protein overexpression (MNNM-p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5 - 8 of the p53 gene were analyzed by PCR and direct sequencing. In addition, mutations in K-ras codon 12 were analyzed by PCR-RFLP methods. MNNM-p53OE was located surrounding and adjoining a coexisting carcinoma and / or dysplasia. A p53 mutation was detected in 12 / 22 (54.5%) MNNM-p53OE samples, 4 / 8 (50%) dysplasia samples and 8 / 8 (100%) carcinoma samples. The p53 mutations detected in MNNM-p53OE were identical to those demonstrated in the adjoining carcinoma and / or dysplasia. No K-ras codon 12 mutation was detected in any of the samples. These results indicate that MNNM-p53OE may share an identical clonal linkage with a coexisting carcinoma and / or dysplasia, and may be an initial and submorphological form of UC-associated neoplasia. Recognition of MNNM-p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.

Adult↗

Heterogeneity of p53 mutational status in intramucosal carcinoma of the colorectum.

The aim of this study was to elucidate whether or not p53 genetic heterogeneity would occur while colorectal carcinoma was limited to the mucosa. Eight cases of endoscopically resected colorectal intramucosal carcinomas were analyzed to determine the p53 gene sequence (exons 5 to 8). Six out of 8 cases showed p53 gene mutations, and in all of them, the mutational status was heterogeneous. In 4 cases, mutated codons were heterogeneous as well. These data indicate that p53 gene alterations in colorectal carcinomas occur and diverge at the stage of intramucosal carcinoma, supporting our previously proposed hypothesis that colorectal carcinomas can be composed of various subclones as regards p53 gene mutation, while the carcinoma is limited to the mucosa, and one of these subclones commences invasion to the submucosa after clonal selection, thus generating a monoclonal invasive carcinoma.

Carcinoma↗

[Serovar-distribution and drug-resistance of Salmonella strains isolated from domestic and imported cases during 1995-1999 in Tokyo].

A total of 2,277 non-typhoidal Salmonella strains consisting of 1,807 domestic strains and 470 imported strains isolated from sporadic cases during 1995-1999 in Tokyo, were examined regarding their serovar-distibution and their drug-resistance. The serological typing results showed that the domestic strains were classified into 17 O-groups and 99 serovars, and the imported strains were classified into 12 O-groups and 58 serovars. Among the serovars identified, Salmonella serovar Enteritidis (S. Enteritidis), S. Thompson, S. Hadar, S. Infantis, S. Typhimurium, and S. Litchfield were predominant in the domestic strains, whereas S. Enteritidis, S. Anatum, S. Hadar, and S. Weltevreden were predominant in the imported strains. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX) showed that 34.0% of the domestic strains and 33.0% of the imported strains were resistant to any of the drugs examined. The serovars of a high resistant rate during this period were S. Blockley (100%), S. Hadar (96.6%), S. Typhimurium (63.6%), and S. Enteritidis (62.2%) in the domestic strains and S. Blockley (100%), S. Hadar (97.1%), S. Rissen (88.9%), S. Emek (83.3%), S. Panama (83.3%), and S. Typhimurium (77.8%) in the imported strains. Drug-resistance patterns of the resistant isolates varied to 60 types. Prevalent patterns recognized were SM, TC.SM, TC, TC.SM.KM.ST, TC.SM.KM, and CP.TC.SM.ABPC in the domestic strains and TC.SM, TC, NA, TC.SM.KM.NA, and TC.SM.NA in the imported strains.

Drug Resistance, Microbial↗

[Serovar-distribution, drug-resistance, and DNA analysis of Salmonella strains isolated from sporadic diarrhea cases or healthy cases in Tama, Tokyo (1991-2000)].

Serovar-distribution and drug-resistance of a total of 421 Salmonella strains, which were 98 stains from sporadic diarrhea cases and 323 strains from healthy cases between 1991 and 2000 in Tama, Tokyo were investigated. In serological typing tests, the strains tested were classified into 26 different kinds of serovar in diarrhea cases, 58 in food handlers, and 25 in individuals for health care. Salmonella serovar Enteritidis (S. Enteritidis) was the most predominant serovar in three cases. Following, S. Typhimurium and S. Infantis in diarrhea cases, S. Hadar, S. Montevideo and S. Thompson in food handlers, or S. Typhimurium, S. Lichfield and S. Oranienburg in healthy individuals were frequent. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, SXT, NA, FOM, and NFLX) showed that 57.1% of the strains from diarrhea cases and 36.8% from the healthy cases were resistant to one or the other of the drugs examined. Drug-resistance patterns of those showed 13 types in diarrhea cases and 25 types in healthy cases. Out of them, strains which showed a predominant and common pattern in both cases were SM resistant-S. Enteritidis and CP.TC.SM.ABPC resistant-S. Typhimurium. In addition, the latter strains were also resistant to sulfiso-xzole (SU). In DNA analysis by RAPD method of their strains, common DNA finger-prints were observed in both cases through out the investigation period.

