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Biomedical subjects

S Fujisaki

Publications and source records attributed to S Fujisaki.

At least 37 records · Page 2Linked to original sources

Relation between gastroduodenal interdigestive migrating motor complex and postoperative gastrointestinal symptoms before and after cisapride therapy following distal gastrectomy for early gastric cancer.

A total of 30 patients (18 men, 12 women; 43-79 years, mean 58.9 years) 1.0 to 1.5 years (mean 1.25 years) after distal gastrectomy for early gastric cancer (Billorth I, D2 lymph node dissection, curability A) were divided into two groups based on the occurrence of interdigestive migrating motor complex (IMMC) phase III (pIII) from the duodenum and their postoperative gastrointestinal symptoms. They were compared before and after cisapride therapy (at an oral dose of 7.5 mg/day for 3 months). Results were as follows. Before cisapride therapy: (1) Patients in the IMMC-pIII-positive group (n = 20) had more appetite and ate more food with less decrease in body weight than those in the IMMC-pIII-negative group (n = 10); (2) patients in the IMMC-pIII-positive group clearly had fewer symptoms, such as early dumping (systemic) symptoms, symptoms of reflux esophagitis (e.g., heartburn, feeling of regurgitation, difficult swallowing), nausea, abdominal pain, diarrhea, abdominal distension, and borborygmus, than the IMMC-pIII-negative group. After cisapride therapy: eight patients (80%) in the IMMC-pIII-negative group became IMMC-pIII-positive, and their appetite and food consumption were obviously improved; body weight increased in six patients (60%), with alleviation of other abdominal symptoms and disappearance of the early dumping syndrome. These results showed a more satisfactory condition in regard to gastrointestinal symptoms in the IMMC-pIII-positive group than in the IMMC-pIII-negative group. It is concluded that cisapride therapy results in the occurrence of IMMC-pIII and subsequently alleviates various abdominal symptoms, contributing to the improved postoperative gastrointestinal condition of patients after gastrectomy.

Adult↗

Effects of SSM (specific substance maruyama) on HBe antigen-positive chronic hepatitis B -clinical efficacy and modulation of cytokines.

Twenty-three patients with HBe antigen-positive chronic hepatitis B were treated with capitalite first letters Maruyama (SSM). HBe antigen turned negative in 15 patients. The levels of various cytokines in pre- and post-treatment frozen serum samples from six patients whose HBe antigen turned negative and from five whose HBe antigen did not were examined. Reduction of serum interleukin (IL) -10 level to below 20 pg/ml was observed after SSM treatment in four of the six patients whose HBe antigen turned negative. SSM was found to stimulate the production of interferon (IFN) -gamma in peripheral blood cells from two healthy volunteers. This stimulatory effect was confirmed in 12 out of 24 healthy volunteers. SSM augmented the production of IFN-gamma in eight out of 10 patients with chronic hepatitis B and nine of 10 with hepatitis C. These results demonstrate for the first time that SSM stimulates the production of IFN-gamma in human peripheral blood cells and also suggest that treatment of HBe antigen-positive chronic hepatitis B patients with SSM leads to the clearance of HBe antigen and normalization of serum aspartate aminotransferase levels through inhibition of IL-10 and stimulation of IFN-gamma.

Adult↗

[A study on development of enzyme immunoassay of human osteopontin: molecular fragility of serum osteopontin].

Osteopontin, a secreted acidic phosphoglycoprotein with calcium binding activity, has been reported to have diverse functions, including cell adhesion, calcium remodeling, cell signaling and cellular transformation. This recalls us to a concept that the osteopontin can be a marker for certain clinicopathological states. However, a method for analysis of osteopontin has not successfully been developed to be utilized. We have isolated osteopontin from human milk, prepared antibodies specific to it, and tried to establish an enzyme immunoassay (EIA) system to determine osteopontin in serum. It was found that serum osteopontin but not milk osteopontin showed paradoxical phenomena in reaction with the antibodies, i.e., no detectable reaction in immunoelectrophoresis and in EIA, but showing positive reaction in Western blot and in inhibition tests. Taking these phenomena and other circumstantial evidence into account, it was concluded that the serum osteopontin had high molecular fragility, fragmenting into small peptides with paucity of epitopes during incubation time. These findings indicate the possible presence of osteopontins with different molecular characteristics among tissues, and that these characteristics of osteopontin will interfere with the development of quantitative assay.

