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S Nishimura

Publications and source records attributed to S Nishimura.

At least 127 records · Page 7Linked to original sources
PubMed2000

TGF-beta1 secreted by gastric fibroblasts up-regulates CD44H expression and stimulates the peritoneal metastatic ability of scirrhous gastric cancer cells.

Gastric fibroblast-derived conditioned medium and TGF-beta1 stimulated the adhesion ability of scirrhous gastric cancer cells to mesothelial cells, but not that of well-differentiated gastric cancer cells. The CD44H expression of scirrhous gastric cancer cells was significantly up-regulated by gastric fibroblast-derived CM and TGF-beta1. The stimulated adhesion ability and CD44H expression was significantly inhibited by anti TGF-beta1 neutralizing antibody. These findings suggested that TGF-beta1 secreted by gastric fibroblasts up-regulated the CD44H expression of scirrhous gastric cancer cells, which resulted in the stimulation of the adhesion ability of scirrhous gastric cancer cells to the mesothelium, and increased the peritoneal dissemination potential. These results might explain one of the reasons why scirrhous gastric carcinomas develop frequent peritoneal dissemination.

Adenocarcinoma, Scirrhous↗
PubMed2000

Guidelines for pacemaker follow-up in Canada: a consensus statement of the Canadian Working Group on Cardiac Pacing.

A survey on Canadian pacing practices conducted in 1997 revealed a widespread desire for national guidelines on pacemaker follow-up. The present guidelines for pacemaker follow-up are a consensus statement of the Canadian Working Group on Cardiac Pacing. Direct patient follow-up rather than transtelephonic monitoring is desirable. Patients should be assessed at a minimum of within 72 h of implantation, at two to 12 weeks and at six months following implantation, and annually thereafter. More frequent assessments may be required for some patients. This depends on associated cardiovascular problems and specific devices. A typical follow-up visit should include a targeted cardiovascular assessment, interrogation of the pacing system, review of telemetered data, assessment of the underlying rhythm, assessment of pacing and sensing thresholds, and appropriate reprogramming of pacing parameters to optimize device function and longevity.

Canada↗
PubMed2000

Lignes directrices pour le suivi des cardiostimulateurs au canada : consensus du groupe de travail canadien sur la cardiostimulation

Un sondage sur les pratiques de cardiostimulation au Canada effectue en 1997 a revele un profond desir pour des lignes directrices nationales sur le suivi des cardiostimulateurs. Ces lignes directrices sur le suivi des cardiostimulateurs representent une declaration de consensus du Groupe de travail canadien sur la cardiostimulation. Le suivi des patients en personne plutot que par moyens transtelephoniques est preferable. Les patients devraient etre examines au minimum dans les 72 heures suivant l'implantation, 2 a 12 semaines et 6 mois apres l'implantation, et annuellement par la suite. Des examens plus frequents peuvent etre requis pour certains patients. Ceci dependra des problemes cardiovasculaires associes et des appareils en particulier. Une visite de suivi typique devrait comprendre un examen cardiovasculaire oriente, l'interrogation du systeme de cardiostimulation et une revue des donnees de telemetrie, un examen du rythme sous-jacent, un examen des seuils de stimulation et de detection et une reprogrammation adequate des parametres pour optimaliser le fonctionnement et la longevite de l'appareil.

Journal Article↗
PubMed2000

[Usefulness and pitfalls in myocardial perfusion SPECT for detecting and assessing coronary artery disease].

Thallium-201(Tl) is the dominant agent employed for myocardial perfusion imaging for detection of coronary artery disease, assessment of myocardial viability and prognostication. Technetium-99m(Tc) labeled radionuclides have been used as excellent alternatives to Tl. This paper will review the usefulness and pitfall in myocardial perfusion single photon emission computed tomography(SPECT) in patients with coronary artery disease. From a practical standpoint, we should know what are clinical questions, clinical status of patients(history and exercise ability of patients, obesity) and diagnostic accuracy of each diagnostic protocol and the performance in the nuclear laboratory. Myocardial perfusion defects during stress SPECT are produced by a heterogeneity in coronary blood flow, which depends on severity of coronary stenosis and consequent abnormalities in flow reserve. Certain factors can affect sensitivity and specificity of Tl SPECT for detection of coronary artery disease. Accurate determination of myocardial viability is vitally important for clinical decision making for patients with left ventricular(LV) dysfunction who will most benefit from revascularization. Hibernated myocardium may result in profound regional LV dysfunction in absence of necrosis. The various approach such as stress-redistribution-reinjection imaging, rest-redistribution imaging and rest-redistribution 24 hours delayed imaging has been utilized to assess myocardial viability with Tl. Alternatively, quantitative assessment of 99mTc-methoxy-isobutyl isonitrile(MIBI) and tetrofosmin uptake reflect the degree of viability. At the present time one of the most important clinical applications of exercise myocardial perfusion SPECT is the assessment of prognosis for patients with suspected and documented coronary artery disease. Patients with normal stress perfusion SPECT have a low event rate and excellent prognosis. Stress perfusion imagings have been widely used to stratify patients into different risk groups in the United State.

