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T Kawabe

Publications and source records attributed to T Kawabe.

At least 73 records · Page 4Linked to original sources
PubMed1999

Endoscopic variceal ligation is a sufficient procedure for the treatment of oesophageal varices in patients with hepatitis C liver cirrhosis: comparison with injection sclerotherapy.

AIMS: Endoscopic variceal ligation (EVL) is a recently developed alternative to endoscopic injection sclerotherapy (EIS) for the treatment of oesophageal varices. Endoscopic variceal ligation and EIS were compared in an attempt to clarify the efficacy and safety of EVL for patients with cirrhosis due to hepatitis C. METHODS: Endoscopic variceal ligation was performed in 60 patients and EIS in 30. Varices were eradicated in all patients by EVL and 87% (26 out of 30) by EIS. RESULTS: There was no significant difference between EVL and EIS in relation to the incidence of bleeding and the 5 year survival rate after treatment. There were no severe complications except mild substernal pain after EVL, while pulmonary embolism occurred in one patient receiving EIS. CONCLUSIONS: Endoscopic variceal ligation is a safe and effective technique for eradicating oesophageal varices in patients with hepatitis C cirrhosis.

Esophageal and Gastric Varices↗
PubMed1999

Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter.

The canalicular multispecific organic anion transporter (cMOAT), also termed MRP2, is a recently identified ATP-binding cassette transporter. We previously established stable human cMOAT cDNA-transfected cells, LLC/cMOAT-1 from LLC-PK1 cells, and LLC/CMV cells that were transfected with an empty vector. We found that LLC/cMOAT-1 cells have increased resistance to vincristine (VCR), 7-ethyl-10-hydroxy-camptothecin, and cisplatin but not to etoposide. The multidrug resistance-reversing agents cyclosporin A (CsA) and 2-[4-(diphenylmethyl)-1-piperazinyl]-5-(trans-4,6-dimethyl-1,3, 2-dioxaphosphorinan-2-yl)-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P) almost completely reversed the resistance to VCR, 7-ethyl-10-hydroxy-camptothecin, and cisplatin of LLC/cMOAT-1 cells; and DL-buthionine-(S,R)-sulfoximine, (3'-oxo-4-butenyl-4-methyl-threonine(1), (valine(2)) cyclosporin (PSC833), and 3-([(3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl)-((3-dimethylamino-3- oxopropyl)-thio)-methyl]thio)propanoic acid (MK571) partially reversed the resistance to these drugs. CsA and PAK-104P at 10 microM enhanced the accumulation of VCR in LLC/cMOAT-1 cells almost to the level in LLC/CMV cells without the agents. The efflux of VCR from LLC/cMOAT-1 cells was enhanced compared with LLC/CMV cells and inhibited by CsA and PAK-104P. Transport of leukotriene C(4) (LTC(4)) and S-(2, 4-dinitrophenyl)glutathione also was studied with membrane vesicles prepared from these cells. LTC(4) and S-(2, 4-dinitrophenyl)glutathione were actively transported into membrane vesicles prepared from LLC/cMOAT-1 cells. The K(m) and V(max) values for the uptake of LTC(4) by the LLC/cMOAT-1 membrane vesicles were 0. 26 +/- 0.05 microM and 7.48 +/- 0.67 pmol/min/mg protein, respectively. LTC(4) transport was competitively inhibited by PAK-104P, CsA, MK571, and PSC833, with K(i) values of 3.7, 4.7, 13.1, and 28.9 microM, respectively. These findings demonstrate that cMOAT confers a novel drug-resistance phenotype. CsA and PAK-104P may be useful for reversing cMOAT-mediated drug resistance in tumors.

Adenosine Triphosphate↗
PubMed1999

High proportion of mutant K-ras gene in pancreatic juice of patients with pancreatic cystic lesions.

