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Biomedical subjects

R Denno

Publications and source records attributed to R Denno.

At least 55 records · Page 3Linked to original sources

Inhibition of liver metastasis of human gastric carcinoma by angiogenesis inhibitor TNP-470.

The anti-tumor and anti-metastatic effects of TNP-470, an angiogenesis inhibitor, and mitomycin C (MMC), a representative anti-neoplastic agent, were investigated using our established liver-metastasizing gastric carcinoma line, AZ-H5c. AZ-H5c was injected into the spleen of nude mice which had been randomly divided into 4 groups; a control group given saline solution, a group receiving 15 mg/kg TNP-470, a group receiving 30 mg/kg TNP-470 and a group receiving 2 mg/kg MMC. TNP-470 was given s.c. on alternate days for 5 weeks from day 10 after intrasplenic injection, and MMC was administered intraperitoneally (i.p.) once a week from day 10 after intrasplenic injection. In the control group, liver metastasis developed in 13 of 16 mice (81%). Liver metastasis developed in 6 of 11 mice (55%) receiving MMC. In contrast, liver metastasis developed in 4 of 8 mice (50%) receiving 15 mg/kg TNP-470, and in 0 of 14 mice (0%) receiving 30 mg/kg TNP-470. However, TNP-470 had no effect on the tumor growth. These results indicate that the angiogenesis inhibitor TNP-470 has a strong inhibitory activity against in vivo liver metastasis of human gastric carcinoma.

Animals↗

Establishment and characterization of human gastric carcinoma lines with high metastatic potential in the liver: changes in integrin expression associated with the ability to metastasize in the liver of nude mice.

There is a need to establish animal models which are suitable for investigation of human gastric cancer metastasis to the liver. To this end, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded "in vitro" and subsequently injected into the spleens of nude mice. By repeating these procedures three times, we were able to obtain a cell line, designated as AZ-H3c, with high metastatic potential in nude mice. Liver metastasis developed in 15 of 21 (71%) animals injected with AZ-H3c, but only in 14% of those injected with parental AZ521. Further, AZ-H3c caused faster tumor development than did AZ521. However, the primary AZ-H3c tumors and liver metastatic AZ-H3c tumors showed essentially the same histological appearance. We also analyzed the cell surface expression of adhesion molecules. The data showed that the expression of VLA-1, VLA-2, VLA-3, VLA-4, VLA-5 was enhanced in AZ-H3c. In contrast, the expression of VLA-6, (alpha(v)beta3), E-cadherin, ICAM-1 and LFA-1 was reduced in this high-metastatic line. These results suggest that (beta1) integrins play an important role in the liver metastasis of human gastric carcinoma cells. Our high-metastatic line should be useful for studies aimed at the prevention of liver metastasis.

Animals↗

[Isolation rate of E. coli from surgical infections and their susceptibilities].

Escherichia coli isolated from surgical infections during the period from July 1983 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Although the isolation rate of E. coli was not high from postoperative infections, it was most frequently isolated from primary infections throughout the study period. E. coli, Klebsiella spp. and anaerobic bacteria were predominant from fresh infections. From the cases that had previous antibiotics treatment, Enterococcus spp. were the most predominant isolates followed by MRSA and Pseudomonas spp. in this order. 2. Against E. coli, cefozopran, carumonam and aztreonam had the strongest activity, followed by cefmenoxime, imipenem, latamoxef, gentamicin and ofloxacin. Recently, we have noticed that antibiotic resistant E. coli strains particularly against cefazolin are increasing year by year.

Anti-Bacterial Agents↗

[Isolation rate of Pseudomonas aeruginosa from surgical infections and their susceptibilities].

Pseudomonas aeruginosa isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of P. aeruginosa was not high from primary infections, it was more frequently isolated from postoperative infections throughout the study period. Enterococcus spp., P. aeruginosa and Staphylococcus aureus including MRSA were predominant among postoperative infections. From the postoperative cases that had previous antibiotic treatment, Enterococcus spp., MRSA and P. aeruginosa were more predominantly isolated than from those without previous treatments with antibiotics. 2. Cefozopran, ceftazidime, cefsulodin, aztreonam, carumonam, gentamicin, amikacin and ofloxacin had strong activities against P. aeruginosa. We recognize recently that antibiotic-resistant strains of P. aeruginosa against imipenem and ofloxacin have been increasing year by year.

Anti-Bacterial Agents↗

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1994 and June 1995].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated by a multicenter study in Japan, and the following results were obtained. One hundred and fifty-three strains were isolated from primary infections, and 143 strains were isolated from postoperative infections. From primary infections, both anaerobic Gram-positive and-negative bacteria were predominant, and from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was highest, followed by that of Staphylococcus aureus from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Streptococcus intermedius was highest from primary infections, but from postoperative infections anaerobic Gram-positive bacteria was uncommon. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order. From postoperative infections, P. aeruginosa was most predominantly isolated, followed by Serratia marcescens and E. coli. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We have noticed that resistant strains against imipenem and ofloxacin were increasing among P. aeruginosa and resistant strains against cefazolin were increasing among E. coli. MICs of cefazolin against four out of 30 strains of E. coli were higher than 100 micrograms/ml, and MICs of imipenem was higher than 50 micrograms/ml against 5 out of 22 strains of P. aeruginosa.

