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Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 271 records · Page 15Linked to original sources
PubMed1996

Role of alpha 2 beta 1- and alpha 3 beta 1-integrin in the peritoneal implantation of scirrhous gastric carcinoma.

We established a highly peritoneal-seeding cell line, OCUM-2MD3, from a poorly peritoneal-seeding cell line, OCUM-2M, of human scirrhous gastric carcinoma. The intraperitoneal inoculation of OCUM-2MD3 cells produced peritoneal dissemination in nude mice, whereas that of OCUM-2M cells did not. We then investigated the correlation between seeding potential and adhesion molecule beta 1-integrins or alpha 6 beta 4-integrin. alpha 2 beta 1- and alpha 3 beta 1-integrin expression on OCUM-2MD3 cells (91.6% and 93.6%) was increased compared with that of OCUM-2M cells (47.8% and 34.3%) by flow cytometric analysis, and the expression level of the other integrins was not different between the two cell lines. The binding ability of OCUM-2MD3 cells to matrigel, fibronectin, laminin and type I collagen was significantly increased, approximately seven times, three times, eight times, and three times greater than that of OCUM-2M cells respectively. The invasiveness of OCUM-2MD3 cells was also significantly increased 8-fold over OCUM-2M cells. The binding and invasive ability of OCUM-2MD3 cells was significantly decreased following the addition of anti-alpha 2 beta 1- and alpha 3 beta 1-integrin antibody, but not by anti-alpha 6 beta 1- and alpha 6 beta 4-integrin antibody. These results suggest that adhesiveness and invasiveness in peritoneal implantation of scirrhous gastric carcinoma might be closely associated with alpha 2 beta 1- and alpha 3 beta 1-integrin.

Adenocarcinoma, Scirrhous↗
PubMed1996

DNA polymerase betas from liver and testes of cherry salmon, Oncorhynchus masou: purification and characterization of DNA polymerase betas with acidic isoelectric points.

DNA polymerase betas from cherry salmon, Oncorhynchus masou, liver and testes were purified to near homogeneity, and no substantial differences between the enzymes were observed. The molecular weight of both enzymes, determined by SDS-polyacrylamide gel electrophoresis, was 39,000. The amino acid sequences of the N-terminus of the liver and testes enzymes were determined and compared with that of the rat enzyme. Of the N-terminal 30 amino acid residues of salmon liver DNA polymerase beta, 21 (70%) were identical to those of the rat enzyme sequence. However, unlike most eukaryotic DNA polymerase betas, the isoelectric points (pIs) of the DNA polymerase betas from salmon liver and testes were both estimated to be 6.2, which is significantly different from the alkaline isoelectric points (pI = 8.5-9.5) established for other highly purified vertebrate DNA polymerase betas. The cherry salmon DNA polymerase betas were still active at below 10 degrees C, compared with the rat enzyme.

Amino Acid Sequence↗
PubMed1996

Antimetastatic effect of a novel indolocarbazole (NB-506) on IMC-HM murine tumor cells metastasized to the liver.

IMC-HM cells were isolated from spontaneously induced ascitic IMC carcinoma cells that had been maintained intraperitoneally in CDF1 mice. Metastasis to the liver of subcutaneously implanted IMC-HM cells was detected 10 days after implantation into the flanks of mice (day 10), but metastasis to other organs was limited. Thereafter, however, tumor cells spread rapidly to lymph nodes, lung, spleen, ovary and other organs, and the mice died on day 13 to 18. We report here, together with the properties of IMC-HM cells, the effects of adriamycin, cisplatin, etoposide and a new indolocarbazole antitumor compound (NB-506) on this model of metastasis. Although these anticancer agents all inhibited the growth of the subcutaneous tumors, their effects on the life span of the tumor-bearing mice varied. Treatment with NB-506, started on day 1, more than doubled the survival period at doses 30 mg/m2 to 900 mg/m2. Further, treatment with NB-506, started on day 4 after resection of the primary tumor, inhibited growth of the metastasized tumor in the liver and other organs. Etoposide also increased the life span at a limited range of doses. However, the life-prolonging effects of adriamycin and cisplatin were marginal. These results demonstrate that IMC-HM carcinoma is a good model for spontaneous metastasis to the liver followed by lethal spread to many organs. Moreover, NB-506 was found to be highly effective against the growth not only of subcutaneous tumors, but also of tumors metastasized to the liver.