Antibodies↗

[Proposed mechanism of action of metalloendopeptidase-F in the treatment of patients with chronic hepatitis B or C infection].

Chronic hepatitis B and C virus infections have been characterized by the pathophysiological features with a high incidence of progression to cirrhosis and development of hepatocellular carcinoma. The viral persistence produced by escape mutations from virus-specific cytotoxic T lymphocytes (CTL) response may lead to upregulation of delayed-type hypersensitivity immune response, which causes hepatic tissue damage through non specific macrophage activation and CTL response and promotes pathogenesis of hepatic fibrosis. In a preliminary clinical study, a novel metalloendopeptidase-F (MEP-F) has been shown to be effective in the treatment of patients with either chronic hepatitis B or C infection. Oral administration of MEP-F resulted in a significant reduction of the serum levels of HBs antigen and HCV RNA and improvement in the liver function abnormalities. However, the mechanism of action of MEP-F is not yet well understood. There are accumulating evidences showing an important role of alpha 2-macroglobulin-proteinase complexes in regulatory mechanisms of immune response and repairing within impaired and inflammatory tissues. In this article, reviewing the pharmacological and biological properties of alpha 2-macroglobulin-proteinase complexes, the mechanism of anti-viral effect of MEP-F is examined based on the clinical findings. It is indicated that alpha 2-macroglobulin-MEP-F complexes may induce macrophage/Kuppfer cell activation and proliferation through binding their receptors on the cells and activating signaling cascades, which enhance both anti-viral specific and nonspecific immune responses. alpha 2-Macroglobulin-MEP-F complexes may also augment cellular immunity and hepatic regeneration by neutralizing the immunosuppressive and fibrogenic activities of transforming growth factor-beta.

Animals↗

Laparoscopic treatment for common bile duct stones by transcystic papilla balloon dilatation technique.

The laparoscopic transcystic common bile duct (CBD) approach is becoming increasingly more refined as an ideal technique to deal with gallbladder stones (GBS) and common bile duct stones (CBDS) during a single operation. Our method, transcystic CBD exploration and papilla balloon dilatation (PBD), is an easier, safer, and less invasive technique than the transcystic approaches that have previously been reported. With our method, a sheath is introduced through the cystic duct into the CBD in order to allow catheter exchange, and the CBDS is flushed out through the papilla into the duodenum after PBD. We applied our new technique, without complication, to a patient with GBS and CBDS. Our technique is one of the safest, easiest, and least invasive methods for the treatment of patients with GBS and CBDS.

Ampulla of Vater↗

The Escherichia coli homologue of yeast RER2, a key enzyme of dolichol synthesis, is essential for carrier lipid formation in bacterial cell wall synthesis.

We found in the Escherichia coli genome sequence a homologue of RER2, a Saccharomyces cerevisiae gene required for proper localization of an endoplasmic reticulum protein, and designated it rth (RER2 homologue). The disruption of this gene was lethal for E. coli. To reveal its biological function, we isolated temperature-sensitive mutants of the rth gene. The mutant cells became swollen and burst at the nonpermissive temperature, indicating that their cell wall integrity was defective. Further analysis showed that the mutant cells were deficient in the activity of cis-prenyltransferase, namely, undecaprenyl diphosphate synthase, a key enzyme of the carrier lipid formation of peptidoglycan synthesis. The cellular level of undecaprenyl phosphate was in fact markedly decreased in the mutants. These results are consistent with the fact that the Rer2 homologue of Micrococcus luteus shows undecaprenyl diphosphate synthase activity (N. Shimizu, T. Koyama, and K. Ogura, J. Biol. Chem. 273:19476-19481, 1998) and demonstrate that E. coli Rth is indeed responsible for the maintenance of cell wall rigidity. Our work on the yeast rer2 mutants shows that they are defective in the activity of cis-prenyltransferase, namely, dehydrodolichyl diphosphate synthase, a key enzyme of dolichol synthesis. Taking these data together, we conclude that the RER2 gene family encodes cis-prenyltransferase, which plays an essential role in cell wall biosynthesis in bacteria and in dolichol synthesis in eukaryotic cells and has been well conserved during evolution.

Alkyl and Aryl Transferases↗

Expression of CD44 in rat liver allografts during rejection.

