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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 91 records · Page 5Linked to original sources

Multivisceral transplantation in pigs: a clinicopathological analysis of tissue rejection.

In this study, we established the surgical procedure and postoperative care of multivisceral transplantation (MVTX) in pigs, and examined the functional changes and rejection pattern of transplanted organs in MVTX. Twenty-two MVTXs were performed without immunosuppression, and nine cases (41%) that survived for 5 days or more after MVTX were used for evaluation. Rejection in grafts including the liver, pancreas, and gastrointestinal tract were assessed histopathologically. On day 5 after transplantation, the duodenum and small bowel already showed signs of mild rejection. On the other hand, in the liver, pancreas and stomach, rejection occurred later and was still mild on day 16. Hepatic rejection in MVTX appeared to occur later than in simple liver transplantation (LTX). These results showed that the susceptibility to rejection of individual visceral organs varies.

Animals↗

31P nuclear magnetic resonance evaluation of rat liver preserved in UW solution.

A persistent problem in orthotopic liver transplantation is primary nonfunction (PNF) of the hepatic allograft. In an attempt to reduce the incidence of graft failure, the feasibility of pretransplant assessment of graft viability was investigated by 31P nuclear magnetic resonance (NMR) spectroscopy. The level of adenosine triphosphate (ATP) was measured as an indicator of liver function by 31P NMR spectroscopy after a 30 min normothermic reperfusion following cold-storage in University of Wisconsin (UW) solution. The mean +/- SD beta-ATP/Pi ratio after preservation for 0, 12, 24 or 48 h was 1.40 +/- 0.34, 0.85 +/- 0.27, 0.64 +/- 0.14 and 0.38 +/- 0.09, respectively. Significance was observed between 12h and 24h and between 12h and 48h of preservation. These results correlated well with the morphological changes in endothelial cells and sinusoidal lining cells examined by transmission electron microscopy. It is suggested strongly that microcirculatory disturbances due to endothelial cell injury impairs the recovery of ATP levels after reperfusion, and that ATP determination by 31P NMR spectroscopy, as a non-invasive modality, may help in the prediction of PNF after liver transplantation.

Adenosine↗

Decreased serum tryptophan in patients with cancer cachexia correlates with increased serum neopterin.

We investigated serum tryptophan (Trp), neopterin (NPT) and immunosuppressive acidic protein (IAP), one of tumor-associated tumor marker, concentrations in 28 patients with gastrointestinal tumors representing cancer cachexia and 10 healthy controls. NPT comes from activated macrophages presumably activated by tumor-sensitized T cells via gamma-interferon (IFN-gamma) excitation of the macrophages. We found that the NPT level was significantly higher than the control value. The negative correlation of NPT and Trp concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO), a Trp degradating enzyme, in cancer-burden patients. The activity of IDO can be induced by cytokines such as IFN-gamma, and therefore low Trp levels may result from endogenous IFN-gamma production due to immune activation against tumors. We also found a positive correlation between NPT and IAP levels, suggesting that host immune activation against tumors played a role in the immunosuppression of cancer-burden states, followed by cancer-cachexia.

Adult↗

Plasma neopterin/C-reactive protein ratio as an adjunct to the assessment of infection and cancer cachexia.

Neopterin (NPT), a pteridine intermediate metabolite in the biopterine synthetic pathway, is synthesized and secreted by monocytes/macrophages upon stimulation, mainly by gamma-interferon produced by activated T cells. C-reactive protein (CRP) is one of the major acute-phase reactants and its release is thought to be mediated by interleukin-6. Plasma concentrations of NPT and CRP were synchronously analyzed in 25 determinations of 5 patients with severe infectious complications and 50 determinations of 10 cancer-burden patients representing cachexia. The mean value of NPT (pmol/ml) was 201.6 in the infection group and 16.5 in the cancer cachexia group. The mean value of CRP (mg/dl) was 12.5 in the infection group and 3.4 in the cancer cachexia group. The number of samples in which NPT alone exceeded the cut-off level were 0/25 (0%) in the infection group and 38/50 (76.0%) in the cancer cachexia group. The number of samples in which both NPT and CRP exceeded the cut-off level was 25/25 (100%) in the infection group and 12/50 (24.0%) in the cancer cachexia group. The mean ratio of NPT to CRP was 11.3 in the infection group and 30.7 in the cancer cachexia group, respectively. These results suggest that gamma-interferon could play the principal role in the pathogenesis of cancer cachexia and that interleukin-6 modified the disease status. Interleukin-6 would be the critical mediator of host responses in infectious complications.

Aged↗

Endoscopic mucosal resection for superficial carcinoma and high-grade dysplasia of the esophagus.

