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Biomedical subjects

T Fukutomi

Publications and source records attributed to T Fukutomi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Preferential occurrence of breast carcinomas with loss of chromosome 16q and der (16) t (1;16) / der (1;16) in middle-aged patients with hyperplasia of mammary glands.

Structural and numerical alterations of chromosome 16 are considered to be commonly involved in the genesis of breast cancer. To reveal etiological factors that predispose cells to these alterations, we examined the frequencies of chromosome 16 aneusomy, 16q loss and 1;16 fusion indicating der (16) t (1;16) / der (1;16) by multi-color fluorescence in situ hybridization in 46 tumors resected mostly from young ( </= 34 years old) or elderly ( >/= 75 years old) women, and compared the results with those in a patient group representing a common age distribution of Japanese patients in whom chromosome 16 status in the tumor had already been studied. The correlation of these chromosome 16 alterations with age, hyperplasia in adjacent mammary glands, cancer history, and obesity indices was investigated in a total of 244 patients. In the present 46 tumors, the frequency of 16q loss and der (16) t (1;16) did not differ between 20 younger patients (30% and 15%) and 23 elderly patients (43% and 13%). However, the incidences of 16q loss and der (16) t (1;16) were low in comparison with the values of 64% and 38% in the 198 Japanese patients representing the common age distribution (P < 0.001). In addition, 16q loss and der (16) t (1;16) were more frequent in tumors arising in hyperplastic mammary glands (68%, 44%) than in those without (52%, 24%) (P < 0.01). Such correlations were not evident for 16cen aneusomy. Other etiological factors examined were not correlated with these chromosome 16 alterations. The 16q loss and der (16) t (1;16) formation were more frequently involved in the development of breast cancer in middle-aged patients than in young and elderly patients. High-level estrogens and / or sensitivity of mammary glandular cells to estrogens might induce breast cancers with structural changes of chromosome 16.

Adult↗
PubMed2000

Adriamycin causes dual inotropic effects through complex modulation of myocardial Ca2+ handling.

Effects of adriamycin (ADR) on the twitch contraction of isolated guinea pig cardiac muscles were examined to elucidate its actions on intracellular Ca2+ mobilization. In right ventricular papillary muscles, ADR (100-300 micromol/L) caused positive inotropy when the muscles were constantly stimulated at low frequencies (0.1-0.5 Hz), whereas it caused negative inotropy when the muscles were stimulated at higher frequencies (2.0-3.0 Hz). Action potential duration was prolonged significantly by ADR, especially at the lower frequencies. The potentiation of twitch contraction of the first beat (B 1) following a short rest period (2-10 s) in ventricular muscles was inhibited by ADR. In untreated papillary muscles, B1 contraction showed time-dependent decay in response to a prolongation of the preceding rest period up to 120 s. ADR (300 micromol/L) caused ryanodin-like acceleration for the early B1 decay with rest period less than 20 s, but a substantial deceleration for the later B1 decay (> or =30 s). In left atrial muscles stimulated constantly, ADR had significant negative inotropy throughout the entire range of stimulation frequencies tested (0.1-4.0 Hz). The post-rest potentiation of B 1 contraction of atrial muscle in the presence of nifedipine was also inhibited by ADR. These findings suggest that ADR has dual inotropic effects through a complex modulation of myocardial Ca2+ handling, which may involve (1) an increase of Ca2+ influx through a prolongation of action potential duration, (2) ryanodine-like inhibition of Ca2+ release from the sarcoplasmic reticulum, and (3) inhibition of sarcolemmal Ca2+ extrusion probably through the Na+/Ca2+ exchange.

Animals↗
PubMed2000

Beneficial application of quantitative coronary angiography (edge detection algorithm) in analysis of dissected coronary arteries to predict long-term patency.

The present study evaluated the application of quantitative coronary angiography (edge detection algorithm) for the analysis of coronary dissection lesions after balloon angioplasty. Acute and late results were obtained by the edge detection algorithm in 60 patients with 66 dissected lesions (NHLBI types B-C). The edge detection algorithm delineated the border of the true lumen in 32 lesions (group with automated analysis alone, 48.5%) and included the dissection cap in the analysis in 34 lesions in which manual editing was adjuncted (group with manual editing, 51.5%). In both groups, the minimal lumen diameter after balloon angioplasty obtained by initial automated analysis was correlated to that obtained at the 5.3-month follow-up similarly (r=0.554, p=0.0010 for the group with automated analysis alone and r=0.613, p=0.0001 after automated analysis for the group with manual editing). However, additional manual editing reduced the correlation coefficient (r=0.240, p=0.1707) in the latter group. Thus, in terms of predicting long-term patency, it is reasonable to let the edge detection algorithm decide the measurements in types B and C dissected lesions.

