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Biomedical subjects

M Onda

Publications and source records attributed to M Onda.

At least 109 records · Page 6Linked to original sources

[Effects of intravenous and oral administration of ondansetron hydrochloride on chemotherapy-induced nausea and vomiting in patients with esophageal cancer].

The effects of ondansetron hydrochloride (OND) were studied through 11 courses of chemotherapy, including 70 mg/m2 of cisplatin, in 9 patients with advanced esophageal cancer. During the observation period of 5 days, 4 mg of OND was given intravenously on the day of cisplatin infusion and orally for consecutive 4 days, and nausea was controlled by over 70%. Vomiting was controlled by over 80%. The inhibitory effect of OND on nausea and vomiting was found in 72.7% on the day of cisplatin injection and 88.9% overall. No other side effects of OND except slight increases in total bilirubin and LDH were found in any patient. These findings suggest that intravenous and oral administration of OND may inhibit chemotherapy-induced nausea and vomiting in patients with advanced esophageal cancer.

Administration, Oral↗

A bivalent disulfide-stabilized Fv with improved antigen binding to erbB2.

We have used protein engineering to generate a stable bivalent Fv molecule of the anti-erbB2 monoclonal antibody e23. The VH and VL domains of the Fv are linked to each other by a disulfide bond and the two Fvs are connected by a flexible 15 amino acid residue (Gly4-Ser)3 linker. The e23 (dsFv)2 molecule is fused to a truncated form of Pseudomonas exotoxin to generate a bivalent disulfide-stabilized, (dsFv)2, immunotoxin. The immunotoxin was expressed in Escherichia coli, refolded in vitro and purified to about 95% purity. Binding studies demonstrated that the (dsFv)2 molecule has a much higher affinity for erbB2 than a monovalent dsFv molecule and a similar binding affinity as the parental antibody e23. The (dsFv)2 immunotoxin was 5 to 20-fold more cytotoxic to two e23 antigen-positive cell lines than the monovalent dsFv immunotoxin. The bivalent dsFv molecule is very stable, retaining 94% of its activity after a 24 hours incubation in human serum at 37 degreesC. Two other molecules with shorter linkers five and ten amino acid residues in length were produced and showed similar activities as the molecule containing a 15 amino acid residue linker. The bivalency, stability and the relative ease of purification makes these e23 (dsFv)2 molecules valuable reagents for cancer immunotherapy and diagnosis.

ADP Ribose Transferases↗

Frequent Allelic Loss at 6q26-27 in Breast Carcinomas of the Solid-tubular Histologic Type.

To characterize the effect that inactivation of a putative tumor suppressor gene on 6q appears to have on breast carcinogenesis, we examined loss of heterozygosity in 528 primary breast carcinomas with a polymorphic marker located at 6q26-27, a frequent target region of allelic loss in ovarian and breast cancers. Ofthe 56 informative tumors of the solid-tubular type, 29(52&precnt;)showed allelic lossat 6q26-27;however, only 10 of 42 papillotubular carcinomas(23%)and 34 of 86 scirrhous carcinomas(39%)showed allelic loss(p = 0.0215). These results are consistent with reported alterations at 6q26-27 in serous and mucinous types of ovariancancers, in that they suggest that inactivation of one or more genes in that region may affect carcinogenic mechanisms in a histologic type-specific manner in neoplasms of the female reproductive organs.

Journal Article↗

Glucocorticoid attenuates a decrease of antithrombin III following major surgery.

BACKGROUND: Major surgery, such as esophagectomy, activates inflammatory responses and the coagulation system, and this activation is characterized by release of inflammatory cytokines and a decrease in antithrombin-III (AT-III), respectively. Preoperative glucocorticoid administration has been reported to suppress circulatory cytokine levels after major surgery. PATIENTS AND METHODS: A total of 28 patients underwent esophagectomy for esophageal carcinoma; 14 of them were given 10 mg/kg of methylprednisolone intravenously upon induction of anesthesia and 14 served as controls. Circulating levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), polymorphonuclear (PMN) elastase, thrombin-antithrombin III complex (TAT), AT-III, and albumin were measured before and immediately after the operation and on postoperative days (PODs) 1, 3, 5, and 7. RESULTS: TNF-alpha, IL-6, and TAT levels significantly increased after esophagectomy in both groups. AT-III and albumin decreased to their minimum levels on POD 1 and POD 3, respectively. Methylprednisolone treatment effectively inhibited the increases in TNF-alpha and IL-6 and the decreases in AT-III and albumin, but did not inhibit the increases in PMN-elastase and TAT levels. There were significant correlations between AT-III, IL-6, and albumin levels. CONCLUSIONS: These results suggest that methylprednisolone pretreatment attenuates the decrease in AT-III by reducing IL-6 production postoperatively.