As CD44 is believed to be a homing receptor involved in lymphoid trafficking and inflammatory responses, it is expected to be closely linked to transplant rejection. In this study, the expression of CD44 during liver transplant rejection was compared with the expression of lymphocyte-function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), which play an essential role in cell interactions and the initiation of immune responses. Male Brown Norway (BN) and Lewis (LEW) rats were used as donors and recipients, respectively. Orthotopic liver transplantation (OLTX) was done using the cuff technique of Kamada and Calne. Animals were killed on days 3, 5, and 7 after OLTX, and a piece of tissue from each of the liver grafts was obtained. Immunohistochemical staining was used to investigate the expression of CD44, ICAM-1, and LFA-1. CD44 was strongly expressed in portal areas of the rejected liver, and LFA-1 and ICAM-1 were expressed mainly on sinusoids and hepatocytes. These findings indicate that CD44 is closely involved in lymphocyte infiltration, which is dominant in portal areas, and that lymphocyte infiltration during the rejection process may involve a homing mechanism.

Animals↗

Cloning of a gene from Escherichia coli that confers resistance to fosmidomycin as a consequence of amplification.

A gene conferring resistance to fosmidomycin (Fs) was cloned from the gene pool of a wild-type strain of Escherichia coli. The cloned DNA fragment was sequenced and shown to encode a putative polypeptide of 406 amino acids (aa) with a molecular weight of 43303. The gene mapped at 10.9 min on the E. coli chromosome and was designated fsr (fosmidomycin resistance). Maxicell analysis revealed that the Fsr protein migrated in sodium dodecyl sulfate-polyacrylamide-gel electrophoresis as a broad band of 35 kDa. A comparison between the aa sequence of Fsr and sequences in a protein database revealed 18% homology to the bacterial drug-export proteins that mediate resistance to tetracycline and chloramphenicol. Hydropathy analysis of the Fsr protein revealed twelve putative transmembrane segments. The degree of FsR of transformants depended on the number of copies of the plasmid that contained fsr. The levels of ubiquinone-8 and undecaprenyl phosphate in cells that harbored a high-copy-number plasmid that included fsr were almost the same as those in the cells without the plasmid. These results suggest that Fsr does not have any direct effect on the biosynthesis of isoprenoid in E. coli, and that the mechanism for FsR involves the efflux of the drug by a process that is facilitated by Fsr.

Amino Acid Sequence↗

Polyprenyl diphosphate synthase essentially defines the length of the side chain of ubiquinone.

Ubiquinone, known as a component of the electron transfer system in many organisms, has a different length of the isoprenoid side chain depending on the species, e.g., Escherichia coli, Saccharomyces cerevisiae and humans have 8, 6, and 10 isoprene units in the side chain, respectively. No direct evidence has yet shown what factors define the length of the side chain of ubiquinone. Here we proved that the polyprenyl diphosphate that was available in cells determined the length of the side chain of ubiquinone. E. coli octaprenyl diphosphate synthase (IspB) was expressed with the mitochondrial import signal in S. cerevisiae. Such cells produced ubiquinone-8 in addition to the originally existing ubiquinone-6. When IspB was expressed in a S. cerevisiae COQ1 defective strain. IspB complemented the defect of the growth on the non-fermentable carbon source. Those cells had the activity of octaprenyl diphosphate synthase and produced only ubiquinone-8. These results opened the possibility of producing the type of ubiquinone that we need in S. cerevisiae simply by expressing the corresponding polyprenyl diphosphate synthase.

Alkyl and Aryl Transferases↗

[Mid mediastinal lipoma--a case report].

Mediastinal lipomas are relatively rare neoplasm in Japan. They are generally asymptomatic tumors because they often arise from anterior mediastinum especially nearby diaphragma. We experienced a 67-year-old man who presented with transient edema on the face and upper limbs. The phlebography showed compression of left brachiocephalic vein, superior vena cava and right pulmonary artery by the tumor. The sagittal view of the chest MRI gave precise and useful anatomical informations. The complete resection of the tumor was performed uneventfully. The tumor was 15 x 12 x 5 cm in size, and there was no secondary change at the superior vena cava. Postoperative chest CT showed the complete decompression of the superior vena cava. The pathological diagnosis of the tumor was benign mature lipoma. Postoperative course was uneventful and the patient is now being well. There is no evidence of recurrence 6 months after the operation. This is the first report of the mediastinal lipoma which arised from the mediastinum in Japanese literature as far as we have reviewed.

Aged↗

Variable chimerism, graft-versus-host disease, and tolerance after different kinds of cell and whole organ transplantation from Lewis to brown Norway rats.