Coronary Circulation↗
PubMed2000

Molecular epidemiology of astroviruses in Japan from 1995 to 1998 by reverse transcription-polymerase chain reaction with serotype-specific primers (1 to 8).

In addition to the serotype-specific primers described previously (1 to 7), a new serotype 8-specific primer has been designed, allowing detection of all astrovirus serotypes. A total of 1,382 diarrheal stool samples in 5 regions in Japan were examined by reverse transcription-polymerase chain reaction (RT-PCR). The incidence of astrovirus infection in all 5 regions was 5.9% (82 of 1,382 samples) and infection occurred mainly from November to April. Serotypes 1, 3, and 4 were detected in 66, 14, and 2 of the 82 positive samples, respectively. None of the other serotypes was detected. The highest detection rate was from 0 to 1 year old, 39.0%, and the next highest was from 1 to 2 years old, 34.1%. The primers provide a useful approach for study of the epidemiology of astroviruses.

Astroviridae Infections↗
PubMed2000

Stable expression of human homomeric and heteromeric AMPA receptor subunits in HEK293 cells.

Human homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors (GluRs) were stably expressed in HEK293 cells with cDNAs encoding the flip splice variant of GluR1, GluR2, GluR3, GluR4 subunit, and the GluR1/GluR2, GluR3/GluR2, and GluR4/GluR2 combination. The lethal combination of GluR2 and GluR4 subunits was found in high expression levels of both receptors. The AMPA-evoked current voltage relationships demonstrated the functional channel properties, such as a double rectification in GluR1, GluR3, and GluR4 receptors, and a linear relation in receptors assembled from GluR2 alone and coexpression of GluR2 with the other subunits. All the transfectants exhibited higher selectivity for AMPA than glutamate in dose-dependent current responses. [3H]AMPA binding revealed that the homomeric and heteromeric receptors displayed a single binding site in Scatchard analysis, with dissociation constant (Kd) values in the range of 14.5-49.3 nM. The Bmax values were in the range of 0.57-7.66 pmol/mg protein. The ligand displacement potency for [3H]AMPA binding was CNQX > glutamate > NS257 in all of the transfectants. These results suggest that stable transformants expressing human homomeric and heteromeric AMPA receptors will be useful tools to define selectivity and potential site of action for AMPA receptor modulators.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Prognostic factors in childhood acute lymphoblastic leukemia in Japan. Japan Association of Childhood Leukemia Study.

A retrospective analysis of children with acute lymphoblastic leukemia (ALL) was performed to evaluate the current status of diagnosis and treatment of ALL in Japanese children. Clinical records of 670 children with ALL were collected and analyzed; these children had been diagnosed between 1991 and 1995 at the 53 institutions in 4 areas participating in the Japan Association of Childhood Leukemia Study. It was found that T-cell ALL was significantly less frequent in Tokai and Hokkaido than in Kansai and Chu-Shikoku. The overall induction rate was 92.4%. The estimated 7-year overall survival rate and event-free survival (EFS) rate were 76.0% +/- 1.9% and 61.4% +/- 2.1%, respectively. EFS rates were significantly different among the geographic areas. In female patients with B-cell precursor (B-pre) ALL and white blood cell counts at diagnosis (WBCsdiag) below 50.0 x 10(9)/L, favorable outcomes were significant. Favorable outcomes were not significant in B-pre ALL patients with a WBCdiag above 50.0 x 10(9)/L or in T-cell ALL patients. The EFS rate for infants was significantly worse than that for patients over 1 year of age. In B-pre ALL, but not in T-cell ALL, it was found that the higher the WBCdiag, the worse the EFS rate. Multivariate analysis showed that the following factors were significantly unfavorable for EFS: the Philadelphia chromosome, an translocations associated with chromosome 11q23, an acute unclassified leukemia, mixed-lineage leukemia, a WBCdiag above 100.0 x 10(9)/L, and male gender. Hyperdiploidy (> 50 chromosomes) was significantly favorable for EFS. For further tailoring of treatment and to improve the outcome in childhood ALL, a prospective large-scale study should be undertaken in Japan.

