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Biomedical subjects

Yuichi Ishikawa

Publications and source records attributed to Yuichi Ishikawa.

At least 55 records · Page 3Linked to original sources

Usefulness of electron beam computed tomography for quantitative estimation of myocardial ischemia in patients.

BACKGROUND: The electron beam computed tomography (EBT) was used as non-invasive methods for estimating mycardial characteristics in patients after onset of Kawasaki disease. METHODS: All of the 22 coronary branches with localized stenosis (LS), and 22 branches without coronary artery lesion after Kawasaki disease were examined for changes of myocardial CT number. In this study, each myocardial region was divided into three parts (endocardial, central, epicardial parts) and the myocardium/lumen (M/L) ratio was calculated. RESULTS: The mean M/L ratio in the endocardial part of early image with LS was significantly lower than the ratios in the other parts of early images with LS (P = 0.0286, P = 0.0069, respectively). and only the mean M/L ratio in the endocardial part was significantly different on images from patients with LS and images from patients without LS (P = 0.0296). Inverse correlations were found in the LS group between coronary artery stenosis rate determined by coronary angiography and M/L ratio in the endocardial part on early images (P = 0.0018, r = -0.614, y = 0.56 -0.605x). CONCLUSIONS: It was possible to quantitatively evalutate myocardial characteristics using EBT. It is suggested that myocardial ischemia progressed from the endocardial region and EBT is useful to detect the endocardial ischemia. We suggested that the rate of coronary stenosis in patients with LS can be estimated by calculating the M/L rations in the endocardial parts of early EBT images. EBT enables accurate evaluation of myocardial characteristics non-invasively.

Adolescent↗

Molecular markers for reinforcement of histological subclassification of neuroendocrine lung tumors.

The degree of malignancy of neuroendocrine lung tumors (NEs) increases in this order: from typical carcinoids (TCs) through atypical carcinoids (ACs) to large cell neuroendocrine carcinomas (LCNECs) and small cell lung carcinomas (SCLCs). However, histological classification has sometimes proved difficult. We here investigated loss of heterozygosity (LOH) using eight microsatellite markers and expression of p53, Bcl-2 and Bax proteins using immunohistochemical methods in 57 NEs (19 TCs, 5 ACs, 14 LCNECs and 19 SCLCs), looking for objective genetic markers to distinguish between subtypes. The frequencies of LOHs on D3S1300, RBi2 and TP53, the combinations of LOH status for RBi2 and TP53, and the immunohistochemically demonstrated Bcl-2/Bax ratios and p53-positive rates significantly differed among histopathologically diagnosed NEs. Differentiation between TC and AC was possible with reference to LOH on D3S1300, RBi2 and TP53, and the combined LOH status on RBi2 and TP53 (i.e., both LOH(-) versus one LOH(+)). For comparison between AC and LCNEC + SCLC, LOH on TP53 or the combination of two markers--one LOH(+) versus both LOH(+)--was applied. Furthermore, in three discordant cases of diagnoses based on histology and LOH markers, diagnoses using the latter were considered to be more probable by survival analysis. The present study indicated that assessment of LOHs using microsatellite markers could provide objective markers that can distinguish subtypes of NEs, for which histological assessment may commonly result in disagreement.

Adult↗

Impact of increasing diabetes on coronary artery disease in the past decade.

We studied the coronary risk factors of hospitalized patients with coronary artery disease (CAD) in the Department of Cardiovascular Internal Medicine of Kobe University Hospital in 1993, 1996, 1999 and 2003, and examined trends in the factors over the past decade. The prevalences of diabetes mellitus (DM) (24.7%, 33.6%, 41.1% and 44.7%, respectively) and impaired glucose tolerance (IGT) (5.9%, 8.0%, 9.3% and 11.0%, respectively) steadily increased, whereas dyslipidemia (high total cholesterolemia, high triglyceridemia, or low high-density lipoproteinemia) and hypertension remained unchanged. We also revealed an increase in hemoglobin A1c levels (5.8%, 5.9%, 6.2% and 6.4%, respectively), in contrast to modest improvements in lipid levels and blood pressure levels. Additionally, patients with multi-vessel disease (MVD, stenosis in more than two major coronary vessels) significantly increased from 44.7% in 1993 to 58.8% in 2003 (p < 0.01). In 1993, DM and dyslipidemia were significant predictors for MVD (Odds Ratio: 2.72 and 2.68, respectively). On the other hand, in 2003, the significant predictor for MVD shifted to DM alone (Odds Ratio: 2.38). In conclusion, the prevalence rate of DM among CAD patients significantly increased in this decade, and the consequent increase in the prevalence of MVD should be recognized as the most important problem clinically.