BACKGROUND/AIMS: It was recently reported that the quantitative analysis of mutant K-ras gene in pancreatic juice could be useful for the diagnosis of pancreatic cancer. This methodology was applied to patients with pancreatic cystic lesions. METHODS: DNA was extracted from pancreatic juice collected at the time of endoscopy with injection of secretin. The ratio of the K-ras mutant allele to the wild-type allele was measured by two methods to detect and semiquantify mutant K-ras gene: polymerase chain reaction/preferential homoduplex formation assay and enriched polymerase chain reaction/enzyme linked mini-sequence assay. RESULTS: A high frequency of K-ras mutation was detected (more than 2% of all K-ras genes) in six of 14 patients (43%) with pancreatic cysts. This frequency was similar to those detected in patients with pancreatic adenocarcinoma and in intraductal papillary neoplasms of the pancreas. In contrast, the frequency of mutation was low (less than 2%) in patients without either pancreatic cysts or pancreatic neoplasms. CONCLUSIONS: K-ras gene mutation may be derived from duct cells in the pancreas with a high potential for tumorigenesis. Therefore careful follow up of patients with a pancreatic cyst is recommended if they are found to have a high level of the mutant gene in the pancreatic juice.

Adenocarcinoma↗
PubMed1999

Enhancement of tumoricidal activity of alveolar macrophages via CD40-CD40 ligand interaction.

CD40-CD40 ligand (CD40L) interaction was originally defined as important molecules for the development of humoral immunity. Thereafter, some investigations have focused on its essential roles for the induction of cell-mediated immunity in host defenses. Here we investigated the antitumor activity of murine alveolar macrophages through CD40-CD40L interaction. The CD40L gene was transfected into murine lung cancer cells (3LLSA), and CD40L-expressing clones (3LLSA-CD40L) were established. Stimulation of CD40 molecules on the surface of alveolar macrophages with 3LLSA-CD40L cells induced the production of nitric oxide, tumor necrosis factor-alpha, and interleukin-12 and the tumoricidal activity of alveolar macrophages in the presence of interferon-gamma, which increased the surface expression of CD40 molecules on alveolar macrophages. These findings were not observed when alveolar macrophages were obtained from CD40-deficient mice. On the other hand, interleukin-6 production by alveolar macrophages did not depend on CD40-CD40L interaction. We also established a murine melanoma cell line expressing CD40L (B16 4A5-CD40L) that could induce tumoricidal activity of alveolar macrophages. Furthermore, when spleen cells were cocultivated with 3LLSA-CD40L cells, specific cytotoxic T lymphocytes for wild-type 3LLSA cells could be induced. These results suggest that CD40L gene transfer into tumor cells may induce antitumor immunity in a tumor-bearing host and may offer a new strategy for cancer gene therapy.

Animals↗
PubMed1999

[CA50].

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Antigens, Tumor-Associated, Carbohydrate↗
PubMed1998

Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport.

The human multidrug resistance protein (MRP) gene encodes a membrane protein involved in the ATP-dependent transport of hydrophobic compounds. We previously isolated a canalicular multispecific organic anion transporter, cMOAT1/MRP2, that belongs to the ATP binding cassette (ABC) superfamily, which is specifically expressed in liver, and cMOAT1/MRP2 is responsible for the defects in hyperbilirubinemia II/Dubin-Johnson syndrome. In this study, we isolated a new cDNA of the ABC superfamily designated cMOAT2/MRP3 that is homologous to human MRP1 and cMOAT1/MRP2: cMOAT2/MRP3 is 56% identical to MRP1 and 45% identical to cMOAT1/MRP2, respectively. Fluorescence in situ hybridization demonstrated the chromosomal locus of this gene on chromosome 17q22. The human cMOAT2 cDNA hybridized to a 6.5-kb mRNA that was mainly expressed in liver and to a lesser extent in colon, small intestine, and prostate. The cMOAT2/MRP3 gene was not overexpressed in cisplatin-resistant cell lines with increased ATP-dependent transport of cisplatin over their parental counterparts derived from human head and neck cancer and human prostatic cancer cell lines. The human cMOAT2/MRP3, a novel member of the ABC superfamily, may function as a membrane transporter in liver, colon, and prostate.

Adenosine Triphosphate↗
PubMed1998

Roles of conserved arginine residues in the metal-tetracycline/H+ antiporter of Escherichia coli.