The bidirectional paradigm of tolerance involving reciprocal host vs. graft and graft vs. host reactions was examined after Lewis (LEW)-->Brown Norway (BN) transplantation of different whole organs (liver, intestine, heart, and kidney) or of 2.5 x 10(8) LEW leukocytes obtained from bone marrow, spleen, lymph nodes, and thymus. The experiments were performed without immunosuppression or under 14 daily doses of postoperative tacrolimus, which were continued in weekly doses to 100 days in a "continuous treatment" subgroup, and to 27 days in a short treatment group. Without immunosuppression, all organs and cell suspensions failed to engraft or were acutely rejected. GVHD (usually fatal) was always caused when either the long or short treatment was used for recipients of intestinal grafts and cell suspensions of spleen and lymph nodes. In contrast, both immunosuppressive protocols allowed engraftment of bone marrow cells, liver, heart, and kidney without clinical GVHD, whereas thymus cell suspensions and small doses of whole blood neither engrafted nor caused GVHD. At 100 days, now drug-free for 73 days, the liver, bone marrow, and heart recipients were tolerant in that they accepted all challenge LEW heart and/or liver grafts for 100 more days despite in vitro evidence of donor-specific reactivity (split tolerance). At 200 days, histopathologic studies of the challenge livers were normal no matter what the priming graft. However, the still-beating challenge hearts had a spectrum from normal to severe chronic rejection that defined the tolerogenicity of the original primary grafts: liver best-->bone marrow next-->heart least. Both the GVHD propensity and tolerogenicity in these experiments were closely associated with recipient tissue chimerism 30 and 100 days after the experiments began. The tissue chimerism was invariably multilineage, but the GVHD outcome was associated with T cell over-representation. These observations provide guidelines that should be considered in devising leukocyte augmentation protocols for human whole organ recipients. The results are discussed in relation to the historical tolerance studies of Billingham, Brent, and Medawar; Good; Monaco; and Calne.

Animals↗

Activated (HLA-DR+) T-lymphocyte subsets in cervical carcinoma and effects of radiotherapy and immunotherapy with sizofiran on cell-mediated immunity and survival.

A prospective randomized trial on 312 patients with locally advanced cervical carcinoma (FIGO stages IB-IV) was carried out. The 5-year survival in 90 patients treated with radiotherapy and antitumor polysaccharide sizofiran, an extract from the culture broth of Schizophyllum commune Fries, in combination was significantly (P = 0.045) better than that in 82 patients treated with radiotherapy alone. Treatment with sizofiran and 5-fluorouracil in combination improved (P = 0.003) the 5-year survival in 60 patients treated with radiotherapy. In 244 cervical carcinoma patients, the percentage of activated CD8+ (CD8+HLA-DR+) T cells in the CD8+ T-cell subsets in peripheral lymphocytes increased significantly as the disease progressed. A similar tendency was observed in the percentage of activated CD4+ (CD4+HLA-DR+) T cells in the CD4+ T-cell subsets. These immunologic parameters were significantly increased by radiotherapy, but not by surgery. Sizofiran accelerated a recovery in the activated CD8+ T cells in the CD8+ T-cell subsets compared with that of sizofiran nontreated patients after radiotherapy. Our data show that possible immune impairment in cervical carcinoma may be caused by disturbances in cell-mediated immunity, and that sizofiran is an effective immunotherapeutic agent for cervical carcinoma because it stimulates a rapid recovery of the immunologic parameters impaired by radiotherapy.

CD4-CD8 Ratio↗

Immunological disorder against the Epstein-Barr virus infection and prognosis in patients with cervical carcinoma.

Epstein-Barr virus antigen-specific killer T cell (EBV-KT) activity and Epstein-Barr virus (EBV) shedding at uterine cervix and oropharynx were examined in patients with cervical carcinoma. EBV-KT activity was determined by a modified EBV-induced B cell focus regression assay. EBV shedding was examined by infectivity assay. EBV-KT activity in the patients was decreased significantly compared with that of controls (P < 0.001) and became increasingly lower as the clinical stage of the disease advanced. EBV-KT activity was changed by treatment, and decreased EBV-KT activity after treatment was clearly related to patient survival. EBV shedding at oropharynx and uterine cervix were also higher in the patients than in the controls (P < 0.01 and < 0.05). These results suggest that EBV-KT activity is closely associated with the prognosis in patients with cervical carcinoma and that it may be a useful parameter in monitoring the cell-mediated immunity of patients with cervical carcinoma.

Adult↗