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Biomedical subjects

F Ito

Publications and source records attributed to F Ito.

At least 127 records · Page 7Linked to original sources
PubMed1994

Feasibility of agarose microbeads with xenogeneic islets as a bioartificial pancreas.

A bioartificial pancreas, that is, transplantation of islets of Langerhans (islets) which are enclosed in a semipermeable membrane, has been proposed as a treatment for type I diabetes. The islets are immuno-isolated from the host by the semipermeable membrane preventing rejection while maintaining control of glucose metabolism for an extended period. The purpose of the current research is to evaluate the feasibility of preparing agarose microbeads with xenogeneic hamster islets as a bioartificial pancreas in streptozotocin induced diabetic mice. In the recipients with a low level of anti-hamster antibodies, the combination of encapsulation of hamster islets in 5% agarose microbeads and in vitro culture of them prolonged xenograft survivals. Four of 6 recipients were still normoglycemic at 100 days after implantation. However, the same procedure was not effective in the recipients which were sensitized in advance by transplantation of free hamster islets and thus had high levels of anti-hamster antibodies. The average normoglycemic period was 32 days. Antibodies permeated through the microbeads and activated complement on the cell surfaces. The network of agarose microbeads was rendered dense by increasing the concentration of agarose to restrict the diffusion of antibodies. Graft survivals were prolonged with increasing concentrations of agarose. As an analysis using diffusion equations predicted, the survivals were inversely proportional to the diffusion coefficient of IgG in each agarose gel. Islet xenotransplantation was enabled by the combination of the microbeads with a concentration of agarose higher than 7.5% and in vitro culture even in recipients having a high level of preformed antibodies.

Animals↗
PubMed1994

Strategy for developing microbeads applicable to islet xenotransplantation into a spontaneous diabetic NOD mouse.

A bioartificial pancreas (BAP) created through the encapsulation of islets of Langerhans (islets) in a semipermeable membrane has been proposed as a promising approach to treating insulin-dependent diabetes patients. A nonobese diabetic (NOD) mouse, which shares many features of human insulin-dependent diabetes mellitus, is an ideal model for evaluating the function of BAP. However, the functions of BAPs that have been developed have been limited in NOD mice. We propose novel microbeads that can realize long-term BAP function in NOD mice. The novel microbeads were composed of agarose and poly(styrene sulfonic acid) (PSSa) mixed gel. A polyion complex layer between PSSa and polycationic polybrene was formed on and just inside the microbead, and the microbead surfaces were further covered by polyanions to produce anionic surface charges. The islets in the novel microbeads were intraperitoneally implanted. Graft-functioning periods were dependent on both PSSa concentration and the kinds of polyanion. Islets in the microbeads composed of 5% agarose and 5% PSSa, which had an outermost surface covered by carboxymethyl cellulose, produced normoglycemic periods of more than 60 days in all five recipients. Control mice receiving either transplants of unenclosed islets or islets in agarose microbeads showed normoglycemic periods of less than 12 days. We believe that agarose/PSSa microbeads are promising for producing semipermeable membranes that enable xenotransplantation of islets in spontaneous diabetes mellitus.

Animals↗
PubMed1994

Surgical treatment of hepatocellular carcinoma.

The effect of surgical treatment for hepatocellular carcinoma (HCC) was evaluated in 149 resected cases, 83.2% of which were associated with liver cirrhosis. The 3- and 5-year survival rates were 60.1% and 39.4%, respectively. The mortality rate was 4.1%. In patients aged over 70 years, liver cirrhosis was found in 53.3% of cases and the mortality rate was 6.7%. The 3- and 5-year survival rates were 50.8% and 33.9%, respectively. Factors that significantly affected survival for more than 5 years were a tumor size of less than 3 cm, Stage I disease, vp(-), IMo, and diploid type. The 5-year survival rate for patients with a single tumor of 3 cm or less was 54.2%, regardless of the surgical procedure. All 15 patients with a solitary tumor of 2 cm or less (Stage I, small liver tumor) were alive with a 5-year survival rate of 100%. The problem is the treatment of patients with a tumor measuring 3-5 cm in diameter and associated liver cirrhosis, because their prognosis after surgery is the worst. HrS (subsegmentectomy) is the minimal procedure of limited hepatectomy for these cases with postoperative multidisciplinary therapy.

Adult↗
PubMed1994

Comparative studies of in vitro and in vivo function of three different shaped bioartificial pancreases made of agarose hydrogel.

