Search PubMed⌕ Search

Biomedical subjects

H Ohyanagi

Publications and source records attributed to H Ohyanagi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Protective effect of the intravenous administration of ursodeoxycholic acid against endotoxemia in rats with obstructive jaundice.

This study was undertaken to elucidate the effect of the intravenous administration of ursodeoxycholic acid (UDCA) on endotoxemia in rats with obstructive jaundice from the viewpoint of the biliary excretion of lipopolysaccharide (LPS) through hepatocytes. In rats with obstructive jaundice, fluorescein isothiocyanate-labeled LPS was administered via the portal vein and then its biliary excretion was examined. A significant increase in the LPS excretion was thus noticed in UDCA-treated rats at a dose of 0.1 micromol/100 g body wt. per min. In place of UDCA, sodium taurocholate at the same dose also enhanced the biliary excretion of LPS. Secondly, we also examined whether or not UDCA protects against endotoxemia. In this experiment, nonlabeled LPS was administered via the portal vein and its peripheral concentration was then measured. In UDCA-treated rats, the endotoxin concentration was significantly lower. Finally, to elucidate the effect of UDCA on Kupffer cells, serum tumor necrosis factor (TNF-alpha) was measured. But UDCA had no effect on the TNF-alpha level. These findings thus demonstrate that the intravenous administration of UDCA protects against endotoxemia by enhancing the transport of LPS across the hepatocytes from blood to bile without affecting Kupffer cells, and that this biliary excretion of LPS is dependent on bile acids.

Analysis of Variance↗
PubMed1997

Experimental studies on potentiation of the antitumor activity of 5-fluorouracil with 3'-azido-3'-deoxythymidine for the gastric cancer cell line MKN28 in vivo.

A new method of biochemical modulation of 5-fluorouracil (5-FU) with 3'-azido-3'-deoxythymidine (AZT) was studied experimentally. Nude mice transplanted with cells of the human gastric cancer cell line MKN28 were divided into 4 groups, i.e., control, 5-FU, AZT, and 5-FU plus AZT, and the antitumor activities were compared. Based on the assessment of tumor volume, significant suppression of tumor growth was observed in the 5-FU and 5-FU plus AZT groups (P<0.05, P<0.01, versus control, respectively). The thymidylate synthase (TS) inhibition rate, an index of inhibition of the de novo pathway, was significantly higher in the 5-FU and 5-FU plus AZT groups than in the control group (P<0.01), but it did not differ from the control in the AZT group. TS-bound FdUMP tended to be higher in the 5-FU plus AZT group than in the 5-FU group. The activity of thymidine kinase (TK) and the uptake ratio of 5-bromo-2'-deoxyuridine (BrdU), indices of salvage pathway activity, were significantly lower in the AZT and 5-FU plus AZT groups than in the control group (TK, P< 0.05, P < 0.01; uptake ratio of BrdU, P < 0.01, P < 0.05, respectively). There were slight losses of body weight in the 5-FU and 5-FU plus AZT groups compared with that in the control group, but no difference between the AZT and control groups in weight loss. These findings suggest that addition of AZT plays an important role in potentiating the antitumor activity of 5-FU through both blockage of a compensatory increase of activity in the salvage pathway and also an increase in TS-bound FdUMP, and has no adverse effects. Thus, the combination of 5-FU and AZT could be useful as a new modality in gastric cancer chemotherapy.

Animals↗
PubMed1996

Improved tumor detection by anti-CEA chimeric Fab oligomers with disulfide linkages in a pancreatic-carcinoma-xenograft model.

We have investigated the effect of Fab oligomerization on imaging efficacy in a pancreatic-carcinoma xenograft model in mice. Recombinant mouse/human chimeric Fab of the anticarcinoembryonic antigen (CEA) monoclonal antibody A10, which has been shown to react specifically with gastrointestinal cancers, was used in this study. Fab homo-oligomers (dimers and trimers) were prepared by linkage of chimeric Fab with N-succinimidyl-3-(2-pyridyldithio)-propionate. Oligomers with S-S bonds showed 10-fold higher binding activity against human CEA than Fab, while the binding activity of oligomers was similar to that of F(ab')2. In mice bearing pancreatic-carcinoma xenografts, tumor uptake of S-S oligomers was significantly greater than that of monomeric Fab, while there was no difference in tumor uptake between S-S Fab trimers and F(ab')2. S-S oligomers showed more rapid clearance rates and uniform percolation in the tumor nodules than F(ab')2. At 18 hr after injection, clear scintigraphic detection of the pancreatic-carcinoma tumors was obtained with 123I-labeled S-S Fab dimers. At 24hr, improved tumor imaging was shown for 123I-labeled S-S Fab oligomers with slightly visible uptake in normal tissues, similar to that of F(ab')2. S-S oligomers of chimeric A10 Fab may be useful as rapid diagnostic tools of pancreatic carcinomas.

Animals↗
PubMed1996

Possible involvement of Rab11 p24, a Ras-like small GTP-binding protein, in intracellular vesicular transport of isolated pancreatic acini.