Anti-Bacterial Agents↗

The ratio of reduced glutathione/oxidized glutathione is maintained in the liver during short-term hepatic hypoxia.

Controversy persists as to whether reperfusion-induced injuries actually occur in the hepatocyte. The liver is the major source of glutathione, a scavenger of hydrogen peroxide. The aim of this study was to evaluate the sensitivity of the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) [GSH:GSSG] as an index of hepatic metabolic stress. A total of 121 rats were studied. The superior mesenteric vein (SMV) was occluded for 30 min, and this was followed by 0, 10, or 120 min of reperfusion. Total glutathione and GSSG levels in the liver, bile, and plasma were quantified, using glutathione reductase-coupled enzymatic assays. Results indicated that the hepatic GSH/GSSG ratio was maintained after an occlusion of the SMV, despite a decrease in adenosine triphosphate (ATP) level and energy charge potential. However, plasma levels of total glutathione and GSSG in the inferior vena cava increased after SMV occlusion and continued to increase after reperfusion. Biliary GSSG efflux decreased during 30-min occlusion of the SMV, and remained low even after reperfusion. The liver maintains homeostasis despite a decrease in biliary GSSG efflux, probably by secreting excess GSSG into the hepatic vein when the SMV is occluded. We conclude that the total amount of glutathione and GSSG in the plasma is directly correlated with oxidative stress in the liver.

Animals↗

Changes in portal hemodynamics and hepatic function after partial splenic embolization (PSE) and percutaneous transhepatic obliteration (PTO).

Since April 1985, we have performed a multidisciplinary therapy consisting of partial splenic embolization (PSE), percutaneous transhepatic obliteration (PTO) or transileocolic vein obliteration (TIO), and endoscopic injection sclerotherapy (EIS) for patients with severe gastroesophageal varices and those with a portacaval shunt associated with portal hypertension. In this study, PSE and percutaneous transhepatic portography (PTP) were performed at the same time in seven liver cirrhosis patients with hypersplenism, gastroesophageal varices, or hepatocellular carcinoma. The changes in portal blood flow/pressure and hemodynamics were examined by a thermodilution method. The effects of PSE on blood biochemical parameters such as the platelet count, ICG R15, redox tolerance index (RTI), and oral glucose tolerance test (75 g OGTT) were also evaluated. PSE induced a decrease in the blood flow of the splenic artery and in the splenic vein pressure without decreasing the portal blood flow. The platelet count in the peripheral blood and the RTI increased significantly. These results suggest the possibility that PSE may reduce the potential perioperative risk in hepatocellular carcinoma complicated with liver cirrhosis.

Carcinoma, Hepatocellular↗

Unusual complications caused by endo-clip migration following a laparoscopic cholecystectomy: report of a case.

We present herein the case of a woman who developed unexpected complications following a laparoscopic cholecystectomy. The clinical manifestations were unique in that symptoms of obstructive jaundice were in fact caused by endo-clips which had migrated into the common bile duct, and the resulting choledochoduodenal fistula presented as persistent cholangitis. While the overall safety of this new procedure appears to be superior to that of open cholecystectomy, the risk of bile duct injury seems more likely. This case stresses the need for caution by surgeons, and emphasizes the necessity for careful surveillance and strict follow-up to ensure the safety of this procedure.

Adult↗

[Bacteria isolated from intraabdominal infection and their susceptibilities to antimicrobial agents].

Bacteria isolated from intraabdominal infections during the period from July 1982 to June 1993 were investigated with regard to their classifications according to a joint research by 9 university hospitals in Japan. The following results were obtained. 1. A total of 971 strains were isolated from 684 out of 597 patients with peritonitis, and 287 strains out of 971 were isolated from postoperative peritonitis. 2. The most predominant organism isolated from patients with acute peritonitis was Escherichia coli (28%), followed by Bacteroides fragilis group (17%), Gram-positive anaerobic cocci (16%), Enterococcus spp. (9%) and Klebsiella spp. (8%). 3. Against E. coli, cefmenoxime, cefuzonam, cefozopran, aztreonam and carumonam showed MIC50 less than 0.05 micrograms/ml. Against B. fragilis group, erthromycin, clindamycin, imipenem, lincomycin and latamoxef showed MIC50 less than 0.78 micrograms/ml. 4. The most predominant organism isolated from patients with postoperative peritonitis was Enterococcus spp. (20%) and followed by Pseudomonas spp. (14%), and Staphylococcus spp. (13%), E. coli (9%), Enterobacter spp. (8%) and Klebsiella spp. (8%). We suggest that cefazolin, cefmetazole, flomoxef, cefmenoxime, cefuzonam, and latamoxef are the first choice agents in empiric therapy for the treatment of acute peritonitis.

