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Biomedical subjects

K Okinaga

Publications and source records attributed to K Okinaga.

At least 19 recordsLinked to original sources
PubMed2006

Effect of immunotherapy and spleen preservation on immunological function in patients with gastric cancer.

Splenectomy is often performed in patients who undergo total gastrectomy for cancer of the upper stomach. Although splenectomy facilitates lymph node dissection of the splenic hilum and recent reports advocate spleen preservation, the role of the spleen is not fully elucidated in gastric cancer treatment. This prospective randomized study was performed to evaluate the role of the spleen in immunological function in gastric cancer patients who underwent total gastrectomy and received postoperative immunochemotherapy. Forty-five patients with gastric cancer were randomly allocated to four groups: 1. splenectomy without immunotherapy (OK-432 administration), 2. splenectomy with immunotherapy, 3. spleen preservation without immunotherapy, 4. spleen preservation with immunotherapy. Postoperative immunological function of these patients was compared among the four groups. NK cell activity of the peripheral blood lymphocytes (PBL) in spleen-preserved patients who received immunotherapy was significantly higher for 24 weeks after surgery than that of the splenectomized patients with and without OK-432 administration. IL-2 production of PBL in spleen-preserved patients with immunotherapy was significantly higher between 4 and 24 weeks after surgery compared with that of the splenectomized patients without immunotherapy. The results suggest that spleen preservation might be beneficial in patients with less advanced gastric cancer who receive postoperative immunochemotherapy after total gastrectomy.

Adenocarcinoma↗
PubMed2004

Dendritic cell vaccine therapy by immunization with fusion cells of interleukin-2 gene-transduced, spleen-derived dendritic cells and tumour cells.

We examined the preventive and therapeutic effects of fusion cells prepared from spleen-derived dendritic cells (DCs) transduced with the interleukin-2 (IL-2) gene and QRsP fibrosarcoma cells in a mouse lung metastasis model. The IL-2 or LacZ gene was introduced into spleen-derived DCs using an adenoviral vector. Irradiated QRsP tumour cells were fused with IL-2 gene-transduced DCs (fusion/IL-2) or LacZ gene-transduced DCs (fusion/LacZ) by polyethylene glycol. These fusion cells expressed major histocompatibility complexes (MHC) class I and II, CD86, CD11c and CD8alpha. Splenocytes from mice vaccinated with fusion cells showed increased production of interferon-gamma (IFN-gamma) and cytotoxic T-lymphocyte (CTL) activity as compared with those vaccinated with DCs or tumour cells alone, and CTL levels were higher in fusion/IL-2-vaccinated mice than in fusion/LacZ-vaccinated mice. In our experiments on the protective and therapeutic effects on lung metastasis, mice vaccinated with fusion/IL-2 fusion/LacZ or fusion showed a significant reduction in pulmonary metastasis compared with those given DCs, tumour or phosphate-buffered saline. The introduction of the IL-2 gene into fusion cells produced more potent preventive and therapeutic effects. These results suggest that immunization with fusion cells prepared from spleen-derived DCs and tumour cells is capable of inducing preventive and therapeutic anti-tumour immunity against lung metastasis, and modification by the IL-2 gene may increase anti-tumour efficacy.

Animals↗
PubMed2001

Segmental intestinal preservation and enteral nutrition help to maintain the intestinal function after a massive intestinal resection: report of a case.

We report a case in which both segmental intestinal preservation and enteral nutrition helped to maintain the intestinal function after a massive bowel resection for superior mesenteric artery (SMA) thrombosis. A 53-year-old Japanese man was admitted to our hospital with acute abdomen. Extensive necrosis of the small intestine was found during the operation; however, a loop of the ileum appeared to be viable. A massive resection of the small intestine which preserved a 50-cm length of the viable ileum loop was thus performed. However, diffuse stenosis of the remaining ileum was found after surgery. An end-to-end anastomosis of the distal end of the preserved ileum loop and the terminal ileum was made in the second operation, and enteral nutrition was infused to improve the remnant intestinal function. A jejunoileostomy was performed in the final operation. An X-ray study after the final operation showed the stenosis of the remaining ileum to have improved. The patient therefore did not need any nutritional support after being discharged.

Constriction, Pathologic↗
PubMed2001

Spontaneous reduction in Epstein-Barr virus (EBV) DNA copy number in EBV-infected epithelial cell lines.

