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Biomedical subjects

Harumasa Ohyanagi

Publications and source records attributed to Harumasa Ohyanagi.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of standard-dose and low-dose gemcitabine regimens in pancreatic adenocarcinoma patients: a prospective randomized trial.

BACKGROUND: A prospective, randomized study was performed to determine whether gemcitabine infusion at a low dose (250 mg/m2) is comparable or superior to the standard-dose infusion (1000 mg/m2) in terms of the survival period, clinical benefit, and frequency of adverse effects in patients with advanced pancreatic adenocarcinoma. METHODS: Twenty-five patients who were histologically proven to have locally advanced pancreatic cancer or pancreatic cancer with distant metastases were initially enrolled in the present study. They were treated with gemcitabine infusion at either a dose of 1000 mg/m2 over 30 min (the standard regimen) on days 1, 8, and 15 of every 4-week cycle or at a dose of 250 mg/m2 over 30 min every week. Survival time, response rate, time to treatment failure, clinical benefit response, and adverse effects were compared between the two groups. RESULTS: Twenty-one patients received gemcitabine for more than 1 month. The median survival period was 7.2 months for patients who received the low-dose infusion regimen, in contrast to 5.2 months for patients administered the standard-dose infusion regimen. The time to treatment failure was 5.6 months for patients in the low-dose infusion regimen, in contrast to 3.4 months for patients in the standard-dose infusion regimen. There were no significant differences in either survival time to time to treatment failure or clinical benefits between the two groups, but the incidence of adverse reactions in patients administered the low-dose therapy was significantly lower than that in patients receiving the standard-dose therapy (P<0.05). In particular, patients in the standard infusion regimen group experienced more hematologic toxicity than those in the low-dose regimen. CONCLUSIONS: These findings suggest that the low-dose gemcitabine infusion regimen can be continuously administered to patients with locally advanced and systemically spreading pancreatic cancer because of its reduced toxicity, resulting in better quality of life and an improved safety profile as compared to the standard infusion treatment regimen.

Adenocarcinoma↗
PubMed2006

Pancreatic and bile duct obstruction exacerbates rat caerulein-induced pancreatitis: a new experimental model of acute hemorrhagic pancreatitis.

BACKGROUND: Pancreatic duct obstruction induces edematous but not hemorrhagic pancreatitis even when combined with maximal secretory stimulation. The aim of the present study was to test the hypothesis that pancreatic and bile duct obstruction exacerbates edematous pancreatitis induced by supramaximal secretory stimulation by caerulein. METHODS: In in vivo studies using rats, biliopancreatic duct ligation was combined with supramaximal stimulation of caerulein, and pancreatic histology, serum amylase level, pancreatic edema, and intrapancreatic trypsin activation were evaluated. In in vitro studies, the pancreatic acini were isolated from the rats with biliopancreatic duct ligation, and amylase secretion, intracellular trypsin activation, and acinar cell fragility were evaluated. RESULTS: Biliopancreatic duct ligation exacerbated caerulein-induced pancreatitis from edematous to hemorrhagic only when the obstruction preceded caerulein administration. The amylase secretion from the acini was inhibited, and intracellular trypsin activation and the acinar cell fragility on the supramaximal stimulation with cholecystokinin in vitro were enhanced by the preceding in vivo biliopancreatic duct obstruction. CONCLUSIONS: Preceding biliopancreatic duct obstruction exacerbates caerulein-induced pancreatitis. Enhancement of intracellular trypsin activation is possibly involved in this mechanism.

Amylases↗
PubMed2005

Apoptosis in human pancreatic cancer cells induced by eicosapentaenoic acid.