Age Factors↗
PubMed2000

[Successful weaning from mechanical ventilation in an infant with congenital tracheal stenosis and bronchial malacia using endobronchial stent, nasal CPAP and continuous sedation].

A 1.9 kg male infant who showed respiratory distress at his birth, was diagnosed by bronchoscopy as having congenital segmental stenosis of trachea with complete ring. Tracheoplasty was performed and the infant was admitted to ICU. After admission to ICU, we suspected the residual tracheal stenosis and the left main bronchial malacia by bronchoscopy. Although we tried to wean him from mechanical ventilation, but failed and re-intubated him four times because of marked respiratory acidosis after extubation. Bronchoscopy was performed repeatedly, and the residual tracheal stenosis and the left main bronchial malacia were apparent. After patch tracheoplasty of the costal cartilage to the residual tracheal stenosis and implantation of angioplastic expandable metallic stent to the left main bronchus, he was successfully extubated under continuous sedation. In addition, nasal CPAP was effective to reduce retraction and wheezing after extubation. He was discharged from ICU on the 183rd ICU day.

Bronchi↗
PubMed2000

Three-dimensional stereotactic surface projection analysis of macaque brain PET: development and initial applications.

UNLABELLED: To characterize better the local brain functions of conscious rhesus macaques, we developed automated image analysis techniques for monkey PET images, examined the cerebral glucose metabolism of monkeys, and compared it with that of humans. METHODS: Glucose metabolic PET images from 11 monkeys were obtained using a high-resolution animal PET scanner after intravenous administration of FDG. T1-weighted MR images were obtained from 6 of the monkeys. Referencing a bicommissural stereotactic macaque brain atlas, we created a PET brain template using coregistered MR images. Each individual PET image set was transformed to the PET template through an automated affine transformation, followed by nonlinear warping along the directions of the major neuronal fiber bundles in the brain. For minimization of residual anatomic variability, metabolic activities were extracted using 3-dimensional stereotactic surface projections. The effects of anatomic standardization were evaluated using MR images. Patterns of cerebral glucose metabolism of young versus aged monkeys were examined. The metabolic activities of aged monkeys were compared with those of elderly healthy human volunteers that had been analyzed similarly. RESULTS: Anatomic standardization reduced individuals' anatomic variability as evidenced by a reduction in the number of MR pixels with higher SDs calculated across monkeys. Coefficient-of-variation maps of conscious monkeys revealed that the greatest metabolic variances were near the central sulci and occipital cortices. Age-associated glucose metabolic reductions were most pronounced in the occipital lobe, caudate nucleus, and temporal lobe. Compared with human brains, the monkey frontal lobe and posterior cingulate gyrus had significantly less metabolic activity and the supramarginal gyrus and vermis had significantly more metabolic activity. CONCLUSION: The proposed method permits pixel-by-pixel characterization of the metabolic activities of rhesus macaque brains in the stereotactic coordinate system. Greater metabolic variances in the central sulcus region and occipital lobe suggest potential difficulties in controlling sensory input and motor output or planning in conscious monkey experiments. The analyses revealed age-related metabolic reductions in monkeys and marked differences in metabolic patterns between aged monkey brains and aged human brains. The proposed brain-mapping technique enables reproducible and observer-independent analyses and will serve as an important investigative tool for primate brain imaging research.

Aging↗
PubMed1999

Synthesis and biological activities of NB-506 analogues: Effects of the positions of two hydroxyl groups at the indole rings.

In the course of a study of 6-N-amino-substituted analogues of NB-506 (1), a more potent anticancer drug, J-109,404 (2), in which the formyl group of NB-506 was replaced with a 1,3-dihydroxypropane group, was reported. A study of further modification in the positions of two hydroxyl groups at the indole rings of 2 resulted in the discovery of a 2,10-dihydroxy analogue, J-107,088 (3), which is a promising anticancer agent with a broader therapeutic window than J-109,404.

Animals↗
PubMed1999

Comparison between chemoradiation protocol intended for organ preservation and conventional surgery for clinical T1-T2 esophageal carcinoma.

