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Biomedical subjects

Y Miyoshi

Publications and source records attributed to Y Miyoshi.

At least 37 records · Page 2Linked to original sources

Usefulness of repeated direct intratumoral gene transfer using hemagglutinating virus of Japan-liposome method for cytosine deaminase suicide gene therapy.

To investigate the feasibility of repeated gene transfection in suicide gene therapy against human solid tumors by a combination of 5- fluorocytosine (5-FC) and its converting enzyme, cytosine deaminase (CD), we repeatedly transfected the yeast CD gene into the human pancreatic cancer cell line BXPC3 using the hemagglutinating virus of Japan-liposome in a new gene transfer method. The in vivo growth of the s.c. transplanted BXPC3 tumor in nude mice given CD-gene transfection was significantly suppressed by i.p. injection of 5-FC when compared with tumors treated with the control vector. Furthermore, the tumor transfected with the CD gene during a 7-day interval was suppressed much more than that of a single transfection. These results suggest that repeated transfection of the suicide gene together with the combination of 5-FC and the yeast CD gene using the hemagglutinating virus of Japan-liposome gene transfer method may be useful for the treatment of human solid tumors, including pancreatic cancer.

Animals↗

Protection of the spinal cord with pentobarbital and hypothermia.

BACKGROUND: Ischemic spinal cord damage during thoracic aortic operations has not been eliminated despite application of various adjuncts. We experimentally investigated the protective effects of pentobarbital and hypothermia on the spinal cord subjected to ischemia. METHODS: Among nine groups of 6 rabbits each, groups AI to AIII underwent 20-minute infrarenal aortic occlusion, and groups BI to BVI underwent 40-minute occlusion. Five milligrams per kilogram of pentobarbital was administered to groups AII and BII; 10 mg/kg in groups AIII, BIII, and BVI; 20 mg/kg in group BIV; and none in groups AI, BI, and BV. In groups BV and BVI, hypothermia was induced. Forty-eight hours postoperatively, the motor function of the lower limbs was evaluated. RESULTS: Statistically significant recovery of motor function was observed in animals in groups AII, AIII, BIII, BIV, BV, and BVI. CONCLUSIONS: Pentobarbital showed dose-dependent protective effects of the spinal cord. Moderate hypothermia alone also showed protective effects. Combined use of pentobarbital and hypothermia resulted in highly significant recovery of spinal cord function.

Animals↗

Syntheses, structures, stability, and insulin-like activities of peroxovanadium(V) complexes with a heteroligand.

Several peroxovanadium(V) complexes were prepared with a tripodal or a quasi-tripodal tetradentate ligand. The structures of K(2)[VO(O(2))(nta)].2H(2)O and K[VO(O(2))(DL-cmhist)].H(2)O have been determined by X-ray crystallography (nta, nitrilotriacetate; cmhist, N-carboxymethylhistidinate). The structure of Cs[VO(O(2))(pda)].2H(2)O (pda, N-pyridylmethyliminodiacetate) has been estimated to be similar to that of K[VO(O(2))(DL-cmhist)].H(2)O. Each complex anion in these compounds adopts a distorted pentagonal bipyramidal structure, which is typical for heptacoordinate oxoperoxovanadium(V) complexes. The peroxide ion binds in a side-on fashion to the vanadium(V) center in the pentagonal plane. The peroxide anion in the cmhist complex dissociates rather easily in an acidic solution (pH approximately 3), while that in the other complexes stays intact under similar conditions. The in vitro insulin mimetic effect of the peroxovanadium(V) complexes has been evaluated by the inhibitory effect on free fatty acid (FFA) release in isolated rat adipocytes treated with epinephrine. The cmhist complex is effective, while the others are almost totally ineffective.

Adipocytes↗

Accumulation of beta-catenin in the cytoplasm and the nuclei during the early hepatic tumorigenesis.

