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Biomedical subjects

T Fukutomi

Publications and source records attributed to T Fukutomi.

At least 73 records · Page 4Linked to original sources

Increased hyperkinesis in noninfarcted areas during short-term follow-up in patients with first anterior acute myocardial infarction treated by direct percutaneous transluminal coronary angioplasty.

The time course and clinical significance of hyperkinetic wall motion (HWM) in a noninfarcted area in direct percutaneous transluminal coronary angioplasty (PTCA) has not been clearly demonstrated in patients with acute myocardial infarction (AMI). The objectives of this study were to examine the change in HWM during one-month follow-up after direct PTCA and determine its impact on the recovery of global left ventricular function. A total of 61 patients with first anteroseptal AMI and one vessel disease were evaluated. The paired left ventriculograms in the 30 degrees right anterior oblique view taken both at baseline and follow-up were analyzed by the centerline and area length methods. The severity of hypokinesis was expressed by mean regional wall motion (standard deviation/chord) in most hypocontractile 50% of chords respondable to left anterior descending coronary artery area and HWM by mean regional wall motion in most hypercontractile 50% of chords of noninfarcted area. HWM increased from 0.18 +/- 1.07 to 0.48 +/- 1.30 (p = 0.0608). The delta global ejection fraction (global ejection fraction at follow-up minus global ejection fraction at baseline) was correlated with both delta infarcted wall motion (infarcted wall motion at follow-up minus infarcted wall motion at baseline) and delta HWM (HWM at follow-up minus HWM at baseline) (r = 0.576, p < 0.0001, r= 0.383, p = 0.0036, respectively) during follow-up. Further, the delta global ejection fraction showed better correlation with delta (HWM + infarcted wall motion) [(HWM plus infarcted wall motion at follow-up) minus (HWM plus infarcted wall motion at baseline)] (r= 0.593, p < 0.0001). Direct PTCA resulted in the enhancement of HWVM, which contributed to the increase in the global ejection fraction with the recovery of infarcted wall motion.

Aged↗

[Hepatic involvement in a case of lysosomal glycogen storage disease with normal acid maltase].

A 19-year-old man, who could run only slowly since childhood and who walked on his toes since 12 years of age, noted difficulty in climbing upstairs at 17 years of age. He was admitted to Kyushu University Hospital because of elevated AST, ALT and CK levels. On admission, the liver was palpable two fingerbreadths beneath the right costal margin. A neurological examination revealed a low IQ on WAIS-R, a decreased muscle tonus in his four limbs, moderate weakness of the neck flexor and bilateral tibialis anterior muscles, contracture of the ankle joints, and bilateral pes cavus. The serum CK was elevated to 1,124U/l. Hepatic enzymes, such as AST, ALT, LDH and gamma-GTP were also moderately increased in the sera. A needle EMG disclosed myogenic patterns in the limb muscles. Biopsied biceps brachii muscle showed a mild variation in the fiber size and multiple tiny vacuoles in 5-10% of the muscle fibers. PAS and acid phosphatase were strongly positive in some vacuoles. On electron microscopy, numerous autophagic vacuoles containing glycogen granules were observed. The acid maltase activities were, however, normal in the peripheral blood lymphocytes, the biopsied muscle, and the cultured skin fibroblasts. He was thus diagnosed to have lysosomal glycogen storage disease with normal acid maltase. A histological examination of the biopsied liver revealed the portal and central veins to be slightly sclerotic. In addition, mild fatty changes and frequent nuclear vacuolization were present in the hepatocytes. On electron microscopy, enlarged mitochondria with irregular cristae were also observed. Due to the fact that the cardiac function was well preserved, these hepatic lesions were thought to result from the metabolic abnormalities underlying in this disorder.

Adult↗

[Assessing the physiologic significance of intermediate coronary lesions: comparison of coronary flow measurements with exercise electrocardiography].