Endoscopic mucosal resection (EMR) is a recently introduced therapeutic method based on the principles of the strip biopsy for resection of flat lesions of the gastrointestinal tract. Eleven asymptomatic patients (nine men, two women) with superficial carcinoma or high-grade dysplasia of the intrathoracic esophagus were treated by EMR during a 6-month period. The patients' mean age was 64 years (range, 49-78). The site of the lesions was the middle third of the esophagus in eight, upper third in two, and lower third in one patient. All patients in this series had a flat (II) type of superficial cancer. The procedure was carried out in all 11 patients without complication. Histopathological examination of the specimens revealed squamous cell carcinoma in nine patients. The remaining two patients were confirmed to have dysplasia only. Free margins measured greater than 5 mm in all cases. No recurrence was detected in a mean follow-up of 8 (5-10) months. For superficial flat lesions, EMR proved to be a safe and curative procedure that provided good quality of life following resection. However, larger trials are needed to confirm these results. Applying EMR to esophageal dysplasia could decrease the incidence of esophageal cancer.

Aged↗

Extracorporeal circulation and hypothermic perfusion for caval tumor thrombus complicating hepatocellular carcinoma: a case report.

A tumor thrombus complicating hepatocellular carcinoma developed in a 61-year-old male patient. Embolization of the right branch of portal vein was performed 2 weeks before operation. Curative resection of the tumor was performed on by extended hepatectomy plus in situ hypothermic perfusion of the liver and extracorporeal circulation. Postoperative course was uneventful until bile leakage occurred on the 11th postoperative day. A bile duct stenosis was diagnosed by cholangiogram, and hepaticojejunostomy was carried out. The patient recovered well without further complications. The pitfalls and technical problems encountered in this case are herein discussed.

Carcinoma, Hepatocellular↗

[Intrathoracic giant tumor accompanied by hypoglycemia].

Some non-islet tumors can induce hypoglycemia. We report a case of an intrathoracic giant tumor accompanied by hypoglycemia. The patient was a 53-year-old woman who was found to have hypoglycemia. Chest X-ray film showed a giant tumor in the left hemithorax and rightward shift to the mediastinum. CT and MRI revealed that the tumor's border was clear. The tumor was removed by sternotomy with third and seventh inter-costal incisions. The tumor was lobulated but its border was clear. It seemed to have grown from the posterolateral thoracic wall. After the tumor was removed, re-expansion pulmonary edema occurred but was relieved by diuretics and respiratory management. Histologic findings indicated that it was probably a thymoma or a localised mesothelioma, but it could not be identified even with special stains. Solitary fibrous mesotheliomas are sometimes complicated by hypoglycemia, and some of them produce insulin-like growth factor (IGF). In this case, the pre-operative level of immuno-reactive insulin was low, so the tumor may have produced IGF.

Female↗

Endogenous gamma-interferon activates thymidine phosphorylase in colorectal cancer tissue.

We measured neopterin (NPT), an indirect marker of gamma (gamma)-interferon, and the activity of thymidine phosphorylase (dThdPase) in the advancing front of colorectal carcinoma and in normal mucosa. Cancer showed a higher concentration of NPT than normal mucosa and also showed significantly higher (p < 0.0001) dThdPase activity than normal mucosa. There was a strong correlation between NPT concentration and dThdPase activity in cancerous and normal mucosa. These results suggest that endogenous gamma-interferon could activate dThdPase activity, which is essential to nucleic acid metabolism because it regulates the availability of thymidine.

Adenocarcinoma↗

Changes in IL-6 and IL-8 after hepatectomy in patients with liver cirrhosis.

Changes in tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) were investigated before and after hepatectomy in patients with or without liver cirrhosis (5 cases without liver cirrhosis and 14 cases with liver cirrhosis). Both the IL-6 and IL-8 values of the cirrhotic patients were significantly higher on the first postoperative day (POD) as compared with the non-cirrhotic patients. Overall, no significant correlation was found between peak values of IL-6 or IL-8 and blood loss or operating time. In the case of the cirrhotic patients, correlation of both IL-6 and IL-8 with operating time was significant at p < 0.05, gamma = 0.534 and 0.586, respectively. No correlation was found between blood loss and the peak value of IL-6, but significant correlation (gamma = 0.647, p < 0.05) was found between them in cirrhotic patients. There was no consistent increase in TNF-alpha and IL-1 beta following hepatectomy. These findings indicate that procedures undertaken to reduce the excessive production of these cytokines may be useful for preventing complications after hepatectomy in cirrhotic patients.

Carcinoma, Hepatocellular↗

Suppressive effect of TNF-alpha on increased production of FdUMP by IFN-alpha.