Seven arginine residues are conserved in all the tetracycline/H+ antiporters of Gram-negative bacteria. Four (Arg67, -70, -71, and -127) of them are located in the putative cytoplasmic loop regions and three (Arg31, -101, and -238) in the putative periplasmic loop regions [Eckert, B., and Beck, C. F. (1989) J. Biol. Chem. 264, 11663-11670]. These arginine residues were replaced by alanine, lysine, or cysteine one by one through site-directed mutagenesis. None of the mutants showed significant alteration of the protein expression level. The mutants resulting in the replacement of Arg31, Arg67, Arg71, and Arg238 with either Ala, Cys, or Lys retained tetracycline resistance levels comparable to that of the wild type. Among them, only the Arg238 --> Ala mutant showed very low transport activity in everted membrane vesicles, probably due to the instability of the mutant protein. The replacement of Arg70 and Arg127 with Ala or Cys resulted in a drastic decrease in the drug resistance and almost complete loss of the transport activity, while the Lys replacement mutants retained significant resistance and transport activity, indicating that the positively charged side chains at these positions conferred the transport function. On the other hand, neither the Ala, Cys, nor Lys replacement mutant of Arg101 exhibited any drug resistance or transport activity. As for the reactivity of the Cys replacement mutants, only two (Arg71 --> Cys and Arg101 --> Cys) were not reactive with NEM, the other five mutants being highly or moderately reactive. The reactivity of the cysteine-scanning mutants around Arg101 with NEM revealed that Arg101 is located in transmembrane helix IV. It is not likely that Arg101 confers the protein folding through a salt bridge with a transmembrane acidic residue because no double mutants involving Arg101 --> Ala and the replacement of one of three transmembrane acidic residues (Asp15, Asp84, and Asp285) showed the recovery of any tetracycline resistance or transport activity. The effect of tetracycline on the [14C]NEM binding to the combined mutants S65C/R101A and L97C/R101A suggests that Arg101 may cause a substrate-induced conformational change of the putative exit gate of TetA(B).

Amino Acid Sequence↗
PubMed1998

T cell development in mice lacking all T cell receptor zeta family members (Zeta, eta, and FcepsilonRIgamma).

The zeta family includes zeta, eta, and FcepsilonRIgamma (Fcgamma). Dimers of the zeta family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking zeta/eta chains, T cell development is impaired, yet low numbers of CD4+ and CD8+ T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a zeta family dimer can promote T cell maturation, or that in the absence of zeta/eta, Fcgamma serves as a subunit in TCR complexes. To elucidate the role of zeta family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only zeta/eta or Fcgamma. The data reveal that surface complexes that are expressed in the absence of zeta family dimers are capable of transducing signals required for alpha/beta-T cell development. Strikingly, T cells generated in both zeta/eta-/- and zeta/eta-/--Fcgamma-/- mice exhibit a memory phenotype and elaborate interferon gamma. Finally, examination of different T cell populations reveals that zeta/eta and Fcgamma have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of zeta family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations.

Animals↗
PubMed1998

Identification of the Meg1/Grb10 imprinted gene on mouse proximal chromosome 11, a candidate for the Silver-Russell syndrome gene.

In a systematic screen for maternally expressed imprinted genes using subtraction hybridization with androgenetic and normal fertilized mouse embryos, seven candidate maternally expressed genes (Megs) have been isolated, including the H19 and p57(Kip2) genes that are known to be maternally expressed. Herein, we demonstrate that an imprinted gene, Meg1, is apparently identical to Grb10 (growth factor receptor-bound protein 10), which is located on mouse proximal chromosome 11. Grb10 protein was reported to bind to the insulin receptor and/or the insulin-like growth factor (IGF) I receptor via its src homology 2 domain and to inhibit the associated tyrosine kinase activity that is involved in the growth promoting activities of insulin and IGFs (IGF-I and -II). Thus, it is probable that Meg1/Grb10 is responsible for the imprinted effects of prenatal growth retardation or growth promotion caused by maternal or paternal duplication of proximal chromosome 11 with reciprocal deficiencies (MatDp.prox11 or PatDp.prox11), respectively. In the human, it has been reported that the maternal uniparental disomy 7 is responsible for the Silver-Russell syndrome (SRS) whose effects include pre- and postnatal growth retardation and other dysmorphologies. The human homologue GRB10 on chromosome 7q11.2-12 is a candidate gene for Silver-Russell syndrome.