We found that spontaneous and 12-0-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus (EBV) reactivation occurred in short-term (ST)-cultured EBV-infected epithelial cell lines GT38 and GT39 after their establishment; however, it diminished in the long-term (LT)-cultured cells passaged for more than 2 years from ST-cultured cells. We hypothesized that the EBV reactivation may be related to the EBV DNA copy number in the cells. A higher level of EBV DNA content was detected in ST-cultured cells than in LT-cultured cells by Southern hybridization using an EBV DNA XhoI probe. Fluorescence in situ hybridization using EBV DNA BamHI W fragments showed that ST-cultured cells contained a higher EBV DNA copy number than that of LT-cultured cells. EBV DNA-negative cells were detected in small proportions in LT-cultured cells, but were undetected in ST-cultured cells. These results demonstrate that EBV genomes are not maintained stably in the cell lines, and some of them are lost in continuous passages of the cells. We discuss the mechanisms of reduction of EBV reactivation and EBV DNA in the cell lines.

Animals↗
PubMed2001

[In vitro assay method for augmention of anti-Candida activity of murine bone marrow cells by cytokines].

It is important to develop a sensitive assay method for evaluation of immunomodulating candidates including granulocyte-colony stimulating factor (G-CSF) which may augment host defense function against opportunistic infections. Effects of CSFs on anti-Candida activity of bone marrow cells (BMC) obtained from normal or cyclophosphamide-treated immunocompromised mice (CY-mice) were investigated. When BMC from CY-mice were preincubated for 24 hours in the presense of more than 0.005 ng/ml of G-CSF, anti-Candida activity was enhanced at 160 of effector (BMC) to target (C. albicans) ratio, whereas anti-Candida activity of BMC from CY-untreated mice was not changed at concentrations less than only by more than 0.5 ng/ml of G-CSF. Similar enhancement of activity was also observed in the presence of more than 0.05 ng/ml of granulocyte-macrophage colony stimulating factor (GM-CSF) in this assay using BMC from CY-mice. These findings suggest that this in vitro assay method can evaluate the activity of G-CSF and GM-CSF to augment leukocyte's anti-Candida activity.

Animals↗
PubMed2000

Tumorigenesis of Epstein-Barr virus-positive epithelial cell lines derived from gastric tissues in the SCID mouse.

To study the tumorigenesis of Epstein-Barr virus (EBV)-positive epithelial cell lines GT38 and GT39 derived from human gastric tissues, we inoculated these cells under the skin of severe combined immunodeficient (SCID) mice. The development of tumors was observed in each of the mice about 2 months after the inoculation. The tumors were diagnosed with undifferentiated carcinoma by hematoxylin/eosin staining. EBV-encoded small RNA1 was detected in the paraffin-embedded tumor sections. The tumor cells had human chromosome. The circular, but not linear, EBV DNA was detected in the tumors. The molecular sizes of EBV DNA termini were the same as that of the inoculated GT38 or GT39 cells. The expressions of EBV nuclear antigen 2 and latent membrane protein 1 reduced in the tumors. Transcripts of BamHI C and W promoters in latency III were detected in the tumors and the cultured cells in vitro. The tumor cells were passaged from one SCID mouse to other SCID mice and to cultures in vitro. This is the first evidence that the EBV-positive epithelial cell lines produced tumors in the SCID mouse.

Animals↗
PubMed2000

Detection of tumor cells in blood using CD45 magnetic cell separation followed by nested mutant allele-specific amplification of p53 and K-ras genes in patients with colorectal cancer.

A new method for detecting circulating tumor cells that is based on magnetic-activated cell separation (MACS) and nested mutant allele-specific amplification (nested MASA) was evaluated in patients with colorectal cancer using the p53 and K-ras genes as genetic markers. By negative selection with anti-CD45 monoclonal antibody-conjugated supermagnetic microbeads, the proportion of tumor cells was enriched 9-fold. By the combination of MACS and nested MASA, 10 tumor cells in 10(7) normal peripheral blood mononuclear cells could be detected without false-positives. Using this method, we examined blood taken from the tumor drainage veins of 23 patients with colorectal cancer. Eighty-seven percent (20/23) of primary tumor tissues showed p53 and/or K-ras gene mutations. Forty-five percent (9/20) of patients with p53 and/or K-ras mutations in the primary tumor showed the same mutated genes in the blood samples. There was a significant association between the presence of p53 and K-ras gene mutation in the blood and tumor size, depth of invasion, and venous invasion. Blood gene mutation was detected in 80% (4/5) of samples from patients with synchronous liver metastases. Sixty percent (3/5) of patients with mutant genes in the blood developed asynchronous liver metastases after surgery. The overall survival of patients with p53 and/or K-ras gene mutation-positive findings in blood was significantly shorter than that of patients testing negative on Kaplan-Meier analysis. Our results suggest that the method may be useful for reliable detection of tumor cells circulating in the blood and may help to identify patients at high risk for relapse.

