Biomedical subjects

T Fukutomi

Publications and source records attributed to T Fukutomi.

At least 19 recordsLinked to original sources

PubMed2005

Frequent overexpression of epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation.

AIMS: To evaluate the expression of common biological markers and the epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation (DCMDs). MATERIALS/METHODS: Thirty DCMDs were clinicopathologically and immunohistochemically analysed and compared with 36 control cases of high grade conventional invasive ductal carcinoma (IDC). RESULTS: EGFR, HER2/neu, oestrogen receptor, progesterone receptor, and p53 expression was seen in 21, one, three, four, and 20 of the 30 DCMDs, compared with eight, nine, 18, 17, and five of the 36 conventional IDCs (p<0.05), respectively. In 16 of the 30 DCMDs, metastases were found in the brain, lung, bone, and liver, within a maximum of 47 months (mean, 13.9) after initial surgery, whereas only four of the 36 conventional IDCs metastasised to the lung and bone within a maximum of 27 months (mean, 18.0) after initial surgery (p=0.0001). There was a significant difference in disease free survival between DCMD and conventional IDC (p=0.001). EGFR was frequently overexpressed in DCMD compared with conventional IDC, whereas the expression of HER2/neu and hormone receptors was lower in DCMD. Fluorescent in situ hybridisation revealed that the mean EGFR to chromosome 7 centromere (CEP7) ratio of the 24 DCMD cases available for evaluation was 1.03, and EGFR gene amplification was not detected in the 21 DCMD cases with EGFR overexpression. CONCLUSION: Immunohistochemistry for myoepithelial markers and EGFR is useful for the accurate diagnosis and molecular target treatment of high grade DCMD.

Adult↗

PubMed2004

The emergence in Japan of Sathuperi virus, a tropical Simbu serogroup virus of the genus Orthobunyavirus.

In 1999, two viruses were isolated from blood samples of sentinel cattle in the Western part of Japan. The physiochemical and morphological properties of these viruses indicated that they belonged to the family Bunyaviridae. Sequence analysis of the S segment indicates that the two viruses are closely related to Sathuperi virus (SATV). The N-terminal 168 amino acid of the G2 protein of the M segment was highly homologous with that of SATV (98.2%). Given these results, we conclude that the newly isolated viruses are closest to SATV, which was initially isolated in India and Nigeria over 30 years ago.

Amino Acid Sequence↗

PubMed2002

High insulin enhances neutrophil transendothelial migration through increasing surface expression of platelet endothelial cell adhesion molecule-1 via activation of mitogen activated protein kinase.

AIMS/HYPOTHESIS: There is increasing evidence that hyperinsulinaemia is linked with the development of atherosclerosis in patients with diabetes. However, the mechanisms by which hyperinsulinaemia causes accelerated atherosclerosis, especially with respect to leukocytes transendothelial migration, are poorly understood. We examined whether hyperinsulinaemia directly affects neutrophil transendothelial migration and surface expression of related endothelial adhesion molecules. METHODS: Experiments on the transmigration of neutrophils from healthy volunteers and from patients with Type II (non-insulin-dependent) diabetes mellitus across human umbilical vein endothelial cells cultured in insulin-rich medium using cell-culture inserts were carried out. Migrated neutrophils were quantified by measuring their myeloperoxidase activities, and the surface expression of endothelial adhesion molecules was examined using an enzyme immunoassay. RESULTS: High insulin (over 50 microU/ml for 24 h) enhanced neutrophil transendothelial migration in a dose-dependent manner. This was associated with increased expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) but not of intercellular adhesion molecule-1 (ICAM-1), P-selectin or E-selectin. Both phenomena were attenuated by pretreatment with a tyrosine kinase inhibitor, especially a mitogen-activated protein kinase inhibitor, but not by inhibitors of other second messengers. In addition, a mitogen-activated protein kinase activator, anisomycin, by itself enhanced both neutrophil transendothelial migration and PECAM-1 expression within 3 h in a dose-dependent manner. Pretreatment with nitric oxide synthase inhibitors had no effect on these events. CONCLUSION/INTERPRETATION: These results suggest that hyperinsulinaemia could accelerate atherosclerosis by directly enhancing neutrophil transendothelial migration through increasing endothelial PECAM-1 expression via mitogen-activated protein kinase activation.