Various kinds of bioartificial pancreas (BAP) have been developed in the past. There have been many disputes about the advantages and disadvantages of each BAP. However, little attention has been paid to the shape of the devices. In this study, three different shaped BAPs were made of the same material, agarose hydrogel. These are microbead-, rod- and disc-shaped BAPs, which are comparable to microcapsules, hollow fibre diffusion chambers and disc-shaped diffusion chambers, respectively, in shape. Their performances were studied by in vitro culture, mathematical simulations and in vivo implantation into diabetic animals. The islets in the BAPs could survive and release insulin for more than 100 d regardless of the BAP shape during in vitro culture. Numerical analyses showed that insulin release kinetics depended greatly on the thickness of the gel membrane but not on the shape of the agarose hydrogel. The microbead BAP normalized blood glucose levels of all five recipients for more than 100 d. Three of eight recipients of the rod BAP and only one of six recipients of the disc BAP demonstrated long normoglycaemia. These results suggest that the shape of the BAPs determines the in vivo functioning period of the BAPs and that the microbead is the most suitable shape for the BAP.

Animals↗
PubMed1994

Basic fibroblast growth factor (FGF-2) in renal cell carcinoma, which is indistinguishable from that in normal kidney, is involved in renal cell carcinoma growth.

To investigate the role of basic fibroblast growth factor (FGF) in renal cell carcinoma growth, we have analyzed the expression of mRNA of basic FGF. In 7 of 15 cases, basic FGF mRNA level in renal cell carcinoma tissues was higher than that in corresponding normal tissues. However, the tumor-to-normal ratios of expression levels are chiefly less than 2.0 and, in 5 cases, are even less than 1.0. Furthermore, there was no correlation between the ratio and the clinical stage. In protein analysis, we could not find any difference between basic FGF extracted from renal cell carcinomas and that from normal kidney tissues in bioactivity, immunoreactivity, molecular weight and affinity to heparin. On the other hand, anti-basic FGF monoclonal antibody inhibited the growth of a renal cell carcinoma cell line, VMRC-RCW, and this inhibition was reversed by an extraphysiological amount of exogenous basic FGF (100 ng./ml.). These results suggest that basic FGF itself may have no pivotal role in renal cell carcinoma etiology but is involved in the growth of renal cell carcinomas in an autocrine manner.

Animals↗
PubMed1994

Two sialidases which preferentially hydrolyze sialyl alpha 2-8 linkage from Bacteroides fragilis SBT3182.

Bacteroides fragilis SBT3182 produced two sialidases which differ in molecular weight on SDS-PAGE. These sialidases, a 50 kDa and a 55 kDa enzymes, were purified separately and their properties were compared. Both enzymes preferentially hydrolyze sialyl alpha 2-8 linkage rather than alpha 2-3 and alpha 2-6 bonds. The Km values for Neu5Ac alpha 2-3lactose, Neu5Ac alpha 2-6lactose, and colominic acid, which is a homopolymer of N-acetylneuraminic acid linked by alpha 2-8 bonds, were identical between the two enzymes. These enzymes had Km value of 1.0-1.2 mM for Neu5Ac alpha 2-3lactose and 1.3-1.5 mM for Neu5Ac alpha 2-6lactose, which are in the ranges reported for other sialidases. However, the Km values for colominic acid (0.03-0.04 mM) were lower than those of other sialidases, indicating that sialidases from B. fragilis SBT3182 show high affinity for the sialyl alpha 2-8 linkage. The two sialidases also had identical N-terminal amino acid sequences and did not reveal any homology to known sialidases. PAS-staining suggested that these two sialidases were glycoproteins. In the lectin analysis, the 50 kDa enzyme was stained with Con A, DBA, and UEA-I while the 55 kDa sialidase was stained only with Con A. This suggested that the difference in molecular weight may be due to the carbohydrate composition. When the 50 kDa enzyme was incubated with UEA-I, which is a lectin specific for alpha-fucose residue, the activity decreased by 20%.

Amino Acid Sequence↗
PubMed1994

Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells.