Angiography may provide limited assessment of intermediate coronary stenoses. Doppler coronary flow reserve has been applied to determine the physiologic significance of such lesions. This study compared coronary flow reserve derived from intracoronary Doppler flow wire with the results of the exercise tolerance test to evaluate the validity of intracoronary flow measurements in the assessment of intermediate stenoses. Sixty eight patients with 91 vessels harboring angiographically mild-to-severe coronary stenoses in the left anterior descending or right coronary artery were studied. All patients had single-vessel disease, and angiography showed the target vessel. Distal coronary flow reserve was measured with the Doppler guide wire during cardiac catheterization. Exercise tolerance tests by bicycle ergometer were performed the day before catheterization. Quantitative coronary angiography showed a mean percentage diameter stenosis of 44 +/- 21%(range 0-90%). Forty seven of 91 vessels combined intermediate lesions(40% to 70%). Percentage diameter stenosis and coronary flow reserve were linearly correlated in both overall and intermediate lesions(r = -0.52 vs -0.42; both p < 0.0001). Percentage diameter stenosis of overall lesions was significantly higher in the positive exercise test group than the negative group(59.8 +/- 17.2% vs 37.7 +/- 18.1%, p < 0.0001), but not significantly different in intermediate lesions(49.1 +/- 7.8% vs 54.7 +/- 6.6%, p = 0.03). The positive exercise test group showed significantly lower coronary flow reserve compared to the negative group in both overall and intermediate lesions(overall: 1.6 +/- 0.5 vs 2.6 +/- 0.9, p < 0.0001; intermediate: 1.6 +/- 0.5 vs 2.5 +/- 0.7, p < 0.0001). Coronary flow reserve < 2.0 and positive exercise test agreed in 38 of 46 intermediate lesions(83%), and percentage diameter stenosis > or = 50% and positive exercise test agreed in 34 of these 46 lesions(74%). Coronary flow reserve, more than percentage diameter stenosis, correlated with the results of the exercise tolerance test, and is considered to be useful to evaluate the functional severity of intermediate stenosis.

Aged↗

Evaluation of adjunctive intracoronary administration of acetylcholine following intravenous infusion of ergonovine to provoke coronary artery spasm.

A dilemma arises in patients with chest pain or other symptoms suggestive of coronary artery disease but without significant coronary artery stenosis or spasm even after the spasm provocation test by either ergonovine or acetylcholine. Incremental doses of intracoronary acetylcholine (up to 100 micrograms for left coronary artery and 50 micrograms for right coronary artery) were administered when intravenous infusion of ergonovine 0.4 mg showed negative results. A total of 39 patients were studied. Provocation test was performed because of chest pain suggestive of coronary artery disease (n = 19), atypical chest pain (n = 6), post balloon angioplasty status (n = 6), silent ischemia (n = 4), Adams-Stokes syndrome (n = 3), and dead-on-arrival (n = 1). Characteristics of chest pain indicated variant angina (n = 11), rest angina (n = 4), and effort angina (n = 4). No electrocardiographic evidence of ischemia was detected before this test in any patient. Spasm was induced in 23 patients (59.0%) with complete obstruction in 7 (30.4%), diffuse vasoconstriction (90-99%) in 14 (60.9%), and focal spasm in 2 (8.7%). The patients with chest pain showed the highest positive rate of 78.9%. Further, the patients with atypical chest pain and miscellaneous reasons also revealed positive rates of 33.3% and 42.9%, respectively. One ventricular tachycardia and 2 atrial fibrillations occurred but terminated spontaneously. This test is useful for detecting spasm in a variety of patients in whom intravenous ergonovine infusion fails to induce spasm.

Acetylcholine↗

Reactive oxygen species enhances the induction of inducible nitric oxide synthase by sphingomyelinase in RAW264.7 cells.

The sphingomyelin pathway, activated by stimuli, such as inflammatory cytokines, results in the formation of ceramide, a second messenger molecule. The purpose of the present study was to examine the mechanism by which macrophage-type nitric oxide synthase (NOS II) is induced by stimulation of the sphingomyelin pathway. When RAW264.7 cells were incubated with sphingomyelinase (SMase), nitrite production, NOS II activity, and NOS II mRNA were increased in a dose-dependent manner. Sphingosine, dihydrosphingosine, N-acetylsphingosine (C2-ceramide), and N-acylsphingosine (natural ceramide) had no effect on nitrite production, suggesting that signal molecules other than these were concomitantly produced by SMase treatment and required for NOS II induction. We then investigated the possible involvement of intracellular reactive oxygen species (ROS) in gene induction. SMase treatment increased the level of intracellular ROS, as assessed by flow cytometric analysis using a ROS-sensitive dye, dichlorofluorescin diacetate. Antioxidants, such as N-acetyl-l-cysteine and alpha-tocopherol, inhibited gene induction as well as nitrite production by SMase. These results suggest that activation of the sphingomyelin pathway induces gene expression and that the elevated ROS were somehow involved in this process.

Acetylcysteine↗

Apocrine Carcinoma of the Breast: Clinicopathological Analysis and Histological Subclassification of 12 Cases.