Animals↗
PubMed1998

Small bowel transplantation in rats using a venous cuff technique.

A venous cuff technique was applied only for venous drainage in orthotopic small bowel transplantation of rats. Rates of technical failure (death within 4 days) and in clinical signs were compared between the groups with (group A) and without (group B) venous cuff technique. Technical failures with and without venous cuff technique were 5% and 25%, respectively. Mean survival days, excluding deaths from technical failure, were 9.2 +/- 2.3 in group A and 8.1 +/- 2.6 days in group B. No significant differences were observed in mean survival days or in weight loss between the two groups. Acute rejection was the cause of death in both groups. Since the model with venous cuff technique showed low mortality, it could be widely employed in small bowel transplantation studies.

Anastomosis, Surgical↗
PubMed1998

Quantitative analysis of ras gene mutation in pancreatic juice for diagnosis of pancreatic adenocarcinoma.

It has recently been demonstrated that mutant ras gene was also detected in patients with mucinous cell hyperplasia without adenocarcinoma, indicating that the presence of the mutation could not be a definite marker for pancreatic adenocarcinoma. The present study was performed to differentiate pancreatic adenocarcinoma from others by quantification of mutant ras gene in pancreatic juice. By measuring mutant ras gene by polymerase chain reaction (PCR) during its logarithmic phase, the amount was semiquantitatively evaluated between 0.1 and 10% of total DNA that was extracted from pancreatic juice obtained via endoscopy. Semiquantitative analysis revealed that the mutant gene occupied more than 1% of total DNA in eight of 15 patients (53%) with pancreatic adenocarcinoma, and in all three patients (100%) with intraductal papillary neoplasm of the pancreas, but in only two of 19 cases (11%) without neoplasm. Semiquantitative analysis may provide a clinical tool for the differential diagnosis of pancreatic carcinoma.

Adenocarcinoma↗
PubMed1998

Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors.

One hundred and forty children with hematologic malignancies undergoing allogeneic BMT were reviewed in order to clarify the incidence, onset time, and risk factors for veno-occlusive disease (VOD) of the liver. Thirty-eight patients (27.1%) developed VOD diagnosed according to the Seattle clinical criteria. Seventeen patients developed VOD within 20 days of transplantation (early-onset) and in 21 patients developed after day 20 (late-onset) including eight patients with histological confirmation. Late-onset VOD occurred from day 21 to day 508 (median day 39). Moderate or severe VOD developed in 11 early-onset and 13 late-onset patients. Death occurred in eight early-onset and 10 late-onset patients. Serum albumin and cholinesterase levels prior to the start of pretransplant conditioning were significantly lower in early-onset VOD than in late-onset VOD. Multivariate analysis showed that low serum albumin levels (< or =3.7 g/dl) prior to the start of pretransplant conditioning was most strongly associated with the development of VOD. Donor mismatch (other than HLA-matched relatives), use of minocycline, and a long interval (> or =13 months) between diagnosis and BMT were also significantly associated with the development of VOD. In contrast, use of fosfomycin was associated with a decreased risk. Our data suggest that hepatic function reserve is important in the development and onset time of VOD. Veno-occlusive disease of the liver is a complication which may occur a long time after transplantation.

Adolescent↗
PubMed1998

IgG-mediated anaphylaxis via Fc gamma receptor in CD40-deficient mice.