Algorithms↗
PubMed2000

Development of non-bacterial thrombotic endocarditis after percutaneous transvenous mitral commissurotomy for severely calcified mitral stenosis.

We encountered a case of mitral stenosis, complicated with non-bacterial thrombotic endocarditis, that developed after percutaneous transvenous mitral commissurotomy (PTMC). A 71-year-old female Japanese patient had severe congestive heart failure and underwent PTMC for critical and severely calcified mitral stenosis. Four weeks later, the echocardiogram demonstrated a highly echoic protrusion in the postero-medial commissure of the mitral valve. There was little evidence of inflammation at that time. She had been anticoagulated adequately since she was admitted. The patient underwent replacement of the mitral valve. She did not show any evidence of systemic embolization. Microscopic evaluation showed only organized thrombus but no evidence of inflammation in the mitral valve. Silent development of non-bacterial thrombotic endocarditis after PTMC should be recognized as a rare but potentially lethal complication of PTMC.

Aged↗
PubMed1999

Clinicopathologic analysis of BRCA1- or BRCA2-associated hereditary breast carcinoma in Japanese women.

BACKGROUND: The purpose of this investigation was to elucidate the clinicopathologic characteristics of BRCA1- and BRCA2-associated hereditary breast carcinomas (HBCs) in Japanese women. METHODS: Various clinicopathologic characteristics of HBCs arising in patients with BRCA1 or BRCA2 germline mutations were compared with those of the control group (sporadic breast carcinomas). RESULTS: The mean age at the time of diagnosis of BRCA1-associated HBCs and that of BRCA2-associated HBCs (44 years for both) were significantly younger than that of the control group (54 years) and the incidence of bilateral tumors was significantly higher in the BRCA1-associated HBCs (32%) and BRCA2-associated HBCs (29%) than in the control group (6%). BRCA1-associated HBCs showed a tendency (P = 0.06) toward an increase in solid-tubular type tumors and a significant increase in histologic grade 3 tumors (P < 0.01) and lymphatic invasion positive tumors (P < 0.05) compared with the control group. BRCA1-associated HBCs were significantly more estrogen receptor negative (P < 0.01), c-erb B-2 negative (P < 0.05), and p53 positive (P < 0.01), and they also showed a significant increase in MIB-1 staining grades (P < 0.01) as well as microvessel counts (P < 0.05) compared with the control group. However, there was no significant difference in these parameters between the BRCA2-associated HBCs and the control group. CONCLUSIONS: BRCA1-associated HBCs in Japanese women have biologically aggressive phenotypes. However, BRCA2-associated HBCs are without distinctive clinicopathologic features compared with sporadic breast carcinomas.

Adult↗
PubMed1999

Breast Carcinoma with Osteoclast-like Giant Cells: A Case Report and Review of the Japanese Literature.

A 41-year-old premenopausal woman with a 3.5 cm freely mobile mass in the upper outer quadrant of the right breast was admitted to our hospital. Fine needle aspiration showed malignant epithelial cells and many multinucleated osteoclast-like giant cells (OGCs). Excisional biopsy revealed an invasive ductal carcinoma. A right modified radical mastectomy was subsequently performed. Macroscopically the tumor was well circumscribed with a dark brown cut surface. Microscopically, the tumor was a grade 2 invasive ductal carcinoma with many multinucleated OGCs adjacent the tumor cells and hemorrhage and infiltration of inflammatory cells in the stroma. The intra-mammary metastasis also contained OGCs and stromal reactions. By enzyme immunoassay, the tumor cells were negative for estrogen receptor but positive for progesterone receptor. The tumor cells were negative for both c-erbB-2 and p53. The OGCs showed positive immunostaining with the monoclonalantibody CD68, demonstrating a histiocytic origin. Lymph nodes were free of metastasis. We also review the Japanese literature concerning breast carcinoma withOGCs.

Journal Article↗
PubMed1999

Bilateral Nonpalpable Breast Carcinomas in a Patient with BRCA2 Germ Line Mutation and Past History of Osteosarcoma.