Aged↗

Obstructive Ileus caused by blood clot after emergency total gastrectomy in a patient with hemophilia A: report of a case.

We report herein the extremely unusual case of a patient with hemophilia A who developed a hematoma ileus soon after undergoing an emergency total gastrectomy. Postoperatively, the patient was found to have an obstruction in the small intestine that was difficult to differentiate from intussusception. Reoperation revealed the cause of the obstruction to be a large blood clot. This case report serves to demonstrate that careful hemostasis and observation during surgery is essential in patients with hemophilia.

Anastomosis, Surgical↗

Primary leiomyoma of the ovary: a case report.

The imaging features of primary ovarian leiomyoma have seldom been described because of the very low prevalence of the tumor. Herein we present a case report on its magnetic resonance imaging features. Both T1- and T2-weighted images revealed a low-signal-intensity mass, which was well circumscribed and sharply demarcated from the uterus. Magnetic resonance imaging was useful in distinguishing it from a malignant ovarian tumor and uterine leiomyoma.

Diagnosis, Differential↗

Ultrathin films of charged polysaccharides assembled alternately with linear polyions.

As a means of preparation of biocompatible molecular surfaces, an alternate assembly of charged polysaccharides and oppositely-charged synthetic polymers was conducted. Cationic chitosan was assembled alternately with anionic poly(sodium styrenesulfonate) (PSS) at pH 4. Regular film growth and its dependence on ionic strength were detected by the quartz crystal microbalance (QCM) method. Averaged film thicknesses for the chitosan + PSS layer were 15, 31, 46, and 69 A, respectively, when 0, 0.25, 0.5, and 1 M of NaCl was contained in aqueous chitosan. Adsorption of chitosan did not reach saturation in 20 min at 0 M NaCl, while the adsorption became saturated within 6 min with 0.25 M NaCl. Anionic sodium chondroitin sulfate was also assembled in alternation with cationic poly(dimethyldiallylammonium chloride) (PDDA) at pH 6.5. The adsorption of chondroitin sulfate was less sensitive to ionic strength. Surface morphology of chitosan-PSS films was investigated by non-contact atomic force microscopy (AFM) observation. Maximum height difference and Ra value for a 1000 x 1000 nm area were 11 and 0.69 nm, respectively, indicating the formation of a molecularly flat surface by alternate layer-by-layer adsorption.

Adsorption↗

Helicobacter pylori infection in the remnant stomach after gastrectomy: with special reference to the difference between Billroth I and II anastomoses.

Helicobacter pylori infection is associated with many gastric diseases, such as peptic ulcer and gastric cancer. We examined the remnant stomach for H. pylori infection after gastrectomy for gastric cancer or peptic ulcer between October 1992 and July 1997. H. pylori DNA in the gastric juice of 109 patients [mean age 62.4 years, male/female 78/31, gastrectomy for gastric cancer 83/peptic ulcer 26, Billroth I (BI) anastomosis 72/Billroth II (BII) 37, mean postoperative interval 6.0 years] was amplified by PCR and detected by Southern blot hybridization. The serum of 135 patients was assayed by ELISA for IgG antibody against H. pylori (mean age 61.8 years, male/female 99/36, gastrectomy for gastric cancer 111/peptic ulcer 24, BI anastomosis 93/BII 42, mean postoperative interval 5.4 years). H. pylori was positive in 68/109 (62.4%) by PCR and 113/ 135 (83.7%) by ELISA. H. pylori cytotoxin gene cagA, a H. pylori virulence factor gene, was found in 15/16 (93.8%) cases by PCR. A significant difference in H. pylori positivity by PCR was found according to the type of anastomosis (BI vs. BII) but not according to age group, sex, disease (cancer or ulcer), or postoperative interval by PCR and ELISA. BII anastomosis was followed by a significantly lower rate of H. pylori infection (17/37; 45.9%) than BI anastomosis (51/72; 70.8%; p=0.01) according to the results of PCR. Moreover, some patients with BII anastomosis (3/8; 37.5%) showed positive to negative seroconversion for H. pylori infection after the operation (mean 2.47 years) according to the results of ELISA, but this phenomenon was not observed in patients with BI (0/12) anastomosis. This may reflect the role of bile reflux, which is more common in BII than BI, because bile reflux interferes with colonization by H. pylori.