PURPOSE: This retrospective study was designed to compare treatment results of the chemoradiation protocol with conventional surgery for thoracic T1-T2 esophageal squamous cell carcinoma. METHODS AND MATERIALS: Sixty-six patients with esophageal carcinoma, clinically diagnosed as T1 (tumor invading lamina propria or submucosa) or T2 (tumor invading muscularis propria) were treated for 12 consecutive years, from July 1986 to January 1998. The conventional surgery group included 30 patients who underwent esophagectomy with regional lymph node dissection. Twenty-one of them received postoperative radiotherapy. Thirty-six patients were assigned to the chemoradiation protocol, consisting of neoadjuvant chemoradiotherapy (44 Gy; CDDP: 60 mg/m2, day 1, bolus; 5-FU: 400 mg/m2, day 1-4, continuous), followed by either definitive radiotherapy with high-dose-rate intraluminal brachytherapy (total 70 Gy) for responders or surgery for nonresponders as in the conventional surgery group. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. RESULTS: In the protocol group, 4 patients underwent radical surgery after neoadjuvant chemoradiotherapy, and the remaining 32 underwent definitive chemoradiotherapy. Local control rates at 1 and 3 years were 85% and 70% in the T1/protocol group versus 91% and 80% in the T1/surgery group, and 83% and 83% in the T2/protocol group versus 94% and 80% in the T2/surgery group, respectively. There was no statistical significance. Overall 1- and 3-year survival rates were 100% and 83% in the T1/protocol group versus 82% and 72% in the T1/surgery group (p = 0.36), and 100% and 51% in the T2/protocol group, versus 95% and 68% in the T2/surgery group p = 0.61), respectively. There was no treatment-related mortality in either group. The rates of esophageal conservation were 92% in the T1/protocol group and 58% in the T2/protocol group. CONCLUSION: The chemoradiation protocol can result in comparable survival with conventional surgery for patients with T1-T2 esophageal carcinoma. A randomized trial between definitive chemoradiotherapy and surgery is required.

Aged↗
PubMed1999

Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I.

J-107088 [6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carb azo le-5,7(6H)-dione] is a new derivative of NB-506, an indolocarbazole antitumor agent. J-107088 induced single-strand DNA cleavage only in the presence of topoisomerase I (top1) more effectively than NB-506 or camptothecin. The preferable sequences of the DNA cleaved by J-107088 were C/T / G as in the case of NB-506. This base-preference of J-107088 in top1-mediated cleavage was different from that of camptothecin, which was T / G/A. top1 poisons stabilize the complex between DNA and top1 (cleavable complex). This cleavable complex is released on addition of a high concentration of monovalent cation or removal of top1 poisons. The complex induced by J-107088 was quite stable; it was scarcely released on the addition of NaCl or dilution of J-107088, contrary to the case with camptothecin and NB-506. J-107088-inducing complexes were also stable in cultured cells, when the compound was added to the culture medium. These unique in vitro activities of J-107088 on top1 that differed from those of camptothecin and NB-506 may be relevant to its more potent in vivo antitumor efficacy in a human tumor xenographted nude mouse model.

Animals↗
PubMed1999

Substitution at the F-ring N-imide of the indolocarbazole antitumor drug NB-506 increases the cytotoxicity, DNA binding, and topoisomerase I inhibition activities.

The antitumor drug NB-506, which is currently undergoing phase I/II clinical trials, contains a DNA-intercalating indolocarbazole chromophore substituted with a glucose residue. In addition to interacting with DNA, the drug stabilizes the topoisomerase I-DNA covalent complex. To reinforce the DNA binding and anti-topoisomerase I activities of NB-506, an analogue containing a new substituent on the naphthalimide ring F was synthesized. The N-formylamino group of NB-506 has been replaced with a more hydrophilic group, N-bis(hydroxymethyl)methylamino. In this study we show that the incorporation of a longer substituent on the N6 position effectively reinforces both the interaction with DNA and the capacity of the drug to maintain the integrity of the topoisomerase I-DNA covalent complexes. The strength and the mode of binding of the drugs to DNA were studied by complementary biophysical techniques including absorption, fluorescence, and circular and linear dichroism. Various biochemical procedures were applied to investigate the effects on human topoisomerase I using plasmid DNA as well as restriction fragments. The drug binding sites and the positions of the topoisomerase I-mediated cleavage sites were mapped with nucleotide resolution using footprinting and sequencing techniques. Cytotoxicity measurements performed with various human cancer cell lines (HCT-116, DLD-1, MKN-45) indicate that the newly designed drug is 3 to 4 times more toxic to colon and gastric cancer cells than NB-506. Therefore, the results suggest that the antitumor activity of indolocarbazole-based drugs can be enhanced by incorporating DNA and/or topoisomerase I reactive groups. They also support the hypothesis that the substituent on the imide nitrogen on the F ring of NB-506 has direct interaction with the molecular target. The study helps to define the structure-activity relationships in the indolocarbazole series of antitumor agents targeting topoisomerase I.

