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Biomedical subjects

S Yoneda

Publications and source records attributed to S Yoneda.

At least 37 records · Page 2Linked to original sources
PubMed2001

A study of the combination of gemcitabine hydrochloride (LY188011) and cisplatin in non-small-cell lung cancer: 3-week schedule.

BACKGROUND: It has been reported that the combination of gemcitabine (LY188011; GEM) and cisplatin (CDDP) in a 4-week schedule showed a high response rate for patients with non-small-cell lung cancer (NSCLC), but GEM could not be administered on day 15 because of increased myelosuppression in many patients. The present study was performed to evaluate the efficacy and safety of GEM and CDDP in a 3-week schedule. METHODS: Patients with unresectable NSCLC without prior chemotherapy were enrolled. We administered 1000 mg/m2 of GEM on days 1 and 8, and 80 mg/m2 of CDDP on day 1. The feasibility of the combination therapy was confirmed in 8 patients, and then 20 more patients were enrolled, to evaluate the efficacy and safety of this combination therapy for all 28 patients. RESULTS: The response rate was 42.9% (12/28) and the median survival time was 12.6 months. Neutropenia, leukopenia, anemia, thrombocytopenia or lymphocytopenia of grade 3 or higher were observed as hematological toxicity, and anorexia, nausea, fatigue, or vomiting of grade 3 were the nonhematological toxicities, but most of these toxicities were of grade 2 or less. For GEM and CDDP, 89% and 91% of the scheduled doses, respectively, were administered. CONCLUSION: This is the first study of the combination of GEM and CDDP with a 3-week schedule in Japan, and the results showed a low level of myelosuppression, high dose intensity, and high response rate, similar to the results reported in other countries. Accordingly, the combination of GEM and CDDP with a 3-week schedule may be a promising regimen for the treatment of NSCLC in Japan.

Adult↗
PubMed2001

Glutathione S-transferase mu1 null genotype is associated with K-ras gene mutation in lung adenocarcinoma among smokers.

Glutathione S-transferase mu1 (GSTM1) plays a role in the detoxification of benzo[a]pyrene (BP) diol epoxide in tobacco smoke. Individuals who genetically lack the GSTM1 gene are likely to have an increased risk of smoking-related lung cancers, however, the target oncogenes for mutation are unknown. To investigate the relation between GSTM1 genotype and K-ras gene mutation we examined 193 adenocarcinomas and 119 squamous cell carcinomas of lung. The GSTM1 genotype was determined by PCR and K-ras gene mutations at codons 12 and 13 were detected by dot-blot hybridization analysis using sequence-specific oligonucleotide probes. K-ras gene mutations were found in 29 of 312 (9.3%) tumors. All of them arose in patients who were habitual smokers. Mutations of the K-ras gene were detected in 6 of 100 (6%) and 15 of 93 (16.1%) adenocarcinoma cases with the GSTM1(+) and GSTM1(-) genotypes, respectively, and the difference was statistically significant. These findings suggest that the cause of K-ras gene mutation in smokers with lung adenocarcinoma may be in part an accumulation of BP diol epoxide which is not well detoxified in individuals with the GSTM1 null genotype.

Adenocarcinoma↗
PubMed2001

Evaluation of the tocolytic effect of a selective cyclooxygenase-2 inhibitor in a mouse model of lipopolysaccharide-induced preterm delivery.

The inflammatory process is known to cause preterm delivery. Recently, a cyclooxygenase (COX)-2 inhibitor has been developed as an anti-inflammatory drug with few side-effects. We evaluated the COX-2 inhibitor, Celecoxib, for its tocolytic effects and side-effects on dams and pups using a lipopolysaccharide (LPS)-induced preterm delivery mouse model (preterm delivery rates; 95%). With administration of Celecoxib (50, 10, 1 and 0.3 mg/kg), the preterm labour rate was significantly reduced to 18, 30, 36 and 60% respectively. The prostaglandin F(2alpha)(PGF(2alpha)) and PGE(2) concentrations in murine uterine tissue 4 and 10 h after LPS treatment with Celecoxib (10 and 1 mg/kg) were significantly lower than those in the LPS-treated group without CELECOXIB: With administration of 10 or 100 mg/kg Celecoxib, the fetal ductus arteriosus was constricted significantly in preterm and near-term rats, although constriction rates in preterm rats were significantly lower than those in near-term rats. Reproductive and renal functions in offspring whose mothers were treated with LPS and Celecoxib were normal. These data demonstrate that Celecoxib could be used as a new therapy for preterm labour. However, careful attention to constriction of the fetal ductus arteriosus should be given.

Animals↗
PubMed2001

Inhibitory actions of indomethacin on electrical and mechanical responses produced by nerve stimulation in circular smooth muscle of the guinea-pig gastric fundus.