Animals↗
PubMed1996

Anti-tumor effects of hyperthermia plus granulocyte colony-stimulating factor.

The role of neutrophils in the anti-tumor effects of hyperthermia was investigated in an experimental rat model, and the efficacy of hyperthermia combined with recombinant human granulocyte colony-stimulating factor (G-CSF) was similarly investigated. AH109A carcinoma cells were transplanted into the hind legs of Donryu rats, then heated by a radio-frequency dielectric heater. In this study, because the myeloperoxidase (MPO) activity of neutrophils was not affected by heating or G-CSF, MPO activity was measured as an index of neutrophil migration into tumor tissue. After hyperthermia, MPO activity in tumor tissue increased significantly, suggesting migration of neutrophils into tumor tissue. Depletion of circulating neutrophils by the intraperitoneal injection of anti-rat neutrophil antibody decreased the anti-tumor effects of hyperthermia. Subsequently, we used hyperthermia plus intraarterial G-CSF to enhance the anti-tumor effect. Hyperthermia was induced 1 h after injection of G-CSF, a time when MPO activity in tumor tissue was maximal. A satisfactory thermal effect was noted even in cases where tissue could not be heated sufficiently. In conclusion, neutrophils have an important role in the anti-tumor effects of hyperthermia, and administration of G-CSF enhances these effects.

Animals↗
PubMed1996

Failure to detect mutations in the retinoblastoma protein-binding domain of the transcription factor E2F-1 in human cancers.

The functions of the transcription factor E2F-1 are regulated by the RB protein through the RB-binding domain of E2F-1 and this factor is considered to be an important molecule that functions downstream of the RB protein. In order to determine whether E2F-1 that cannot bind to RB might be associated with various human cancers, we searched for mutations in the RB-binding domain of E2F-1 using samples of DNA from various clinical specimens obtained from 406 cancer patients (with lung, pancreatic, stomach, colon, esophageal, and hepatic cancers) by analysis of polymerase chain reaction-mediated single-strand conformational polymorphism. No mutations or deletions were detected in genes for E2F-1 from any of the tumor tissues examined. These results suggest that a mutation or deletion in E2F-1 that might affect binding of the RB protein is not involved in human cancers.

Base Sequence↗
PubMed1996

CD44H plays an important role in peritoneal dissemination of scirrhous gastric cancer cells.

The role of the adhesion molecule CD44H in the peritoneal adhesion and invasion of cancer cells was assessed using cell lines with low and high peritoneal seeding ability, OCUM-2M (2M) and OCUM-2MD3 (2MD3), respectively. The in vitro binding ability to peritoneal components (mesothelial cells, fibronectin and type I collagen) and invasive ability of 2MD3 cells were higher than those of 2M cells. The expression level of CD44H on 2MD3 cells was higher than that on 2M cells as determined by western blot analysis and flow cytometry. The adhesiveness of 2MD3 cells to hyaluronic acid, which is expressed on the surfaces of mesothelial cells, was greater than that of 2M cells. The binding ability of 2MD3 cells to mesothelial cells was inhibited in the presence of anti-CD44H monoclonal antibody, but that of 2M cells was not. These results suggested that the 2MD3 cell binding to mesothelial cells is regulated by the CD44-hyaluronic acid dependent system. The in vitro binding to submesothelial components and the invasiveness of 2MD3 cells were also inhibited in the presence of anti-CD44H antiody. The in vivo inoculation of 2MD3 cells treated with an anti-CD44H antibody resulted in a significiant prolongation of survival time as compared with control mice that were inoculated with 2MD3 cells alone. In conclusion, CD44H was associated with attachment not only to hyaluronic acid on mesothelial cells, but also to peritoneal stromal components. Thus, CD44H may play an important role in cancer cell binding and invasion in the peritoneal dissemination of scirrhous gastric cancer cells.

Adenocarcinoma, Scirrhous↗
PubMed1996

Keratinocyte growth factor is an endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.

Mesenchymal-epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal-epithelial interaction.

Animals↗
PubMed1996

Effects of clobazam and its active metabolite on GABA-activated currents in rat cerebral neurons in culture.