Anaphylaxis denotes an immediate hypersensitivity reaction to allergen, exclusively mediated by IgE antibodies. However, IgE antibodies do not explain all the syndromes that are encountered. We investigated potent IgG-mediated anaphylaxis in CD40-deficient mice that lack the immunoglobulin class switching for T cell-dependent antigens. Immunization with ovalbumin did not induce either humoral responses of IgG, IgA, and IgE, or systemic anaphylaxis in CD40-deficient mice. Although systemic anaphylaxis by active immunization was not observed in CD40-deficient mice, both passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis assessed by mouse blood pressure monitoring with cervical artery catheterization did take place when antigen-specific IgG was transferred and then antigen challenge given. Further, to investigate the inflammatory pathway of IgG-mediated immediate hypersensitivity reactions, we focused on the Fc gamma receptor (Fc gammaR) function. Pretreatment of the mice with the anti-Fc gammaRII/Fc gammaRIII MoAb clearly blocked the response of PCA and passive systemic anaphylaxis, suggesting that they were initiated through Fc gammaR. In conclusion, we directly demonstrate the IgG-mediated anaphylaxis and its triggering mechanism through Fc gammaR in in vivo conditions. In addition to IgE-mediated anaphylaxis, IgG-mediated anaphylaxis should be considered and the blocking of Fc gammaR would provide one of the therapeutic targets for the control of IgG-mediated hypersensitivity diseases.

Anaphylaxis↗
PubMed1998

Endoscopic papillary balloon dilation for the management of common bile duct stones: experience of 226 cases.

BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy is a widely accepted technique for the treatment of patients with common bile duct stones. However, it is still associated with occasional complications. The recently developed technique of endoscopic papillary balloon dilation seems to be a safe and effective procedure, and to have great potential for replacing endoscopic sphincterotomy. However, few reports have been published on the use of this technique for bile duct stones. The present study was undertaken to evaluate its safety and efficacy. PATIENTS AND METHODS: Endoscopic papillary balloon dilation was used to remove common bile duct stones in 226 consecutive patients including 41 patients of ASA classification III/IV, 41 elderly patients (> 80 years) 24 with liver cirrhosis, and 86 with periampullary diverticulum. After dilation of the papilla with a balloon diameter of 8 mm, the stones were retrieved. RESULTS: In conjunction with the use of a mechanical or/and electrohydraulic lithotriptor in 79 patients (35%) with large stones (> 10 mm in diameter), clearance of the common bile duct was achieved in 225 of 226 patients (99%) without serious complications, such as hemorrhage or severe pancreatitis; mild (n = 13) or moderate (n = 2) pancreatitis occurred in 7% of cases. CONCLUSIONS: Endoscopic papillary balloon dilation is a safe and effective technique for the treatment of common bile duct stones, even in high-risk patients.

Adult↗
PubMed1998

In vivo adenovirus-mediated prodrug gene therapy for carcinoembryonic antigen-producing pancreatic cancer.

In gene therapy for malignancy, the herpes simplex virus thymidine kinase (HSVtk)-ganciclovir (GCV) system has been widely used. For pancreatic cancer targeting, we estimated the therapeutic efficacy of gene transduction by an adenovirus-carrying HSVtk gene under the control of a carcinoembryonic antigen (CEA) promoter (AdCEAtk) followed by systemic administration of GCV. Four cell lines, CEA-producing Su.86.86. BxPC-3 (pancreatic cancer cells), MKN45 (gastric cancer cells) and CEA-nonproducing HeLa, were used for analysis of GCV sensitivity induced by adenoviral gene transduction. To evaluate the therapeutic efficacy of AdCEAtk and GCV administration in human CEA-positive pancreatic cancer in vivo, a subcutaneously implanted tumor-bearing nude mouse model was used. When the HSVtk gene was transduced with a ubiquitous promoter into these cells, increase of the GCV sensitivity was independent of CEA-production. In contrast, when the cells were transduced with a CEA promoter, the cell-killing effect of GCV was increased in only CEA-producing cells. For in vivo analysis, AdCEAtk was delivered into subcutaneously established tumors of Su.86.86 cells. Immunohistochemical staining of the tumor showed that HSVtk protein was expressed only in tumor cells, and tumor growth was markedly suppressed by administration of GCV. These results suggest that the adenovirus-mediated transfer of HSVtk gene with CEA promoter specifically increases the GCV sensitivity of CEA-producing pancreatic cancer cells in vitro and in vivo. This strategy may provide a useful tool for treating pancreatic cancer, especially CEA-producing tumor cells.

Adenoviridae↗