OBJECTIVES: Clinical studies have shown that administration of eicosapentaenoic acid (EPA) to patients who have unresectable pancreatic cancer induces marked attenuation of cachexia. However, the exact mechanisms of the beneficial effect of EPA on pancreatic cancer are unknown. This examined the effect of EPA on proliferation of human pancreatic cancer cell lines and sought to clarify its mechanisms. METHODS: The effects of EPA on proliferation of three human pancreatic cancer cell lines (SW1990, AsPC-1, and PANC-1) were assessed. Induction of apoptosis and expressions of apoptosis-related proteins were measured. The effect of EPA on cyclo-oxygenase-2 expression in these cell lines was determined. RESULTS: EPA inhibited proliferation of all three human pancreatic cancer cell lines in a dose-dependent fashion. Simultaneously, EPA treatment induced apoptosis and this was associated with caspase-3 activation. EPA treatment was also associated with a decrease in intracellular levels of cyclo-oxygenase-2 protein. CONCLUSION: We have demonstrated that EPA inhibits human pancreatic cancer cell growth due at least in part to the induction of apoptotic cell death. Such apoptosis is associated with activation of caspase-3 and suppression of cyclo-oxygenase-2 expression. Greater understanding of the molecular events associated with the biological activity of EPA should enhance the therapeutic potential of administration of EPA to patients who have pancreatic cancer.

Apoptosis↗
PubMed2004

A partial hepatectomy results in altered expression of clock-related and cyclic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes.

The liver is among the peripheral organs that display a clear circadian rhythmicity. To investigate whether specific pathological conditions affect circadian rhythms in the liver, we examined the expression profiles of the clock-related and glyceraldehyde 3-phosphate dehydrogenase (GADPH) genes following a partial hepatectomy in the mouse. This surgical procedure causes dynamic proliferation of residual hepatocytes and within one day of the operation the hepatectomized mice demonstrated higher expression of both mPer1 and mPer2 genes in the remaining liver tissue when compared to control mice that had undergone a Sham-operation. In contrast, the mCry1 gene in hepatectomized mice displayed a circadian gene expression profile that was similar to the control group. In addition, GAPDH levels, that demonstrated no oscillations in Sham-hepatectomized mice, underwent daily alterations following a partial hepatectomy. These findings suggest that the regenerative state of the liver affects the expression not only of clock-related genes but also of genes that are constitutively expressed under steady state conditions.

Animals↗
PubMed2004

[Advance and perspective of clinical nutrition].

Although nutritional support using nutrient enemas was recorded almost 3,500 years ago, the modern era of clinical dietetics commenced with the development of intravenous hyperalimentation by Dudrick et al. and the development of the chemically defined diet by Greenstein et al. Thereafter, clinical nutritional support became widely accepted as one of the basic tools of patient care, and knowledge of the metabolism of nutrients has been extended. In particular, the significance of micronutrients in systemic function, importance of gut function on the systemic metabolism and immune system, and involvement of amino acids and fat elements in the development and amelioration of specific disease status such as renal and hepatic failure have been recognized, and specific nutritional support has been created as a treatment strategy. In addition to knowledge of renal and hepatic failure or metabolic disorders, accumulated information on tumor metabolism and pathophysiology in cancer cachexia has also enabled cancer treatment using a nutritional approach. An enteral diet containing certain amino acids such as arginine or glutamate, omega-3 unsaturated fatty acids, and nucleic acids has been developed, and its clinical application under the new concept of "immunonutrition" has demonstrated reduction of the incidence of infection and shortening of hospital stay. Many questions on Immunonutrition remain to be answered such as its mechanism or optimal composition, although it is a promising field for future evolution. Currently, the assessment of nutritional status and gut function is required through lifelong education of medical doctors as well as the popularization of nutritional support teams. In the near future, tailor-made nutritional support will be required based on gene polymorphisms.

Adjuvants, Immunologic↗
PubMed2004

[Recent trends in the clinical practice of nutritional support in Japan: results of a national survey carried out in 2001].