Cells, Cultured↗

PubMed2002

High insulin exacerbates neutrophil-endothelial cell adhesion through endothelial surface expression of intercellular adhesion molecule-1 via activation of protein kinase C and mitogen-activated protein kinase.

AIMS/HYPOTHESIS: The association of insulin resistance and compensatory hyperinsulinaemia with increased coronary events in diabetic patients is poorly understood. There are few publications about the direct atherogenic actions of insulin on the endothelium compared with those on vascular smooth muscle cells. The aim of this study was to elucidate whether high insulin directly affects neutrophil-endothelial cell adhesion and surface expression of endothelial adhesion molecules. We also examined what intracellular mechanisms are involved in these events. METHODS: Studies of adhesion between neutrophils from healthy volunteers and human umbilical vein endothelial cells incubated in insulin-rich medium were carried out. Adhered neutrophils were quantified by measuring their myeloperoxidase activities and surface expression of endothelial adhesion molecules was examined using an enzyme immunoassay. RESULTS: High insulin enhanced neutrophil-endothelial cell adhesion with an increase in the expression of intercellular adhesion molecule-1 but not E-selectin or P-selectin. Both phenomena were attenuated by pretreatment with protein kinase C inhibitors and a mitogen activated protein kinase inhibitor. CONCLUSIONS/INTERPRETATION: These results suggest that hyperinsulinaemia causes vascular injury by directly exacerbating neutrophil-endothelial cell adhesion through increasing endothelial expression of intercellular adhesion molecule-1 via activation of protein kinase and mitogen activated protein kinase pathways.

Cell Adhesion↗

PubMed2001

Accuracy of contrast-enhanced computed tomography in the prediction of residual breast cancer after neoadjuvant chemotherapy.

Determination of the extent of residual disease after neoadjuvant chemotherapy is sometimes inaccurate by conventional diagnostic methods. The purpose of this study was to evaluate the accuracy of contrast-enhanced computed tomography (CE-CT) in depicting the extent of residual carcinomas. Fifty-seven patients with breast carcinomas of 3 cm diameter or more received neoadjuvant chemotherapy with four cycles of AT (doxorubicin and docetaxel). Before surgery, the patients underwent clinical examination, mammogram (MMG), ultrasonography (US), and CE-CT. Thirteen patients were not evaluated by CE-CT before surgery. Enhancement patterns on CE-CT were classified into multiple spots, tumor and spots, solid tumor type, and no enhancement. When all types of cancers were included in the analysis, clinical examination showed the best correlation with the pathology of the extent of residual carcinomas. However, except in invasive lobular carcinoma (ILC) and inflammatory breast carcinoma (IBC), CE-CT showed the best correlation (R insertion mark2 = 0.537). More than half of the residual microcalcifications on MMG after neoadjuvant chemotherapy suggested residual viable tumor. In conclusion, CE-CT is the most accurate noninvasive technique for identifying the extent of the residual carcinoma after neoadjuvant chemotherapy if cases of IBC and ILC are excluded.

Adult↗

PubMed2001

Effect of carvedilol on atrioventricular conduction in the ischemic heart.

We compared the effects of carvedilol on atrial-His and His-ventricular conduction with those of propranolol in isolated rat hearts. Hearts were perfused retrograde, and atrial-His and His-ventricular intervals were measured. The effective doses that increased conduction times by 25% were 10(-6) M for atrial-His and 3x10(-6) M for His-ventricular for propranolol, and 8x10(-8) M for atrial-His and 10(-8) M for His-ventricular for carvedilol. Prazosin did not affect the atrial-His and His-ventricular intervals. After ischemia-reperfusion, atrial-His and His-ventricular intervals increased to a greater extent with 10(-6) M carvedilol. To determine the direct membrane effect, we examined the transmembrane action potential in guinea pig papillary muscle. Both drugs decreased the maximum upstroke velocity equally. Our data indicate that carvedilol had a greater effect on atrioventricular conduction in the setting of ischemia-reperfusion than did propranolol. This effect of carvedilol was not due to its alpha-adrenoceptor blocking property or to a direct membrane effect.