Aged↗

[The result of VIP chemotherapy as an induction therapy in 6 patients with non-seminomatous extragonadal germ cell tumor].

We treated 6 patients with non-seminomatous extragonadal germ cell tumor (NSEGCT) by VP-16 + ifosfamide + cisplatin (VIP) chemotherapy as an induction therapy to investigate the effectiveness and safety. Primary lesions were located at the mediastinum in 4 patients and the retroperitoneum in 2 patients. As a rule, all patients were treated with VIP chemotherapy of 4 courses with or without second-line treatment such as chemotherapy, residual tumor resection and/or radiation. Following the induction therapy (VIP), 4 of 6 patients (67%) achieved complete or partial responses. After salvage therapy, 4 patients (67%) achieved complete responses and two other patients also achieved partial responses. However, only 2 of the 5 patients who had been follow-up for more than 2 years have remained disease free. The effects of VIP chemotherapy on non-seminomatous extragonadal germ cell tumor appeared to be similar to those of the conventional chemotherapies though the number of patients was small in the current study. It appears to be necessary to design more effective regimen.

Adult↗

[PSA change and morbidity of prostate cancer after dietary intervention of low-fat and high-soybean-protein diet for patients with high serum PSA level].

A total of 164 patients with a high serum prostate specific antigen (PSA) level were enrolled in a supervised program of dietary intervention with a low-fat and high-soybean-protein diet. The primary endpoints were the evaluation of PSA change and morbidity of prostate cancer in this population. In the evaluable cases, the average serum PSA level had decreased 0.5 ng/ml after 3 months, 0.3 ng/ml after 6 months, and increased 0.1 ng/ml after 1 year. The change after 3 months was statistically significant (p=0.018, paired t-test). The average PSA doubling time was 444 months. During this study period, 9 of the patients developed prostate cancer. These findings indicate that this dietary intervention method was temporarily able to decrease serum PSA level, and indicates the possibility of prevention of prostate cancer by dietary intervention. However, more detailed analysis is necessary to determine why PSA did not keep decreasing.

Aged↗

Biological activities of alpha-mangostin derivatives against acidic sphingomyelinase.

Deprenyl and benzofenone-type congeners of alpha-mangostin 1 have been synthesized to understand their role for the inhibitory activity against sphingomyelinase (SMase). While removal of the prenyl group of the right side (11 and 12) caused loss of the selectivity between ASMase (acidic sphingomyelinase) and NSMase (neutral sphingomyelinase), the prenyl group of the left side appeared to increase the inhibitory activities (16 and 17).

Enzyme Inhibitors↗

Control of Cu(II) and Cu(III) states in N-confused porphyrin by protonation/deprotonation at the peripheral nitrogen.

The square-planar structure of a diamagnetic Cu(III) complex of tetrakis(pentafluorophenyl)-substituted N-confused porphyrin was elucidated by X-ray diffraction analysis. The facile interconversion between Cu(II) (1) and Cu(III) (2) complexes was achieved by chemical oxidation/reduction, and the Cu(III)/Cu(II) redox potential was controlled by adding anions through the hydrogen-bonding interaction to the peripheral NH.

Journal Article↗

High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells.

In diabetes mellitus (DM), hyperglycemia causes cardiovascular lesions through endothelial dysfunction. Monocyte chemoattractant protein-1 (MCP-1) is implicated in the pathogenesis of cardiovascular lesions. By using human umbilical vein endothelial cells, we investigated the effect of hyperglycemia on MCP-1 production and its signaling pathways. Chronic incubation with high glucose increased mRNA expression and production rate of MCP-1 in a time (1-7 days)- and concentration (10-35 mM)-dependent manner. Chronic exposure to high glucose resulted in enhancement of generation of reactive oxygen species (ROS), as determined by increasing level of 2,7-dichlorofluorescein (DCF), and subsequent activation of p38 mitogen-activated protein kinase (MAPK). Neither c-Jun NH(2)-terminal kinase nor extracellular signal-regulated kinase1/2 was affected. SB203580 or FR167653, p38 MAPK specific inhibitors, completely suppressed MCP-1 expression. Catalase suppressed p38 MAPK phosphorylation and MCP-1 expression. These results indicate that hyperglycemia can accelerate MCP-1 production through the mechanism involving p38 MAPK, ROS-sensitive signaling pathway, in vascular endothelial cells.

Antioxidants↗

N-confused porphyrin-bearing meso-perfluorophenyl groups: a potential agent that forms stable square-planar complexes with Cu(II) and Ag(III).