Adenocarcinoma↗
PubMed2000

Impaired Kupffer cell function and effect of immunotherapy in obstructive jaundice.

BACKGROUND: Obstructive jaundice is frequently associated with septic complications. This study examined the influence of biliary obstruction on bacterial clearance and translocation. The study focused on the phagocytic and killing activities of Kupffer cells and the preventive effect on bacterial translocation of OK-432, which is a hemolytic streptococcal preparation developed as a biological response modifier. METHODS: To study the mechanism of sepsis in obstructive jaundice, two groups of Wistar rats were examined: rats subjected to common bile duct ligation (CBDL) and rats subjected to a sham operation. Bacterial clearance, organ distribution, hepatic blood flow, and phagocytic function of Kupffer cells were examined. To evaluate the effect of OK-432 on bacterial translocation, rats were divided into three groups: sham operation + phosphate-buffered saline (PBS), CBDL + PBS, and CBDL + OK-432. RESULTS: In this study, clearance of Escherichia coli. from the peripheral blood in CBDL rats was decreased significantly compared with that in sham-operated rats. Significant decreases in E.coli trapped in the liver and in hepatic blood flow were observed in CBDL rats compared with sham-operated rats. Phagocytic activity and superoxide production of Kupffer cells isolated from CBDL rats were significantly lower than in sham-operated rats. The incidence of bacterial translocation in CBDL rats was increased significantly, and oral administration of OK-432 prevented it. CONCLUSION: The results suggest that susceptibility to infection in obstructive jaundice is due to impaired phagocytic function of Kupffer cells. Furthermore, obstructive jaundice promotes bacterial translocation, and OK-432 may be useful in preventing this translocation.

Animals↗
PubMed2000

Flat adenoma of the large bowel: re-evaluation with special reference to central depression.

PURPOSE: The aim of this study was to re-evaluate the clinicopathologic features of flat adenomas with special reference to the role of central depression found in flat adenomas. METHODS: Clinicopathologic features, such as grade of atypia by size, site, central depression, coexisting lesions, gender, and family history of cancer, were evaluated in 236 flat adenomas from 183 patients selected retrospectively and prospectively. RESULTS: Of the 236 flat adenomas, 175 had mild, 33 had moderate, and 28 had severe (i.e., intramucosal carcinoma) atypia. The frequency of severe atypia correlated positively with size. Severe atypia were significantly more frequent in females (21 percent in females and 10 percent in males; P < 0.05). Sixteen percent of flat adenomas in patients with coexisting cancer showed severe atypia, which was significantly more than those without coexisting cancer (P < 0.05). The frequency of multiple flat adenomas in patients with two or more family members with cancer was 53 percent, which was significantly higher than in patients with one or no family members with cancer (P < 0.05). Central depression was observed in 19 percent of flat adenomas. The rate of severe atypia (22 percent) of flat adenomas with central depression was significantly higher than that (9 percent) of flat adenoma without central depression (P < 0.05). Patients who had flat adenomas with central depression had a higher incidence of coexisting cancer and cancer in the family (P < 0.05 and P < 0.01). CONCLUSION: At colonoscopic examination consideration should be given for the increased potential to become malignant in flat adenomas, especially those with central depression and in patients with a history of malignancy or with a family history of malignancy.

Adenoma↗
PubMed2000

Emergency abdominal surgery in patients aged 80 years and older.

