Biomedical subjects
Publications and source records attributed to M Sekimoto.
We measured the invariant mass spectra of electron-positron pairs in the target rapidity region of 12-GeV p+A reactions. We have observed a significant difference in the mass spectra below the omega meson between p+C and p+Cu interactions. This difference indicates that the spectral shape of mesons is modified at normal nuclear-matter density.
We report on the first measurement of a hypernuclear gamma-transition probability. gamma rays emitted in the E2(5/2(+)-->1/2(+)) transition of (7)(Lambda)Li were detected by a large-acceptance germanium detector array (Hyperball), and the lifetime of the parent state ( 5/2(+)) was determined by the Doppler shift attenuation method. The obtained result, 5.8(+0.9)(-0.7)+/-0.7 ps, was then converted into the reduced transition probability [ B(E2)] to be B(E2;5/2(+)-->1/2(+)) = 3.6+/-0.5(+0.5)(-0.4) e(2) fm(4). Compared with the B(E2) of the corresponding E2(3(+)-->1(+)) transition in the 6Li nucleus, our result gives evidence that the size of the 6Li core in (7)(Lambda)Li is smaller than the 6Li nucleus in the free space.
To investigate the feasibility of repeated gene transfection in suicide gene therapy against human solid tumors by a combination of 5- fluorocytosine (5-FC) and its converting enzyme, cytosine deaminase (CD), we repeatedly transfected the yeast CD gene into the human pancreatic cancer cell line BXPC3 using the hemagglutinating virus of Japan-liposome in a new gene transfer method. The in vivo growth of the s.c. transplanted BXPC3 tumor in nude mice given CD-gene transfection was significantly suppressed by i.p. injection of 5-FC when compared with tumors treated with the control vector. Furthermore, the tumor transfected with the CD gene during a 7-day interval was suppressed much more than that of a single transfection. These results suggest that repeated transfection of the suicide gene together with the combination of 5-FC and the yeast CD gene using the hemagglutinating virus of Japan-liposome gene transfer method may be useful for the treatment of human solid tumors, including pancreatic cancer.
Low incidence of bystander-initiated cardiopulmonary resuscitation (CPR) is allegedly responsible for poor survival from out-of-hospital cardiac arrest (OHCA) in Japan. This study was conducted to determine significant predictors for survival after collapse-witnessed OHCA of presumed cardiac etiology to investigate the impact of bystander-initiated CPR. Logistic regression analysis of OHCA of presumed cardiac etiology was performed on retrospective data sets from three Japanese suburban communities. All arrest incidents were witnessed and occurred prior to the arrival of EMS personnel. Outcome measure was survival to discharge. Initial electrocardiogram (ECG) rhythm (ventricular fibrillation (VF) or not), interval from collapse to CPR (within 5 min or not), and initial ECG rhythm/collapse-to-CPR interval interaction were significantly associated with survival. Patient age (70 years or less/over 70 years), interval from collapse to EMS response, and bystander-initiated CPR were significantly associated with VF in an initial ECG. The effectiveness of bystander-initiated CPR for OHCA can be successfully predicted based on the interval from collapse to CPR and initial ECG rhythm. The increase in the proportion of bystander-initiated CPR from the present level of 20-50% would be expected to rescue another 1800 victims of OHCA per year in Japan.
PURPOSE: To evaluate a new prognostic factor of breast cancer, bone marrow micrometastases which was detected by RT-PCR for mammaglobin, a sensitive molecular marker of breast cancer, was examined. MATERIALS AND METHODS: One hundred and eleven samples from stage I-III breast cancer patients were examined. Bone marrow micrometastases and clinicopathological parameters, which were age, tumor size, lymph node metastasis and status of the estrogen receptor, were evaluated for the prognostic factor by statistical analysis. RESULTS: Median follow-up time was 21.1 months. Thirty-three (29.7%) out of 111 samples were RT-PCR positive. Eight cases (24.2%) in this group showed recurrent lesions in the distant organs. Whereas six (7.7%) out of 78 RT-PCR negative patients had distant recurrences. In the premenoposal patients, and in the patients with axillary lymph node metastases, RT-PCR positive cases showed significantly higher distant recurrent rate. Bone marrow micrometastases, axillary nodal status, and estrogen receptor were independent prognostic factors for breast cancer by both univariate and multivariate analysis. CONCLUSIONS: Bone marrow micrometastases detected by RT-PCR for mammaglobin can be a useful predictive marker for early distant recurrence of breast cancer.
Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24). We analyzed the human period3 (hPer3) gene, one of the human homologs of the Drosophila clock-gene period (Per), as a possible candidate for rhythm disorder susceptibility. All of the coding exons in the hPer3 gene were screened for polymorphisms by a PCR-based strategy using genomic DNA samples from sleep disorder patients and control subjects. We identified six sequence variations with amino acid changes, of which five were common and predicted four haplotypes of the hPer3 gene. One of the haplotypes was significantly associated with DSPS (Bonferroni's corrected P = 0.037; odds ratio = 7.79; 95% CI 1.59-38.3) in our study population. Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.
BACKGROUND: The international controversy surrounding the use and effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine and the low incidence of tuberculosis (TB) among Japanese children prompted this study. METHODS: We compared 'universal BCG vaccination' with 'no vaccination at all' using a cost-effectiveness analysis. The study population was a hypothetical cohort comprising a total of 1.2 million infants born in 1996 at locations all over Japan. A model was developed to calculate the number of TB cases prevented by the vaccination programme. Assuming 40-80% overall vaccine efficacy (64-86% for TB-meningitis) and 10 years of protection, we calculated the cost and number of immunizations required to prevent one child from developing TB, the total number of TB cases averted by vaccination and total costs required for the programme. RESULTS: Based on an assumption of flexible vaccine efficacy (40-80%), we estimated that 111-542 TB cases including 10-27 of TB-meningitis would be prevented during the 10 years after BCG vaccination among the cohort of infants born in 1996. About US$35 950-175 862 or 2125-10 399 immunizations would be required to prevent one child from developing TB. Sensitivity analyses covering a wide duration of protection, incidence of TB, vaccine coverage and discount rate, revealed that other than vaccine efficacy, the cost of preventing a single case of TB is highly sensitive to the duration of BCG protection and TB incidence. CONCLUSION: The cost per case of TB prevented is heavily dependent on vaccine efficacy and the duration of protection, and is high compared with the cost of treating one child who has developed TB.
Six patients with breast cancer in the upper inner quadrant underwent endoscopy-assisted partial mastectomy. The tumor was removed with a 2-cm-wide surgical margin through a periareolar semicircular incision using a special retractor and endoscope system for plastic surgery. Another small incision was made in the axilla for total lymph node dissection or sentinel lymph node biopsy. The average of total operation time in five patients who underwent partial mastectomy was 241 minutes (range, 190-315 minutes), and the average time for the procedure of partial mastectomy in six cases was 84 minutes (range, 69-113 minutes). The cosmetic outcome was excellent. Transareolar endoscopic partial mastectomy can be considered as an alternative surgery option and can offer great cosmetic advantage for patients with small cancers in the inner quadrants of the breast.
OBJECTIVE: Beta-catenin activates transcription by TCF/LEF and has been regarded as an oncogene in a wide range of malignant tumors. Among various molecules regulated by beta-catenin/Tcf, cyclin D1 is the most likely candidate for stimulation of the oncogenic pathway. The association between beta-catenin and cyclin D1 was investigated using clinical samples from colorectal cancers. METHODS: The expression of beta-catenin and cyclin D1 was investigated by immunohistochemical analyses of samples from 70 patients with colorectal cancers. In 28 of the fresh tumor samples, beta-catenin protein was separated into soluble and insoluble fractions and quantitatively correlated with cyclin D1 protein by Western blot analysis. RESULTS: Compared with noncancerous epithelium, beta-catenin and cyclin D1 were overexpressed (+) in 35 (50%) and 30 cases (43%), respectively. Cyclin D1 (+) was observed in 74% (26/35) of beta-catenin (+) cases, but only in 11% (4/35) of the beta-catenin (-) cases. Thus, there was a strong association between the expression of beta-catenin and that of cyclin D1 (p < 0.001). In the Western blot analysis, the amount of cyclin D1 correlated well with beta-catenin expression in the soluble fraction (p = 0.0016), but not with beta-catenin in the insoluble fraction or with E-cadherin expression. Beta-catenin (-)/cyclin D1 (-) cases displayed less tumor invasion than the remaining cases. However, there were no significant differences in lymph node metastasis or other clinicopathological findings. CONCLUSION: Our results indicate that beta-catenin overexpression in the cytoplasm may promote malignant transformation by triggering cyclin D1 expression in colorectal cancers.