Nutritional support has advanced and patients can now be given more effective nutritional care. On the other hand, some problems remain, such as inadequate administration of total parenteral nutrition (TPN), catheter-related sepsis, etc. The Committee of the National Survey on Nutritional Support, established under the Japanese Society for Parenteral and Enteral Nutrition, investigated the recent trends in the clinical practice of nutritional support in Japan by mailing a questionnaire containing 90 questions to a total of 6,500 physicians in 10 medical departments. The results showed that: 1) surgeons have more interest in nutritional support than physicians in other fields. 2) More than 90% of physicians in Japan still use intravenous hyperalimentation(IVH) instead of TPN and they place more focus on the central venous catheter and insertion of the central venous catheter than on hyperalimentation in the term IVH. 3) There remains a tendency for surgeons to prefer parenteral nutrition to enteral nutrition. This tendency is supported by data showing that the rate of administering TPN to gastroenterological surgical patients as a postoperative management method is high. To the question, "How did you learn about nutritional support?," only 18.3% of physicians answered that they studied it in medical school. We may conclude this to be the most important problem in nutritional support in Japan.

General Surgery↗
PubMed2003

Preparation of poly-lactic acid microspheres containing the angiogenesis inhibitor TNP-470 with medium-chain triglyceride and the in vitro evaluation of release profiles.

TNP-470 (AGM-1470, 6-0-(N-chloroacetylcarbamoyl)-fumagillol), a derivative of fumagillin, is a promising angiogenesis inhibitor. However, as TNP-470 is very unstable in in vitro and in vivo, it has been difficult to verify its pharmacological efficacy in the clinical medicine. The preparation of a drug delivery system (DDS) in a microsphere form was studied for the stable inclusion and controlled release of TNP-470. Medium-chain triglyceride (MCTG) as an effective stabilizer and poly-lactic acid (PLA) as a biodegradable carrier were used for this purpose. The release of TNP-470 from the MCTG containing DDS continued for approximately 2 weeks, while the release of TNP-470 from the one without MCTG stopped after only 5 days. It was proved that TNP-470 could be released much more stable for much longer period from the MCTG containing DDS compared to the one without DDS.

Angiogenesis Inhibitors↗
PubMed2003

Effect of glicentin on gut mucosal growth in rats with jejunal and ileal Thiry-Vella fistulas.

BACKGROUND/PURPOSE: Glicentin stimulates growth of normal and atrophic small bowel mucosa; the mechanisms for this trophic effect of glicentin are not completely known. The purpose of this study was to determine whether the trophic effect of glicentin is mediated by mechanism involving luminal or nonluminal factors and determine whether glicentin exerts a differential trophic effect on either jejunal or ileal mucosa. METHODS: Thirty-two male Wistar rats underwent construction of either a jejunal or ileal Thiry-Vella fistula (TVF). After 10 days recovery period, rats were further subdivided into groups to receive either saline (control) or glicentin (100 microg/kg/d). Rats were killed on day 8, and TVF as well as corresponding segments of intact jejunum or ileum were removed. Mucosa was scraped, weighed, and analyzed for protein content and Alp activity. In addition, representative sections of full-thickness bowel from each group were examined histologically. RESULTS: In the jejunal TVF group, glicentin increased mucosal growth measurements in both the TVF and the intact jejunum. However, in the ileal TVF group, glicentin stimulated proliferation of intact ileal mucosa only; it had no effect on ileal mucosa in the TVF. CONCLUSIONS: These results suggest that glicentin exerts a systemic effect independent of luminal factors on the proliferation of proximal gut mucosa in addition to an indirect effect produced by stimulation of endogenous luminal secretions. In contrast, an indirect mechanism appears to be the predominant action of glicentin on growth of distal gut mucosa.

Anastomosis, Surgical↗
PubMed2002

Expression of manganese superoxide disumutase influences chemosensitivity in esophageal and gastric cancers.