Action Potentials↗

PubMed2001

Differences in estrogen receptor status, HER2, and p53 comparing metachronous bilateral breast carcinoma.

BACKGROUND AND OBJECTIVES: We analyzed the clinicopathologic characteristics and tumor biology of metachronous bilateral breast carcinoma with regard to p53, HER2 and hormone receptor status. METHODS: A consecutive series of 54 female metachronous bilateral breast carcinoma patients treated at the National Cancer Center Hospital between 1980 and 1997 were the primary source of these retrospective data. Clinicopathologic background factors were analyzed, and immunohistochemical staining for p53, HER2, and hormone receptor status was carried out on paraffin-embedded specimens. RESULTS: There were no significant differences in clinical stage, p53 and HER2 expression levels between the first and second primary tumors. The positive rates for ER and PR were 48% (25 of 52) and 46% (25 of 54) for the first tumors, but only 19% (10 of 52) and 32% (17 of 54) for the second tumors (P = 0.004 for ER, P = 0.16 for PR), showing a significant loss of ER. CONCLUSIONS: Our findings indicate that p53 and HER2 expression levels in the second tumors might be the same as those of the first tumors in metachronous bilateral breast carcinoma; however, loss of ER was more frequently observed in the second primary tumors than in the first tumors.

Adult↗

PubMed2001

Contrast-enhanced computed tomography for diagnosing the intraductal component and small invasive foci of breast cancer.

It is important to eliminate local residual cancer to avoid local recurrence after breast conserving treatment. Many efforts have been made to detect extensive intraductal components (EICs) and small invasive foci of breast cancer by diagnostic imaging including MRI and contrast-enhanced computed tomography (CE-CT). The abilities and limitations of CE-CT are reviewed in this article. The sensitivity of EIC detection by CE-CT ranges from 76% to 88%, and specificity from 79% to 89%. The sensitivity for detecting EIC and cancerous lesions were significantly higher for CE-CT than for US or MMG. The enhanced patterns of CE-CT demonstrating EIC and small invasive foci were classified into diffuse, spotty, linear and multiple types. The differences of the size of cancerous extension by CE-CT from the pathological EIC were within 2 cm in almost all cases. CE-CT is useful for visualizing EIC and small invasive foci of breast cancer.

Breast Neoplasms↗

PubMed2001

A case of malignant phyllodes tumor of the breast with osteosarcomatous features.

A 64-year postmenopausal woman had noticed a left breast lump 5 months before presentation and was admitted due to increasing tumor size. Physical examination showed a well demarcated, movable mass 5 cm in diameter in the upper outer quadrant of the left breast. The lesion was not painful. She had no past history of malignancy or chest wall irradiation. She had no family history of malignancy. Mammography revealed an irregular tumorous lesion with coarse calcifications in the left breast. Intracystic papillary cancer was suspected by ultrasonography. Aspiration breast cytology yielded insufficient material for diagnosis. Laboratory findings were all within the normal limits including alkaline phosphatase and three tumor markers (CEA, CA 15-3, ST-439). An excisional biopsy of the left breast tumor was performed. Histopathological examination revealed malignant phyllodes tumor with osteosarcomatous features and negative tumor margins. Positive vimentin and negative cytokeratin staining was confirmed by immunohistochemistry, suggesting that the tumor did not originate from epithelial cells of the breast. The estrogen receptor (ER) status of the tumor was negative but progesterone receptor (PgR) was weakly positive. Positive p53 nuclear immunoreaction but negative c-erbB-2 overexpression by immunohistochemical staining was observed in this tumor. There was no evidence of generalized disease. She has been well 6 months after surgery without adjuvant therapy.

Breast Neoplasms↗

PubMed2001

Two special types of breast cancer presenting as progressive disease after neoadjuvant chemotherapy with docetaxel plus doxorubicin.

