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Biomedical subjects

Y Onishi

Publications and source records attributed to Y Onishi.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Neoadjuvant chemotherapy for advanced epithelial ovarian cancer].

Primary surgical cytoreduction followed by paclitaxel/carboplatin combination chemotherapy currently is the treatment of choice for advanced epithelial ovarian cancer. Aggressive surgery is widely accepted as a valid approach to initial cytoreduction of stage III disease, but suboptimal residual disease following primary surgical resection is one of the most important adverse prognostic factors in these patients. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery for initial management of bulky ovarian cancer, with the goal of improving surgical quality. General acceptance of neoadjuvant chemotherapy as an alternative to primary surgery for patients who are not ideal surgical candidates remains limited, because equivalent or superior survival has not yet been demonstrated in a prospective randomized study. A large-scale, prospective, randomized study is being conducted by the European Organization for Research and Treatment of Cancer (EORTC) Gynecologic Cancer Cooperative Group and Gynecologic Oncology Group (GOG) to compare outcomes (overall and progression-free survival, quality of life, treatment complications) of neoadjuvant chemotherapy/interval debulking surgery versus primary cytoreductive surgery/adjuvant chemotherapy in patients with advanced epithelial ovarian carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Identification of missense mutation (G365R) of the butyrylcholinesterase (BCHE) gene in a Japanese patient with familial cholinesterasemia.

A point mutation which caused a silent phenotype of human serum butyrylcholinesterase (BChE) was identified in the genomic DNA of a 57-year-old Japanese woman who visited our hospital because of pneumonia. The propositus exhibited an unusually low level of BChE activity, whereas her son and daughter had an intermediate level. Immunologically, there was an absence of BChE protein in the propositus's serum. DNA sequence analysis of the propositus demonstrated a point mutation at codon 365 (GGA-CGA), resulting in a Gly-Arg substitution. A family study showed her son and daughter to have the same mutation.

Butyrylcholinesterase↗
PubMed2001

[An autopsied case of pachymeningitis associated with a ruptured, cerebral aneurysm due to Aspergillus infection].

We reported a 64-years-old woman with pachymeningitis associated with a ruptured mycotic cerebral aneurysm due to Aspergillus infection. She had suffered from diabetes mellitus and been treated since she was 49 years old. She complained of headache at the age of 62 and loss of her left visual acuity three months later. She was treated by the pulse therapy of methylprednisolone as neuritis retrobulbaris and her visual acuity recovered. But her headache continued. Three months later, her right visual acuity was lost, and the pulse therapy was not effective this time. Six months later, she died of subarachnoid hemorrhage following acute meningitis. The autopsy was granted, but limited to the cranial cavity. Macroscopically, it disclosed brownish thickened dura around sella turucica involving trigeminal ganglion and optic nerve, and fresh subarachnoid hemorrhage in the basal cisterns and a ruptured aneurysm (3 mm in diameter) between internal carotid and posterior cerebral artery on the left side. Histologically, the brownish thickened dura was infiltrated by lymphocytes, plasma cells, and multinucleated giant cells. The wall around the aneurysm was infiltrated by lymphocytes and plasma cells as well as many fungi. Immunohistochemistry demonstrated the presence of Aspergillus in the thickened dura and the arterial wall around the aneurysm. There were lymphocytes and plasma cell infiltration in the basal subarachnoid space and scattered microabcesses in the brain. Although the first entry of Aspergillus to the dura was unclear, we assume that the final intravascular dissemination of Aspergillus from the dura caused meningitis and mycotic aneurysm.

Aneurysm, Infected↗
PubMed2000

Conservation of DNA bend sites with identical superhelical twists among the human, mouse, bovine, rabbit and chicken beta-globin genes.

We reported previously that DNA bend sites appear in the human beta-globin locus at an average distance of 680 bp. The relative locations of the sites were conserved among the five active beta-like globin genes and one pseudogene. Here, we mapped the sites in the beta-like globin genes from various species and examined their conservation. The locations of the bend sites in the bovine, rabbit and chicken beta-globin genes mapped here showed marked conservation in their locations relative to the cap site and showed similar locations to the previously mapped sites in the human beta- and mouse betamaj-globin genes. Further analysis of the first bend sites from the cap site (B-1 sites) indicated that they contained tracts of adenines and thymines longer than or equal to two bases. This sequence feature contributed mostly to the curvature profiles revealed by gel assays and/or by computer-based TRIF analysis. TRIF analysis indicated that most of the B-1 sites showed right-handed superhelical twists accompanied by left handed twists. This was confirmed by the effect of ethidium bromide on the superhelical twists in the assays.