Hepatocellular carcinomas (HCCs) are thought to develop as well-differentiated tumors and progress to less-differentiated tumors. However, the genetic changes underlying the development and progression of HCCs are not well understood. Recent studies have shown frequent beta-catenin gene activation in HCCs by somatic alterations involving exon 3, resulting in the activation of the Wnt/Wingless signal transduction pathway. However, the exact process in which activation of Wnt/Wingless signal transduction pathway occurs during hepatic tumorigenesis remains to be elucidated. The aim of the present study was to investigate at what stage of hepatocellular tumorigenesis this pathway was activated. Altered expression of beta-catenin was investigated immunohistochemically with special reference to the grade of histological differentiation in 41 HCCs and eight dysplastic nodules. Mutational analysis of the beta-catenin gene with single-strand conformation polymorphism method and polymerase chain reaction amplification was related with the expression of this protein. beta-Catenin was expressed in the cytoplasm and the nuclei in three cases among eight dysplastic nodules, in four cases among 20 well differentiated HCCs, in five cases among 15 moderately differentiated HCCs, and one case among six poorly differentiated HCCs, respectively. Expression of beta-catenin in the cytoplasm and the nuclei was associated in one case with mutation and two cases without mutation for beta-catenin gene among 11 screened HCCs. It was concluded that beta-catenin was accumulated in the cytoplasm and the nuclei in pre-cancerous lesions of the liver and might contribute, at least in part, to hepatic tumorigenesis.

Journal Article↗

Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer.

PURPOSE: To evaluate a new prognostic factor of breast cancer, bone marrow micrometastases which was detected by RT-PCR for mammaglobin, a sensitive molecular marker of breast cancer, was examined. MATERIALS AND METHODS: One hundred and eleven samples from stage I-III breast cancer patients were examined. Bone marrow micrometastases and clinicopathological parameters, which were age, tumor size, lymph node metastasis and status of the estrogen receptor, were evaluated for the prognostic factor by statistical analysis. RESULTS: Median follow-up time was 21.1 months. Thirty-three (29.7%) out of 111 samples were RT-PCR positive. Eight cases (24.2%) in this group showed recurrent lesions in the distant organs. Whereas six (7.7%) out of 78 RT-PCR negative patients had distant recurrences. In the premenoposal patients, and in the patients with axillary lymph node metastases, RT-PCR positive cases showed significantly higher distant recurrent rate. Bone marrow micrometastases, axillary nodal status, and estrogen receptor were independent prognostic factors for breast cancer by both univariate and multivariate analysis. CONCLUSIONS: Bone marrow micrometastases detected by RT-PCR for mammaglobin can be a useful predictive marker for early distant recurrence of breast cancer.

Adult↗

Prospective study of mother-to-infant transmission of hepatitis C virus.

BACKGROUND: Mother-to-infant transmission of hepatitis C virus (HCV) could become the main route of HCV infection in the future because there are no methods available to prevent vertical infection. The aim of this study was to determine the incidence of mother-to-infant transmission in infants born to mothers who tested positive for anti-HCV antibodies and to elucidate associated risk factors for transmission. METHODS: Screening was conducted for 16,800 pregnant women with an anti-HCV antibodies test, and 154 mothers were positive. From the positive group 141 mothers were enrolled in the study and their 147 infants were followed from birth for serum alanine aminotransferase activity, anti-HCV antibodies and HCV RNA. HIV infection was tested in 73 of 141 mothers, all of whom were negative. RESULTS: Thirty-three infants were dropped from the study because they were followed for <6 months or were not tested adequately. Of the 114 infants finally evaluated 9 (7.8%) had detectable HCV RNA. The transmission rate was not influenced by the mode of delivery [vaginal delivery, 8 of 90 vs. cesarean section, 1 of 24 (P = 0.396)] or by the type of feeding [9 of 98 for breast-fed infants vs. 0 of 16 for formula-fed infants (P = 0.243)]. All infected infants were born to mothers who had HCV viremia at the delivery (P = 0.040) and to those with a high viral load (P = 0.019). CONCLUSIONS: Our prospective study showed that the transmission rate of mother-to-infant HCV infection was 7.8% in anti-HCV antibody-positive mothers. Risk was related to the presence of maternal HCV viremia at delivery and a high viral load in the mothers.