A 34-year-old premenopausal woman developed asynchronous bilateral nonpalpable breast cancers at the age of 32 and 34 years. She had undergone amputation of her left lower leg because of osteosarcoma at the age of 16. Her mother had beendiagnosed with breast cancer at the age of 45. The clinicopathological features of the two breast tumors in this patient closely resembled each other; both were nonpalpable, and detectable only by helical CT scan. Histologically, they consisted mainly of an intraductal component with small grade 3 invasive foci. In addition, both tumors estrogen receptor (ER) status was negative, and both were positive for c-erbB-2 protein on immunohistochemical staining. A missense germ line mutation of BRCA2 (exon 25 codon 3118; Met3118Thr) was detected in this patient. These data may provide useful information on the carcinogenesis and biological behavior of breast cancers which develop in patients with BRCA2 germ line mutations.

Journal Article↗
PubMed1999

Prognosis of a series of 763 consecutive node-negative invasive breast cancer patients without adjuvant therapy: analysis of clinicopathological prognostic factor.

BACKGROUND AND OBJECTIVES: The objectives of this study were to confirm the favorable outcome of Japanese invasive breast cancer patients without lymph node metastasis, after treatment with surgery alone, and to evaluate clinicopathological prognostic factors in this population. METHODS: The subjects were 763 consecutive node-negative invasive breast cancer patients who underwent surgery without adjuvant therapies between 1988 and 1993 at our hospital. Disease-free survival (DFS) and overall survival (OS) rates were analyzed by clinicopathological factors. RESULTS: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 74 months. At 5 years, the respective DFS and OS rates of all patients were 90.8% and 93.9%. Patients with a pathological tumor size of invasive component of more than 2 cm (319 patients) had a significantly lower DFS than those with tumors measuring 2 cm or less (361 patients) (P = 0.045). Patients with positive hormone receptor status (280 patients) (estrogen and/or progesterone receptor positive) tended to have a better OS than those negative for both hormone receptors (92 patients) (P = 0.078). Meanwhile, patients with tumors of histological grade 3 (328 patients) had a much poorer prognosis than those with tumors of histological grade 1 or 2 (413 patients) (P = 0.008 for OS and P = 0.042 for DFS). The respective 5-year DFS and OS rates of patients with histological grade 3 tumors larger than 2 cm in pathological tumor size of invasive component (195 patients) were 85.5% and 87.6%, indicating that these node-negative patients form a high risk group. CONCLUSIONS: Japanese invasive breast cancer patients without lymph node metastasis tended to show a survival advantage compared with their Caucasian counterparts. Histological grade was the most useful prognostic factor in this population.

Adult↗
PubMed1999

der(16)t(1;16)/der(1;16) in breast cancer detected by fluorescence in situ hybridization is an indicator of better patient prognosis.

By two-color fluorescence in situ hybridization (FISH), der(16)t(1;16) or der(1;16) was frequently detected in low-grade papillary carcinoma but not in benign intraductal papilloma of the breast. In order to clarify the incidence and clinicopathological significance of der(16)t(1;16)/der(1;16) in common breast cancers, der(16)t(1;16)/der(1;16) was examined by two-color FISH in breast cancers resected from 51 patients by using DNA probes for 16cen, 16q11.2, and 1q12 labeled with biotin or digoxigenin. der(16)t(1;16)/der(1;16) was clonally detected in 16 cancers (31%), being more frequent in ductal carcinomas of lower grade and invasive lobular carcinoma than in high-grade invasive ductal carcinoma (P<0.001). der(16)t(1;16)/der(1;16) was also correlated with a higher amount of hormone receptors in the tumor (P<0.05). Disease-free and overall survival rates of the patient group with der(16)t(1;16)/der(1;16)-positive cancer were higher (88% and 94%) than those of the group with der(16)t(1;16)/der(1; 16)-negative cancer (39% and 68%) (P<0.05). Among the 16 patients with lymph node metastasis who received one of two similar forms of postsurgical adjuvant chemo-endocrine therapy, the prognosis of those with der(16)t(1;16)/der(1;16)-positive cancer was better than that of those with der(16)t(1;16)/der(1;16)-negative cancer (P<0.05). der(16)t(1;16)/der(1;16) detected by FISH is considered helpful in identifying patients with a better prognosis and for stratification of patients in randomized clinical trials of adjuvant chemo-endocrine therapies.

Breast Neoplasms↗
PubMed1999

A subclavian artery aneurysm associated with aortitis syndrome.

