Biomedical subjects

J Matsui

Publications and source records attributed to J Matsui.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effective cancer targeting using an anti-tumor tissue vascular endothelium-specific monoclonal antibody (TES-23).

Immunoconjugate targeting of solid tumors has not been routinely successful because the endo-thelial cells of blood vessels act as a physical barrier against the transport of macromolecules, such as antibodies. In the present study, we attempted to achieve tumor vascular targeting with an anti-tumor tissue endothelium-specific monoclonal antibody (TES-23). TES-23, an IgG1 monoclonal antibody raised against rat KMT-17 fibrosarcoma-derived endothelial cells, was covalently conjugated with neocarzinostatin (NCS) in a previous study. The TES-23-NCS conjugate induced tumor hemorrhagic necrosis, and showed marked anti-tumor effects against rat KMT-17 fibrosarcoma. This result prompted us to investigate whether this approach would be applicable to various other types of solid tumors. One hour after injection of (125)I-labeled TES-23 into BALB / c mice bearing Meth-A fibrosarcoma and Colon 26 adenocarcinoma, the tumor accumulation of TES-23 was greater than that of the control IgG. In the present study, we report the anti-tumor effects of this monoclonal antibody in mice bearing Meth-A fibrosarcoma. Mice treated with the immunoconjugate showed improved survival with no side effects. This result indicates that common antigens may be found in different kinds of tumor endothelial cells, and that TES-23 might recognize these antigens.

Animals↗

PubMed2000

[Insulin resistance induced by drugs or agents].

Glucocorticoids, oral contraceptives and nicotinic acid are associated with glucose intolerance, and the main cause of the glucose intolerance induced by these drugs is insulin resistance. Particularly glucocorticoids are difficult to substitute for another drugs, and frequency cause glucose intolerance. Now thiazolidinediones is available for reducing insulin resistance in clinical. And there are several evidences that thiazolidinediones can reduce insulin resistance induced by glucocorticoids in rats. But the clinical evidences are little. In future, it is necessary to investigate whether thiazolidinediones would be effective on reducing glucocorticoid-induced insulin resistance in clinical.

Animals↗

PubMed1999

Tumor vascular targeting using a tumor-tissue endothelium-specific monoclonal antibody as an effective strategy for cancer chemotherapy.

In this study, we attempted to develop tumor vascular targeting with a tumor tissue endothelium-specific monoclonal antibody. TES-23, which strongly and selectively recognizes tumor tissue endothelial cells, was chemically conjugated with Neocarzinostatin (NCS), and the anti-tumor effect was examined. The immunoconjugate, TES-23-NCS, showed, through the use of tumor hemorrhagic necrosis, a marked anti-tumor effect on KMT-17 tumors in rats at a dosage of 17 micrograms/kg (NCS equivalent) without any side effects, probably due to specific tumor vascular injury. By contrast, TES-23 alone (107 micrograms/kg), NCS alone (17 micrograms/kg), and Mopc-NCS (Mopc, 107 micrograms/kg; NCS, 17 micrograms/kg), the immunoconjugate of control antibody, did not have any anti-tumor activities. By tissue distribution analysis, TES-23 and TES-23-NCS showed high accumulation in KMT-17 tumors 1 h after intravenous administration. Moreover TES-23 also accumulated in Sarcoma-180 tumors in mice 1 h after intravenous administration. These results suggest that TES-23 may be a candidate for a potential tumor vascular targeting agent that is applicable to a wide variety of tumor types.

Animals↗

PubMed1999

Expression of extended polyglutamine sequentially activates initiator and effector caspases.

To date, eight neurodegenerative disorders, including Huntington's disease and dentatorubral-pallidoluysian atrophy, have been identified to be caused by expansion of a CAG repeat coding for a polyglutamine (polyQ) stretch. It is, however, unclear how polyQ expansion mediates neuronal cell death observed in these disorders. Here, we have established a tetracycline-regulated expression system producing 19 and 56 repeats of glutamine fused with green fluorescent protein. Induced expression of the 56 polyQ, but not of the 19 polyQ stretch caused marked nuclear aggregation and apoptotic morphological changes of the nucleus. In vitro enzyme assays and Western blotting showed that polyQ56 expression sequentially activated initiator and effector caspases, such as caspase-8 or -9, and caspase-3, respectively. Furthermore, using cell-permeable fluorogenic substrate, the activation of caspase-3-like proteases was demonstrated in intact cells with aggregated polyQ. This is the first direct evidence that the expression of extended polyQ activates caspases and together with the previous findings that some of the products of genes responsible for CAG repeat diseases are substrates of caspase-3 indicates an important role of caspases in the pathogenesis of these diseases.