The purpose of this study was to examine whether the increased sensitivity of cancer cells to adriamycin (ADM), which is known to produce superoxide radicals, was brought through suppressed manganese superoxide disumutase (MnSOD) expression in the presence of transforming growth factor beta1 (TGFbeta1). T.T., MKN28, and MKN45 cell lines were treated with TGFbeta1 before exposure to ADM. Athymic female mice bearing the MKN28 cells were treated with TGFbeta1, ADM, or TGFbeta1 + ADM. Pretreatment of T.T., MKN28, and MKN45 cell lines with TGFbeta1 resulted in increased sensitivity to ADM. In contrast, simultaneous exposure to TNFalpha, which increased MnSOD expression, decreased sensitivity of cancer cells to ADM. In vivo studies demonstrated that the combined administration of TGFbeta1 and ADM delayed tumor growth better than either treatment alone. Our results suggest that the synergistic antitumor effects of TGFbeta1 and ADM may be due to decreased MnSOD expression in cancer cells. Thus, combined administration of TGFbeta1 and ADM might prove useful for treatment of malignant disease.

Animals↗
PubMedDate not supplied

Systemic factors are trophic in Thiry-Vella loop in the absence of luminal contents.

BACKGROUND/AIMS: Mucosal histology, crypt cell proliferation and brush border enzymes were measured in rats with varying degrees of Thiry-Vella fistulas, in order to compare the effect of systemic and luminal factors on adaptive growth and differentiation (brush border enzymes) in small intestinal epithelium. METHODOLOGY: Twenty-four male Wistar rats (300-350 g) were divided with three groups of eight which underwent the following operations: 20% Thiry-Vella fistula, 80% Thiry-Vella fistula and sham operation. RESULTS: 80% Thirty-Vella fistulas caused a functional short gut; in intestine remaining in continuity there were significant increases in segmental weight, protein, Alp activity and villus height, compared with sham-operated controls and 20% Thiry-Vella fistulas. There was a significant fall in villus height, crypt cell production in loops of 20% Thiry-Vella fistula rats not exposed to luminal contents compared with control segments of sham-operated rats. In contrast, loops of the 80% Thiry-Vella fistula rats were not atrophied despite the much greater distance from luminal nutrients; the villus height and PCNA-LI were higher than in 20% Thiry-Vella fistula rats, and at least as great as in sham-operated rats. CONCLUSIONS: This study indicates that atrophy does not occur in loops after 80% Thiry-Vella fistula because crypt cell proliferation is maintained in Thiry-Vella fistulas. Thus, the atrophic effect of diversion of luminal nutrients can be counteracted by systemic growth factors released as part of the adaptive response; luminal factors are not essential for maintenance of normal cellular turnover when there is a powerful stimulus to cell proliferation.

Animals↗
PubMedDate not supplied

Pancreatic juice output and amylase level in the drainage fluid after pancreatoduodenectomy in relation to leakage.

BACKGROUND/AIMS: The objective of this study was to clarify the relationship between the consistency of the pancreas and pancreatic anastomotic leakage after pancreatectomy. METHODOLOGY: Sixty-two patients who underwent proximal pancreatectomy with pancreaticoenterostomy were reviewed with regard to the consistency of the pancreas, size of the main pancreatic duct, postoperative pancreatic juice output, and pancreatic leakage after partial pancreatoduodenectomy. The pancreatic parenchyma was classified as having soft, intermediate and hard consistency (group 1, 2 and 3, respectively). Monitoring the output of pancreatic juice and amylase level in the drainage fluid after operation for the purpose of detecting of dehiscence of pancreaticoenterostomy. RESULTS: The mean pancreatic juice output during a period of 10 days (postoperative days 5 to 14) was 2446 +/- 27 cc in group 1 (n = 26), 846 +/- 13.5 cc in group 2 (n = 19) and 460 +/- 8.1 cc in group 3 (n = 17). Anastomotic leakage occurred in four (15%) patients in group 1, three (15%) in group 2, and none in group 3. In patients with leakage, abrupt decrease or fluctuating output of pancreatic juice occurred and amylase level in the drainage fluid was more than 10,000 IU/L POD 7. CONCLUSIONS: Patients with a pancreatic parenchyma with an intermediate or normal consistency produced more pancreatic juice and had a higher leak rate. Monitoring the output of pancreatic juice and amylase level in the drainage fluid after operation may provide a clue to the detection of dehiscence of pancreaticoenterostomy.