Alanine Transaminase↗

Transareolar endoscopy-assisted partial mastectomy: a preliminary report of six cases.

Six patients with breast cancer in the upper inner quadrant underwent endoscopy-assisted partial mastectomy. The tumor was removed with a 2-cm-wide surgical margin through a periareolar semicircular incision using a special retractor and endoscope system for plastic surgery. Another small incision was made in the axilla for total lymph node dissection or sentinel lymph node biopsy. The average of total operation time in five patients who underwent partial mastectomy was 241 minutes (range, 190-315 minutes), and the average time for the procedure of partial mastectomy in six cases was 84 minutes (range, 69-113 minutes). The cosmetic outcome was excellent. Transareolar endoscopic partial mastectomy can be considered as an alternative surgery option and can offer great cosmetic advantage for patients with small cancers in the inner quadrants of the breast.

Adult↗

Clinicopathological characteristics of estrogen receptor-beta-positive human breast cancers.

Recent studies have identified the presence of estrogen receptor (ER)-beta in addition to ER-alpha in human breast cancers, but the clinicopathological characteristics of ER-beta-positive tumors remain to be established. In this study, we have conducted an immunohistochemical analysis of ER-alpha and ER-beta expression in human breast cancers. In addition, we investigated the correlation of ER-alpha and ER-beta expression with progesterone receptor (PR) status, determined by enzyme immunoassay, and with various clinicopathological factors. Of 79 tumors, 49 (62%) were positive for ER-alpha and 24 (30%) were positive for ER-beta, and there was no significant association between ER-alpha and ER-beta expression. ER-alpha-positive tumors were significantly more likely to be PR-positive than were ER-alpha-negative tumors (P < 0.0001), but there was no significant association between ER-beta expression and PR status. However, the PR values of ER-alpha-positive and ER-beta-positive tumors (65 +/- 17 fmol / mg protein, mean +/- SE) were marginally significantly lower than those of ER-alpha-positive and ER-beta-negative tumors (340 +/- 109) (P = 0.08). ER-beta positivity was significantly associated with small tumor size ( < or = 2 cm) and high histological grade (P < 0.05), and this association was also observed when only ER-alpha-positive tumors were considered. These results suggest that determination of ER-beta status might be clinically useful for further defining the characteristics of ER-alpha-positive tumors.

Breast Neoplasms↗

Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas and its relationship with clinicopathological characteristics.

BRCA1 and BRCA2 mRNA expression in sporadic breast cancers was quantified by a real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and the relationship of their expression with various clinicopathological factors was studied. BRCA2 mRNA levels (0.993 +/- 1.395, mean +/- SD (BRCA2 / beta-glucuronidase mRNA ratios)) were significantly (P < 0.01) higher than BRCA1 mRNA levels (0.519 +/- 0.570 (BRCA1 / beta-glucuronidase mRNA ratios)), and a weak but significant (r = 0.390, P < 0.01) correlation was observed between BRCA1 and BRCA2 mRNA expression levels. There was no significant association between BRCA1 mRNA expression and clinicopathological factors such as menstrual status, tumor size, lymph node status, estrogen and progesterone receptor status, and histological grade. On the other hand, there was a significant association between higher BRCA2 mRNA expression and estrogen receptor (ER) negativity (P < 0.01) or progesterone receptor (PR) negativity (P < 0.01) or high histological grade (P < 0.01). These results suggest a differential contribution of BRCA1 and BRCA2 in the pathogenesis of sporadic breast cancers. BRCA2 mRNA is speculated to be up-regulated in response to proliferation and genomic instability in high histological grade tumors.

Adult↗

Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in normal and malignant thyroid tissues by real-time polymerase chain reaction.