Amino Acid Chloromethyl Ketones↗

PubMed1999

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy.

The tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer.

Adenocarcinoma↗

PubMed1999

Evaluation of pylorus-preserving pancreatoduodenectomy with the Imanaga reconstruction by hepatobiliary and gastrointestinal dual scintigraphy.

BACKGROUND: Following pylorus-preserving pancreatoduodenectomy (PPPD), most surgeons use gastrointestinal reconstruction with an end-to-side duodenojejunostomy placed distally to the pancreatojejunostomy and choledochojejunostomy. In contrast, the authors have consistently used PPPD with the Imanaga reconstruction (PPPD-Imanaga) which consists of end-to-end duodeno- jejunostomy, end-to-side pancreatojejunostomy and choledochojejunostomy, performed in that order. In this study, the movement of bile and food after PPPD-Imanaga was evaluated to document the functional advantages of this method. METHODS: Twenty-four patients who had undergone PPPD-Imanaga were subjected to hepatobiliary and gastrointestinal dual scintigraphy. The interval between operation and scintigraphy ranged from 28 days to 67 months. Six of the 24 patients underwent repeated dual scintigraphy for the observation of temporal changes in gastrointestinal function. RESULTS: The incidence of biliogastric reflux and bile stasis in the jejunal loop was markedly decreased at times later than 2 months after operation. Delay of gastric emptying and bile evacuation, sometimes accompanied by stasis in the jejunal loop, affected the mixing status of bile and food at 1 h after the beginning of imaging. A majority of the patients, however, had a satisfactory mixing status at 2 h. CONCLUSION: The Imanaga reconstruction appears to be a recommendable procedure following PPPD, in light of the bile and food movement achieved in the gastrointestinal tract.

Adult↗

PubMed1999

Enhanced antitumor potency of polyethylene glycolylated tumor necrosis factor-alpha: a novel polymer-conjugation technique with a reversible amino-protective reagent.

We attempted to develop a novel method for the chemical modification of cytokines with synthetic polymers to increase in vivo therapeutic efficacy. A pH-reversible amino-protective reagent, dimethylmaleic anhydride (DMMAn), was used for polymer conjugation of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG). The novel PEGylated TNF-alpha, PEG-TNF-alpha(+), which was pretreated with DMMAn before PEGylation, had 20% to 40% higher specific activity than PEG-TNF-alpha(-) (not treated with DMMAn) in vitro. Moreover, PEG-TNF-alpha(+) more potently caused tumor necrosis in Meth-A solid tumors in mice than did PEG-TNF-alpha(-). The middle fraction (M) of PEG-TNF-alpha(+), which was of the optimal degree of modification among PEG-TNF-alpha(+)s with different molecular weights, caused the highest degree of tumor hemorrhagic necrosis: 30-fold higher than native TNF-alpha and 2-fold higher than the most potent MPEG-TNF-alpha(-) that also had nearly the same molecular weight. Significantly, improvements in antitumor activity in vivo were more marked than were changes in specific activity. Furthermore, native TNF-alpha caused a dose-dependent body weight loss in mice, whereas no obvious side effects were observed in any PEG-TNF-alpha-treated mice. These results suggest that PEGylation using DMMAn is a useful for clinical cytokine delivery.

Animals↗

PubMed1998

Identification of tumor vascular antigens by monoclonal antibodies prepared from rat-tumor-derived endothelial cells.

We have reported the isolation and specific in vitro properties of tumor-derived endothelial cells (TEC) from rat KMT-17 fibrosarcomas transplanted into rats. To develop antibody-based tumor vascular targeting therapy for solid tumors, we have generated monoclonal antibodies (MAbs) using passive immunization of outside-out membrane vesicles of rat epididymal-fat-pad-derived capillary endothelial cells (FCEC) followed by active immunization of those of rat TEC. The MAbs produced were screened against TEC and FCEC. Of all cultured hybridomas, 75 (3.3%) of the secreted MAbs preferentially recognized TEC. We selected a total of 7 MAbs which detected antigens highly abundant in TEC, although 5 of the 7 MAbs were weakly positive for FCEC in cell-ELISA and FACS analyses. The antigens recognized by these MAbs, with the exception of MAb TES-7, were present on endothelial cells of tumor blood vessels in KMT-17 fibrosarcoma tissues, as shown by immunohistochemical analysis. Antigens of 40- and 80-kDa were recognized by MAbs TES-1, 7, 17, 21 and 26 and by MAbs TES-23 and 27 respectively. Although the function of these antigens, which are preferentially expressed on rat tumor-derived endothelial cells, is still unknown, we believe that future studies of such antigens will help elucidate the role of endothelial cells in tumor vasculature. Our results indicate that MAbs may provide a novel tool for the development of antibody-based therapy targeting tumor vasculature.