Adenine↗
PubMed2000

The N-terminal 34 residues of the 55 kDa regulatory subunits of phosphoinositide 3-kinase interact with tubulin.

There are five regulatory subunit isoforms of phosphoinositide 3-kinase (PI 3-kinase), which are classified into three groups: proteins of 85 kDa (p85alpha and p85beta), 55 kDa (p55alpha and p55gamma) and 50 kDa (p50alpha). Structural differences between the three groups reside in the N-terminus. To elucidate the unique functional role of the 55 kDa regulatory subunits, GST (glutathione S-transferase) fusion proteins containing a unique N-terminal portion consisting of a 34-amino-acid sequence of p55alpha or p55gamma (GST-p55alpha/gammaN(1-34)) were used as affinity matrices to screen rat brain cell extracts for proteins to which this portion binds specifically. A protein that bound was identified as beta-tubulin by protein sequencing. In addition, not only the beta isoform of tubulin, but also the alpha and gamma isoforms, were detected in the protein absorbed from cell lysates with GST-p55gammaN(1-34) and GST-p55alphaN(1-34) by immunoblotting. Indeed, the only regulatory subunit present in the purified microtubule assembly from rat brain was the 55 kDa isoform; neither 85 kDa nor 50 kDa subunits were detected. These results indicate endogenous binding of 55 kDa regulatory subunits of PI 3-kinase to tubulin in the brain. Finally, we measured tubulin-associated PI 3-kinase activity in CHO/IR cells overexpressing each of the five regulatory subunit isoforms. Only in cells expressing p55alpha or p55gamma was there a significant elevation of tubulin-associated PI 3-kinase activity in response to insulin. These results suggest that the p55alpha and p55gamma regulatory subunits have important roles in regulating PI 3-kinase activity, particularly for microtubules at the cell periphery.

Amino Acid Sequence↗
PubMed2000

Molecular analysis of familial androgen insensitivity syndrome due to replacement of glutamic acid 802 by lysine.

We studied a Japanese family presenting at least two cases of complete androgen insensitivity syndrome (CAIS) and negative androgen receptor binding. The index subject showed a 46, XY karyotype and a complete female phenotype. For the purpose of further diagnosis and genetic counseling, molecular analysis of the androgen receptor (AR) gene was performed. Direct sequencing of the AR gene identified a mutation at nucleotide 2935 (A-->G). This replacement was a novel missense mutation, resulting in the substitution of glutamic acid 802 by lysine which deleted a recognition site for EcoRI in exon 6 of the AR gene. We identified another affected individual, using chromosome and molecular analysis of the AR gene at exon 6. Furthermore, although heterozygote carriers could not be identified on clinical grounds, molecular identification of healthy individuals and heterozygote carriers in the family members provided definitive information for genetic counseling. We believe that the molecular analysis of familial CAIS is very informative for both the affected individuals and other family members.

Adolescent↗
PubMed2000

Acquired digital arteriovenous malformation: a report of six cases.

Arteriovenous malformation (AVM) is usually congenital, but an acquired type is also known, of which most are due to a previous injury. We report six patients with acquired digital AVM, all having a small patch of AVM localized to the tip of one finger, and therefore quite different from ordinary AVM which consists of a large pulsatile mass. Histologically, dilated venous and arterial vessels were present in the dermis. Tumour-like growth was absent; thus, these six cases could be differentiated from arteriovenous haemangioma. Because of the characteristic anatomical site, unique clinical manifestations and histology, this appears to be a new and distinctive entity.

Adolescent↗
PubMed2000

Transmyocardial revascularization aggravates myocardial ischemia around the channels in the immediate phase.