[reaction: see text] N-Confused porphyrin (NCP) bearing pentafluorophenyl groups at meso-positions, which were obtained from N-confused dipyrromethane in ca. 20% yield, can form Cu(II) complex as well as Ag(III), Ni(II), and Pd(II) complexes. The square-planar structures of all these metal complexes were elucidated by X-ray single-crystal analyses.

Journal Article↗

Chylomicron remnants induce monocyte chemoattractant protein-1 expression via p38 MAPK activation in vascular smooth muscle cells.

Chylomicron remnants, major lipoproteins at postprandial hyperlipidemia, have been considered to be proatherogenic lipoproteins. However, the mechanisms by which chylomicron remnants enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of chylomicron remnants on MCP-1 expression in cultured vascular smooth muscle cells (VSMCs). We prepared chylomicrons from the lymph of gastrostomized rats fed with egg solution and obtained chylomicron remnants from the plasma of hepatectomized rats which were injected with chylomicrons. Treatment of VSMC with chylomicron remnants resulted in a significant increase of the expression of MCP-1 mRNA and protein in a time-and a dose-dependent manner. Further, chylomicron remnants activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK1/2). Pretreatment of VSMCs with p38 MAPK inhibitors, SB203580 and SB202190, resulted in a dose-dependent inhibition of chylomicron remnants-induced MCP-1 mRNA and protein expression, whereas a MAPK kinase inhibitor, PD98059, had no effect on these responses. MCP-1 secretion by chylomicron remnants was much more pronounced than those by chylomicrons, oxidized low-density lipoproteins, or lysophosphatidylcholine. These results indicated that chylomicron remnants stimulated MCP-1 expression in VSMCs, and suggested that chylomicron remnants might contribute to the formation of atherosclerosis through this proinflammatory effect.

Animals↗

Early-stage lung adenocarcinomas with a micropapillary pattern, a distinct pathologic marker for a significantly poor prognosis.

Adenocarcinomas with a micropapillary pattern (MPP), featuring small papillary tufts lacking a central fibrovascular core, are thought to have a poor prognosis. To examine whether the MPP is a predictor of prognosis, clinicopathologic characteristics of adenocarcinomas were analyzed with particular reference to survival of early-stage patients. The subjects were 344 consecutive patients (female/male ratio 163:181) for whom complete surgical resection was undertaken at the Cancer Institute Hospital, Japan, during 1986-1995. Histologically, they were divided into two groups: MPP-positive (n = 139; 40%) and MPP-negative (n = 205; 60%). The following items were significantly more frequent in the MPP-positive group: metastasis to lymph nodes (p <0.001), pleural invasion (p = 0.02), intrapulmonary metastasis (p <0.001), and nonsmoking status (p = 0.002). In stage I patients (i.e., without lymph node metastasis, n = 154), 5-year survival of the MPP-positive group (n = 45) was 79%, significantly lower than the MPP-negative group (n = 109) of 93% (p = 0.004). In many cases of the c-stage I MPP-positive group, upstaging was necessary on the basis of pathologic findings for metastases, and the survival was between stage I and stage II. Our study clearly indicated that the MPP is a distinct prognostic marker for lung adenocarcinoma, particularly regarding apparent stage I diseases.

Adenocarcinoma, Papillary↗

A case of severe hyperlipidemia caused by long-term tube feedings.

A 77-year-old woman with type II diabetes mellitus was admitted to our hospital in August/ 1995 with severe hyperlipidemia. She had taken feedings through a nasogastric tube with 1000 ml (1000 kcal) of Ensureliquid daily since 1993 because of the muscle weakness after rhabdomyolysis. Her serum total cholesterol was 515 mg/dl and triglyceride was 3378 mg/dl despite administration of 10 mg of simvastatin daily. After substitution of a standard diet starting August 21, we found significant decreases of total cholesterol from 725 mg/dl to 194 mg/dl and triglyceride from 4680 mg/dl to 550 mg/dl within 37 days. We also found a severe decrease in her serum total carnitine level of 22 micromol/l (normal range 45-91 micromol/l) before changing the diet, suggesting secondary carnitine deficiency. Severe hyperlipidemia was reversed by changing the carnitine deficient diet (Ensureliquid) to a carnitine-containing diet. We suggested that the development of hyperlipidemia was related to the carnitine deficiency.

Aged↗

[Clinico-statistical analysis of renal cell carcinomas in patients on hemodialysis].