BACKGROUND: Apocrine carcinoma is rare and most of its clinicopathological features are still unknown. The purpose of this study was to identify the clinicopathological characteristics of apocrine carcinoma. METHODS: We clinicopathologically analyzed apocrine breast carcinomas resected from 12 Japanese women and subclassified them histopathologically. RESULTS: The average age of the patients at diagnosis was 60.1 years (range: 38-78). Tumor diameters ranged from 0.5 to 4.5 cm (median 2.4). Mammography revealed tumor shadows without microcalcifications in all patients. Two (17%) of the12 patients were lymph node metastasis-positive, and lymphatic permeation by tumor cells was observed in 3 (25%). Apocrine carcinoma in this study could be classified into three subtypes according to predominant histopathological growth pattern: type I, intraductal spreading type (4 patients); type II, adenosis-associated type (3 patients); and type III, infiltrating type (5 patients). Types I and II showed no lymph node metastasis and had an excellent prognosis, whereas theinfiltrating type was associated with lymph node metastasis and death from cancer. Estrogen receptors and progesterone receptors were positive in 17% (1/6) and 60% (3/5), respectively, of the tumors tested. CONCLUSION: In the present study, apocrine carcinoma of the breast was characterized by higher patient age and tumor shadows without microcalcifications on mammography. However, the tumors were heterogenous with regard to pattern of local spread.

Journal Article↗

Local Recurrence after Conservative Surgery without Postoperative Radiation for Pure Tubular Carcinoma of the Breast:A Case Report with Reference to Multifocality of Tubular Carcinoma.

A 49-year-old premenopausal woman with stage I breast carcinoma underwent left quadrantectomy with axillary dissection in 1992. The tumor was 0.7x0.5 cm Histopathologically, this was a pure tubular carcinoma without lymph node metastasis or lymphatic or vascular invasion. Although the surgical margin was pathologically negative, atypical ductal hyperplasia was present close to the cut margin's edge. Neither adjuvant chemotherapy nor radiotherapy had been given after the operation. Approximately 5 years after the first surgery, she had a local recurrence in the vicinity of the operative wound. There was no clinical evidence of distant metastasis. A salvage mastectomy was performed. Histopathological examination revealed that the second tumor was an invasive ductal carcinoma, histological grade 2, with extensive intraductal component. It was difficult to determine whether this was a true in-breast recurrence or a second primary cancer. Overexpression of p53 and c-erbB-2 was observed in the second tumor. Estrogen receptor and progesterone receptor were both negative. No postoperative chemotherapy was given. Multifocality and atypical ductal hyperplasia were observed in 7(87.5%)and 6(75%) of 8 patients, respectively, with tubular carcinoma between 1991and 1997 at the National Cancer Center Hospital. Coexisting disease associated with tubular carcinoma suggests that radiotherapy may be an important component of breast conservation treatment to prevent local recurrence in this type of tumor.

Journal Article↗

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.

Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon-intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.

BRCA2 Protein↗

A prospective study of the significance of gene and chromosome alterations as prognostic indicators of breast cancer patients with lymph node metastases.

In 150 surgically resected primary breast carcinomas that had axillary lymph-node metastases, we examined the incidence of loss of heterozygosity on chromosomes 16p, 16q, 17p, 17q, and 18q, point mutation of the p53 tumor-suppressor gene, nuclear immunoreaction of p53 protein, and amplifications of the c-erbB-2 and int-2 oncogenes by Southern blotting, single-strand conformation polymorphism analysis, and immunohistochemistry. We analyzed the association of these factors and conventional prognostic parameters with outcome of the patients, using Cox's univariate and multivariate analyses. The univariate analysis revealed that nuclear p53 immunoreaction, p53 mutation, and c-erbB-2 amplification as well as the number of metastatic lymph nodes, histological grade, and hormone-receptor statuses were significant prognostic indicators for both recurrence and cancer death. p53 immunoreaction was correlated more strongly with a poor prognosis than p53 mutations. The combination of p53 and c-erbB-2 effectively identified the high-risk patient group, and even among Grade 3 cases the subgroup with these alterations tended to have poorer clinical outcomes. The multivariate analysis including p53, c-erbB-2, and conventional factors. Lymph node status, grade, and p53 had independent impacts on the survival of patients. Under identical adjuvant systemic therapies, prognoses differed between the patient groups with and without alterations of p53 or c-erbB-2. Appropriate combinations of conventional factors with nuclear p53 immunoreaction and c-erbB-2 amplification would help to identify highly aggressive node-positive breast carcinomas and would aid stratification of patient groups in randomized clinical trials of adjuvant systemic therapies.

Adult↗

Diagnostic value of contrast-enhanced computed tomography for diagnosing the intraductal component of breast cancer.