Seventy-eight patients with primary breast cancer over 3 cm in diameter in stages II A, II B, III A and III B according to the UICC classification received neoadjuvant chemotherapy from August 1, 1998 to June 30, 2000 at the Breast Division of the National Cancer Center Hospital. Neoadjuvant chemotherapy consisted of doxorubicin (Adriamycin: ADM) 50 mg/m(2) and docetaxel (Taxotere: DOC) 60 mg/m(2) every three weeks. The overall clinical response to this regimen was 88% (69/78). Although neoadjuvant chemotherapy with this regimen achieved good responses in patients with breast cancer, 2 patients presented with progressive disease (PD) after treatment. One patient had inflammatory breast cancer (IBC) and the other had primary squamous cell carcinoma (SCC) of the breast. There were 4 cases of IBC and one case of SCC of the breast who received neoadjuvant chemotherapy in this series. Our observations suggest that this regimen might not be effective for these types of breast cancer.

Adult↗

PubMed2001

Diabetic mastopathy: a case report with reference to the findings of enhanced computed tomography.

We report a case of insulin-dependent diabetic fibrous mastopathy with special reference to the findings of computed tomography (CT). The patient was a 27-year-old woman with a history of insulin-dependent diabetes mellitus from childhood who presented with a right breast tumor. Physical examination showed a stony-hard, ill-defined but freely movable mass under the nipple of the right breast without nipple discharge. Mammography revealed a high-density mass shadow without microcalcifications or spicular formation. Ultrasonographic examination revealed an irregularly-shaped hypoechoic lesion with marked posterior acoustical shadowing. Contrast-enhanced CT revealed poor early phase contrast enhancement and slight delayed phase heterogeneous enhancement. Since core needle biopsy revealed fibrocystic disease, the lesion was suspicious for diabetic mastopathy. Incisional biopsy of the right breast lump was performed. On histopathological examination, the lesion showed fibrosis with dense lymphocytic infiltration around the lobules. Diabetic fibrous mastopathy was diagnosed. Physicians should be aware of the association of long-standing diabetes mellitus with the development of fibrous mastopathy. CT is considered a useful tool to differentiate diabetic mastopathy from breast cancer.

Adult↗

PubMed2001

Multicentricity and histopathological background features of familial breast cancers stratified by menopausal status.

BACKGROUND: We investigated histopathological background and multicentricity in patients with familial breast cancers (FBCs) in comparison with these features in patients with sporadic breast cancers (SBCs), stratifying patients by menopausal status. METHODS: We collected a consecutive series of 469 FBC patients and 3334 SBC patients treated at our hospital between 1965 and 1995. The following criteria were used to define FBC, regardless of the presence or absence of a family history of other cancer or the patient's past history of malignancies: (1) Three or more second-degree relatives had been affected by breast cancer; (2) two first-degree relatives had been affected by breast cancer, and either one of them was under 40 years of age and/or had had bilateral breast cancers. The presence or absence of background proliferative lesions (PL; ductal/lobular hyperplasia and/or adenosis) and the multicentricity of breast carcinomas in FBCs and SBCs were analyzed for each group. RESULTS: In premenopausal FBC patients, there was a non-significant trend towards a high frequency of multicentricity compared with findings in patients with SBCs overall (P = 0.087; odds ratio [OR], 1.43; 95% confidence interval [CI], 0.96-2.13). In premenopausal FBC patients, the frequency of background proliferative lesions with/or without fibroadenomas (FA) in the resected specimen was significantly higher than that in SBC patients overall (P = 0.001 for PL; OR, 1.47; 95% CI, 1.18-1.83; P < 0.001 for PL +/- FA; OR, 6.84; 95% CI, 4.93-9.49). With regard to the other clinicopathological factors examined, there were no significant differences between the two groups, except for the higher frequency of premenopausal patients among the FBC patients. CONCLUSION: These results indicate that premenopausal patients with FBCs had more proliferative lesions in the histopathological background and more multicentric breast cancers than premenopausal patients with SBCs.

Adult↗

PubMed2001

Differences in the progesterone receptor contents between familial breast cancers and sporadic breast cancers stratified by patient age.