Rab11 p24 is a Ras-like small guanosine triphosphate (GTP)-binding protein, and specific antibodies against it were newly developed to explore its function. Using the antibody, Rab11 p24 was shown to be abundant in rat pancreas as well as in most rat tissues. To explore the involvement of Rab11 p24 into the exocytotic process, the subcellular distribution of Rab11 p24 in rat pancreatic acini was evaluated also by use of the antibody. When the isolated acini were incubated with 1 x 10(-10) M cholecystokinin octapeptide (CCK-8) that induced the maximal stimulation, the amount of Rab11 p24 increased in the fractions of plasma membrane and zymogen granules, but decreased in the cytosol fraction. This redistribution was time-dependent and occurred within 1 min after the CCK-8 stimulation and reached a maximal level within 2 min after the stimulation. Moreover, a light microscopic immunolabeling technique on the isolated rat pancreatic acini also revealed that higher immunoreactivity with Rab11 p24 was observed over the zymogen granule membrane under CCK-8 stimulation. The present results indicate that Rab11 p24 is translocated from cytosol to the membrane fraction during stimulation with CCK-8 and suggest that Rab11 p24 is involved in the intracellular vesicular transport of isolated acini.

Animals↗
PubMed1996

Enhanced expression of manganese superoxide dismutase mRNA and increased TNFalpha mRNA expression by gastric mucosa in gastric cancer.

Manganese superoxide dismutase (Mn-SOD), a mitochondrial enzyme, is a cytokine-regulated acute-phase protein that protects cells from free radicals. The current investigations examined the in vivo regulation of the expression of Mn-SOD mRNA and tumor necrosis factor alpha (TNFalpha) mRNA in gastric carcinoma tissue. The expression of these transcripts in breast carcinoma tissue also was examined because breast cancer is a much more TNF-sensitive tumor than gastric cancer. TNFalpha mRNA was markedly increased in gastric carcinoma tissue (p < 0.005). There were significantly higher levels of Mn-SOD mRNA in gastric carcinoma tissue than in noncancerous tissue (p < 0.0001). The level of Mn-SOD mRNA in gastric carcinoma tissue was higher than that in breast carcinoma tissue (p < 0.005). Up-regulation of Mn-SOD mRNA in gastric carcinoma tissue most likely serves as a protective mechanism against superoxide radicals and TNF cytotoxicity.

Adult↗
PubMed1996

[Rhabdomyosarcoma of the bladder: a case report].

A 15-year-old man with the chief complaint of general fatigue was referred to our hospital on November 11, 1993. Bilateral percutaneous nephrostomy was performed for postrenal anuria. X-ray examinations revealed a huge intrapelvic tumor, and it was histopathologically diagnosed as rhabdomyosarcoma by transrectal needle biopsy. He was initially treated with combination chemotherapy regimen of vincristine, actinomycin-D and cyclophosphamide (VAC therapy). Pelvic exenteration was performed on December 15, 1993. Histopathological findings were alveolar rhabdomyosarcoma with degenerative change and partial necrosis. After the operation, he was given two course of VAC therapy. In May, 1994, brain metastasis occurred, so 4 courses of VAC therapy were administered. For a very short period, neurological symptoms improved, but he died of pneumonia on November 15, 1994.

Adolescent↗
PubMed1995

Radiolocalization of pancreatic carcinoma xenografts in nude mice with radiolabeled chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal antibody A10.

Recombinant mouse-human chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal antibody (MAb) A10 react with various GI carcinomas. We tested radiolocalization of pancreatic carcinoma xenografts in nude mice using radiolabeled chimeric A10 Fab fragments, comparing them with murine Fab fragments and parental MAb. For mice injected with chimeric A10 Fab fragments, we obtained significantly higher uptake in tumors than in normal tissues at 24 and 48 h after injection. In addition, tumor/normal tissues labeling ratios for chimeric A10 Fab fragment were significantly greater than those for murine MAb at 24 h postinfusion. However, no significant difference in biodistribution was observed between chimeric and murine Fab fragments. In autoradiography imaging studies, we obtained clearer tumor detection without visible uptake in normal organs for chimeric Fab fragments than for murine MAb. These results suggest that chimeric Fab fragments of A10 could be a potentially useful candidate for radioimmunodetection of pancreatic carcinomas.

Animals↗
PubMed1995

Therapy and imaging of pancreatic carcinoma xenografts with radioiodine-labeled chimeric monoclonal antibody A10 and its Fab fragment.