OBJECTIVES: We have conducted a quantitative analysis of estrogen receptor-alpha (ER-alpha) and -beta (ER-beta) mRNA expression in normal thyroid and tumor tissues. METHODS: Normal thyroid tissues (n = 10) and tumor tissues [(follicular adenoma (n = 14), follicular carcinoma (n = 8), papillary carcinoma (n = 14), anaplastic carcinoma (n = 3) and medullary carcinoma (n = 6)] were obtained at surgery from 45 female patients. ER-alpha and ER-beta mRNA expression has been studied by a quantitative polymerase chain reaction. RESULTS: ER-alpha mRNA levels in the normal thyroid were not significantly different from those in follicular adenomas, papillary carcinomas and medullary carcinomas but were marginally (p = 0.08) higher than those in follicular and anaplastic carcinomas. ER-beta mRNA levels in the normal thyroid tissues were not significantly different from those in any other tumor tissues. ER-beta to ER-alpha mRNA ratios were significantly (p < 0.05) higher in the normal thyroid tissues than in follicular adenomas. Proportions of ER-beta mRNA variants (ER-beta 1, 2, 5, and 5') did not significantly differ among the normal and tumor tissues. CONCLUSIONS: A downregulation of ER-alpha mRNA in follicular and anaplastic carcinomas seems to suggest that estrogens are unlikely to play an important role in the carcinogenesis and progression of these carcinomas. On the other hand, a significant decrease in ER-beta to ER-alpha mRNA ratios in follicular adenomas suggests a possible involvement of estrogens in the pathogenesis of this disease since the same phenomenon has been reported on estrogen-dependent breast cancers.

Adenocarcinoma, Follicular↗

Spontaneous echo contrast in descending aorta correlates with low blood-flow velocity in carotid arteries and hemostatic abnormalities.

Spontaneous echo contrast in the descending aorta (DA-SEC) was examined as a possible risk factor for cerebral thromboembolism. In 19 patients (10 males, 9 females) in the chronic stage of cerebral infarction, abnormal findings by transesophageal echocardiography, flow dynamics of the common carotid artery (CCA), and hemostatic factors including blood coagulation and fibrinolysis were investigated. In nine patients, DA-SEC was detected, and SEC in left atrium (LA-SEC) was detected in nine patients. The DA-SEC positive group showed decreased blood-flow velocity (BFV) in bilateral CCA, high levels of thrombin-antithrombin III complex (TAT) and prothrombin fragment 1.2 (F1+2), a decrease in platelet count and a slight increase in D-dimer, which means an activated state of thrombin generation and resulting fibrinolysis, compared to the DA-SEC negative group. On the other hand, the LA-SEC positive group showed normal BFV in CCA and only a slight increase in D-dimer. We conclude that the condition producing DA-SEC is a stronger risk factor for cerebral infarction than that producing LA-SEC.

Aged↗

Adult T-cell leukemia with hypercalcemia-induced metastatic calcification in the lungs due to production of parathyroid hormone-related protein.

A 60-year-old man was diagnosed as adult T-cell leukemia with severe hypercalcemia because of production of parathyroid hormone-related protein. After admission, the patient had respiratory insufficiency with an infiltrative shadow in his lungs suggestive of pneumonia. However, neither improvement in respiratory function nor disappearance of the abnormal chest shadow was observed with administration of various antibiotics. An autopsy demonstrated the chest shadow had been caused by metastatic calcification associated with hypercalcemia due to production of parathyroid hormone-related protein. The possibility of metastatic calcification should be considered in patients with adult T-cell leukemia and hypercalcemia who have an abnormal chest shadow.

Calcinosis↗

[Clinical outcome and analysis of radical prostatectomy in clinical stage B and C prostate cancer].

Between 1989 and 1999, 40 patients treated with radical prostatectomy for clinical stage B and C prostate cancer were analyzed. Prostate-specific antigen (PSA) failure after radical prostatectomy occurred in four patients, and one of them died of clinical recurrence of prostate cancer. Cause-specific survival at 5 years was 91.7% and PSA failure-free rate at 5 years was 76.8%. Staging accuracy of CT and MRI image was not satisfactory. In 41.7% patients, extracapsular extension can not be determined. Preoperative serum PSA levels of pathologically organ-confined disease (OCD) patients were significantly lower than those of pathologically non-OCD patients. Further analysis indicated that preoperative serum PSA levels of greater than 20.1 ng/ml are useful predictors for pathologically non-OCD.