PURPOSE: The antiepileptic effects of clobazam, a 1,5-benzodiazepine, have been well documented in animal experiments and clinical trials. However, the drug's mechanisms of antiepileptic actions are still undetermined. The purpose of this study was to learn how clobazam and its active metabolite modulate gamma-aminobutyric acid (GABA)-activated currents in rat cerebral neurons in culture. METHODS: Whole-cell voltage-clamp recordings were performed on cultured cerebral neurons of the rat. Clobazam or its metabolite N-desmethylclobazam was dissolved in the extracellular solution and applied for 2 s by pressure ejection from a micropipette. To maintain GABA-activated currents, 2 mM Mg adenosine triphosphate (ATP) was added to the intracellular solution. RESULTS: GABA elicited outward currents that were mediated by GABAA receptor-coupled Cl- channels. Applying clobazam with 10 microM GABA elicited enhanced outward currents. Flumazenil, an antagonist of the benzodiazepine receptor, inhibited the enhancing effect of clobazam. The enhancement ratio increased as much as 2.28-fold in a dose-dependent manner at a concentration of 3 microM clobazam. However, it started to decrease at a concentration of 10 microM clobazam. The metabolite N-desmethylclobazam was tested in the same manner, and exhibited an identical dose-dependent enhancement of GABA-activated currents. CONCLUSIONS: The antiepileptic effects of the 1,5-benzodiazepines are attributed to the enhancement of GABAergic inhibitory neurotransmission. The antiepileptic effects of clobazam are thought to depend mainly on its active metabolite N-desmethylclobazam, which is present in high concentrations in patients who receive long-term clobazam. Clobazam's enhancement of GABA-activated currents was most marked on weaker GABA currents. We therefore infer that clobazam acts more efficiently on tissues in which the release of GABA is diminished.

Animals↗
PubMed1996

Production of agglutinating monoclonal antibody against antigen 8 specific for Cryptococcus neoformans serotype D.

A hybridoma (clone CRND-8) that produced agglutinating monoclonal antibody (MAb) against Cryptococcus neoformans serotype D was established by using a soluble capsular polysaccharide-keyhole limpet hemocyanin conjugate for immunization. The isotype was immunoglobulin M(kappa). Specificity was determined by cell slide agglutination and enzyme-linked immunosorbent assay (ELISA). In both tests, the MAb reacted to serotypes D and A-D but not to serotypes A, B, and C. Furthermore, the specificity of the MAb determined by ELISA was the same as that of polyclonal antibody factor serum (PAb factor) 8, which showed high-level reactivity with serotypes D and A-D. These results supported the deduced specificity of the PAb-based antigenic factor 8. A total of 15 isolates of serotypes D and A-D but no serotype A isolates reacted with the MAb in cell slide agglutination tests. CRND-8 MAb can be used in place of PAb factor 8 for serotyping C. neoformans isolates and for the analysis of the antigen 8 epitope.

Agglutination Tests↗
PubMed1996

Positivity for antinuclear antibody in patients with advanced rheumatoid arthritis.

Some patients with rheumatoid arthritis (RA) as well as those with other collagen diseases are positive for antinuclear antibody (ANA). We investigated the frequency of positivity for ANA in 104 patients with RA and evaluated the clinical features and laboratory data in the ANA-positive and -negative groups. The presence of ANA in sera was studied by indirect immunofluorescence using HEp-2 cells as the antigen substrate. Sera with a positive fluorescence at a dilution of 1:20 were considered to be positive for ANA. Of the 104 patients, 39 (37.5%) were positive for ANA. The staining pattern in the positive cases varied, but most were speckled (64.1%) and homogeneous (48.7%). A small number showed a nucleolar (20.5%) or a centromere (10.3%) pattern. None showed a shaggy pattern. The ANA titer was lower in RA patients compared with those with other collagen-related diseases such as systemic lupus erythematosus or progressive systematic sclerosis. None of the patients positive for ANA with either a nucleolar or centromere staining pattern had progressive systemic sclerosis or the CREST syndrome. One patient each had Raynaud's phenomenon and pulmonary fibrosis. There was no correlation between ANA positivity and indicators of joint inflammation. The prevalence of ANA positivity in patients with advanced or prolonged disease was higher than those with early stages or short durations. There was no correlation with drug therapy.

Adult↗
PubMed1996

Survey of cardiac pacing in Canada (1993).