We examined whether transmyocardial revascularization (TMR) relieves myocardial ischemia by increasing regional perfusion via the transmural channels in acute canine experiments. Regional blood flow during transient coronary ligation (2 min) was compared before and 30 min after TMR, and at the third transient ischemia the mid-left ventricle (LV) was cut and immediately frozen along the short axis for the analysis of NADH fluorescence in the regions around the TMR channels. In low-resolution analysis (2-4 g tissue or 2-3 cm(2) area), regional perfusion was not significantly altered after TMR, and NADH fluorescence was observed throughout the ischemic region without significant spatial variation. High-resolution analysis (2.8 mg, 1 mm x 1 mm) revealed that the flow after TMR was lower, and NADH fluorescence was higher in the regions close to the channels (1-2 mm) than in the regions 3-4 mm away from them. Creating TMR channels did not improve the regional perfusion and rather aggravated the local ischemia in the vicinity of the channels in the immediate phase.

Analysis of Variance↗
PubMed2000

Dissolution profiles of principal ingredients in Kampo medicinal powders by high-performance liquid chromatography.

We describe here a method using HPLC for the simultaneous determination of albiflorin, paeoniflorin, glycyrrhizin and six flavanone glycosides (liquiritin, liquiritin apioside, naringin, neohesperidin, hesperidin and narirutin) in the Kampo medicines, Shigyaku-san and Haino-san. All nine components were separated in less than 40 min by linear gradient elution using a mobile phase containing aqueous phosphoric acid and acetonitrile. The dissolution of these components from powders of Shigyaku-san in aqueous solution at pH 1.80, 4.08 and 6.89 was examined. All of the components except glycyrrhizin were dissolved entirely within 5 min regardless of pH. Dissolution of glycyrrhizin was dependent on the pH of the aqueous solution, and increased with increasing pH.

Chromatography, High Pressure Liquid↗
PubMed2000

Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction.

Glucocorticoids reportedly induce insulin resistance. In this study, we investigated the mechanism of glucocorticoid-induced insulin resistance using 3T3-L1 adipocytes in which treatment with dexamethasone has been shown to impair the insulin-induced increase in glucose uptake. In 3T3-L1 adipocytes treated with dexamethasone, the GLUT1 protein expression level was decreased by 30%, which possibly caused decreased basal glucose uptake. On the other hand, dexamethasone treatment did not alter the amount of GLUT4 protein in total cell lysates but decreased the insulin-stimulated GLUT4 translocation to the plasma membrane, which possibly caused decreased insulin-stimulated glucose uptake. Dexamethasone did not alter tyrosine phosphorylation of insulin receptors, and it significantly decreased protein expression and tyrosine phosphorylation of insulin receptor substrate (IRS)-1. Interestingly, however, protein expression and tyrosine phosphorylation of IRS-2 were increased. To investigate whether the reduced IRS-1 content is involved in insulin resistance, IRS-1 was overexpressed in dexamethasone-treated 3T3-L1 adipocytes using an adenovirus transfection system. Despite protein expression and phosphorylation levels of IRS-1 being normalized, insulin-induced 2-deoxy-D-[3H]glucose uptake impaired by dexamethasone showed no significant improvement. Subsequently, we examined the effect of dexamethasone on the glucose uptake increase induced by overexpression of GLUT2-tagged p110alpha, constitutively active Akt (myristoylated Akt), oxidative stress (30 mU glucose oxidase for 2 h), 2 mmol/l 5-aminoimidazole-4-carboxamide ribonucleoside for 30 min, and osmotic shock (600 mmol/l sorbitol for 30 min). Dexamethasone treatment clearly inhibited the increases in glucose uptake produced by these agents. Thus, in conclusion, the GLUT1 decrease may be involved in the dexamethasone-induced decrease in basal glucose transport activity, and the mechanism of dexamethasone-induced insulin resistance in glucose transport activity (rather than the inhibition of phosphatidylinositol 3-kinase activation resulting from a decreased IRS-1 content) is likely to underlie impaired glucose transporter regulation.

3T3 Cells↗
PubMed2000

Expression levels of thymidine phosphorylase and dihydropyrimidine dehydrogenase in various human tumor tissues.