DNA, Bacterial↗

Design of synchrotron light source and its beamline dedicated to dual-energy x-ray computed tomography.

A synchrotron light source dedicated to medical applications has been designed at National Institute of Radiological Sciences. The storage ring, with circumference of 80 m, is designed for acceleration of 2.3 GeV and a stored current of 420 mA. It is equipped with two multipole wigglers to produce sufficient photon flux in a hard x-ray region required for medical applications. The purposes of the synchrotron light source are clinical performance of medical diagnoses clinically and research and development relating with medical applications. One of the most interesting applications for us is dual-energy x-ray computed tomography (CT). It gives the information about electron density of human tissue. The information plays an important role in advancing heavy-ion radiotherapy of cancers. Electron density can be derived from attenuation coefficients measured by different energy x rays. In this paper, a practical method of the dual-energy x-ray CT with synchrotron radiation is proposed with the theoretical consideration. The primitive experiment using monochromatic x rays emitted from radioisotopes proved the procedure of analysis mentioned here effective to derive electron densities from linear attenuation coefficients for two x rays of a different energy. The beamline dedicated to dual-energy x-ray CT is also proposed. It has a multipole wiggler as a light source and it mainly consists of a dual crystal monochromator and a rotating filter for attenuating photon flux of x rays and two-dimensional detector.

Equipment Design↗

Platelet monoamine oxidase B and plasma beta-phenylethylamine in Parkinson's disease.

OBJECTIVE: To evaluate the correlation between changes in platelet monoamine oxidase type B (MAO-B) activity and plasma beta-phenylethylamine (PEA) concentrations in patients with Parkinson's disease and controls. METHODS: Platelet MAO-B activity and plasma PEA were measured with gas chromatography-mass spectrometry (GC-MS) in patients with Parkinson's disease treated with levodopa (12 men and 12 women) or selegiline (three men and three women), and physically healthy subjects as a control group (10 men and 10 women). RESULTS: Platelet MAO-B activity was significantly higher in the Parkinson's disease group (mean 542 (SD 318) pmol/10(7) platelets/30 min) than in the control group (mean 349 (SD 307) pmol/10(7) platelets/30 min) (p<0.05). By contrast, the plasma PEA concentrations in patients with Parkinson's disease were significantly lower than in the control group (mean 532 (SD 243) pg/ml; 931 (SD 560) pg/ml) (p<0.01). The plasma PEA concentrations in patients with Parkinson's disease treated with selegiline were prominently higher than in patients with no selegiline treatment (p<0.001). There was a significantly negative correlation between platelet MAO-B activity and plasma PEA concentrations in patients (n=24, r=-0.466, p<0.001). CONCLUSIONS: The increase in platelet MAO-B activity and decrease in plasma PEA concentrations in patients with Parkinson's disease may be involved in the pathophysiological processes of the disease, and these changes are reversed by treatment with selegiline.

Aged↗

Differentiation of immature enterocytes into enteroendocrine cells by Pdx1 overexpression.

The development of a variety of enteroendocrine cells of the gut is poorly understood. We tested whether immature intestinal stem cells were switched to multiple enteroendocrine hormone-producing cells by in vitro transfer of a homeobox gene. We transfected the pancreatic-duodenal homeobox 1 gene (Pdx1) into IEC-6 cells, an embryonic intestinal epithelial cell line derived from a normal rat, and selected the cells that overexpressed Pdx1 by 150-fold compared with control. The cells were examined for differentiation into enteroendocrine cells by immunocytochemical and electron microscopic analyses. Transfected cells cultured on micropore filters formed a trabecular network piled up on monolayer cells. These trabecular cells showed nuclear localization of Pdx1 protein and contained well-developed rough endoplasmic reticulum as well as many secretory granules of pleomorphic shape in the cytoplasm. Antibodies against chromogranin A, serotonin, cholecystokinin, gastrin, and somatostatin stained these secretory granules in the cytoplasm. Furthermore, immunofluorescence double staining analysis showed that different hormones were produced within a cell. These results provide the evidence that immature intestinal epithelial cells can differentiate into multiple hormone-producing enteroendocrine cells in response to overexpression of Pdx1.