The effect of hepatocyte growth factor/scatter factor (HGF/SF) and epidermal growth factor (EGF) on cadherin-mediated adhesion of human carcinoma cells was studied. HGF/SF induced scattering of colonic adenocarcinoma HT29 and gastric adenocarcinomas MKN7 and MKN74 cells. Likewise, EGF induced scattering of HT29 and MKN7 cells. These cells expressed E-cadherin, which was concentrated at cell-cell contact sites. When the scattering of these cells was induced by HGF/SF or EGF, the E-cadherin concentration at cell-cell boundaries tended to decrease. Immunoblotting analyses, however, demonstrated that these growth factor treatments did not alter the expression of E-cadherin and E-cadherin-associated proteins, alpha- and beta-catenin and plakoglobin. beta-Catenin, plakoglobin and an unidentified 115-kDa molecule associated with E-cadherin were found to be phosphorylated at tyrosine residues, and these phosphorylations were enhanced by the growth factor treatments. These results suggest that HGF/SF and EGF may modulate the function of the cadherin-catenin system via tyrosine phosphorylation of cadherin-associated proteins.

Cadherins↗
PubMed1994

[Flow cytometric DNA analysis on renal cell carcinoma--a study of 116 cases on fresh surgical specimens].

DNA ploidy was investigated using flow cytometry on fresh surgical specimens from 116 cases with renal cell carcinoma. DNA diploid tumor was observed in 39 cases (33.6%) and aneuploid in 77 cases (66.4%). DNA aneuploid group was further classified into 3 subgroups by DNA index (D.I.); near-diploid group (D.I.: 0.8-1.2, 21.6%), near-tetraploid group (D.I.: 1.8-2.2, 12.9%) and other aneuploid group (31.9%). DNA ploidy pattern correlated with clinical stages and histological grading, indicating significantly a higher incidence of DNA diploid in cases in stage I and grade 1. DNA clonal heterogeneity was observed in 48.1%, and homogeneously diploid was in 28.6% of 77 cases who were analyzed more than 2 specimens. Incidences of DNA heterogeneity and homogeneous diploid correlated with the number of analyzed specimens and our results showed that more than 4 specimens were necessary to diagnose the DNA ploidy patterns. The near-tetraploid group was shown to have an extremely poor prognosis compared with the diploid group and the other aneuploid group. There were no significant difference between the diploid group and the aneuploid group in terms of the early prognosis, however, the incidence of disease recurrence was significantly higher in the aneuploid group. Our results demonstrated that DNA ploidy was an useful prognostic factor in the evaluation of patients with renal cell carcinoma.

Adult↗
PubMed1994

[A ornithine decarboxylase activity and proliferating cell nuclear antigen in gastric cancer].

To investigate ornithine decarboxylase (ODC) activity and proliferating cell nuclear antigen (PCNA) in gastric cancer, ODC activity and PCNA were measured in 50 resected samples. The relationship between both and clinicopathologic factors was examined. ODC activity was 473.3 +/- 54.7 pmol CO2/60 min/mg protein in tumors, and 273.5 +/- 38.3 pmol CO2/60 min/mg protein in normal mucosa. ODC activity in tumors was significantly higher than that of normal mucosa. ODC activity in tumors was significantly high in gross type 4, maximum diameter more than 10 cm, depth se, infiltrative growth (INF) gamma, positive lymph vessel invasion and positive lymph node metastasis. PCNA-LI was 24.7 +/- 1.5% in tumors, and 13.9 +/- 1.1% in normal mucosa. PCNA-LI of tumors was significantly higher than that of normal mucosa. PCNA-LI of tumors was significantly high in gross type 2, histological type tub 2 and por, depth ss beta and se, IFN beta, positive lymph vessel invasion, positive venous invasion, and positive lymph node metastasis. ODC activity and PCNA-LI were closely related in normal mucosa, showing a correlation coefficient of 0.730. On the other hand, their relationship was weak in tumors, showing a correlation coefficient of 0.417. These results suggest the differentiation of value between ODC activity and PCNA-LI in gastric cancer. In gastric cancer, ODC activity and PCNA-LI in tumors may be good markers of lymph node metastasis. Furthermore, PCNA-LI may be a good marker of hematogenous metastasis.

Adult↗
PubMed1994

[Present situation in self-injection therapy with interferon-alpha for patients with renal cell carcinoma].