Thymidine phosphorylase (dThdPase) is the rate-limiting enzyme that metabolizes 5'-deoxy-5-fluorouridine (5'-dFUrd, doxifluridine), an intermediate metabolite of capecitabine, to the active drug 5-fluorouracil (5-FUra), while dihydropyrimidine dehydrogenase (DPD) catabolizes 5-FUra to an inactive molecule. The susceptibility of tumors to fluoropyrimidines is reported to correlate with tumor levels of these enzymes. To obtain some insight into the tumor types susceptible to fluoropyrimidine therapy, we measured expression levels of these two enzymes in various types of human cancer tissues (241 tissue samples) by the ELISA methods. DPD exists in all the cancer types studied, such as bladder, breast, cervical, colorectal, esophageal, gastric, hepatic, pancreatic, prostate, and renal cancers. Among them, the cervical, hepatic, pancreatic, esophageal, and breast cancer tissues expressed high levels of DPD (median >70 U/mg protein), while high concentrations of the dThdPase were expressed in esophageal, cervical, breast, and pancreatic cancers and hepatoma (median >150 U/mg protein). The dThdPase/DPD ratio, which was reported to correlate with the susceptibility of human cancer xenografts to capecitabine, was high in esophageal, renal, breast, colorectal, and gastric cancers (median ratio of >1.5). In any of these three parameters, the inter-patient DPD variability for each cancer type was much larger than the DPD variability among cancer types; highest/lowest ratios for dThdPase, DPD, and dThdPase/DPD were 10-321, 7-513, and 2-293, respectively. These results indicate that measurements of the three parameters, DPD, dThdPase and dThdPase/DPD, would be useful criteria for selecting cancer patients suitable for fluoropyrimidine therapy rather than for selecting cancer types.

Animals↗
PubMed2000

[Evaluation of paclitaxel and carboplatin in patients with endometrial cancer].

The purpose of this study was to evaluate the combination of paclitaxel and carboplatin in patients with endometrial cancer who have high-risk histopathologic criteria with vessel permeation and low grade, advanced or recurrent disease. The combination of paclitaxel (180 mg/m2 over 3 hours) and carboplatin (dosed at an area under the curve of 5-6) was given intravenously every 3 weeks. Response and toxicity were evaluated according to the Japan Society of Clinical Oncology's response and adverse effect criteria. Eighteen patients were entered in this study and a total of 94 courses were administered. Eleven patients had evaluable lesions. Complete and partial responses were achieved in 5 (45.5%) and 3 (27.3%) patients, respectively. Grade 3 or 4 leukopenia and neutropenia occurred in 49.2% and 90.5% of the patients. G-CSF support was needed in 52.4% of the patients. Only one patient received a platelet transfusion. As a high response rate was obtained, this regimen is considered to be promising treatment for endometrial carcinoma. Prospective comparative study between this combination therapy and the conventional therapy for endometrial carcinoma is warranted.

Adenocarcinoma↗
PubMed2000

An analysis of risk factors of perioperative bleeding in surgical repair of abdominal aortic aneurysm.

BACKGROUND: In surgical repair of abdominal aortic aneurysm (AAA), excessive bleeding which causes postoperative complications is sometimes observed. To determine the risk factors of perioperative excessive blood loss, this retrospective study was performed. METHODS: Design. A retrospective study. Setting. An academic medical center. Participants. One hundred and forty patients underwent elective surgical repair of an abdominal aortic aneurysm (AAA) at our institution from 1995 through 1997. Measurements. The present study includes critical review of 140 consecutive charts of patients undergoing elective surgical repair of AAA. Preoperative laboratory data, intraoperative data and amount of blood loss to identify risk factors of perioperative blood loss. Factors which were found to be significantly associated with the amount of perioperative blood loss were preoperative plasma fibrin degradation product (FDP) level (r=0.445), amount of immediate re-infusion of shed blood (r=0.438), and duration of operation (r=0.411). RESULTS: Preoperative fibrinogen level correlated with perioperative blood loss little (r=-0.187). Preoperative platelet count or the other coagulation profile did not affect the amount of perioperative blood loss. The patients whose preoperative FDP were more than 40 microg x ml(-1) significantly increased the risk of excessive blood loss compared with less than 40 microg x ml(-1). CONCLUSIONS: The significant preoperative risk factor of perioperative blood loss was only FDP level in present study. Especially, the patients whose preoperative FDP were more than 40 microg x ml(-1) increased the risk of excessive blood loss.