Animals↗

George Austin, MD.

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History, 20th Century↗

Pericapillary arteriovenous malformations angiographically manifested as cerebral venous malformations.

Cerebral venous malformations have been diagnosed by angiographic features and are considered to be a benign anomaly. However, ample evidence indicates that stroke or similar symptomatology occurs in patients harboring a cerebral vascular malformation that was diagnosed angiographically as a venous malformation. The purpose of the study is to confirm the presence of a pericapillary arteriovenous malformation in these patients by analyzing the clinical history and surgical findings and correlating them with histological features. Thirteen patients were included in this study. Each patient fulfilled four criteria: 1. the patient was neurologically symptomatic; 2. the angiographic diagnosis was a venous malformation; 3. at operation, shunting arterioles (50-100 microns) were found to contribute to the malformation; and 4. histologically, a mixture of venous channels and arterioles with arterioles directly connected to venules was found. Based on the above findings, the malformation present in the 13 patients can be termed a 'pericapillary arteriovenous malformation'. Its angiographic distinction from the cerebral venous malformation requires technological advancement in the capability of magnifying images of arterioles and venules, along with improvement in image resolution.

Adult↗

Genetic dissection of nodal function in patterning the mouse embryo.

Loss-of-function analysis has shown that the transforming growth factor-like signaling molecule nodal is essential for mouse mesoderm development. However, definitive proof of nodal function in other developmental processes in the mouse embryo has been lacking because the null mutation blocks gastrulation. We describe the generation and analysis of a hypomorphic nodal allele. Mouse embryos heterozygous for the hypomorphic allele and a null allele undergo gastrulation but then display abnormalities that fall into three distinct mutant phenotypic classes, which may result from expression levels falling below critical thresholds in one or more domains of nodal expression. Our analysis of each of these classes provides conclusive evidence for nodal-mediated regulation of several developmental processes in the mouse embryo, beyond its role in mesoderm formation. We find that nodal signaling is required for correct positioning of the anteroposterior axis, normal anterior and midline patterning, and the left-right asymmetric development of the heart, vasculature, lungs and stomach.

Alleles↗

Muscarinic receptor binding characteristics in rat tissues after oral administration of oxybutynin and propiverine.

Ex vivo muscarinic receptor binding of oxybutynin and propiverine, the most commonly used anticholinergic agents for the treatment in patients with urinary incontinence, was investigated in rat tissues. The oral administration of oxybutynin (50.8 and 127 micromol/kg) caused a significant increase in the apparent dissociation constant (Kd) for specific (-)-[3H]QNB binding in the rat bladder, prostate, submaxillary gland, heart and cerebral cortex, compared with each of the control values. Also, in the submaxillary gland of these rats, there was a reduction in the maximal number of binding sites (Bmax) for (-)-[3H]QNB binding. Similarly, oral administration of propiverine at doses of 74.3-297 micromol/kg brought about a significant increase in the Kd values for (-)-[3H]QNB binding in rat tissues including the bladder, and greater increase in Kd values was seen in the rat prostate, heart and submaxillary gland. On the other hand, oral administration of propiverine, unlike oxybutynin, resulted in very little reduction in the Bmax valules for (-)-[3H]QNB binding in the submaxillary gland. In conclusion, the present study has shown that oxybutynin and propiverine, after oral administration, bind significantly to muscarinic receptors in tissues such as the bladder, which is the target organ for the treatment of urinary incontinence, and that oxybutynin appears to exhibit long-term binding to muscarinic receptors in the salivary gland.

Administration, Oral↗

Characterization of specific [3H]nociceptin binding in rat brain and spinal cord.

The present study was undertaken to characterize simultaneously [3H]nociceptin binding to opioid receptor-like 1 (ORL1) receptors in the rat brain and spinal cord. Specific binding of [3H]nociceptin to crude membranes from the rat brain and spinal cord at 25 degrees C was saturable, reversible and of high affinity, and it also exhibited a pharmacological specificity involving the ORL1 receptor. The Kd and Bmax values for [3H]nociceptin in the spinal cord were significantly lower than those in the brain. At 4 degrees C, there was a significant increase in the dissociation constant (Kd) for [3H]nociceptin in the brain and spinal cord with little change in the maximal number of binding sites (Bmax) compared with that at 25 degrees C. Nociceptin and its analogue, [Phe1 psi(CH2-NH)-Gly2]nociceptin(1-13)NH2 were found to be potent inhibitors of [3H]nociceptin binding to crude membranes from the brain and spinal cord, while opioid ligands such as naloxone-benzoylhydrazone, naltrindole and nor-binaltorphimine, exhibited an inhibitory effect only at high concentrations. The Ki values for nociceptin, its analogue and opioid ligands in the spinal cord were significantly lower than those in the brain. There were regional variations in the specific [3H]nociceptin binding to crude membranes from the rat brain: a relatively high density of [3H]nociceptin binding in the cerebral cortex, hippocampus, thalamus and midbrain, moderately dense binding in the corpus striatum and pons/medulla oblongata, and the lowest density of binding in the cerebellum. In conclusion, the present study has shown that [3H]nociceptin binds selectively to ORL1 receptors in the rat brain and spinal cord.