Interferon-alpha (IFN alpha) is often used for the treatment of renal cell carcinomas. The injections are frequently self-administered at home. To assess how this therapy was accepted by the patient we sent out a questionnaire. For the past 2 years until March 1993, this therapy was performed in our department on 52 patients, of whom 45 were selected for the study. All patients were informed of their disease and consented to the necessity of this treatment. Thirty-eight patients answered this questionnaire. Almost all patients injected this agent mainly by themselves. These findings suggested that they regarded this therapy as a strategy to be executed by themselves for the treatment of carcinoma. The main toxic symptoms in this therapy were asthenia, fever and loss of appetite. Leukocytopenia occurred in about half of the patients, of whom 1 patient required medication because of a rapid decrease in the white blood cell count shortly after inception of this therapy. The treatment was discontinued in 50% of the patients because of these adverse effects. Systemic toxicity disappeared after cessation of IFN alpha administration. Additionally, over 80% of the patients expressed concern about effectiveness, the duration and high cost of this therapy. The patients had to be repeatedly instructed about the method of disposing used needles and syringes. This study revealed that self injection of IFN alpha, which required strict management particularly at the initiation, can be performed at home. However, countermeasures must be taken against the side actions and an optimum regimen of IFN alpha should be established as soon as possible.

Adult↗
PubMed1994

Cadherin-dependent organization and disorganization of epithelial architecture.

Epithelial cell layers exhibit an ordered polarized architecture. However, such structures are disrupted during malignant transformation, which generally coincides with a loss of regulate cell growth. We are investigating how the cadherin cell adhesion system controls these processes. Cadherins form a molecular complex with alpha-catenin, and beta-catenin or plakoglobin at the cytoplasmic side in normal cells. Lung carcinoma PC9 cells express E-cadherin. Although they express other catenins, they lack alpha-catenin and cannot firmly aggregate, suggesting that their E-cadherin is inactive. Transfection of the PC9 cells with alpha-catenin cDNA leads to activation of the E-cadherin, inducing their compact aggregation. In these aggregates, an almost complete epithelial-specific architecture is organized, including the formation of microvilli and a junctional complex. We also studied the effect of hepatocyte growth factor/scatter factor (HGF/SF) on cell-cell contacts in keratinocyte cell lines, and found that this growth factor can disrupt desmosomal cell-cell contacts. HGF/SF, and also epidermal growth factor, enhance tyrosine phosphorylation of beta-catenin or plakoglobin in human carcinoma lines as they induce scattering of these cells. These findings suggest that the cadherin adhesion system is central in organizing epithelial structures and that tyrosine phosphorylation of catenins may modulate this organization process.

Cadherins↗
PubMed1993

Stimulation of prostaglandin production by hepatocyte growth factor in human gastric carcinoma cells.

Hepatocyte growth factor (HGF), a protein with pleiotropic biological activity affecting cell growth and motility, was found to markedly activate prostaglandin production in human gastric carcinoma TMK-1 cells. HPLC analysis revealed that HGF stimulated the production of prostaglandin E2 (PGE2), which is the major prostaglandin produced in these cells. HGF maximally stimulated PGE2 production at a concentration of 10 ng/ml, and it was a more potent stimulator of PGE2 production than epidermal growth factor (EGF), which is known to stimulate prostaglandin production in various cell lines. The simultaneous addition of HGF and EGF caused no further stimulation of the PGE2 production observed in HGF-treated cells. We showed also that HGF increased the arachidonate release from TMK-1 cells, which release was completely suppressed by the addition of phospholipase A2 (PLA2) inhibitors. Further studies in vitro showed that HGF enhanced cellular activities of cytosolic PLA2 and cyclooxygenase 1.5-fold each. These results indicate that HGF stimulates prostaglandin production through increases in both cytosolic PLA2 and cyclooxygenase activities.

Chromatography, High Pressure Liquid↗
PubMed1993

Proteolytic processing of the hepatocyte growth factor/scatter factor receptor by furin.

The hepatocyte growth factor/scatter factor (HGF/SF) receptor consists of an alpha- and a beta-subunit, which are derived from a single-chain precursor by endoproteolytic processing. The precursor is not proteolytically processed in LoVo colon carcinoma cells. The uncleaved receptor immunopurified from the cells was cleaved in vitro by furin. Furthermore, the HGF/SF receptor was proteolytically processed in LoVo cells transfected with furin cDNA. These results indicate that furin is a processing endoprotease for the HGF/SF receptor. Tyrosine autophosphorylation of the uncleaved receptor was induced by HGF/SF, and the growth of the cells expressing the uncleaved receptor was stimulated by HGF/SF, indicating that the proteolytic processing of the receptor is not essential for the signal transduction of HGF/SF.

Amino Acid Sequence↗