In the present study, we investigated the estrogen (ER) and progesterone receptor (PR) contents of familial breast cancers (FBCs) and compared the findings with those of sporadic breast cancers., stratified by the patients' age. To evaluate the hormone receptor contents of Japanese FBCs, we collected a consecutive series of 250 FBCs and 2,533 sporadic breast cancers (SBCs). These patients were divided into the three groups stratified by the patients' age at initial surgery (group I, under 40 years old; group II, 40-60 years old; group III, over 60 years old). The clinicopathological features of FBCs and SBCs, including ERs and PRs, were analyzed for each group. In all age groups, the PR contents of FBCs were significantly lower than those of SBCs, particularly for group III. In FBCs, the PR content was significantly lower in group III than in groups I or II. In addition, there was a nonsignificant trend towards a high frequency of ER-positive, PR-negative tumors in FBC patients aged 60 years and over. These data indicate that the loss of ER function and/or loss of binding capacity of PR to progesterone was associated with some late-onset FBCS.

Adult↗

PubMed2001

Correlation of genetic etiology with response to beta-adrenergic blockade among symptomatic patients with familial long-QT syndrome.

Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that entails a high risk of sudden death. beta-Adrenergic blocking agents are the first therapeutic choice, and 80% of patients treated with these agents show symptomatic relief; however the remaining 20% do not respond well. We previously performed a nationwide analysis of familial long QT syndrome (LQTS) in Japan and identified 32 mutations in the KCNQ1 and KCNH2 genes. In the present retrospective study, we found that patients carrying mutations in the KCNQ1 gene responded better to beta-adrenergic blocking agents than those with KCNH2 mutations (12 of 13 vs 1 of 5; P = 0.0077, Fisher's exact test). This is a good example of the power of genetic diagnosis to direct the selection of appropriate therapy for patients with diseases of heterogeneous genetic etiology.

Adolescent↗

PubMed2001

Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects: a study based on coronary angiography.

We undertook a cross-sectional analysis on CETP and atherosclerosis among Japanese subjects, by means of CETP mass assay, its gene polymorphism and coronary angiogram. The 110 consecutive patients who underwent coronary angiography were enrolled into the study except for those over 70 years and taking lipid-lowering drugs. Association was analyzed among plasma lipid and lipoproteins, CETP mass, its gene polymorphisms and the finding in coronary angiography. Four CETP-deficiency heterozygotes were identified and excluded from the analysis. CETP mass level showed neither significant correlation with the coronary score (CS) (r=0.06, P=0.52) nor the difference between the groups eventually diagnosed as coronary heart disease (CHD) positive and CHD negative (2.36+/-0.57 vs. 2.24+/-0.21, P=0.24). CETP mass correlated with the total and LDL cholesterol (r=0.43, P<0.001; r=0.36, P<0.001, respectively) but not with HDL cholesterol (r=0.08, P=0.40). While I405V polymorphism had no impact on CETP mass, HDL cholesterol or CS, CETP mass was low with TaqIB polymorphism (B1B1>B2B2, P<0.05) only in the low CS group (<4). Among the lipid and lipoprotein, HDL cholesterol had a greater impact than LDL cholesterol on coronary atherosclerosis. We concluded that CETP mass in plasma does not correlate with coronary atherosclerosis as whole in the non-CETP-deficient. However, the B2B2 genotype in CETP TaqIB polymorphism, only when it decreases the CETP level, may act as a protective factor against atherosclerosis. It should also be noted that CETP mass in general correlates to total and LDL cholesterol, so that it would be an indirect atherogenic parameter.

Carrier Proteins↗

PubMed2001

Decline of hepatitis C virus load in serum during the first 24 h after administration of interferon-beta as a predictor of the efficacy of therapy.