The effects of indomethacin on electrical and mechanical responses produced by transmural nerve stimulation (TNS) were investigated in isolated circular smooth muscle of the guinea-pig gastric fundus. TNS evoked a cholinergic excitatory junction potential (e.j.p.). The e.j.p.s were inhibited by 1-10 microM indomethacin, in a concentration-dependent manner, with no marked alteration of the resting membrane potential. Exogenously applied acetylcholine caused a depolarization of the membrane that was not altered by indomethacin. TNS evoked a cholinergic twitch contraction at low frequencies (0.1 Hz). A train of TNS's at high frequency (1 Hz) produced a transient contraction with a subsequent sustained relaxation. Indomethacin reduced the resting tension and inhibited these TNS-induced contractions. Application of Nomega-nitro-L-arginine (NOLA), an inhibitor of nitric oxide (NO) synthesis, increased the amplitude of twitch contractions, and altered transient contractions to tetanic contractions during TNS at a frequency of 1 Hz, also with an increased amplitude. In the presence of NOLA, indomethacin (5 microM) again reduced the resting tension and inhibited TNS-induced contractions. This inhibition was greater for twitch contractions than for tetanic contractions. Nifedipine reduced the TNS-induced contractions, while addition of indomethacin further reduced the amplitude of contractions. Contractions produced by low concentrations of acetylcholine (0.1 microM) were inhibited by indomethacin, while those produced by 1 microM were not. These results indicate that the inhibitory actions of indomethacin on TNS-induced contractions do not involve enhanced production of NO or selective inhibition of voltage-gated Ca-channels. Prejunctional autoregulatory mechanisms may also not be altered by indomethacin. As indomethacin inhibits the enzyme cyclooxygenase, it is speculated that endogenously produced prostaglandins exert excitatory actions on gastric smooth muscle, and act mainly postjunctionally to facilitate spontaneous and neurogenic electrical and mechanical activity.

Acetylcholine↗
PubMed2001

Nitric oxide inhibits smooth muscle responses evoked by cholinergic nerve stimulation in the guinea pig gastric fundus.

In circular smooth muscle tissues of the guinea pig gastric fundus, transmural nerve stimulation (TNS) evoked an atropine-sensitive cholinergic excitatory junction potential (e.j.p.) and, after inhibiting the e.j.p. with atropine, an apamin-sensitive nonadrenergic noncholinergic (NANC) inhibitory junction potential (i.j.p.). The amplitude of e.j.p.s was similar when the frequency of TNS was low (<0.5 Hz), but it decreased successively (depression phenomenon) when the frequency was high (>1 Hz). The depression phenomenon was attenuated after inhibiting the production of nitric oxide (NO) with N(omega)-nitro-L-arginine (NOLA), but was not altered by inhibiting the i.j.p. with apamin. The e.j.p.s were increased in amplitude by the inhibition of cholinesterase activity, but they were decreased by NO produced from SNP with no alteration of their depression phenomenon. Isometric twitch contractions were depressed during high-frequency TNS. NOLA caused an increase in the amplitude of twitch contractions and the attenuation of their depression that changed the transient contraction produced by high-frequency TNS (1 Hz) to a tetanic one. SNP reduced the amplitude of twitch contractions, with no alteration of the depression phenomena. Contractions produced by low concentrations of acetylcholine, but not by high concentrations, were attenuated by SNP, with no alteration of the membrane depolarization. The results suggest that NO produced during TNS has inhibitory actions on cholinergic transmission; the depression of e.j.p.s is mainly prejunctional events, and the depression of mechanical responses is mainly postjunctional events.

Acetylcholine↗
PubMed2001

Rhythmic spontaneous contractions in the rat proximal colon.

C-kit immunoreactive cells are known to be interstitial cells of Cajal (ICCs), and they generate pacemaker activity of the gastrointestinal tract. Recently a large number of special smooth muscle cells corresponding to c-kit immunoreactive cells were found in the proximal colon of the guinea pig. We learned that the rat proximal colon showed tetrodotoxin-insensitive regular rhythmic spontaneous contractions (RSCs) and hypothesized that RSCs are generated and/or regulated by ICCs. To prove our hypothesis, we investigated whether RSCs are absent in homozygous Ws/Ws mutant rats, since c-kit positive ICCs along the submucosal surface of the circular muscle (ICC(SM)) and myenteric plexus (ICC(MY)) are lacking. In contrast to our hypothesis, we found that RSCs were still present in the proximal colon of the Ws/Ws mutant rats. A recent study has reported that c-kit negative ICC(SM) remains in Ws/Ws mutant rats. Taken together, RSCs may be generated by c-kit negative ICC(SM) in the rat proximal colon. The blockade of sarcoplasmic reticulum Ca(2+)-ATPase by cyclopiazonic acid (CPA) (10(-6)M) or by thapsigargin (10(-6)M) increased the frequency of RSCs. The increasing effects of CPA on the frequency of RSCs were more prominent in Ws/Ws mutant rats than in +/+ rats. We concluded that the functional coordination between c-kit negative ICC(SM) and other mutationally impaired c-kit positive ICC(MY) and ICC(SM) may be required for moderate regulation in the frequency of spontaneous activity.

Animals↗
PubMed2001

[Result of surgical treatment to early stage peripheral non-small cell lung cancer].