Animals↗

PubMed1998

Utilization of the TEF1-alpha gene (TEF1) promoter for expression of polygalacturonase genes, pgaA and pgaB, in Aspergillus oryzae.

For the development of an efficient gene expression system in a shoyu koji mold Aspergillus oryzae KBN616, the TEF1 gene, encoding translation-elongation factor 1 alpha, was cloned from the same strain and used for expression of polygalacturonase genes. The TEF1 gene comprised 1647 bp with three introns. The TEF1-alpha protein consisted of 460 amino acids possessing high identify to other fungal TEF proteins. Two nucleotide sequences homologous to the upstream activation sequence, characterized for the ribosomal protein genes in Saccharomyces cerevisiae, as well as the pyrimidine-rich sequences were present in the TEF1 gene promoter region, suggesting that the A, oryzae TEF1 gene has a strong promoter activity. Two expression vectors, pTFGA300 and pTFGB200 for production of polygalacturonases A and B respectively, were constructed by using the TEF1 gene promoter. A polygalacturonase (PGB) gene cloned from the same strain comprised 1226 bp with two introns and encoded a protein of 367 amino acids with high similarity to other fungal polygalacturonases. PGA and PGB were secreted at approximately 100 mg/l in glucose medium and purified to homogeneity. PGA had a molecular mass of 41 kDa, a pH optimum of 5.0 and temperature optimum of 45 degrees C. PGB had a molecular mass of 39 kDa, a pH optimum of 5.0 and temperature optimum of 55 degrees C.

Amino Acid Sequence↗

PubMed1998

Results of surgery and adjuvant radiotherapy for pancreatic cancer.

We retrospectively reviewed the cases of 34 patients with pancreatic cancer who underwent resection between January 1988 and December 1996. Adjuvant radiotherapy was performed in 24 patients, with 13 receiving both intra- and postoperative radiotherapy, 2 receiving postoperative radiotherapy (PORT) alone, and 9 receiving intraoperative radiotherapy (IORT) alone. The 1- and 3-year survival rates for all 34 patients were 59% and 19%, respectively, with a median survival of 13 months. At the time of the analysis, three patients were still alive. Recurrence patterns were assessed in 25 patients who had had no distant metastases at the time of surgery, had survived more than 3 months after surgery, and had undergone close surveillance for recurrence. Based on computed tomography (CT) and autopsy findings, a total of 15 (60%) of these 25 patients had local recurrence, 13 (52%) had liver metastases, and 8 (32%) had both. Eight (62%) of the 13 patients who received IORT and/or PORT developed local recurrence, and we failed to detect any survival advantage of IORT and/or PORT over surgery alone. However, autopsies revealed a suppressive effect of radiation on cancer growth, and local recurrence was not considered to be the direct cause of death in any of the patients, nor did any of the patients develop gastrointestinal obstruction due to local recurrence. The incidence of liver metastasis in the patients with and without tumor invasion of the portal system was 80% (8/10) and 33% (5/15), respectively. The patients who did not develop liver metastasis had significantly longer survivals than who did. Further improvements of survival await effective prophylactic treatment for liver metastases.

Adult↗

PubMed1998

Complications after pylorus-preserving pancreatoduodenectomy with gastrointestinal reconstruction by the Imanaga method.