BACKGROUND: It is important to reduce local residual cancer to avoid local recurrence after breast conserving treatment. We therefore tried to detect the intraductal components and small invasive foci of breast cancers by contrast-enhanced helical computed tomography (CE-CT). METHODS: In 122 women whose breasts were examined by CE-CT preoperatively, intraductal spread detected on ultrasound (US), mammography (MMG), and CE-CT, and extensive intraductal components (EICs) detected by histological examination were analyzed for correlations among the extent and subtypes of intraductal components, and deviations in tumor size. RESULTS: EICs were present in 44 patients. The sensitivities of EIC detection by US, MMG, and CE-CT were 35%, 61%, and 88%, respectively, and the corresponding specificities were 83%, 86%, and 79%, respectively. The sensitivities of detecting EIC and small invasive foci were 34%, 57%, and 91%, respectively. In 5 patients, EIC could only be visualized by CE-CT. The median deviation of the size of intraductal spread revealed by CE-CT from pathological EIC was 0.0 cm (range + 3.0 to - 1.7 cm). CONCLUSIONS: CE-CT is useful for visualizing intraductal spread and small invasive foci of breast cancer.

Adult↗

Breast cancer in Cowden's disease: a case report with review of the literature.

We report a case of invasive breast cancer in a 62-year-old female patient with Cowden's disease. A left modified radical mastectomy was performed and histopathology of the tumor showed invasive ductal carcinoma, histological grade 3, without lymph node metastasis. The patient had a past history of endometrial cancer at 55 but did not have a family history of malignant disease. Goiter was palpable but aspiration cytology revealed no malignancy. There were several papillomas on the oral mucosa and multiple papillomatous lesions on the right femur. Barium X-ray and endoscopic examination revealed multiple, small, hyperplastic polypoid lesions on the esophagus, stomach and rectum. Histopathology of the biopsy specimens from the esophagus and stomach showed acanthotic squamous epithelium and foveolar hyperplastic polyps. The patient was followed up closely to monitor the thyroid lesions and polyposis of the digestive tract. A total of 12 breast cancer patients who also had Cowden's disease have been reported in Japan and these cases are reviewed in this report.

Breast Neoplasms↗

Microinvasive breast carcinoma with extensive involvement of level III axillary lymph nodes: a case report.

A 44-year-old woman presented with a right huge axillary mass. Both mammography and ultrasonography revealed a primary cancer of 2.8 cm maximum diameter in the right breast and metastases in the axillary lymph nodes, both being confirmed by aspiration cytology as ductal carcinoma. Right standard radical mastectomy with level III axillary lymph node dissection was carried out. Pathologically, the tumor was diagnosed as ductal carcinoma in situ with microinvasion (DCISM), histologic grade 3. The area of stromal invasion measured 1 mm at its widest point. Sixteen of the 17 resected axillary lymph nodes contained metastases, including six level III lymph nodes. Immunohistochemical studies of the tumor revealed overexpression of p53 protein, but not that of c-erbB-2 protein. The frequency of lymph node metastases from DCISM is reported to be very low. Therefore, the present case with extensive involvement of level III lymph nodes was unusual.

Adult↗

Prognostic significance of accumulation of gene and chromosome alterations and histological grade in node-negative breast carcinoma.

The histological grade of atypia is a known prognostic indicator for breast cancer patients and correlates with many gene and chromosome alterations. To investigate the independent prognostic significance of gene and chromosome alterations in axillary node-negative (n0) breast cancers of the invasive ductal and invasive lobular types, the prevalence of eight gene and chromosome alterations and their association with histological grade and recurrence was studied in 129 consecutive patients who had undergone resection over an average follow-up period of 43.4 months. Loss of heterozygosity on 16q, 17p, 16p, 17q and 18q, p53 gene mutation and c-erbB-2 and int-2 gene amplifications were detected in 55%, 37%, 25%, 24%, 22%, 23%, 15% and 11% respectively. Individual alterations in 17p, 17q, 18q, c-erbB-2 and p53 were detected most frequently and gene and chromosome alterations tended to be accumulated in Grade 3 n0 invasive ductal/lobular carcinomas. Histological grade, 18q, int-2 and the number of these gene and chromosome alterations were significant prognostic indicators on Cox's univariate proportional hazard model, and 18q and int-2 were still significant after adjustment for histological grade. Results suggested that examination of the presence of certain gene and chromosome alterations, as well as histological grade, were effective in identifying n0 breast cancer patients at high risk of early recurrence.

Breast Neoplasms↗

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup.