Aged↗

[Year to year changes in isolation frequencies of different bacteria from postoperative infections].

Bacterial species isolated from postoperative infections during the period from July 1982 to June 1993 were studied regarding isolation frequencies of different species in different years in a joint research project involving nine (9) university hospitals in Japan. The obtained results are summarized as follows. (1) Altogether, 1,453 strains were isolated with 153 strains obtained during the most recent one year from July of 1992 through June of 1993. The most numerous source of isolation was postoperative intra-abdominal sepsis. (2) Gram-positive cocci were the most often isolated, among them methicillin-resistant Staphylococcus aureus was isolated in increasing frequencies until June, 1992. (3) In the last one year, Enterococcus spp. was isolated the most from postoperative infections followed by Staphylococcus spp. and Pseudomonas spp. Rates of isolation of anaerobic bacteria were relatively low with annual isolation frequencies ranging 8 to 15 per cent.

Digestive System Diseases↗

An experimental study on the effects of selected drugs on pancreatic regeneration after partial pancreatectomy.

This study was undertaken to determine the effect of the single and combined administration of caerulein, hydrocortisone, and FOY-305 (camostat) on the regeneration of the remnant pancreas after a 90% pancreatectomy in rats. After undergoing either a sham operation or a 90% pancreatectomy, the rats were administered the three drugs either singly or in combination. After the rats were killed, the pancreas was weighed and examined for tissue amylase activity, tissue protein content and total DNA content. The results were as follows: In the sham operation group, the caerulein among three drugs produced a significant trophic effect. The trophic effect in the combined administration group was greater than that in the single administration group. In the 90% pancreatectomy group, of the three drugs administered, hydrocortisone produced the most significant trophic effect. The trophic effect in the combined administration group was greater than that in the single administration group. These data suggest that the trophic effect of caerulein is significant in mature pancreatic cells while that of hydrocortisone is an immature one and that an additive effect of the three drugs was observed.

Amylases↗

Ileal duplication cyst associated with heterotopic pancreas: report of a case and literature review.

A rare case of solitary ileal duplication cyst accompanied by heterotopic pancreas in the terminal ileum is presented. An 8 year old boy with an ovoid shaped, elastic soft and pendant-growing ileal duplication cyst associated with aberrant pancreatic tissue but not communicating with the lumen of the ileum, underwent an adhesiotomy for a small intestinal adhesion that caused bowel obstruction. The obstructive state of the intestine seemed to be caused by an inflammation of the duplication cyst which was 4.5 x 2.7 x 2.5 cm and oval in shape. Excision of the cyst and the heterotopic pancreas was curative. The histological findings were identical to heterotopic pancreas accompanied by ileal duplication without any clinical features of heterotopic pancreas. A review of the literature is presented along with the author's experience in a case of ileal duplication cyst associated with heterotopic pancreas located in the ileum.

Child↗

[A case of breast cancer with pleural metastasis responding to administration of intrapleural adriamycin and systemic chemotherapy with FEMP].

A 51-year-old woman with breast cancer metastatic to the pleura was treated with intrapleural instillation of adriamycin after thoracentesis, and systemic administration of FEMP, with complete response for more than 11 months. She underwent radical mastectomy and bilateral oophorectomy for advanced breast cancer, and 18 months later presented radiological evidence of pleural fluid contralateral to the affected breast. Initially, thoracentesis for symptomatic relief was done with a positive cytology in the pleural effusion. Intrapleural instillation of adriamycin was followed by partial resolution, and administration of FEMP achieved complete disappearance of both pleural metastasis and pleural effusion.

Administration, Oral↗

[Hepatic glycolytic intermediates and glucoregulatory enzymes in septic shock due to peritonitis: experimental study in rats].

The hypoglycemia in septic shock due to peritonitis indicates deranged carbohydrate metabolism. To determine if this metabolic failure could be attributed to changes of glucoregulatory enzymes and glycolytic intermediates, activities and changes of these substances in septic shock have been studied in rats. Liver tissue was sampled 5 hours after induction of peritonitis by cecal incision in fasted male rats. Hepatic glycolytic intermediates were assayed by UV-spectrophotometry. Peritonitis caused 33% decrease in glucose-6-phosphate (G6P), a 2.5 fold increase in fructose-1,6-diphosphate (FDP) and a 3.5 fold increase in lactate. Phosphoenolpyruvate (PEP) levels did not show a significant increase in peritonitis. We investigated activities of glucose-6-phosphatase (G6Pase), fructose-1,6-diphosphatase (FDPase), phosphofructokinase ( PFKase ) and pyruvate kinase ( PKase ) in mitochondria-free supernatants from rat liver homogenates. Tissue was sampled 5 hours after induction of peritonitis by cecal incision. Assays were conducted at optimal substrate levels at pH 7.4; NADH charges produced by coupled reactions were determined by UV-spectrophotometry. A significant increase of PFKase and PKase specific activity was observed. These changes were consistent with stimulated glycolysis. For gluconeogenesis to achieve maximum efficiency it would be necessary to inhibit PFKase and PKase completely.

Animals↗