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Mamoru Fukuda

Publications and source records attributed to Mamoru Fukuda.

33 records · Page 2Linked to original sources
PubMed2004

Validity of sentinel lymph node concept for patients with prostate cancer.

PURPOSE: We investigated the feasibility and validity of the sentinel lymph node concept for patients with prostate cancer. MATERIALS AND METHODS: A total of 24 patients (mean age 68.1 years) with prostate cancer but without detectable distant metastases were enrolled in this study. Radioactive tracer (technetium labeled phytate) was injected into the prostate 5 to 6 hours before surgery. Preoperative lymphoscintigraphy was viewed, and in vivo and ex vivo gamma probing was performed during the surgery, which included backup extended lymph node dissection. Radioactivity of the excised lymph nodes was measured and validated with an autowell scintillation counter. RESULTS: Radioactive positive (hot) nodes were identified in 17 of the 24 (70.8%) patients by lymphoscintigraphy, in 21 of 24 (87.5%) patients by in vivo probing and in 23 of 24 (95.8%) patients by ex vivo probing. On an individual basis the numbers of hot nodes identified by lymphoscintigraphy and in vivo probing were low (40% and 36%, respectively) compared to the high detection rate for ex vivo probing (91%). CONCLUSIONS: Although sentinel lymph nodes can be used for prostate cancer, detailed lymph node mapping and extended dissection backup are currently needed. It is also important to establish novel procedures for accurate and complete removal of all hot nodes.

Aged↗
PubMed2003

Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase.

The breast and ovarian cancer suppressor BRCA1 acquires significant ubiquitin ligase activity when bound to BARD1 as a RING heterodimer. Although the activity may well be important for the role of BRCA1 as a tumor suppressor, the biochemical consequence of the activity is not yet known. Here we report that BRCA1-BARD1 catalyzes Lys-6-linked polyubiquitin chain formation. K6R mutation of ubiquitin dramatically reduces the polyubiquitin products mediated by BRCA1-BARD1 in vitro. BRCA1-BARD1 preferentially utilizes ubiquitin with a single Lys residue at Lys-6 or Lys-29 to mediate autoubiquitination of BRCA1 in vivo. Furthermore, mass spectrometry analysis identified the Lys-6-linked branched ubiquitin fragment from the polyubiquitin chain produced by BRCA1-BARD1 using wild type ubiquitin. The BRCA1-BARD1-mediated Lys-6-linked polyubiquitin chains are deubiquitinated by 26 S proteasome in vitro, whereas autoubiquitinated CUL1 through Lys-48-linked polyubiquitin chains is degraded. Proteasome inhibitors do not alter the steady state level of the autoubiquitinated BRCA1 in vivo. Hence, the results indicate that BRCA1-BARD1 mediates novel polyubiquitin chains that may be distinctly edited by 26 S proteasome from conventional Lys-48-linked polyubiquitin chains.

Amino Acid Sequence↗
PubMed2003

Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex.

BRCA1 is a breast and ovarian cancer tumor suppressor protein that associates with BARD1 to form a RINGRING heterodimer. The BRCA1BARD1 RING complex functions as an ubiquitin (Ub) ligase with activity substantially greater than individual BRCA1 or BARD1 subunits. By using NMR spectroscopy and site-directed mutagenesis, we have mapped the binding site on the BRCA1BARD1 heterodimer for the Ub-conjugating enzyme UbcH5c. The results demonstrate that UbcH5c binds only to the BRCA1 RING domain and not the BARD1 RING. The binding interface is formed by the first and second Zn(2+)-loops and central alpha-helix of the BRCA1 RING domain, a region disrupted by cancer-predisposing mutations. Unexpectedly, a second Ub-conjugating enzyme, UbcH7, also interacts with the BRCA1BARD1 complex with similar affinity, although it is not active in Ub-ligase activity assays. Thus, binding alone is not sufficient for BRCA1-dependent Ub-ligase activity.

Amino Acid Sequence↗
PubMed2003

Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer.

BACKGROUND: A phase I clinical study of combination chemotherapy with docetaxel and cyclophosphamide (CPA) was performed to determine the maximum tolerated dose (MTD), the incidence and severity of toxicities and the pharmacokinetics in patients with advanced or recurrent breast cancer. METHODS: Docetaxel was administered by intravenous drip infusion over 60 minutes, followed by intravenous bolus injection of CPA every 3-4 weeks. The dosage of docetaxel/CPA was 40/200, 40/400, 50/400, or 60/400 mg/m(2)/day. RESULTS: Fifteen patients were enrolled and received a total of 33 cycles of the combined therapy. The dose limiting toxicities (DLTs) were leukopenia, neutropenia and thrombocytopenia. The MTD was estimated to be docetaxel 60 mg/m(2) in combination with CPA 400 mg/m(2) per day. Plasma clearance of both drugs was similar regardless of dose. The recommended doses of docetaxel/CPA for a phase Utrial are 50/400 mg/m(2)/day every 3-4 weeks. CONCLUSION: The MTD of this combined therapy was docetaxel 60 mg/m(2) and CPA 400 mg/m(2). Neutropenia and leukopeina were common and severe. It is important to stress the need for modification of the dosing scheme.