Interferon-alpha (IFN-alpha) exhibits synergistic antitumor activity when combined with tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo and increases the cytotoxicity of 5-fluorouracil (5-FU) in vitro. Using a colon cancer cell line transplanted into nude mice, we examined the effects of pretreatment for 3 days with IFN-alpha (10(6) IU) and/or TNF-alpha (2.9 x 10(3) JRU) on 5-FU metabolism. 5-FU 30 mg/kg was administered after the pretreatment. IFN-alpha increased the tumor level of 5-fluorodeoxuridine monophosphate (FdUMP), and decreased the free level of thymidylate synthetase. Pretreatment with TNT-alpha alone decreased HUMP whereas TNF-alpha plus IFN-alpha abolished the enhancement of FdUMP production by IFN-alpha. TNF-alpha also suppressed thymidine kinase activity. Neither IFN-alpha nor TNF-alpha altered the incorporation of 5-FU into RNA.

Animals↗

Role of endotoxin in wound healing impairment.

We studied the effect of endotoxin on cutaneous wound healing and the mechanism involved. Rats underwent dorsal skin incision and subcutaneous placement of plastic nylon wound chambers. Immediately after this procedure, lipopolysaccharide (LPS) was administered intraperitoneally at doses of 1 to 10 mg/kg. In the rats given LPS at doses of 3 mg/kg or higher, the wound breaking strength and the production of hydroxyproline in the wound chambers were significantly reduced in a dose-dependent manner. The wound fluid serially collected from the wound chambers after surgery was examined for the effect on the growth of fibroblast. While the wound fluid from control rats showed a marked fibroblast growth-accelerating activity on postoperative day 7, this activity in the wound fluid from LPS-treated rats was significantly decreased. In the wound fluid from LPS-treated rats, the fibroblast growth-accelerating activity recovered to the control level by the addition of anti-TNF-alpha neutralizing antibody. These results suggested the following: wound healing is accelerated as a result of the production of fibroblast growth factor(s) in the site of the wound. The production of tumor necrosis factor-alpha (TNF-alpha) induced by endotoxin inhibits the effect of the growth factor(s) in the wound area, which results in decreased collagen production. Subsequently the wound healing process is impaired.

Animals↗

Intratumoral injection of a streptococcal preparation, OK-432, before surgery for gastric cancer. A randomized trial. Cooperative Study Group of Preoperative Intratumoral Immunotherapy for Cancer.

BACKGROUND: The preoperative intratumoral injection with OK-432 (Picibanil, Chugai Pharmaceutical Co., Tokyo, Japan), an immunomodulatory agent prepared from an attenuated strain of streptococcus pyogenes, activates the regional immune system and causes degeneration of cancer tissue in carcinoma of the stomach. METHODS: A multi-institutional randomized trial of OK-432 to determine its clinical usefulness was conducted. Three hundred and ninety-five patients with gastric cancer were assigned randomly either to receive or not to receive a preoperative intratumoral injection of OK-432. Among them, 277 patients with advanced cancer were treated by common postoperative chemoimmunotherapy consisting of mitomycin C, tegafur, and OK-432. All patients were followed for at least 5 years. RESULTS: The adverse effects of OK-432 injected intratumorally predominantly were mild fever, anorexia, and abdominal pain, however, no treatment was required for these symptoms. Overall, there were no differences in outcome between the OK-432 and control groups. However, analysis based on stage showed that a preoperative intratumoral injection of OK-432 significantly improved the 5-year survival rate of patients with Stage III cancer (P = 0.0229), at 47.7% for the OK-432 group and 27.5% for the control group. In subset analysis, when the 5-year survival of patients with and without tumor infiltrating lymphocytes (TIL) was compared, OK-432 injected intratumorally had a significant positive effect on the group showing a moderate to marked number of TIL (P = 0.0438). CONCLUSION: These results showed that the intratumoral injection of OK-432 may improve survival of patients with Stage III gastric cancer. Cancer 1994;3097-3103.

Adjuvants, Immunologic↗

Lateral lymph node dissection for rectal carcinoma below the peritoneal reflection.

Lateral lymph node dissection has been advocated for advanced low rectal tumours. However, its benefit is debatable because of the possibility of postoperative bladder and sexual impairment. To assess the role of lateral lymph node dissection 95 patients who underwent the procedure between 1981 and 1991 were reviewed and compared with 83 who had resection of rectal cancer without lateral node dissection. Only ten (11 per cent) of the 95 patients had lateral lymph node involvement; all had Dukes' C tumours. Lymphovascular invasion was present in 50.6 per cent of all patients and neural invasion in 27 per cent of 65 examined specimens. Local recurrence, distant metastasis and overall 5-year survival rates were 7, 9 and 76 per cent respectively in patients undergoing extended lymphadenectomy and 16, 7 and 72 per cent respectively in those who had resection alone. There were no statistically significant differences in survival between the two groups for any Dukes' stage. Recurrence, metastasis and survival were related more to venous or neural invasion and tumour spread than to node dissection. These results demonstrate that patients with Dukes' A tumours do not benefit from lateral lymph node dissection, and that local recurrence rates in those with Dukes' B and C lesions are not significantly decreased. It is concluded that extended lymphadenectomy is unlikely to provide significant benefit to patients with low rectal cancer.

Adenocarcinoma↗