Biomedical subjects
Publications and source records attributed to Mitsukazu Gotoh.
In patients with afibrinogenemia who require operation, prophylaxis against bleeding is important. We report the case of a 14-year-old boy with Marfan syndrome and congenital afibrinogenemia in whom hemopneumothorax developed. Video-assisted thoracoscopic surgery was performed successfully under intravenous administration of fibrinogen and with careful monitoring of plasma fibrinogen level.
The aim of this study was to quantitatively measure tissue blood flow (TBF) in hepatocellular carcinoma (HCC) by a noninvasive method using xenon (Xe) inhalation/CT scans and to correlate the measured TBF with histological features. TBF was measured in HCC with xenon-enhanced CT (xenon/CT) in 20 patients. In 15 patients with HCC diagnosed as hypervascular tumors by conventional CT, TBF of the tumors was significantly higher than that of noncancerous liver tissue (151.1 +/- 20 vs 42.6 +/- 20 ml/min/100 g). Histologically, these tumors were diagnosed as moderately-to-poorly differentiated HCC. In contrast, in five patients with hypovascular HCC, TBF of HCC was almost comparable to that of the noncancerous regions (45.3 +/- 6 vs 48.3 +/- 6 ml/min/100 g). All these tumors were well-differentiated HCC. In conclusions, the measured values of TBF correlate with the clinicopathologic features of liver tumors and nontumorous liver tissue in patients with HCC.
p53R2, which is regulated by tumor suppressor p53, is a small subunit of ribonucleotide reductase. To determine whether it is involved in DNA repair by supplying deoxyribonucleotides (dNTPs) for resting cells in vivo, we generated a strain of mice lacking Rrm2b (encoding p53R2). These mice developed normally until they were weaned but from then on had growth retardation and early mortality. Pathological examination indicated that multiple organs had failed, and all Rrm2b-null mice died from severe renal failure by the age of 14 weeks. TUNEL staining showed a greater number of apoptotic cells in kidneys of 8-week-old Rrm2b-/- mice relative to wild-type mice. p53 was activated in kidney tissues of Rrm2b-/- mice, leading to transcriptional induction of p53 target genes. Rrm2b-/- mouse embryonic fibroblasts (MEFs) became immortal much earlier than Rrm2b+/+ MEFs. dNTP pools were severely attenuated in Rrm2b-/- MEFs under oxidative stress. Rrm2b deficiency caused higher rates of spontaneous mutation in the kidneys of Rrm2b-/- mice. Our results suggest that p53R2 has a pivotal role in maintaining dNTP levels for repair of DNA in resting cells. Impairment of this pathway may enhance spontaneous mutation frequency and activate p53-dependent apoptotic pathway(s) in vivo, causing severe renal failure, growth retardation and early mortality.
To identify p53-target genes we have been using a cDNA-microarray system to assess gene expression in a p53-mutated glioblastoma cell line (U373MG) after adenovirus-mediated transfer of wild-type p53 into the p53-deficient cells. In the work reported here, expression of hCDC4b, which encodes one of the four subunits of the SCF (ubiquitin ligase) complex responsible for degradation of cyclin E, was dramatically up-regulated by infection with Ad-p53. An electrophoretic mobility-shift assay and a chromatin immunoprecipitation assay indicated that a potential p53-binding site (p53BS) present in exon 1b of the hCDC4 gene was able to bind to p53, and a reporter assay confirmed that this p53BS had p53-dependent transcriptional activity. Expression of endogenous hCDC4b, but not the alternative transcript of this gene, hCDC4a, was induced in a p53-dependent manner in response to genotoxic stresses caused by UV irradiation and adriamycin treatment, suggesting that each transcript has a different functional role. These results suggest that hCDC4b is a previously unrecognized transcriptional target of the p53 protein, and that by negatively regulating cyclin E through induction of hCDC4b, p53 might stop cell-cycle progression at G0-G1. This would represent a novel mechanism for p53-dependent control of the cell cycle, in addition to the well-known p21(WAF1) machinery.
Inflammatory bowel disease, notably ulcerative colitis (UC) or Crohn disease (CD), is basically benign, but sometimes develops into serious or fatal cancer. While the primary therapies are medical, such as pharmacotherapy and dietetic modification, intractable, serious, and cancerous cases can require surgical intervention. Surgery represents only one of the treatment options, but prediction of whether UC and CD are likely to progress to serious conditions and determination of when to undertake surgery is essential. Various surgical procedures have been developed over time, and the postoperative results are now generally good. Regarding laparoscopic surgeries, relatively few cases have been accumulated, and addressing the indications and limitations is premature at this point. However, this procedure is likely to fulfill a central role in surgical treatment strategies and represent a major benefit to patients. This paper discusses surgical treatment indications and methods for UC and CD, and explains the practical aspects of laparoscopic surgery, which has made remarkable progress in recent years, for such cases.