Recombinant mouse/human chimeric monoclonal antibody A10 (ch-A10) and its Fab fragment (ch-Fab) react with carcinoembryonic antigen on various gastrointestinal carcinomas. We performed biodistribution studies with 125I-labeled ch-A10 and ch-Fab in an antigen-positive human pancreatic carcinoma (BxPC-3) xenograft model. We also evaluated the anti-tumor effect of 131I-labeled ch-A10, and studied the detection of BxPC-3 xenografts with 123I-labeled ch-Fab in whole body scintigraphy. In comparative biodistribution studies, the tumor uptake of 125I-labeled ch-A10 was significantly greater than that of 125I-labeled ch-Fab 24 h post-injection. However, the tumor-to-blood ratio was 46.8 for ch-Fab at 24 h post-injection, while it was only 1.4 for ch-A10. Microautoradiography studies showed that ch-Fab penetrated more uniformly into the tumor nodules than did ch-A10. In mice given a therapeutic dose of 131I-labeled ch-A10, a significant inhibition of tumor growth was seen, while control 131-I-labeled human IgG did not affect tumor growth. Leukocyte toxicity was observed within 3 weeks after injection of 131I-labeled ch-A10, but leukocyte counts recovered to normal levels at 8 weeks post-injection. In whole-body scintigraphy, clear and rapid tumor imaging was obtained with 200 microCi of 123I-labeled ch-Fab 24 h post-injection. These results suggest that radioiodine-labeled chimeric A10 antibodies could potentially be useful candidates for radioimmunotherapy and radioimmunodetection of pancreatic carcinomas.

Adult↗
PubMed1994

Quantitative PCR for detection of femtogram quantities of interleukin-8 mRNA expression.

A quantitative polymerase chain reaction (PCR) assay for mRNA expression of interleukin-8 (IL-8), a neutrophil chemotactant and activator, was developed to examine the expression of this cytokine by colonic mucosa. A synthetic IL-8 RNA deleted in size of native IL-8 mRNA was used as an external control. The synthetic IL-8 RNA was mixed with total RNA from cells and converted to cDNA and amplified by PCR simultaneously. The lower limit of sensitivity for the assay was found to be more than 1 femtogram of IL-8 mRNA. The assay determined IL-8 mRNA expression when the RNA was isolated from either human histiocytic lymphoma cell line U937 cells or human colonic mucosa obtained from colitis patients and healthy controls. The development of the rapid and sensitive assay should provide a means to more fully evaluate the role of this cytokine in diverse disease states with small scale.

Base Sequence↗
PubMed1994

Development and characterization of chimeric anti-carcinoembryonic antigen monoclonal antibodies and their Fab fragments.

In an attempt to reduce the immunogenicity of two different murine anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAbs), KM10 and A10, we produced recombinant mouse/human chimeric MAbs and the respective Fab fragments carrying the variable regions of the murine MAbs. Chimeric A10 Fab fragment was expressed in Escherichia coli, and produced in large quantities in a mini-jar fermentation system. In competitive binding assays, chimeric MAbs and their Fab fragments showed identical specificity to human CEA epitopes, as compared to the parental MAbs or Fab fragments. Both chimeric Fab fragments exhibited strong immunohistochemical reactivity with various gastrointestinal carcinomas and no reactivity with CEA-related antigens, such as NCA (nonspecific cross-reacting antigen) or BGPI (biliary glycoprotein I). Furthermore, chimeric KM10 MAb elicited substantially higher antibody-dependent cellular cytotoxicity than the murine MAb. Complement-dependent cytotoxicity in vitro was much weaker with chimeric KM10 MAb. These results indicate that chimeric MAbs or Fab fragments could potentially replace the parental murine antibodies or their Fab fragments in therapy or diagnosis of human gastrointestinal carcinomas.

Animals↗
PubMed1994

[Anal prolapse].

Explore the source record for details and available documents.

Humans↗
PubMed1994

Effect of nucleosides and a nucleotide mixture on proliferation of human gastric cancer cells (KATO III).

The effect of the nucleotides and a nucleotide mixture (OG-VI), consisting of inosine, guanosine 5'-monophosphate (5'-GMP), cytidine, uridine, thymidine (TdR) (4:4:4:3:1 in molar ratio), and TdR co-administration on proliferation of KATO III human gastric cancer cells in culture was evaluated. Consumption of purine and pyrimidine by cancer cells and changes in cell number with OG-VI or TdR were compared with the control culture medium (Williams E) after 72 hour-culture. Addition of OG-VI or TdR did not enhance the cellular proliferation, but inhibited growth when given in higher concentrations (0.3-3 mM inosine, 0.3-3 mM 5'-GMP, 0.22-2.2 mM uridine, 74-740 microM TdR). Consumption rate of TdR in the medium was less in the TdR group, 33.7%, than in the OG-VI group, 72.2% (p < 0.05). This suggests that TdR metabolism is modulated by other nucleosides and nucleotide included in OG-VI. Under the coadministration of 5-fluorouracil (FUra), addition of OG-VI or TdR suppressed cellular proliferation (p < 0.05). The inhibition rate of cellular proliferation in the OG-VI group was slightly higher than the TdR group, but there was no statistically significant difference between the two groups. The combination of FUra with OG-VI or TdR enhances the antitumor effect of FUra. It is concluded that the OG-VI does not enhance the tumor cell proliferation and it is a potential biochemical modulator of FUra metabolism in human cancer cells.

Cell Division↗
PubMed1994

[Anal prolapse].

Explore the source record for details and available documents.

Humans↗