Aged↗

Bi-directional single anastomotic technique for the proximal anastomosis of free grafts (the saphenous vein or radial artery) to the ascending aorta in coronary artery bypass grafting surgery.

In an operation involving coronary bypass grafting, anastomoses to the ascending aorta with saphenous vein or radial artery grafts may increase the possibility of post-operative strokes by the dislodgement of embolic particles into the arterial vasculature. We report a bi-directional single anastomotic technique to decrease the possibility of intra and postoperative strokes and to allow earlier cardiac perfusion by the graft anastomosed to the ascending aorta, in case of CABG with 2 free grafts from there.

Anastomosis, Surgical↗

Fluorescence in situ hybridization evaluation of c-erbB-2 gene amplification and chromosomal anomalies in bladder cancer.

Oncogene amplification and chromosomal anomalies are found in many solid tumors and are often associated with aggressiveness of cancer. We evaluated the frequency and the role of c-erbB-2 gene amplification, relative increase in c-erbB-2 gene copy number, and gain of chromosome 17 in bladder cancer. A total of 29 bladder cancer specimens were examined using fluorescence in situ hybridization (FISH). Dual labeling hybridization with a directly labeled centromere probe for chromosome 17 together with a probe for the c-erbB-2 locus was performed. c-erbB-2 gene amplification was found in 3.4% (1 of 29) of specimens. Relative increase in c-erbB-2 gene copy number was found in 41.4% (12 of 29) of specimens and was significantly associated with tumor grade (P = 0.044 by Fisher's exact test). Gain of chromosome 17 was identified in 65.5% (19 of 29) of specimens and was significantly associated with tumor grade (P = 0.002 by Fisher's exact test) and tumor stage (P = 0.003 by Fisher's exact test). Our results suggest that c-erbB-2 gene amplification, relative increase in c-erbB-2 gene copy number, and gain of chromosome 17 may play important roles in the development and progression of bladder cancers. Moreover, the use of c-erbB-2 amplification, relative increase in c-erbB-2 gene copy number, and gain of chromosome 17 using FISH, together with tumor grade and stage, may provide a more useful clinical indicator in bladder cancer.

Chromosome Aberrations↗

[Hepatitis virus C infection in children].

The prevalence of hepatitis C virus(HCV) infection has been becoming much lower in childhood. Blood transfusion was the principal transmission route of HCV in children. Since the year of 1989, screening of the blood products for HCV antibodies has markedly reduced transfusion-related HCV infection. Mother-to-infant transmission occurs in less than 10% of infants born to HCV-infected mothers. The maternal viral load is the most important factor determining the risk. The natural history and the outcome of HCV infection in childhood dependent on host and viral factors. The rate of progression to chronicity is 60% in post-transfusion infection and 80% in vertical infection. Experience of interferon therapy of chronic hepatitis C in children is limited, with about 50% having a sustained response to the therapy.

Child↗

[Evaluation of usefulness of urinary nuclear matrix protein 22 (NMP22) in the detection of urothelial transitional cell carcinoma].

We evaluated the usefulness of urinary nuclear matrix protein 22 (NMP22) compared to urinary cytology in the detection of urothelial transitional cell carcinoma (TCC). Between July 1999 and March 2000, 227 patients complaining of microscopic or gross hematuria were analyzed. Twenty-four patients (10.6%) had urothelial TCC. The urinary NMP22 level was significantly higher in the patients with urinary TCC compared to the other patients. The sensitivity and specificity of the results obtained with urinary NMP22 were 58.3% and 84.2%, respectively, and those obtained by urinary cytology were 45.8% and 98.0%, respectively. False-positive results were obtained with urinary NMP22 in the patients with urinary diversion using intestine, bladder invasion from other cancers, urinary tract infection, and urolithiasis. The urinary NMP22 level was significantly associated with tumor stage, suggesting its usefulness for detection of urothelial TCC. However, although urinary NMP22 showed equal sensitivity for the detection of TCC, it was not superior to urinary cytology.

Adult↗