BACKGROUND: Pylorus-preserving pancreatoduodenectomies (PPPDs) have been performed for disorders of the pancreatic head and periampullary region. The most commonly used reconstructive technique anastomoses the duodenum end-to-side to the jejunum, with pancreatic and biliary anastomoses placed proximally to the end-to-side duodenojejunostomy. In contrast, we have favored PPPD with gastrointestinal reconstruction by the Imanaga method (PPPD-Imanaga), which consists of end-to-end duodenojejunostomy, end-to-side pancreatojejunostomy, and choledochojejunostomy, performed in that order, because the PPPD-Imanaga provides a physiologic mixture of food, pancreatic juice, and bile in the upper portion of the jejunum. STUDY DESIGN: To identify their postoperative complications, we retrospectively reviewed the cases of 55 patients who underwent a PPPD-Imanaga between December 1986 and December 1996. In all cases, the right gastric artery was divided and the pancreatic duct was sewn directly to a small opening in the jejunal mucosa. Twenty patients with malignancy received adjuvant radiotherapy. RESULTS: Five patients died without being discharged, including one who died of cancer progression, for a postoperative mortality rate of 9%. These deaths were limited to patients who had received adjuvant radiotherapy, with only two deaths being procedure related. Delayed gastric emptying, pancreatic leak, and marginal ulcer were observed in 25 (45%), 3 (5%), and 3 (5%) patients, respectively. The delay in gastric emptying was transient and resolved spontaneously, with no patients undergoing reoperation. Only one patient required a reoperation, for the control of intraabdominal bleeding. CONCLUSIONS: A PPPD-Imanaga can be performed with acceptable morbidity and mortality risks. We conclude that the Imanaga method is a favorable complement to PPPD.

Adult↗

PubMed1998

Preoperative radiotherapy for cancer of the extrahepatic bile duct.

From January 1988 through June 1996, 12 patients who had extrahepatic bile-duct cancer received preoperative radiotherapy at doses of 40.6 Gy to 58.4 Gy. At restaging, 1 patient was found to have liver metastases and the remaining 11 patients were taken to surgery. Nine patients underwent resection, and 8 of the 9 received intraoperative radiotherapy. Complications occurred in 4 patients, 3 of whom died postoperatively. The 2 patients who died of intraabdominal complications received both preoperative radiation doses of more than 55 Gy and intraoperative radiotherapy doses of 14 Gy or more. Histologic evidence of irradiation effects was present in all specimens. Irradiation effects on perineural invasion were observed in varying degrees. Two of the four patients who had marked irradiation effects on perineural invasion developed local recurrence, which was found at autopsy to have infiltrated the hepatic hilum without obstructing the hepatic ducts. One patient who had minimal irradiation effects on perineural invasion developed local recurrence with obstructing the hepatic ducts. Of the 2 patients who had positive margins, the patient with marked irradiation effects on perineural invasion survived 18 months, but the patient with slight irradiation effects on perineural invasion survived only 5 months. The high complication rate requires modification of this strategy. The propriety of combining preoperative radiotherapy with intraoperative radiotherapy as well as the radiation dose should be reinvestigated.

Aged↗

PubMed1997

Reduction of oxysterol levels up-regulates HMG-CoA reductase activity in rat liver.

Cholesterol regulates hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity by feedback inhibition. It has been suggested that oxidized derivatives of cholesterol (oxysterols) play an important role, as an intracellular mediator, in the feedback inhibition of cholesterol biosynthesis. We, therefore, investigated the role of intracellular oxysterols in the regulation of HMG-CoA reductase activity. Rats were fed with food (control), cholesterol, clofibrate as a potentiator of the microsomal monooxygenase cytochrome P-450 enzyme system, ketoconazole as a strong inhibitor of the system, or butylated hydroxytoluene (BHT) as an antioxidant. We analyzed and compared hepatic microsomal oxysterol levels among the groups. The results of this study indicated that the oxysterol level, especially 7beta-hydroxycholesterol and 7-ketocholestrol, in the liver was lowered by the administration of ketoconazole and BHT, and HMG-CoA reductase activity was increased in response to these agents. However, there was no change in the HMG-CoA reductase activity, after the administration of clofibrate. We conclude that reduced levels of oxysterol may release the inhibitory effect on the HMG-CoA reductase enzyme and lead to up-regulation of the enzyme.

Animals↗

PubMed1997

Effects of inhaled nitric oxide on postoperative pulmonary circulation in patients with congenital heart disease.

We studied 22 patients with residual pulmonary hypertension or symptoms of postoperative pulmonary hypertensive crisis. They received low-dose inhalation (10 ppm) of nitric oxide (NO), a selective pulmonary vasodilator, after total correction for congenital heart anomalies. Fifteen minutes of NO inhalation improved the pulmonary circulation and lessened the imbalance in the ventilation-perfusion ratio in both groups. Thus, NO inhalation is effective in the treatment of pulmonary hypertension and in the prevention of pulmonary hypertensive crises after total correction for congenital heart anomalies. All patients continued to receive NO therapeutically. The duration of such therapeutic NO inhalation was well correlated with postoperative Qp/Qs (p = 0.014) and Rp/Rs (p = 0.029).