Animals↗

(10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3: an improved synthesis via 19-nor-10-oxo-vitamin D.

An efficient synthetic route to (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3 was developed. The key feature of this pathway is the introduction of a 19-fluoromethylene group to a (5E)-19-nor-10-oxo-vitamin D derivative. The 10-oxo-compound was obtained via a 1,3-dipolar cycloaddition reaction of (5E)-1alpha,25-dihydroxyvitamin D with in situ generated nitrile oxide followed by ring cleavage of the formed isoxazoline moiety with molybdenum hexacarbonyl. Conversion of the keto group of (5E)-19-nor-10-oxo-vitamin D to the E and Z fluoromethylene group was achieved through a two-step sequence involving a reaction of lithiofluoromethyl phenyl sulfone followed by the reductive desulfonylation of the alpha-fluoro-beta-hydroxy sulfone. The dye-sensitized photoisomerization of the (5E)-19-fluorovitamin D afforded the desired (5Z)-19-fluorovitamin D derivatives, (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3.

Calcifediol↗

Torsade de pointes induced by intravenous and long-term oral amiodarone therapy in a patient with dilated cardiomyopathy.

A 70-year-old woman with dilated cardiomyopathy and ventricular tachyarrhythmia was initially treated in 1990 with intravenous amiodarone (240 mg). She developed a junctional escape rhythm (48 beats/min) with QT prolongation (QT: 0.68 s) and 8 h later developed torsade de pointes (TdP). Because other antiarrhythmic drugs did not suppress the arrhythmia, oral amiodarone (100 mg/day) was started in 1995, 7 weeks before she presented with congestive heart failure. The QT prolongation (QTc: 0.64) increased after administration of dopamine, and TdP again developed. This case suggests that amiodarone induces proarrhythmias by different mechanisms when administered intravenously or orally.

Administration, Oral↗

Echocardiographical demonstration of a progressively expanding left ventricular aneurysm preceded by endomyocardial tearing.

A 70-year-old woman with acute myocardial infarction (AMI) had a narrow necked left ventricular (LV) aneurysm and pericardial effusion. Although there had been no obvious sign of pseudoaneurysm at the first operation on the 13th day after onset, LV volume increased so dramatically that dyspnea on mild exertion was induced only 2 months after the onset of AMI. She underwent Dor's operation for the expanded LV aneurysm. The histological findings of the resected tissue, which were fibrotic epicardial lesion with small myocyte islands, indicated a true aneurysm. The ultrasound manifestation of a narrow necked aneurysm with abrupt thinning of the myocardium at the hinge point may be a valuable predictor of free wall rupture in the early phase and severely progressive LV remodeling in the late phase. Such aneurysms need to be considered as high risk.

Aged↗

Conservative treatment of hemolytic complication following coil embolization in two adult cases of patent ductus arteriosus.

Two adult cases of relatively large patent ductus arteriosus (PDA) were treated by coil embolization, but were complicated by hemolysis that was successfully managed by medical treatment. Case 1 was a 67-year-old woman and Case 2 was a 71-year-old woman with a PDA of minimal diameter of 5.3 mm and 5.5 mm, respectively. The approach was via the pulmonary artery and 2 coils were delivered simultaneously into the ductus, known as the 'kissing coil technique'. Although immediately after the procedure only a small residual shunt was revealed by aortogram, hemolysis occurred for several hours after the procedure in both cases. A hemolytic complication usually needs additional coil embolization or surgical treatment, but in these 2 cases it was successfully treated by haptoglobin infusion to prevent nephropathy and by antiplasmin infusion to promote thrombus formation. Hemolytic complications of coil embolization of PDA can managed by medication when the residual shunt is minimal and the degree of hemolysis is mild.

Aged↗