Adult↗

Allelic loss on chromosome 9q is associated with lymph node metastasis of primary breast cancer.

Frequent allelic losses on chromosome 9 are seen in a wide variety of human tumors; moreover, two genes (P16 and PTC) whose mutant alleles confer predispositions to some inherited cancer syndromes have been identified on this chromosome. Using 15 highly polymorphic microsatellite markers distributed on both arms of chromosome 9, we tested 96 primary breast carcinomas for allelic loss in order to define the locations of genes that might be involved in this type of tumor. Allelic loss was observed in 37 of the tumors (39%) and detailed deletion mapping identified target regions at 9p21, 9q22.3 and 9q33. Losses at 9q22.3 and 9q33 were correlated with the presence of lymph node metastasis, and allelic loss at 9q22.3 was observed more frequently in scirrhous tumors than in less aggressive histologic types. Therefore, inactivation of tumor suppressor genes in 9q22.3 and 9q33 regions might play a role in progression of breast cancers, especially in metastasis to lymph nodes and in development of scirrhous tumors.

Adenocarcinoma, Scirrhous↗

Immunohistochemical demonstration of angiogenic growth factors and EGF receptor in hepatic metastases and primary human gastric cancer.

Angiogenic growth factors are essential for cancer metastasis, and the growth of metastatic foci also depends on these angiogenic growth factors as well as autocrine or paracrine growth factors. We therefore investigated whether vascular endothelial growth factor (VEGF) and thymidine phosphorylase (dThdPase) are localized more often in primary tumors with hepatic metastasis than in those without such metastasis and whether transforming growth factor (TGF-alpha) and epidermal growth factor receptor (EGF-R) are coexisted more often in hepatic metastases than in primary tumors of gastric cancer. Resected specimens from 82 patients with gastric cancer were examined immunohistochemically. The primary antibodies used were anti-VEGF, anti-dThdPase, anti-TGF-alpha and anti-EGF-R. VEGF expression was found to be higher in primary cancers with than in those without hepatic metastasis (p < 0.001), while VEGF was frequently observed in both hepatic metastases and in the primary tumors. Localization of dThdPase was also higher in advanced than in early gastric cancers (p = 0.021). High co-presence of TGF-alpha and EGF-R was detected more frequently in cancers with deep gastric wall invasion than in those without such invasion (p = 0.050), and also more often in cancers with venous invasion (p = 0.007) and those in the advanced stage (p = 0.020). Co-presence of TGF-alpha and EGF-R was found to be higher, though not significantly, in hepatic metastases (58.8%) than in primary tumors (29.4%). These findings suggest that localization of VEGF may play an important role in hepatic metastasis, and that the expression of VEGF, dThdPase and the TGF-alpha/EGF-R pathway may be responsible for the growth of hepatic metastasis.

Endothelial Growth Factors↗

Systemic and pulmonary responses of inflammatory cytokines following esophagectomy.

Inflammatory cytokines in plasma and bronchoalveolar lavage fluid (BALF) from 16 post-esophagectomy patients with and without preoperative methylprednisolone administration were studied. Interleukin-8 (IL-8), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) concentrations in plasma and BALF were measured by ELISA immediately after surgery (0-POD) and on the postoperative day 1 (1-POD). In patients without methylprednisolone treatment, IL-8 levels in BALF were 362 +/- 67 pg/ml on 0-POD and 948 +/- 359 pg/ml on 1-POD, and were approximately 10 times higher than those in plasma levels. IL-6 levels in plasma were significantly higher than those in BALF. The TNF-alpha concentration was similarly low in plasma and BALF. The patients with preoperative methylprednisolone treatment had significantly lower IL-8 levels in BALF and plasma compared with the patients without the treatment. Immunocytochemically, each cytokine was identified in the cytoplasm of bronchoalveolar macrophage. The percentage of polymorphonuclear cells (PMN) among BAL cells was significantly increased on 1-POD when compared with that of 0-POD, and tended to be decreased by preoperative methylprednisolone treatment. These results suggest that IL-6 was markedly increased in the peripheral circulation and that increased pulmonary IL-8 might be related to an accumulation of PMN in the lung under surgical stress. Further, methylprednisolone administration could possibly reduce postoperative cytokine responses at the local and systemic levels.