The outcome of emergency abdominal surgery in elderly patients remains unsatisfactory. We studied factors contributing to the outcome of abdominal emergency surgery in elderly patients, particularly in those aged 80 years and older. Subjects were 61 patients aged 80 years and older (group A) and 108 patients aged from 65 to 79 years (group B) who underwent emergency abdominal surgery between 1983 and 1997. Complications were significantly higher in group A than in group B, with respiratory failure the most common postoperative complication. Mortality rate within 30 days after surgery was also higher in group A (9.8%) than in group B (3.3%). Complications and mortality did not differ significantly between those with and without preexisting concomitant disease in group A. Systemic inflammatory response syndrome (SIRS) was seen in 35 patients in group A and 50 in group B. Severe complications occurred in 62.5% of group A with preoperative SIRS. Mortality in those with SIRS was significantly higher than those without. SIRS is thus a feasible predictor of poor outcome in patients aged 80 years and older who have emergency abdominal surgery and in those aged from 65 to 79 years. Patients with SIRS should initially receive minimal treatment whenever possible, rather than be overtreated, until their conditions stabilize.

Abdomen↗
PubMed2000

Differential effect of TPA on cell growth and Epstein-Barr virus reactivation in epithelial cell lines derived from gastric tissues and B cell line Raji.

We characterized the cell growth and Epstein-Barr virus (EBV) reactivation for EBV infected epithelial cell lines, GT38, GT39, and GTC-4 using 12-O-tetradecanoylphorbol-13-acetate (TPA). These cell lines grew similarly in liquid medium, and formed colonies in soft agar. The cell growth was inhibited with TPA, dose-dependently in liquid medium. The colony formation was enhanced with low concentrations of TPA, but was inhibited with high concentrations. The latent EBV was reactivated with high concentrations of TPA as shown by the expression of EBV BZLF1 gene product ZEBRA. The effects of TPA on GTC-4 were compared with a Burkitt's lymphoma cell line Raji. The mode of actions of TPA in GTC-4 was different from Raji in terms of cell growth and EBV reactivation. The effective concentrations of TPA for cell growth inhibition and EBV reactivation were higher in Raji than GTC-4. Cell cycle analysis showed that TPA (20 ng/ml) induced cell cycle arrest to Raji but not to GTC-4; however, the rate of trypan blue stained cells increased in the TPA treated GTC-4 but not Raji. These results demonstrated that TPA affects differentially for the stimulation and inhibition of cell growth, and also EBV reactivation depends on TPA concentrations and cell types.

Blotting, Western↗
PubMed2000

Pancreatoblastoma treated by delayed operation after effective chemotherapy.

A case of pancreatoblastoma in a 4-year-old girl is presented. She was admitted with an abdominal mass and vomiting in August 1994. Computed tomography scan showed a 10- x 8- x 7-cm mass occupying both the head and body of the pancreas. Serum alpha-fetoprotein (AFP) level was 9,600 ng/mL (normal, <8.3 ng/mL). Results of open biopsy of the tumor showed pancreatoblastoma. Chemotherapy was administered using the new A-1 regimen consisting of cyclophosphamide, etoposide, pirarubicin, and cisplatin. After 3 cycles of chemotherapy, the size of the tumor was reduced to 5 x 4 x 3 cm, the portal vein became patent, and the AFP value decreased to 98.1 ng/mL. Total removal of the tumor was performed leaving the head and tail of the pancreas. Postoperative chemotherapy continued for 2 years. The patient has been disease free for 5 years, and her serum AFP remained within normal levels.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Productive infection of Epstein-Barr virus (EBV) in EBV-genome-positive epithelial cell lines (GT38 and GT39) derived from gastric tissues.

We characterized the expression of Epstein-Barr virus (EBV) on two epithelial cell lines, GT38 and GT39, derived from human gastric tissues. The EBV nuclear antigen (EBNA) was detected in all cells of both cell lines. The EBV immediate-early BZLF 1 protein (ZEBRA), the early antigen diffuse component (EA-D), and one of the EBV envelope proteins (gp350/220) were expressed spontaneously in small proportions in the cells. EBNA 1, EBNA2, latent membrane protein 1, ZEBRA, and EA-D molecules were then observed by Western blotting in the cells. The lytic cycle was enhanced with treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or n-butyrate. The virus particles were observed in the TPA treated GT38 cells by electron microscopy. Infectious EBV was detected with the transformation of cord blood lymphocytes and also with the induction of early antigen to Raji cells by the supernatants of both cells lines. A major single and minor multiple fused terminal fragments and a ladder of smaller fragments of the EBV genome were detected with a Xhol probe in both cell lines. These epithelial cells lines and viruses will be useful in studying their association with EBV in gastric epithelial cells.