Administration, Inhalation↗

PubMed1997

Long-term sedation with isoflurane in postoperative intensive care in cardiac surgery.

After cardiac surgery, patients often require prolonged mechanical ventilation. We studied the effectiveness and potential toxicity of isoflurane sedation in 40 patients undergoing mechanical ventilation after cardiovascular surgery. All patients who received isoflurane (0.5-1.0 minimum alveolar concentration [MAC] were well sedated by it without significant adverse effects, such as renal, hepatic, or cardiovascular dysfunction. The highest serum inorganic fluoride concentration recorded was 45 mumol/L after 98 MAC h. Patients on isoflurane recovered more rapidly and were weaned from mechanical ventilation sooner than those sedated with intravenous drugs including fentanyl/midazolam. Patients who received intravenous sedatives, but not those on isoflurane, often showed tachyphylaxis in the early stages, and some exhibited an abstinence syndrome involving nonpurposeful movements. Patients sedated with isoflurane did not show these two side effects. In conclusion, isoflurane can provide effective long-term sedation for patients after cardiovascular surgery without significant adverse effects.

Acute Kidney Injury↗

PubMed1997

Helium/oxygen breathing improves hypoxemia after cardiac surgery.

The effects of helium/oxygen (He/O2) on oxygenation (respiratory index [PaO2/FiO2] and intrapulmonary shunt [Qs/Qt]) and on lung parameters (dynamic compliance [Cdyn] and peak inspiratory pressure [PIP]) were studied in 12 patients. After cardiac surgery, they had impairment of oxygenation without physiological findings and with normal chest radiographs despite having a positive end expiratory pressure of up to 10 cm H2O. After 90 min of inhalation of He/O2, oxygenation had improved significantly; that is, PaO2/FidO2 increased significantly (from 113 to 174 mm Hg; mean values are given; p < 0.01), and there was a significant fall in Qs/Qt (from 29 to 19%; p < 0.001) together with an increase in Cdyn (from 60 ml/cm H2O to 64 ml/cm H2O; p < 0.05). These results suggest that He/O2 may have improved oxygenation by recruiting previously obstructed small airways and alveoli.

Administration, Inhalation↗

PubMed1997

Successful treatment of mediastinitis after cardiovascular surgery using electrolyzed strong acid aqueous solution.

Dilute povidone-iodine solution has been widely used as an irrigant for the treatment of mediastinitis. However, its use is not without adverse effects and often causes poor growth of granulation tissues. To avoid the problems seen with the use of povidone-iodine solution, we applied electrolyzed strong acid aqueous solution (ESAAS) to mediastinal irrigation in 4 patients (2 infants and 2 adults) who developed mediastinitis after cardiovascular surgery. According to the "open" method, the mediastinal wound was left open and irrigated with ESAAS 1 to 3 times a day until the infection was eradicated. Satisfactory growth of granulation tissues was observed in all patients treated with no evidence of adverse effects attributable to ESAAS. Delayed primary sternum closure was performed for 2 patients, and musculocutaneous transposition of rectus abdominis for 1. Our experience suggests that irrigation with ESAAS is a safe and effective method of therapy for mediastinitis.

Acids↗

PubMed1997

[Indication and results of pancreatectomy with combined resection of vessels for adenocarcinoma of the pancreas].

Of 192 patients who received pancreatectomy for invasive adenocarcinoma of the pancreas, 107 (55. 7%) underwent combined resection of vessels at Keio University Hospital and Tochigi Cancer Center, from July 1974 until March 1996. Vascular resections included the portal and/or mesenteric vein in 103, the common hepatic artery in 14, the superior artery in 2 and the celiac axis in 5 cases. The morbidity and mortality rate are 20.2%, 1.2% in the standard resected group and 23.1%, 5.6% in the vessel resected group, respectively. Comparison of the survival rate of curability A and B patients between two groups shows no significant difference. Six patients who underwent resection of the portal and/or mesenteric vein survived more than 5 years. The longest survivor is living 13 years 6 months after surgery. Among the patients who underwent resection of the artery, two patients survived 44 and 22 months after distal pancreatectomy with resection of the celiac axis and the common hepatic artery preserving whole stomach.

Adenocarcinoma↗