INTRODUCTION: The status of cardiac pacing in Canada in 1993 was determined from data provided by 33 of 128 physicians surveyed (25% response) and four major manufacturer/distributors. DEMOGRAPHICS: There were 268 new implants per million population, similar to the 1989 data, 279 per million. INDICATIONS: Sinus node disorders accounted for 38.2% of implants, atrial fibrillation with slow ventricular response for 18.1% and atrioventricular node dysfunction for 33.1% of patients. Implants for tachyarrhythmias accounted for only 3.5%. TECHNOLOGY: Single chamber units were implanted in 76% of patients and dual chamber in 23%, with rate modulation used in 35% of primary implants. There was an increase in the use of single chamber rate adaptive units from 1989 (from 15.9% to 25%). The per venous sheath introducer technique was used in 55% of lead insertions. Bipolar leads were used in 78% of atrial and 63% of ventricular leads; passive steroid leads were used in 50% of atrial and 55% of ventricular lead implants; 40% of atrial leads and 7.5% of ventricular leads had active fixation. FOLLOW-UP: Most pulse generators were reprogrammed peri-operatively or within three months (97.4%). Most patients with new implants (92%) required hospital admission for 2.5 days, while 75% of replacements were out-patient procedures. CONCLUSIONS: Comparison with previous surveys and other countries revealed little growth in pacemaker sales or new implant rates per million population; conservative indications and relatively constant use of dual chamber devices; and an increase in single chamber rate responsive units. The authors express concern regarding budget constraints and resource availability as factors limiting growth in pacemaker therapy.

Aged↗
PubMed1996

Intra-arterial chemotherapy for muscle-invasive urinary bladder cancer.

A total of 9 patients with muscle-invasive bladder cancer (T3 or T4N0M0) were treated with a modified intra-arterial M-VEC (IA-M-VEC) regimen beginning in October 1992 to evaluate its therapeutic efficacy, and in 3 evaluable patients who subsequently underwent radical cystectomy, the possibility of bladder preservation was assessed. The responses of the 8 evaluable patients were rated as complete response (CRs) in 3, partial response (PRs) in 3 and no change (NCs) in 2. The objective response rate (PR + CR) was 75%. An obvious down-staging (T3 --> pT1b) was confirmed in 2 of the 3 evaluable patients, suggesting the possibility of bladder preservation. Otherwise similar changes to hemorrhagic cystitis with minimal muscular fibrosis were conspicuous in the normal bladder wall. These pathological findings corresponded with those obtained by dynamic single photon emission computed tomography (D-SPECT) using 99mTC-macroaggregate albumin (99mTC-MAA). Besides a buttock-to-perianal erosion with neuralgia on the injection side, mild to moderate sensory disturbance of the sacral plexus was observed.

Aged↗
PubMed1996

[Bronchobiliary fistula].

A 57-year-old woman with congenital syphilis had a productive cough, fever, cholecystolithiasis, and paralytic ileus. She had a 30-year history of recurrent bronchitis accompanied by yellowish serous sputum. A chest radiograph showed bilateral infiltrates resulting from aspiration pneumonia, and a reduction in volume of the right middle and right lower lobes. After recovering from paralytic ileus, she still had fever and biliptysis. Bronchoscopy revealed bile filling the right basal bronchi. Emergency laparotomy and throacotomy revealed a gall stone, splenomegaly, marked atrophy of the right lobe of the liver, and adhesion between the right pleura and the diaphragm. A T-tube cholangiogram showed that the right hepatic duct communicated with the right basal bronchus. Despite ligation of the right hepatic duct, biliptysis continued. The patient died due to rapidly progressing hepatorenal failure. Syphilis gummosa due to congenital syphilis was suspected as a cause of the bronchobiliary fistula, but was not confirmed pathologically. The surgical specimen showed only nonspecific fibrosis with calcification. Bronchobiliary fistula is rare in Japan; we know of only 6 other reported cases.

Biliary Fistula↗
PubMed1996

Maltal binding mechanism and a role of the mobile loop of soybean beta-amylase.

The inhibition of hydration of maltal (alpha-D-glucopyranosyl-(1-->4)-2-deoxy-D-glucal) catalyzed by soybean beta-amylase with 4-O-alpha-D-glucopyranosyl-(1-->4)-1-deoxynojirimycin (GDN) was investigated at 25 degrees C and at pH 5.4. As the concentrations of GDN used were comparable to that of the enzyme, Henderson's treatment was applied to this system. It was found that two maltal molecules bind to the enzyme according to a random mechanism and GDN inhibits the hydration of maltal competitively at subsites 1 and 2, and noncompetitively at the other site. On the basis of this result, it was inferred that the role of the mobile loop of this enzyme is to create a convenient catalytic environment for the hydration, and the closing of the active site by the mobile loop is induced by the binding of maltal.