Adult↗
PubMed2003

Transurethral fulguration for empyema of ectopic ureteral stump.

A 55-year-old woman who had undergone left nephrectomy 7 years prior because of pyonephrosis, suffered from refractory cystitis and was diagnosed with empyema of the left ureteral stump associated with ectopic ureter. Although removal of the stump is a popular treatment for this disease, transurethral fulguration of the stump lumen was performed in the patient described here. The procedure was technically easy and safe, resulting in the disappearance of the dilated stump and cessation of recurring cystitis.

Electrocoagulation↗
PubMed2003

[Pseudotuberculous pyelonephritis associated with staghorn calculus: a case report].

This report describes a 56-year old woman with an unusual form of chronic pyelonephritis mimicking tuberculosis on histopathological findings. She visited our hospital complaining of left flank pain. Left staghorn calculus and retroperitoneal abscess extending from the kidney were demonstrated on CT. No bacteria, including mycobacteria were identified in preoperative urine bacterial culture. Left nephrectomy with drainage of retroperitoneal abscess was performed. Microscopically, the nephrectomy specimen showed caseating granulomas, formed by epitheloid cells, highly suggestive renal tuberculosis. In spite of these findings, acid-fast bacteria were not revealed in the renal lesion nor the abscess, and cultures of the abscess for mycobacteria were also negative. Because of failure of identifying Mycobacterium tuberculosis, this case should be diagnosed as not renal tuberculosis, but pseudotuberculous pyelonehritis, which has been mentioned in recent literatures. Although this disease is not widely recognized, we must be aware of it to avoid unnecessary antituberculous therapy.

Abscess↗
PubMed2003

Pixel Value Measurement of Microcalcification Specks in Digitized X-ray Film Images for Image Quality Assessment: Automatic Procedure Developed Using Excel Functions.

We previously reported a method of pixel value averaging for microcalcification specks on digitized mammographic phantom images. These average values are considered to represent the pixel value of a speck for quality control in comparison to its maximal peak value. In this report, we described an automatic processing procedure using a spreadsheet to derive the average and peak values of the pixel value of a speck. A hundred and twenty specks in 10 phantoms were processed using the spreadsheet, and average and peak values were compared. In the examination of the digitized mammography images of RMI 156 phantoms for two calcification speck groups, the average and peak values showed good correlation. Therefore, we concluded the peak values could be used as substitutes for the average values for a quality control purpose. However, as the regression coefficients of the two speck groups were significantly different, the relationship between the average and peak value seemed to depend on speck sizes.

Breast Diseases↗
PubMed2002

Targeted substrate degradation by an engineered double RING ubiquitin ligase.

Recognition of the substrates by ubiquitin ligases is crucial for substrate specificity in the ubiquitin-proteasome proteolytic pathway. In the present study, we designed a double RING finger ubiquitin ligase to direct the ubiquitin machinery to a specific substrate. The engineered ligase contains the RING finger domains of both BRCA1 and BARD1 linked to a substrate recognition site PCNA, which is known to interact with cyclin-dependent kinase inhibitor p57. The double RING finger ubiquitin ligase formed a homo-oligomer complex and exhibited significant ligase activity. Co-transfection of the ligase reduced the expression of transfected p57 to the background level in a proteasome-dependent manner and restored the colony formation ability of U2OS cells that is otherwise inhibited by overexpressed p57. The results indicate the ability of the engineered double RING ubiquitin ligase to target the intended substrate. By redesigning the substrate recognition site, expression of engineered double RING ubiquitin ligases may provide a useful tool for removing many different gene products at the protein level.

Cell Line↗
PubMed2002

[Toxic shock syndrome due to methicillin resistant staphylococcus aureus (MRSA) after total prostatectomy].

A 55-year-old man with prostate cancer received a total prostatectomy. Two days after the operation, he suffered from high fever and shaking chilliness, followed by skin eruption, hypotension, diarrhea and chest pain. The results of blood bacterial culture and endotoxin were negative. Toxic shock syndrome was suspected, and the administration of vancomycin (VCM) and continuous hemodialysis-filtration (CHDF) were performed. The steroid pulse therapy for adult respiratory distress syndrome (ARDS) and the treatments for DIC were also done, and they were effective. The desquamation of the extremity was observed on 10 days after the operation. MRSA was finally identified from pus discharge of the operation wound 13 days after the operation. The prevention and treatments for toxic shock syndrome were discussed.