Animals↗
PubMed1998

Reperfusion induces sublethal endothelial injury.

BACKGROUND: Endothelial cells are pivotal in regulating thrombosis and hemostasis. In this study, we sought to characterize endothelial dysfunction and endothelial cell injury in vitro after hypoxia/reoxygenation. MATERIALS AND METHODS: Cultured human umbilical vein endothelial cells (ECs) were exposed to 120 min of hypoxia followed by reoxygenation. The release of thrombomodulin (TM) and the production of prostaglandin I2 (PGI2) were measured. Endothelial cell injury in hypoxia/reoxygenation was measured by two assays, the Fura-2 release assay and the 51chromium (51Cr) release assay. RESULTS: TM release from ECs during normoxic incubation was undetectable, while it was slightly increased during hypoxic incubation. After reoxygenation, the release of TM increased, and it became significantly higher at 120 min after reoxygenation compared with hypoxic incubation. The production of PGI2 significantly decreased during hypoxic incubation and further decreased within 30 min after reoxygenation, but returned to normoxic levels at 120 min after reoxygenation. In the Fura-2 release assay, a rapid and significantly greater release of Fura-2 was observed in hypoxia/reoxygenation compared with hypoxic incubation. In the 51Cr release assay which demonstrates cell death, 51Cr release did not increase in hypoxia/reoxygenation. CONCLUSIONS: The present study suggests that 120 min of hypoxia/reoxygenation induces endothelial dysfunction of ECs but does not cause cell death.

Cell Death↗
PubMed1998

Establishment of Epstein-Barr virus-positive human gastric epithelial cell lines.

We have established two Epstein-Barr virus (EBV)-positive cell lines, GT38 and GT39, derived from human gastric tissues of two patients bearing gastric carcinoma. Both cell lines were positive for cytokeratin, an epithelial marker, but not for lymphocyte-related markers. Unlike GT39 cell line, GT38 cells lacked the property of contact inhibition. EBV genome was detected in both cell lines. The cell lines were positive for latent membrane protein 1, and EBV-determined nuclear antigen 1 (EBNA1). EBNA2 was also detected in GT38. These cell lines should be useful for studying the interaction of EBV with gastric epithelial cells and its role in gastric carcinogenesis.

Cell Line↗
PubMed1998

[Bacterial translocation in multiple organ failure].

Bacterial translocation has been defined as the passage of both viable and nonviable bacteria and their products (e.g., endotoxins) across the intestinal barrier to extraintestinal sites such as the mesenteric lymph nodes, liver, etc. It has been hypothesized that intestinally derived bacteria or endotoxins serve as triggers to initiate, perpetuate, or exacerbate the septic state and thereby promote the development of multiple organ failure (MOF). In various animal studies, bacterial translocation has been associated with mortality and septic complications. Although most data on translocation have been derived from animal studies, convincing evidence has been provided that translocation may occur in humans during various disease states. The question still remains, however, of whether bacterial translocation is an important pathophysiological event in human disease or simply an epiphenomenon of severe disease, since the results are variable. Recent studies have indicated that the gut can produce important amounts of immunoinflammatory factors and that intestinal injury predisposes to distant organ injury even in the absence of detectable bacteria or endotoxins in the portal blood or tissues. This hypothesis may in part explain the inconsistent causal relationship between bacterial translocation and MOF.

Animals↗
PubMed1996

[Suppression of anti-Candida activity of human neutrophils by glucose and diminishment of the glucose effect by an amino acid mixture].

Effects of a glucose and amino acid mixture prescribed for parenteral alimentation on anti-Candida activity of neutrophils were examined. Neutrophils obtained from peripheral blood of healthy humans inhibited the growth of Candida albicans in vitro. More than 1.0% of glucose inhibited the anti-Candida activity of the neutrophils in a dose-dependent manner. This glucose effect was reduced by the addition of an amino acid mixture clinically prescribed with a carbohydrate solution (PN-twin) in Japan. The amino acid mixture neutralized the suppression of anti-Candida activity of neutrophils by dexamethasone. These results suggest that an amino acid mixture prescribed in an alimentation solution may play a role as a neutralizer of the suppressive action of glucose for anti-Candida activity of neutrophils in a limited area near the top of a catheter in a blood vessel.

Amino Acids↗