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.

Adult↗

Changes in the treatment outcome of node-positive breast cancer stratified by menopausal status: comparison of patients treated in 1965-75 versus those treated in 1976-86.

OBJECTIVE: The objective of this study was to examine whether and to what extent the outcome of treatment for lymph-node positive breast cancer patients improved between the periods 1965-75 and 1976-86. METHODS: The subjects were 1595 patients with breast cancer positive for lymph node metastasis who were treated at the National Cancer Center Hospital between 1965 and 1986. In order to analyze background factors and treatment outcome, we classified the patients into four groups stratified by the time of initial surgery (1965-75/1976-86) and menopausal status (premenopause/postmenopause). RESULTS: With respect to the clinicopathological background factors, significant changes between the periods 1965-75 and 1976-86 were more frequent use of modified radical mastectomy and postoperative adjuvant chemoendocrine therapy and less frequent use of postoperative radiotherapy in both pre- and postmenopausal patients. The 10-year disease-free and overall survival rates improved by approximately 15-20% between 1965-75 and 1976-86 in this group of patients, regardless of menopausal status. CONCLUSION: The patients with node-positive disease treated at our hospital showed an increase in both disease-free and overall survival from 1965 to 1986.

Adult↗

Germline mutations of the PTEN/MMAC1 gene in Japanese patients with Cowden disease.

Cowden disease (CD) is an autosomal dominant disorder which confers a high susceptibility to diverse benign and malignant tumors. The PTEN/MMAC1 gene was identified as being responsible for CD, since its germline mutations have been identified in affected individuals in the United States and Europe. We identified three novel germline PTEN mutations, a 2-bp deletion, a 1-bp insertion and a missense mutation, in three of five Japanese patients with CD. The missense mutation resided outside of the region encoding a putative phosphatase domain of the predicted PTEN protein, where previously reported missense mutations in CD patients have been clustered. The present result suggests that a wide range of germline PTEN mutations may play a role in the pathogenesis of CD.

Female↗

BRCA1 and BRCA2 Germline Mutations in Japanese with Hereditary Breast Cancer Families.

We examined germline mutations in BRCA1 and BRCA2 in 23 Japanese breast cancer families, using PCR-SSCP analysis. The same nonsense mutation (exon 5, Leu63ter) of BRCA1 was detected in two defferent families. Three different mutations resulting in a truncated BRCA2 protein (exon 9, 20, 24) were detected in three different families, including one male case of breast cancer. One base substitution mutation in BRCA2, A10462G, was detected in the other two families. Although the mean age of onset for breast cancer in families with the BRCA1-mutation was 50 years, the age of onset in families with the BRCA2-mutation was from 28 to 43 years. Among the 23 families examined, two families had members with ovarian cancers, three had members with prostate cancers, and one had a pancreatic cancer. However, none of these families was positive for the BRCA1 orBRCA2 mutation. Histopathologically, we observed a prevalence of histological grade 3 in BRCA1/2-associated familial breast cancers, because of nuclear atypia, structural atypia and mitotic activity. It is suggested that BRCA2 may play a more important role than BRCA1 in Japanese familial breast cancers, and these mutations are related to the aggressive nature and highly proliferative activity of the tumors.

Journal Article↗

Clinical Use of Contrast-Enhanced Computed Tomography for Decision Making in Breast Conserving Surgery.

BACKGROUND: A reduction in local residual breast cancer is important to avoid local recurrence after breast conserving treatment (BCT). Previous studies suggested the usefulness of contrast-enhanced computed tomography (CE-CT) in detecting extensive intraductal component(EIC), which is associated with local recurrence. This study investigates the practical role of CE-CT in BCT. METHODS: In 130 women whose breasts were examined by CE-CT preoperatively, intraductal spread detected using ultrasound (US), mammography (MMG) and CE-CT, and EIC detected by histological examination were analyzed to determine possible correlations among the extent and subtypes of intraductal components. RESULTS: The sensitivities of EIC detection by US, MMG and CE-CT were 29%, 53% and 88%, respectively, and the corresponding specificities were 58%, 70% and 72%, respectively. In 6 patients, EIC could only be visualized using CE-CT. CE-CT demonstrated the extent of cancerous lesions more accurately than standard diagnostic modalities. Intraductal components with a higher histological grade tended to show stronger enhancement. Most false negative intraductal components obtained on CE-CT (6/7) were of a low histological grade. CONCLUSIONS: CE-CT is useful for visualizing EIC and small invasive foci of breast cancer, and can suggest the optimal extent of resection.

Journal Article↗