Animals↗
PubMed1999

Discovery of FR166124, a novel water-soluble pyrazolo-[1,5-a]pyridine adenosine A1 receptor antagonist.

Novel 3-(2-cycloalkyl and cycloalkenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazo lo [1,5-a]-pyridines were synthesized and evaluated for their adenosine A1 receptor binding activities. In this series, FR166124 (3) was found to be the most potent and selective adenosine A1 receptor antagonist, and the double bond of the cyclohexenyl acetic acid group was essential for selectivity of A1 receptor binding. Furthermore, the solubility in water of the sodium salt of FR 166124 was high.

Antihypertensive Agents↗
PubMed1999

Transplacental administration of diethylstilbestrol (DES) causes lesions in female reproductive organs of Donryu rats, including endometrial neoplasia.

The effects of transplacental administration of diethylstilbestrol (DES) on female reproductive organs were investigated using Donryu rats. The animals were given subcutaneous injections of DES dissolved in olive oil at doses of 0.01 or 0.1 mg/kg on days 17 and 19 of gestation. In female offspring, clinical signs, body weights and estrous cycles were continuously assessed until all survivors were killed at month 18. A low mean litter size and shortening of period of pregnancy were recognized in the 0.1 mg/kg group. Disorder and/or suspension of the estrous cycle (so called persistent estrus) also appeared very early in the 0.1 mg/kg group. Macroscopically, the incidences of hypoplasia of the oviduct, cystic dilatation of the uterus and small size of the uterine cervix were higher in the 0.1 mg/kg group than those in the control group. Histologically, in the ovary, the incidence and degree of atrophy were increased in both 0.01 and 0.1 mg/kg groups. In the uterus, total incidences of endometrial hyperplasias were about the same in all groups. However, endometrial adenocarcinomas were dose-dependently increased in the treated groups, the incidence in the 0.1 mg/kg group being significant, compared to that in the control. In the vagina, mucification was more prominent in the treated animals, especially at the higher dose, but no tumors were observed. The present results indicate that prenatal exposure to DES can produce uterine adenocarcinomas in rats, as reported earlier for mice, although its carcinogenic activity is not so strong. Increase of endometrial adenocarcinoma incidence might depend on hormonal imbalance resulting from the ovarian atrophy due to transplacental treatment of DES.

Adenocarcinoma↗
PubMed1999

FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, restores the regional cerebral blood flow response abolished by scopolamine but not by HA-966: a positron emission tomography study with unanesthetized rhesus monkeys.

The interactions of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, with cholinergic and glutamatergic neuronal systems were evaluated with respect to its effects on the regional cerebral blood flow (rCBF) response to vibrotactile stimulation in unanesthetized rhesus monkeys with [15O]H2O and high resolution positron emission tomography (PET). Under a saline condition, the vibrotactile stimulation given on the right forepaw induced a significant increase in the rCBF response in the contralateral somatosensory cortex of the monkey brain. Systemic administration of scopolamine (50 microg/kg, i.v.), a muscarinic cholinergic receptor antagonist, completely abolished the rCBF response to the stimulation, and the abolishment lasted, at least, up to 4 h after scopolamine injection. The scopolamine-induced abolishment of rCBF response was restored by the administration of FK960 at relatively wide dosing range from 1 to 1000 microg/kg (i.v. ), and the recovery by FK960 on the rCBF response lasted for 1 h following the administration of FK960 at doses of 100 and 1000 microg/kg. On the other hand, the rCBF response abolished by 1000 microg/kg of (+)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), an antagonist of the glycine modulatory site on the N-methyl-d-aspartate (NMDA) receptors, was not restored by FK960 (1000 microg/kg, i.v.). These findings suggest that FK960 reverses the abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission but not via the glutamatergic one.

Animals↗