Amylases↗
PubMedDate not supplied

Effect of acute portal hypertension on gut mucosa.

BACKGROUND/AIMS: Patients with cirrhosis are predisposed to develop spontaneous bacteremias and peritonitis, mainly by enteric bacteria. Portal hypertension, by producing congestion and edema of the bowel wall, could increase the passage of bacteria from the intestinal lumen to regional lymph nodes to the systemic circulation or to both, a process termed bacterial translocation. The aim of this study was to investigate bacterial translocation, brush border enzyme activity and intestinal permeability of experimental acute portal hypertension. METHODOLOGY: Twenty-six male Wistar rats were used for all experiments. Rats were studied two days after the induction of portal hypertension (n = 13). Control animals were also studied two days after sham operation (n = 13). Samples of mesenteric lymph nodes for standard bacteriological cultures and a fragment of ileum for histological examination and mucosal contents of protein, Alp were obtained. Moreover, we evaluated the intestinal permeability by using the phenolsulfonphthalein test. RESULTS: Two days after surgery, a significantly greater properties of rats with acute portal hypertension (12 of 13, 92%) had positive mesenteric lymph node cultures compared with control group: sham operated (2 of 13, 15%). A significant increase in disappearance of phenol red from the luminal solution was observed in rats with acute portal hypertension. Brush border enzyme of Alp was also significantly decreased in acute portal hypertension, compared with in sham operated controls. CONCLUSIONS: The results of our study suggested that acute portal hypertension may be a major factor in the development of spontaneous infections in cirrhosis.

Alkaline Phosphatase↗
PubMedDate not supplied

Hyperamylasemia after hepatic resection.

BACKGROUND/AIMS: Hyperamylasemia often occurs after hepatectomy, but the detailed mechanism of this phenomenon remains unclear. The aim of this study was to analyze factors that may be associated with the development of hyperamylasemia following hepatic resection. METHODOLOGY: The Pringle maneuver was performed in 12 patients (Pringle group), the hemihepatic vascular occlusion technique in 11 patients (Hemihepatic group). RESULTS: In the Pringle group, postoperative serum amylase levels were elevated significantly in comparison with the preoperative levels, but were not elevated in the hemihepatic group. CONCLUSIONS: It is suggested that portal congestion by portal triad interruption carries a potential risk of serum amylase elevation and pancreatitis after hepatectomy.

Adult↗
PubMedDate not supplied

Pancreatic fistula after pancreatic head resection; incidence, significance and management.

BACKGROUND/AIMS: Anastomotic leak at the pancreatojejunostomy remains a common and dreaded complication after pancreaticoduodenectomy. Our aim was to determine the incidence, presentation, methods of management, and preoperative and postoperative factors that influence the clinical outcome. METHODOLOGY: We reviewed our collective experience with 70 consecutive patients from 1985 to 2000 for a variety of pathologic indications. Clinical, biochemical, intraoperative and postoperative factors were reviewed in an attempt to determine prognostic factors. RESULTS: Nine patients (12%) developed a pancreatic anastomotic leak as determined by increased amylase in drainage fluid (70%), were clinically insignificant and were managed by simple maintenance of intraoperatively placed drains. Although octreotide was used therapeutically in 4 patients (44%), significant, objective response was noted in all patients. Of the clinical, biochemical, intraoperative and postoperative factors reviewed to determine prognostic factors, a large amount of postoperative pancreatic juice output (P = 0.02) was a significant risk factor for pancreatic fistula formation. CONCLUSIONS: We conclude that most anastomotic leak at pancreaticoenterostomy after pancreaticoduodenectomy can be managed conservatively. Use of octreotide to aid in closure of the pancreatic leak was satisfactory.

Drainage↗