BACKGROUND/AIMS: Hepatitis C virus (HCV) kinetics during interferon (IFN)-alpha treatment have been evaluated recently, however, little is known about the resultant viral kinetics in IFN-beta treatment. In this study, we evaluated HCV kinetics during the first 24 h of IFN-beta treatment, and also assessed their relationship to therapeutic outcomes. METHODS: We measured HCV RNA levels at 0 and 24 h after the initiation of IFN-beta treatment, and we calculated the decay slope, viral half-life, and viral production and clearance. Then we analyzed these factors as they related to therapeutic responses with IFN-beta as well as to clinical variables, i.e. genotype, diversity of hyper variable region, and histological findings. RESULTS: Patients with sustained responses (SR) displayed steeper decay slopes of the viral load than those without SR (2.87 +/- 1.41 vs. 1.82 +/- 1.66, P = 0.031). On the other hand, the decay slope was not affected by the clinical variables. The values of viral half-life and viral production and clearance showed no significant correlation to the response and the clinical variables. CONCLUSION: This study demonstrated that the decay slope of the viral load during the first 24 h is related to the virological response to IFN-beta treatment.

Adolescent↗

PubMed2001

Pattern of chromosome 16q loss differs between an atypical proliferative lesion and an intraductal or invasive ductal carcinoma occurring subsequently in the same area of the breast.

Atypical proliferative lesions of the breast, such as atypical ductal hyperplasia and atypical papilloma, are considered to be precursors of breast carcinomas and have frequently been shown to have loss of heterozygosity (LOH) on chromosome 16q at the DNA level. We evaluated whether an atypical proliferative lesion and a carcinoma that subsequently occurred in the same area of the ipsilateral breast were of identical clonal origin in seven patients. Using DNA isolated from microdissected archival tissue of epithelial components of both the biopsy specimen of the atypical proliferative lesion and the mastectomy specimen of the carcinoma, the pattern of LOH on 16q was compared between these two lesions using polymerase chain reaction -microsatellite LOH analysis. As a control, LOH on 16q was examined in 13 cases of usual ductal hyperplasia, 10 usual papillomas, and 6 atypical ductal hyperplasias. In the seven cases, LOH on 16q was detected in three of the six atypical proliferative lesions and in five of the seven carcinomas, but the allele with LOH or a deleted region always differed between the two. LOH was detected in both atypical proliferative lesions and carcinomas in one case, only in the atypical proliferative lesion in two cases, and only in carcinomas in three cases. In the controls, LOH on 16q was absent in usual ductal hyperplasias or usual papillomas but was detected in two of six atypical ductal hyperplasias. Although atypical proliferative lesions were frequently confirmed to be of clonal nature with LOH on 16q, these lesions and carcinomas were considered to be clones, probably originated from a field with these clones.

Adult↗

PubMed2001

Kinetics of the hepatitis C virus during interferon therapy as a marker of therapeutic response.

BACKGROUND: The viral load and subtype of hepatitis C virus (HCV) are predictors of the efficacy of interferon (IFN) therapy. The kinetics of HCV during IFN therapy have been described recently, suggesting that HCV infection is highly dynamic. These observations have raised the issue as to whether early monitoring of the viral load can help guide IFN therapy. METHODS: We measured HCV-RNA levels at 0, 24 and 48 h after the start of IFN-alpha treatment (10 MU daily for 2 weeks and then three times weekly for 22 weeks) or IFN-beta treatment (6 MU daily for 6 weeks). Then we analyzed the relationship between HCV kinetics and therapeutic response using stepwise multivariate logistic regression analysis. RESULTS: The exponential decay slope of the viral load during the first 24 h, not the first 48 h or the next 24 h, was a predictor of viral eradication at 6 months after completion of the treatment (sustained response; P = 0.0023). This decay slope was not affected by the HCV serotype or the type of IFN used. Initial viral load and HCV serotype were also predictors, as reported previously (P < 0.0001 and P = 0.0347, respectively). We also proposed a model using a prognostic index that predicted a sustained response with more than 80% sensitivity, specificity and efficacy in an independent and external group of patients. CONCLUSION: This study demonstrated that the exponential decay slope of the viral load during the first 24 h was an important predictor of the response to IFN therapy as well as the initial viral load and HCV serotype. The model may also be useful for the clinical management of IFN therapy.

Antiviral Agents↗