We performed surgery on a 61-year-old woman who had increasingly severe right shoulder pain and paresthesia in her right upper extremity as a result of a large right subclavian artery aneurysm. She had suffered from aortitis syndrome for 10 years for which she was treated with steroids and had multiple arterial lesions, including bilateral subclavian artery aneurysms, abdominal aortic aneurysm and obstruction of bilateral superficial femoral arteries. The right subclavian artery aneurysm measured 4 cm in diameter and rupture appeared imminent, prompting surgical therapy. Via the supraclavicular incision approach and additional partial sternotomy, the aneurysm was excluded and the brachiocephalic to right axillar arterial bypass was set up using an extended polytetrafluoroethylene graft. The patient recovered without complications and a subclavian artery aneurysm demonstrated by computed tomography was thrombosed 1 month after surgery. In conclusion, we recommend the exclusion technique to treat subclavian artery aneurysms in cases in which aneurysmectomy is likely to injure adjacent veins and nerves.

Aneurysm↗
PubMed1999

Detection of bovine coronaviruses from adult cows with epizootic diarrhea and their antigenic and biological diversities.

Bovine coronavirus (BCV) was detected by reverse transcriptase-PCR, immune electron microscopy or virus isolation from adult cows at 6 out of 6 outbreaks of epizootic diarrhea in Japan. Six BCVs isolated in feces, intestinal content or tracheal exudate of the cows were analyzed for their antigenic properties by cross virus neutralization (VN) tests. The isolates were divided into two groups, one of which had closely related antigenicity with the reference Mebus and Kakegawa strains of BCV, and another which showed significant differences in VN antibody titers from the reference strains. Two isolates in the latter group, which were from the enteric and respiratory tracts of the same cows, respectively, were distinguished from each other by ELISA using monoclonal antibodies against the Kakegawa strain. The isolates showed various hemagglutination and receptor destroying enzyme titers against chicken or mouse erythrocytes.

Animals↗
PubMed1999

Detection and differentiation of Aino and Akabane Simbu serogroup bunyaviruses by nested polymerase chain reaction.

Reverse transcription-polymerase chain reaction (RT-PCR) and nested PCR were developed to detect and differentiate Aino (AINO) and Akabane (AKA) virus S RNA. Two pairs of AINO- and AKA-specific primers for nested PCR were synthesized and examined for their capacity to amplify PCR products using 7 Simbu serogroup viruses isolated in Japan and Australia. RT- and nested PCR using AKA-specific primers amplified cDNA from Tinaroo virus RNA as well as homologous RNA. Nested PCR products were differentiated by Hph I and Bst EII digestion. Peaton (PEA) virus S cDNA was also amplified using AINO- specific primers. The nested PCR products of PEA virus were not digested by 3 restriction enzymes (Ava II, Eco RI and Hae II), whereras those of AINO virus were digested as expected. Using this technique, AINO and AKA viruses were detected at concentrations as low as 10(-3) plaque-forming units (PFU) and 10(-5) PFU, respectively, in a supernatant of virus-infected cells. It was possible to detect AINO and AKA genome from various tissues of experimentally infected mice, and also the AKA nested PCR products from serum samples from sentinel cattle naturally infected with AKA virus. The present nested PCR appears a simple, rapid and valuable method for diagnosing AINO and AKA infection.

Animals↗
PubMed1999

Intraoperative detection of embedded coronary arteries in MIDCAB using a color Doppler microprobe.

Intraoperative detection of deeply embedded coronary arteries is difficult, especially in minimally invasive coronary artery bypass grafts. This report describes an effective method to identify embedded coronary arteries by using a color Doppler microprobe. Five embedded left anterior descending coronary arteries were successfully identified by intraoperative ultrasonography. We believe that the color Doppler microprobe is helpful for surgeons in this difficult situation.

Coronary Artery Bypass↗
PubMed1999

A phase I/II study of continuous intra-arterial chemotherapy using an implantable reservoir for the treatment of liver metastases from breast cancer: a Japan Clinical Oncology Group (JCOG) study 9113. JCOG Breast Cancer Study Group.