Eleven patients on hemodialysis that were surgically treated for renal cell carcinomas during the recent 10 years at our institutes were clinically analyzed. Patients' ages at presentation ranged from 35 to 70 years with an average of 54.8 years. Nine of the 11 patients were males and 2 were females. Periods between the introduction of hemodialysis and the presentation ranged from 1 to 21 years with an average of 11.7 years. The most frequent cause of hemodialysis was chronic glomerulonephritis. Five patients presented with macroscopic hematuria, which was the most frequent clinical manifestation. Transperitoneal nephrectomy through a lumbar oblique incision was performed in 9 of 12 surgical procedures. Transperitoneal resection and retroperitoneal endoscopic resection were performed on 2 patients and 1 patient, respectively. Blood transfusion was performed on 2 patients with retroperitoneal hemorrhage before or after operation and 2 patients with pre-existing renal anemia. Pathologically, 9 patients had pT1a disease. Patients were followed up for up to 7 years and 11 months. One patient died of the disease and 2 patients died of unknown causes. In conclusion, surgical removal of renal cell carcinomas was well tolerated, safe and effective treatment in patients under hemodialysis.

Adult↗

[Not Available].

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Journal Article↗

Loss of heterozygosity and the smoking index increase with decrease in differentiation of lung adenocarcinomas: etiologic implications.

To better understand causative relations of smoking to lung adenocarcinomas, the frequency of loss of heterozygosity (LOH) of all autosomal chromosomes was compared among the three grades of histological differentiation with 119 pulmonary adenocarcinomas (AC) and 41 squamous cell carcinomas (SCC), using Southern blotting. The fractional allelic loss (FAL) values, defined as (number of chromosome arms with LOH)/(number of informative arms), and smoking index (a product of number of cigarettes per day and duration in years) for all ACs were 0.19 and 520 whereas those for SCCs were 0.34 and 1,160, respectively. Those for well- (n=33), moderately (n=63) and poorly (n=23) differentiated ACs were 0.100, 0.197, 0.295 and 310, 480, 1,010, respectively. These results showed that less differentiated ACs are more similar to SCC in terms of LOH frequency and smoking.

Adenocarcinoma↗

Microsatellite instability in thorotrast-induced human intrahepatic cholangiocarcinoma.

Thorotrast, a colloidal suspension of radioactive (232)ThO(2) that emits alpha particles, was used as a radiographic contrast during World War II. It is known to induce liver cancers, most frequently ICC, decades after injection. Since radiation induces genomic instability, we analyzed MSI in Thorotrast-induced ICC. The frequency of MSI(+) cases was 62.5% in Thorotrast ICC, whereas it was 22.7% in non-Thorotrast ICC. However, frameshift mutations of mononucleotide repeats were not observed in Thorotrast ICC. In addition, the MSI(+) phenotype was not associated with the quantity of Thorotrast deposited or the latency period of ICC induction. Promoter regions of both the hMLH1 and the hMSH2 MMR genes tended to be hypermethylated in the tumor part compared to the adjacent nontumor part in Thorotrast ICC. Methylation of the hMLH1 promoter was associated with the MSI(+) phenotype in Thorotrast ICC. In contrast, methylation status of these promoter regions was not related to MSI in non-Thorotrast ICC cases. These findings suggest that MSI induced by exposure to Thorotrast mainly reflects clonal expansion of cancer cells and is partly due to inactivation of hMLH1 by hypermethylation.

Adaptor Proteins, Signal Transducing↗

Pulmonary metastases from a low-grade endometrial stromal sarcoma confirmed by chromosome aberration and fluorescence in-situ hybridization approaches: a case of recurrence 13 years after hysterectomy.

Pulmonary metastasis from low-grade endometrial stromal sarcomas (ESSs) occasionally are found after long, disease-free periods, mostly as incidental histological or radiological discoveries. We describe a case of low-grade ESS presenting as nodular pulmonary metastases finally diagnosed by estrogen-receptor staining, cytogenetic and fluorescence in situ hybridization (FISH) analyses, and perusal of the histology of hysterectomy material. An abnormal nodule in the lung field was discovered by means of chest X-ray of a 47-year-old woman. She had been disease free for 13 years after hysterectomy for an alleged leiomyoma. A computed tomographic scan revealed nodules, with fluctuation in size over the 2-year period, in both lungs. Finally the lesion in the left lung was resected, and pulmonary endometriosis was suspected because of the lack of stromal cell nuclear atypia and positive immunohistochemical reactions for estrogen and progesterone receptors. However, a characteristic karyotype was identified cytogenetically: 46, XX, t(7;17)(p15;q11), the translocation of which, specific to ESS, was confirmed by FISH analysis. A final diagnosis of pulmonary metastases from an ESS could be made by reviewing the histology of the previous uterine tumor. In this case, metastatic lesions from an ESS showed a decrease as well as an increase in size, despite the malignant potential. Immunostaining for estrogen and progesterone receptors and cytogenetic and FISH analyses, together with clinical information on the past gynecological history, are valuable diagnostic keys.

Chromosomes, Human, Pair 17↗