Although seven years have passed after basic emergency medical technician (EMT) defibrillation system was introduced in Japan, the overall survival for out-of-hospital cardiac arrest (OHCA) remains poor. We investigated factors leading to such an unanticipated result in Japan by comparing the data of OHCA in Japan with those in other countries. We obtained population-based OHCA data from three communities in Japan. We also performed a comprehensive literature and manual search to identify reports that included rates for incidence and survival or provided sufficient data for the calculation of these rates of OHCA. Statistical analysis was performed to compare survival and incidence rates between the communities. We identified 36 articles from 16 countries by a comprehensive literature search. There was no significant difference in incidence and survival rates among communities in Japan. Although the incidence rate of collapse-witnessed OHCA with ventricular fibrillation (VF) was much lower in Japan than western countries, the proportions of survival from it were comparable to those. Basic-EMT defibrillation system in Japan has yielded excellent result in terms of the survival of VF cases. However, much lower proportion of VF to all cases is responsible for lower overall rates of survival from OHCA in Japan.
Explore the source record for details and available documents.
p57KIP2, the second class of KIP family protein, is one of the negative regulators of the cell cycle. To elucidate the role of p57KIP2 in colorectal normal mucosa and cancer, we examined the expression of p57KIP2 protein in 110 pairs of colorectal non-tumor and cancer tissues. Immunohistochemical analysis showed that p57KIP2 was weakly detected in the normal colonic epithelium and lymph follicles. A unique expression pattern of p57KIP2 was exclusively noted in the elastic fibers within the walls of relatively large blood vessels (diameter > 100 microm). In cancer tissues, p57KIP2 protein was localized mainly in nuclei. Using the mean percentage of nuclear p57KIP2 expression (25%) as the cut-off value, we divided our cases into those with high expression (n = 44, 40%) and low expression (n = 66, 60%) of p57KIP2 among 110 colorectal cancer cases tested. The clinical and pathological survey showed a significant correlation between low expression of p57KIP2 and large tumor size (p < 0.05) or the presence of tumors in females (p < 0.01). Survival analysis showed that p57KIP2 expression did not influence prognosis. RT-PCR analysis was also performed using RNA extracts from 6 colorectal cancer tissues. When the levels of p57KIP2 mRNAs were compared with expression of p57KIP2 protein, a clear correlation was found, suggesting that expression of the p57KIP2 protein may be regulated at the transcription level. The present study revealed p57KIP2 expression in colorectal cancer and suggests that p57KIP2 may not play a central role in the progression of colorectal cancer.
To provide a detailed assessment of micrometastases of colorectal cancer by anatomical mapping of regional lymph nodes (LNs), we analyzed 237 LNs from 11 patients with colorectal cancer by reverse transcription-PCR (RT-PCR) using carcinoembryonic antigen and cytokeratin 20 as genetic markers. All dissected LNs were mapped anatomically and subjected to detection assays for micrometastases. Immunohistochemical analysis was also performed using anti-pancytokeratin antibody AE1/AE3 to confirm the existence of occult cancer cells. By histological analysis, 20 of 237 LNs contained metastatic cells, and they were all positive by both immunohistochemistry and RT-PCR. Of the 217 histologically negative LNs, 14 (6.5%) harbored micrometastases by immunohistochemistry, and 57 (26.2%) were positive for at least one of the two genetic markers. Lymphatic mappings of all patients showed that micrometastases were distributed not only at the pericolic LNs but often at distant LNS: Clinical follow-up study showed that two patients developed recurrence within 1 year after surgery, and both of them had RT-PCR-positive micrometastases in not less than 70% of LNs examined. Moreover, both patients had frequent micrometastases at distant LNs, i.e., those around the root or along the inferior mesenteric artery, when compared with patients with no recurrence. Our findings suggest that genetic diagnosis using the RT-PCR method may be clinically useful along with conventional pathological diagnosis, especially when micrometastases spread to distant LNS:
Liver metastasis is the most serious event for physicians and surgeons treating patients with colorectal cancer. Gene therapy is expected to become a novel strategy to prevent liver metastasis. Four types of clinical studies are currently underway: 1) suicide-gene therapy with the cytosine deaminase gene; 2) immune gene therapy with cytokine (inter leukin-2) or major histocompatibility complex class I gene HLA-B7; 3) tumor suppressor gene p53 therapy; and 4) lysis of p53 mutant cancer cells with E1B55k-deleted adenovirus (Onyx-015). Basic research provided several candidates for the liver metastasis-associated genes, including MMP7, DCC, CDC25B, E-cadherin, CD44, vascular endothelial growth factor, etc. There is an alternative approach to liver metastasis, which attempts to introduce a specific gene such as cytosine deaminase and TIMP-2 into the hepatocytes but not into the tumor itself. This concept is based on results showing that hepatocytes can incorporate genes more readily than cancer cells can. Recently, mutant virus therapy has been developed, which includes Onyx-015, adenovirus dl922-947, and mutant-type herpes simplex virus. These mutant types of virus specifically proliferate in the cancer cells and result in their lysis. In the future, development of gene delivery systems that are powerful and specific to cancer type is essential.