1-Deoxynojirimycin↗
PubMed1996

p53-independent induction of apoptosis by cyclin-dependent kinase inhibition.

The G1 checkpoint and terminal differentiation may be associated with apoptosis, the induction of which is in large part dependent on the presence of active p53. However, cells lacking wild-type p53 can undergo apoptotic cell death during normal development and during terminal differentiation of malignant cells. Using the specific inhibitor for cyclin-dependent kinases (cdks), we show here that an inhibition of cdk activity per se can induce apoptotic cell death during G1-S transition of the cell cycle in a p53-independent manner. The apoptotic process triggered by cdk inhibition was associated with an overriding of the G1-S boundary and was inhibited by arresting the cells in G1. These results raise the possibility that aberrant cell cycle machinery may result in self-elimination, even in the absence of p53, and further indicate that cdk activity is not necessarily required during this process.

4-Butyrolactone↗
PubMed1996

[Pharmacokinetic, bacteriological and clinical studies on cefozopran in neonates and premature infants. A study of cefozopran in the perinatal co-research group].

The following results were obtained in pharmacokinetic, bacteriological and clinical investigations of a cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), administered to neonates and premature infants. 1. Pharmacokinetics (1) Half-lives (T 1/2's) of CZOP in 0-day-old (less than 24 hours after birth) neonates and premature infants were longer than those in 1-day-old or older infants. When half-lives were compared between 0-day-old neonates and 0-day-old premature infants, longer half-lives were observed in premature infants. (2) When CZOP was intravenously administered to 1-day-old or older neonates and premature infants at a dose of 20 mg/kg, no differences were noted in blood concentrations between neonates and premature infants from 30 minutes to 6 hours after administration as well as T 1/2's. (3) Blood concentration of CZOP administered at doses of 10, 20 and 40 mg/kg were dose-dependent. (4) Urine excretion rates of CZOP administered to 1-day-old or older neonates and premature infants were approximately 30 to 60% in the first 6 hours after administration. Urine excretion rates in 0-day-old neonates and premature infants were low. 2. Clinical results (1) Of a total of 136 cases to which CZOP was administered, clinical efficacy evaluation was possible in 96 cases, and safety evaluation in 132 cases. (2) The clinical efficacy rates were 78.6% (22/28) in 28 cases in which causative organisms were detected (Group A), and 97.1% (66/68) in 68 cases in which no such organisms were detected (Group B), with the total efficacy rate (Groups A and B) of as high as 91.7% (88/96). (3) Bacteriological evaluations were made with 33 strains isolated from the 28 cases of Group A. Elimination rates for Gram-positive and Gram-negative bacteria were 88.2% (15/17) and 92.3% (12/13), respectively, with the total elimination rate of 90.0% (27/30). No microbial substitution was noted. (4) As an adverse reaction, diarrhea was noted in one case (0.8%). Abnormal laboratory test values were noted in 15 cases (12.3%) including eosinophilia, elevated GPT, and elevated gamma-GTP. All of these abnormalities were transitory, and none of them critical. As a result of above pharmacokinetic and clinical investigations, CZOP is considered to be highly useful in the treatment of indicated infections in neonates and premature infants. It appears that 20 mg/kg of CZOP can be administered by intravenous injection or intravenous drip infusion to neonates and premature infants aged 0-day (less than 24 hours after birth) once or twice daily, to those aged 1 (24 or more hours after birth) to 7 days twice or three times daily, and to those aged 8 or more days three to four times daily, and that the dose can be increased up to 40 mg/kg in cases of critical or intractable infections.

Bacterial Infections↗
PubMed1996

[Mechanism of peritoneal metastasis and the possibility of therapeutic agents].

Peritoneal metastasis has been clinically considered to be a terminal stage, so aggressive therapy has not been performed. Recently, the molecular biologic study of cancer metastasis has progressed, so it should be important in the future to examine new therapies based on the mechanism of metastasis. In this paper, the mechanism of peritoneal metastasis, especially adhesion to peritoneum, was investigated using a scirrhous gastric cancer cell line, OCUM-2MD3. The possibility of therapeutic agents for the metastasis based on the mechanism was discussed.

Animals↗