Adult↗

Clinicopathological studies on association of gallbladder carcinoma and pancreaticobiliary maljunction.

During the past 17 years, 1,722 of 4,832 consecutive patients investigated with endoscopic retrograde cholangiopancreatography (ERCP) were assessed by the radiological criteria of the Japanese Study Group of Pancreaticobiliary Maljunction (PBM). Out of these 1,722 patients, PBM was found in a total of 52, representing 3.0%, of which gallbladder carcinoma was associated with 14. These 14 with gallbladder carcinoma consisted of 10 (62.5%) of the 16 with PBM without association of congenital bile duct dilatation (CBDD) and 4 (11.1%) of the 36 PBM with CBDD. The relationship between PBM and gallbladder carcinoma was closely examined; PBM was noted in 14 (32.6%) of a total of 43 patients with gallbladder carcinoma compared to 38 (2.3%) among the 1,679 patients with various diseases excluding gallbladder carcinoma. Similarly, it was revealed that gallbladder carcinoma was predominantly noted in the 14 (26.5%) of the 52 patients with PBM in contrast to an incidence of 1.7% (29) among the 1,670 patients without PBM. As we studied the characteristic clinical features of the 14 gallbladder carcinoma patients with PBM when compared with 29 of those without PBM, the following was disclosed: on average, the patients with PBM were 10 years younger (49.4 vs 61.4 years in mean age); there was a preponderance of women (0/14 vs 12/17, male-female ratio); there existed a significantly lower incidence of associated gallstone disease (7.1% vs 72.4%). These figures were shown to be statistically significant. We concluded that the results prove a link between the crucial features of gallbladder carcinoma and PBM, and also suggest the promotive role of PBM in carcinogenesis of the gallbladder.

Adenocarcinoma↗

[Successful treatment of hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan].

Satisfactory therapeutic effects are rarely obtained with oral chemotherapy for gastric cancer. We have experienced successful treatment for synchronous hepatic metastasis of gastric cancer with 5'-DFUR and Lentinan. The patient was a 78-year-old female, diagnosed as having gastric cancer with multiple hepatic metastases, who underwent gastrectomy. Immunohistochemistry of the resected specimens with anti-thymidine phosphorylase (dThdPase) antibody yielded positive results for dThdPase in the primary tumor as well as the hepatic metastases. Two months after surgery, administration of 400 mg of 5'-DFUR per day and 2 mg i.v. of Lentinan every other week was started. Four months after discharge, carcinoembryonic antigen (CEA) in plasma showed an abrupt logarithmic decline. Furthermore, a 99% reduction in hepatic metastases was demonstrated by abdominal CT. At present, 22 months after surgery, the patient is managed on an outpatient basis with no complaints of any side effects. Immunochemotherapy using 5'-DFUR and Lentinan may be effective against gastric malignancies expressing dThdPase activity.

Adenocarcinoma↗

[Analysis of microsatellite alteration in colorectal cancer].

We investigated the possible correlation between the microsatellite alterations (replication error: RER, and loss of heterozygosity: LOH) and clinicopathologic factors and survival in colorectal cancer. A total of 78 colorectal cancers was examined for microsatellite alteration at three microsatellite loci containing D2S123, D18S58 and C117-703. RER is considered positive when at least one microsatellite locus is detected. RER was positive in 28.2%, and the respective positivity was 12.8%, 15.3% and 11.5%. The positivity of LOH was 6.4%, 10.3% and 19.2%, in that order. RER-positive cancers were more significantly found in the proximal colon than the distal colorectum. Node-negative colorectal cancers were more noted in RER (+)-positive cancers. Multivariate analysis showed that LOH in D18S58 locus and RER in CI17-703 locus were independent prognostic factors.

Aged↗

[A case report of esophageal carcinoma with grade 3 response by preoperative chemotherapy using CDDP/5-FU/LV].

A 67-year-old man was diagnosed as having a type 3 advanced esophageal carcinoma by barium swallow and endoscopy. Biopsy specimens showed well-differentiated squamous cell carcinoma with positive immunostaining for p53, C-erb B-2 and negative for bcl-2. Two courses of chemotherapy using 5-FU, leucovorin and CDDP were performed before operation. Because no cancer cells were present in the surgical specimens, the effect was evaluated as grade 3. This neoadjuvant chemotherapy may be effective for esophageal carcinoma with a possible apoptosis mechanism.

Aged↗