OBJECTIVE: We evaluated preoperative pulmonary function as a predictor of respiratory complications and mortality in patients undergoing lung cancer resection to confirm the guideline of the British Thoracic Society: lung cancer surgery in patients with predictive postoperative FEV(1.0) (%FEV(1.0)ppo) > 40% and predictive postoperative diffusion capacity for carbon monoxide (%DL(co)ppo) > 40% can be carried out with average risk. METHODS: We retrospectively studied 356 consecutive patients who underwent pulmonary resection at our Department from January 1992 to December 2001. Preoperative pulmonary function tests included vital capacity (VC), %VC, forced expiratory volume in one second (FEV(1.0)), FEV(1.0)%, diffusion capacity for carbon monoxide (DL(co)), predictive postoperative FEV(1.0) (FEV(1.0)ppo), postoperative respiratory function expressed as a percentage of the predicted normal value (%FEV(1.0) ppo, %DL(co)ppo). Postoperative complications were divided into 2 groups: respiratory complications (pneumonia, atelectasis, etc) and other complications (bronchopleural fistula, prolonged air leak, arrhythmia, etc). RESULTS: Postoperative deaths occurred in 14 (3.9%) patients. Postoperative respiratory complications developed in 27 (7.6%) patients. Pneumonectomy (p < 0.001), preoperative chemotherapy (p < 0.01) and advanced stage (p < 0.05) were identified as risk factors of postoperative deaths. Patients undergoing lobectomy with FEV(1.0) > or = 1,500 ml did not die of respiratory complications. Patients undergoing pneumonectomy with FEV(1.0)ppo > or = 800ml/m2 did not die of respiratory complications. Patients undergoing pneumonectomy with %FEV(1.0)ppo < 40% and %DL(co)ppo < 40% did not survive. Five of the 7 patients who died of respiratory complications were treated with preoperative chemotherapy. The values of their %DL(co)ppo were all less than 40%. By multivariate analysis, %FEV(1.0)ppo was significant independent factor associated postoperative death. CONCLUSIONS: We conclude that the guideline is useful for the selection for surgery of lung cancer patients. If preoperative chemotherapy is performed, the measurement of %DL(co) is recommended before surgery.
The expression of 15 kinds of lectin-binding carbohydrates was examined histochemically in lung adenocarcinoma. The relation between expression of lectin binding carbohydrates and clinicopathologic factors was studied. The expression of peanut agglutinin (PNA) binding carbohydrates showed a high lymph node metastatic rate. Relation between PNA-binding carbohydrate expression and lymphatic vessel invasion was also recognized. Multivariate analysis showed that PNA-binding carbohydrate expression was an independent predictive factor of lymph node metastasis (odds ratio: 2.8) and of lymphatic vessel invasion (odds ratio: 5.2). The expression of PNA-binding carbohydrates would be a significant predictive factor for lymph node metastasis of lung adenocarcinomas.
We report two cases of a bronchopleural fistula with, and without, empyema treated by endoscopic submucosal injection of polidocanol (sclerotherapy) and application of cyanoacrylate. Case 1: A 60-year-old man underwent left pleuropneumonectomy for lung cancer. He developed bronchopleural fistula with empyema at 32 days after the operation. We performed sclerotherapy around the fistula. The air leakage stopped at 2 weeks after the sclerotherapy, and the fistula was closed. He was eventually cured of the empyema by pleural drainage. Case 2: A 61-year-old man underwent left pneumonectomy for lung cancer. He developed bronchopleural fistula without empyema at 50 days after the operation. We performed sclerotherapy and application of cyanoacrylate. After this therapy, the air leakage stopped immediately, and the bronchopleural fistula was closed. The sclerotherapy and application of cyanoacrylate are not only technically easy, but also very effective for treatment of bronchopleural fistula. Sclerotherapy and cyanoacrylate may be advocated as a first therapeutic step.
We report a 15-year-old boy with bilateral chylothorax complicating Gorham's syndrome. Thoracic duct ligation failed to prevent fluid reaccumulation. The patient died of lymphocytopenia. Autopsy revealed vascular proliferation in the parietal and visceral pleura as well as in the ribs, which seemed to cause persistent chylothorax responsible for the poor prognosis of this patient. We reviewed treatments provided to 22 patients reported in the literature with Gorham's syndrome and chylothorax.
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Among the gastrointestinal cancers, esophageal cancer is supposed to be relatively sensitive to both radiotherapy and chemotherapy. The efficacy of combined chemo-radiotherapy in unresectable patients has been confirmed by several investigators. However, no prospective randomized controlled trials with surgery alone as a control had demonstrated significant survival benefit by postoperative adjuvant radiotherapy or chemotherapy in resectable patients. Only a slight prolongation of disease-free survival has been demonstrated with postoperative CDDP + 5-FU therapy. Thus, at present time, postoperative adjuvant therapy is not considered to be a standard therapy for resectable esophageal cancer. Clinical trials with more active combination chemotherapy including new anticancer drugs and new therapeutic strategies such as specific cancer immunotherapy and molecular targeting agents are hoped for in the future.
BACKGROUND: The streptococcal preparation OK-432 induces maturation of T cells and dendritic cells (DCs). However, the mechanisms by which OK-432 induces DC maturation are not well understood. MATERIALS AND METHODS: The effects of OK-432 and TNF-alpha on peripheral blood mononuclear cells (PBMCs) were compared. Antibody-based approaches were used to detect proteins characteristic of antigen-presenting cells and cytokines. Cytotoxicity was evaluated by measuring the release of LDH after incubation of effector and target cells. The TLR-4 levels were measured by real-time quantitative PCR. RESULTS: Changes in cell surface marker levels were detected in both treatment groups but OK-432 had a greater effect on induction of Th-1-type cytokines. Furthermore, TLR-4 mRNA was up-regulated in cells from two out of five patients in response to OK-432, but not in response to TNF-alpha. CONCLUSION: OK-432 has a more profound effect on human DCs than TNF-alpha and may act through multiple signaling pathways.