Humans↗
PubMed2002

[Prostatic cancer with multiple pulmonary metastases treated successfully with hormonal therapy: a case report].

A 66-year-old, man was referred to our hospital for further examination of multiple pulmonary nodules on chest X-ray performed on medical examination. He was referred to our clinic because his chief complaint was poor urinary stream. Prostatic cancer was suspected on digital rectal examination and magnetic resonance imaging. Serum prostatic specific antigen (PSA) level was 134.9 ng/ml. Histological examination of transrectal prostatic sextant biopsy revealed well differentiated adenocarcinoma of prostate. Abdominal computed tomography-scan, gastro-intestinal tract examination and bone scintigraphy demonstrated no other primary lesions or distant metastases. Under the diagnosis of prostatic cancer with multiple pulmonary metastasis, we performed total androgen blockade (TAB) consisting of luteinizing hormone releasing hormone agonist and flutamide following dietylstilbestrol (DES) intravenous injection therapy. After three months, pulmonary nodules disappeared on chest X-ray and PSA level decreased to below 0.1 ng/ml. Pulmonary nodules also disappeared on CT-scan after six months after TAB. He is alive and free from the recurrence for 42 months.

Adenocarcinoma↗
PubMed2002

[Breast cancer].

In Japan the mortality and incidence rates of breast cancer have been increasing. In 2000, the number of breast cancer deaths in female was 9,171. In 1996, the aged adjusted incidence rate of breast cancer was 38.9, top among all of female cancers and the estimated number of female breast cancer patients was 29,448 in Japan. Therefore, efficient breast cancer screening system is urgently needed. In April 2000, breast screening using biennial mammography in combination with clinical breast examination instead of annual clinical breast examination alone was introduced for women aged 50 and over in Japan. However, the compliance of screening using mammography was less than 1% in the fiscal 2000 year. On the other hand, the compliance of screening with clinical breast examination alone was 6.5% in same period. These compliances were significantly lower than that of about 65% in the USA. Given the importance of the control of quality in screening mammography, a central committee for the quality control of mammographic screening has been established in order to educate doctors and radiographers and to assess image apparatus in each facility. As of April 2002, 1,409 out of 1,978 doctors that participated in the training program had obtained either grade A (instructor level) or grade B (adequate level). Gøtzche and Olsen reassessed previous meta-analyses of screening mammography and concluded that screening for breast cancer with mammography was unjustified. Subsequently, reviews by U. S. Preventive Services Task Forces and the WHO reconfirmed the effectiveness of screening mammography in reducing breast cancer mortality. These controversies show the importance of assessment of screening mammography effectiveness in Japan.

Adult↗
PubMed2002

[Breast-conserving surgery: quadrantectomy].

The surgical techniques and clinical results of quadrantectomy as a form of breast-conserving surgery are described. A quadrantectomy is a breast-conserving technique including wide resection and tumorectomy. A quadrantectomy is designed to remove an anatomic segment of breast tissue (duct-lobular system). It has the advantage of greater surgical curability than other conserving techniques in cases with ductal spread, because breast cancer arising in the terminal duct often spreads in the duct-lobular system. However, quadrantectomy poses some cosmetic problems due to the large volume of breast tissue excised. Additionally, quadrantectomy has failed to show better results in local recurrence rates compared with wide resection. Therefore quadrantectomy should be limited to breast cancer with segmental and wide ductal spread. It is important to determine the surgical technique that compromises between local curability and cosmetic results for each patient with breast cancer.

Breast↗
PubMed2002

Defects of a mammography quality control phantom visualized by synchrotron radiation imaging.

Synchrotron radiation (SR) imaging of an RMI 156 mammography quality control phantom, serial number 156-15330, revealed some defects which degraded the visibility of calcification specks. SR imaging was performed at SPring-8, in Harima, Japan by using a monochromatic energy of 20 KeV with a field-of-view of 24 X 24 mm. Different kinds of images were obtained by changing sample-to-detector distances; absorption images and refraction-enhanced images. Specks were embedded in a wax matrix and were imaged as black in an absorption image. In a refraction-enhanced image, they were imaged as a black region with white margins. Foreign objects with opposite contrast were detected near, or overlapped with, some specks. As they were depicted as white in the absorption images and as white with a black margin in the refraction-enhanced image, it seemed that they had low X-ray attenuation and a low refraction index compared with the surrounding wax. They might presumably be air bubbles. Visibility of specks in an absorption image was seriously interfered with when those object(s) overlapped with specks. This kind of defect may cause a difficulty in meeting quality assurance specifications when a facility inadvertently purchases defective phantoms.

Artifacts↗