Aged↗
PubMed1999

Localization of curved DNA and its association with nucleosome phasing in the promoter region of the human estrogen receptor alpha gene.

We determined DNA bend sites in the promoter region of the human estrogen receptor (ER) gene by the circular permutation assay. A total of five sites (ERB-4 to -1, and ERB+1) mapped in the 3 kb region showed an average distance of 688 bp. Most of the sites were accompanied by short poly(dA) x poly(dT) tracts including the potential bend core sequence A2N8A2N8A2 (A/A/A). Fine mapping of the ERB-2 site indicated that this A/A/A and the 20 bp immediate flanking sequence containing one half of the estrogen response element were the sites of DNA curvature. All of the experimentally mapped bend sites corresponded to the positions of DNA curvature as well as to nucleosomes predicted by computer analysis. In vitro nucleosome mapping at ERB-2 revealed that the bend center was located 10-30 bp from the experimental and predicted nucleosome dyad axes.

Base Sequence↗
PubMed1999

Imidapril, an angiotensin-converting enzyme inhibitor, improves insulin sensitivity by enhancing signal transduction via insulin receptor substrate proteins and improving vascular resistance in the Zucker fatty rat.

Angiotensin-converting enzyme (ACE) inhibitors are antihypertensive agents, that inhibit the conversion of angiotensin I to angiotensin II, resulting in smooth-muscle relaxation and a reduction of vascular resistance. Recently, it has been suggested that ACE inhibitors improve insulin resistance in diabetic patients. To investigate the effect of an ACE inhibitor on insulin sensitivity, insulin signaling, and circulation, imidapril was administered orally or intraduodenally to Zucker fatty rats. Oral administration of imidapril improved insulin sensitivity based on the results of an oral glucose tolerance test (OGTT) and a decrease in urinary glucose secretion. Phosphatidylinositol 3-kinase (PI 3-kinase) activity associated with hepatic insulin receptor substrate-1 (IRS-1) in the insulin-stimulated condition was significantly enhanced 110% without a significant alteration in tyrosine phosphorylation of IRS-1 in the imidapril-treated group. In muscle, IRS-1 tyrosine phosphorylation and PI 3-kinase activity associated with IRS-1 in the insulin-stimulated condition were enhanced 70% and 20%, respectively, in the imidapril-treated group. In contrast, an alteration of the IRS-2 pathway was observed only in liver; a significant insulin-induced increase in the IRS-2-associated PI 3-kinase over the basal level was observed in the imidapril-treated group but not in the control. In addition, treatment with imidapril was shown to significantly reduce blood pressure and increase blood flow in the liver and muscle. These results suggest that the ACE inhibitor imidapril may improve insulin sensitivity not only by acting directly on the insulin signaling pathway but also by increasing blood flow in tissues via normalization of vascular resistance, a major cause of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Angiolymphoid hyperplasia with eosinophilia associated with arteriovenous malformation: a clinicopathological correlation with angiography and serial estimation of serum levels of renin, eosinophil cationic protein and interleukin 5.

We present a case of angiolymphoid hyperplasia with eosinophilia (ALHE) affecting the auricular area of a 31-year-old man, which clinically mimicked arteriovenous malformation (AVM). The histology and laboratory data distinctively revealed ALHE, while angiography demonstrated typical findings of AVM. Although several reports have hitherto mentioned the relationship between ALHE and AVM, the aetiology of the disease remains unknown. During the 3 years treatment course, we performed angiography several times to assess the efficacy of the treatments and compared the clinical and pathological findings, based on the hypothesis that AVM might be a cause of ALHE. This study showed first, that the clinicopathological findings of ALHE correlated with the extent of AVM shown by angiography, so that AVM could be a primary cause of ALHE. Secondly, systemic corticosteroids and local irradiation therapy produced only a temporary effect on the inflammatory changes of ALHE; therefore, surgical resection is recommended as a curative treatment. Thirdly, the patient's serum levels of renin, eosinophil cationic protein and interleukin 5 corresponded closely with the clinical course of ALHE.

Adult↗