Surgery is the main therapy for malignancies of the gastrointestinal tract. Lymph node metastasis is one of the major factors in predicting patients' clinical course and choosing appropriate adjuvant therapy after surgery. The concept of micrometastasis to regional lymph nodes emerged over 10 years ago, but its significance has been controversial. To clarify the relevance of micrometastasis of gastrointestinal tract cancers, we have established RT-PCT based-diagnostic methods using multi-markers such as CEA, CK20, and Mage 3. Prospective studies have shown that not a few micrometastasis-positive patients with carcinoma of the colon, stomach, and esophagus suffered disease recurrence, even though they did not show histologically positive lymph node metastasis. They were initially diagnosed as node-negative, and thus predicted to be disease free. A retrospective study of 62 patients with stage II node-negative colorectal cancer showed that 5-year overall survival was 78.2% among micrometastasis-positive patients, against 95.3% micrometastasis-negative patients. Moreover, there was a marked difference in 5-year disease-free survival, with 61.4% versus 88.4%, respectively. These data warrant further prospective study with a large population since RT-PCR based detection systems for micrometastasis appear to have the potential to improve conventional diagnosis and therapy for colorectal cancer.
CEA and CA19-9 are the two most common tumor markers for colorectal cancer that are currently utilized clinically. The positive rate of CEA is 40-60% and that of CA19-9 is 30-50%. Simultaneous use of the two markers is useful in evaluating the therapeutic effect and monitoring the recurrence of advanced colorectal cancer. Surgical specimens may also provide useful information for the appropriate treatment of patients. Using surgically resected lymph nodes, we examined micrometastasis to assess the spread of the cancer cells and the malignant potential of colorectal cancer. Immunohistochemical analysis using anti-cytokeratin antibody revealed no significant impact of micrometastasis on patient prognosis, while RT-PCR assay using CEA as a genetic marker suggested a positive value in predicting a rapid recurrence. Among various molecular markers, we found that CDC25B phosphatase was a powerful prognostic factor for colorectal cancer. Diagnosis of the existence and malignant potential of cancer cells, together with serum tumor marker levels, may help to construct a more useful system for the better treatment of colorectal cancer.
In colorectal cancer, liver metastasis is the most common and most important prognostic factor. To elucidate the significance of liver resection, we examined 72 cases (H2: 29 cases, H3: 43 cases). The 3-year survival rate for H2 and H3 patients was 71.5% and 4.5%, respectively. The liver resection rate in H2 and H3 patients was 58.6% (17/29) and 16.3% (7/43), respectively. In H2 patients the 3-year survival rate of those with liver resection and non-resection was 71.3% and 9.2%, respectively (p < 0.001). However, in H3 patients the 3-year survival rate in liver resection and non-resection patients was 80.0% and 43.9%, respectively (not significant). Many therapies, such as liver resection, hepatic arterial infusion, and systemic chemotherapy, were attempted for patients with hepatic metastases. Our data show that liver resection can prolong the survival of H2 patients only. On the other hand, hepatic arterial infusion therapy prolongs the survival of H3 patients only. Systemic chemotherapy does not prolong the survival of either H2 or H3 patients.
We report the development and characterization of a novel model of severe hepatitis induced against hepatitis B virus surface Ag (HBsAg). HBsAg was successfully targeted into the liver in soluble form. Using this unique property of HBsAg, we established a liver injury model induced by HBsAg-specific Th1 cells. Severe liver injury was induced in C57BL/6 mice by injection of HBsAg together with HBsAg-specific Th1 cells. Histochemical examination demonstrated extensive necroinflammatory hepatic lesions in these animals. Application of this liver injury model to mutant or gene knockout mice enabled us to define the effector mechanisms of Th1 cells in fulminant hepatitis. When Fas-deficient lpr mice were used as recipients, a similar degree of liver injury was induced as in wild-type mice. Moreover, HBsAg-specific Th1 cells obtained from perforin-/- mice could induce severe liver injury in both wild-type and lpr mice. These results indicated that neither Fas ligand nor perforin are essential for Th1-mediated liver injury in this model. Pretreatment with anti-TNF-alpha mAb prevented liver injury, whereas severe liver injury was induced in TNF-alpha-/- mice. Moreover, IFN-gamma receptor-deficient mice were resistant to Th1-mediated liver injury. Therefore, TNF-alpha and IFN-gamma, which were produced by HBsAg-specific Th1 cells during the effector phase, appeared to be indispensable in the pathogenesis of fulminant hepatitis.