BACKGROUND: Liver metastasis from breast cancer has a poor prognosis. While there are some reports of good response rates of hepatic metastasis from breast cancer by hepatic intra-arterial infusion chemotherapy, no phase I study including pharmacokinetic analysis has been reported. We performed a phase I/II study of intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find the maximum tolerated dose and response rate in patients with advanced or recurrent breast cancer. METHODS: A hepatic arterial catheter with an access port was inserted into the proper hepatic artery. Patients received 30 mg/m2 adriamycin on days 1 and 8 and 100 mg/m2 5-fluorouracil at level 1, 200 mg/m2 at level 2,300 mg/m2 at level 3 and 400 mg/m2 at level 4 continuously from day 1 through day 14 every 28 days. At least two cycles were required before evaluation. Twenty-eight patients were entered into this study and 26 patients were evaluable. Seventeen patients had hepatic metastasis only, although nine patients had additional metastasis to other sites. RESULTS: Dose-limiting toxicity of thrombocytopenia and neurotoxicity occurred at level 4. Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in three (12%) and anemia in two (8%) patients. There were 11 catheter-related complications which were not dose dependent. Seven out of 13 evaluable patients (54%) responded at level 3. The median duration of response was 5.8 months (range, 1-23+) and median survival was 25.3 months (range, 6.2-54.7+). CONCLUSION: Hepatic arterial infusion therapy appears to be safe and effective but catheter-related complications must be overcome before starting a phase III trial.

Adolescent↗
PubMed1999

A dose-finding study of lenograstim (glycosylated rHuG-CSF) for peripheral blood stem cell mobilization during postoperative adjuvant chemotherapy in patients with breast cancer. Lenograstim/Breast Cancer Study Group.

BACKGROUND: The optimum dose of granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell (PBSC) mobilization after disease-oriented, conventional-dose chemotherapy remains unknown. METHODS: A multicenter dose-finding study of glycosylated G-CSF (lenograstim) for the mobilization of PBSCs following adjuvant CAF chemotherapy (cyclophosphamide, doxorubicin and 5-fluorouracil) was performed in 38 patients with postoperative breast cancer. Each 10, ten and eight patients were sequentially allocated to one of the three dose groups (2, 5 and 10 micrograms/kg, respectively) of lenograstim. Lenograstim was administered subcutaneously (s.c.) daily from day 8 to the day of the last apheresis and CD34+ cells and colony-forming units-granulocyte macrophage (CFU-GMs) in peripheral blood were measured serially. Additionally, 10 patients who received adjuvant CAF chemotherapy alone also participated in the study, as a control. RESULTS: Lenograstim was well tolerated up to 10 micrograms/kg, except for one patient given 10 micrograms/kg who developed transient grade 3 hepatic enzyme elevation. The peak levels of CD34+ cells and CFU-GMs in peripheral blood showed dose-response relationships. The median peak CD34+ cells for the 0, 2, 5 and 10 micrograms/kg dose groups were 5.4, 34.3, 55.0 and 127.6 cells/microliter, respectively, and those of CFU-GMs for the 0, 2, 5 and 10 micrograms/kg dose groups were 0.01, 0.33, 1.32 and 3.30 CFU-GMs/microliter, respectively. CONCLUSIONS: Considering the previous reports suggesting that a pre-apheresis number of 40-50 CD34+ cells/microliter in peripheral blood is highly predictive for achievement of more than 2.5 x 10(6) CD34+ cells/kg in a standard apheresis procedure of 10 litres, the optimum dose of lenograstim for PBSC mobilization following CAF chemotherapy in patients with postoperative breast cancer is 5 micrograms/kg/day s.c.

Adjuvants, Immunologic↗
PubMed1999

Histological factors associated with initial bone metastasis of invasive ductal carcinoma of the breast.

Bone is one of the most common sites of recurrence of breast cancer. Therefore, it would be clinically very useful if breast cancers with a high probability of bone metastasis (BM) could be identified by histopathological examination of the primary lesions. To elucidate histological characteristics associated with predisposition to initial BM, we examined nine histopathological parameters in the primary lesions of 110 invasive ductal carcinomas (IDCs) of the breast with 0 to 3 regional node metastases. These cases had recurrence between 4 months and 10.1 years after the initial radical surgery. The first metastatic site was bone in 24 cases, whereas other sites were involved in 86 cases. IDCs growing in a strand growth pattern or with fibrotic focus (FF) had a significantly higher frequency of initial BM than those growing in a non-strand growth pattern or without FF, respectively. Strand growth pattern was a significant predictor of the initial BM in multivariate analysis. In all 54 IDCs that developed BM during the follow-up period, osteolytic metastasis was significantly more frequent in the group with FF than in that without FF. This study demonstrated that strand growth pattern and the presence of FF are significant histopathological factors associated with initial BM. The combination of those predictive factors along with prognostic factors may provide a useful approach to identify patients at high risk for initial BM, enabling early treatment for the recurrent cancer.

Analysis of Variance↗