In the lung cancer, the announcement of the definition, the clinical behavior and the treatment result of the central early stage lung cancer, especially in situ lung cancer, have been seen. However, the definition and a clinicopathological concept of the peripheral lung cancer are still uncertain. The so-called small lung cancer of the tumor diameter 20 mm or less are peripheral lung adenocarcinoma. These patients' prognosis is excellent better, in contradiction to the prognosis of the patients with positive for pleural involvement or vessels invasion is worse. We studied the clinicopathological features, the Noguchi's classification, and prognosis of the 101 patients with small lung adenocarcinoma which were performed the operation, and refere about the selection of the operation method including the VATS and the limited operation.

Adult↗
PubMed2000

Nociceptin inhibits capsaicin-sensitive contraction to mesenteric nerve stimulation in the guinea-pig isolated ileum.

Mesenteric nerve stimulation (MNS) in the presence of guanethidine and hexamethonium antidromically stimulated extrinsic sensory nerve fibers and cholinergic myenteric motor neurons, resulting in longitudinal muscle contraction in the isolated guinea-pig ileum. Nociceptin (NC) is a recently discovered neuropeptide that structurally resembles an opioid peptide. The aim of the current study was to examine how NC affects the contractile responses to MNS in the isolated guinea-pig ileum, in comparison with an opiate, methionine-enkephalin. These contractions were auxotonically recorded and their amplitude was analyzed. NC (1-100 nM) and methionine-enkephalin (0.1-10 microM) concentration-dependently inhibited the response to MNS (20 Hz, 0.5 ms, supramaximal currents). Naloxone (10 microM) significantly diminished the inhibitory effect of methionine-enkephalin (0.1-10 microM), but did not antagonize the inhibitory effect of NC (1-100 nM). We conclude that NC receptors, distinct from opioid receptors, exist on the capsaicin-sensitive sensory nerve fibers and/or myenteric cholinergic motor neurons in the guinea-pig ileum and that specific antagonists for these NC receptors are not found yet.

Animals↗
PubMed2000

UFT plus cisplatin combination chemotherapy in the treatment of patients with advanced nonsmall cell lung carcinoma: a multiinstitutional phase II trial. For the Japan UFT Lung Cancer Study Group.

BACKGROUND: Combination chemotherapy comprised of oral UFT (a combination of tegafur and uracil) and cisplatin was shown to be an effective regimen for the treatment of advanced nonsmall cell lung carcinoma and to be associated with a low incidence rate of toxicity in a previous, single institution, Phase II trial on a small patient sample. Therefore, the current multiinstitutional Phase II trial was conducted to confirm the earlier results. METHODS: Eligible patients had histologically or cytologically confirmed Stage IIIB or IV nonsmall cell lung carcinoma and good performance status. Patients who had received prior treatment were excluded. All had measurable disease. UFT (400 mg/m(2)) was administered orally on Days 1-14, and cisplatin (80 mg/m(2)) was injected intravenously on Day 8. Treatment was repeated every 3-4 weeks. RESULTS: Approximately 70% of the 108 eligible patients had systemic metastatic disease. All 108 patients were assessable for toxicity and survival, and 103 were assessable for response. Among these 103 patients there was 1 complete response and 29 partial responses, for an overall response rate of 29.1% (95% confidence limits [CL], 20.4-37.9%). The median survival time was 40 weeks and the 1-year survival rate was 39% (95% CL, 30-49%). The median progression free survival time was 28 weeks. Eastern Cooperative Oncology Group Grade 3 leukopenia and thrombocytopenia were observed in only 1 patient (0.9%) and 3 patients (2.8%), respectively. Grade 3/4 nonhematologic toxicities included elevated bilirubin (6.5%) and emesis (7.4%). One patient who had a past history of duodenal ulcer died of ulcer perforation 15 days after completing the first treatment cycle. CONCLUSIONS: Oral UFT plus cisplatin is a moderately active regimen with an extremely low rate of incidence of myelosuppression as an adverse event, and warrants comparison with other cisplatin-based regimens in a prospective randomized trial.

Administration, Oral↗
PubMed2000

Lymph node metastasis and prognosis in small peripheral non-small-cell lung cancers.

OBJECTIVE: The lymph node dissection and curative resection for small peripheral non-small-cell lung cancers, it is essential to know the incidence and distribution of lymph node metastasis to confirm the pathological stage. METHODS: Between January 1984 and August 1996, lobectomy with systemic mediastinal dissection (standard lobectomy) was conducted in 49 patients with small peripheral non-small-cell lung cancers (2.0 cm or less in diameter), and limited resection was conducted in 15 with cardiopulmonary insufficiency. RESULTS: Lymph node metastasis was confirmed histologically in 14 patients undergoing standard lobectomy (28.6%). The incidence of lymph node metastasis was high in tumors with pleural (p2) or subpleural (p1) involvement (63.6%) (7/14). The 5-year survival between standard lobectomy and limited resection patients (83% vs. 71%) was not statistically significant. In patients undergoing standard lobectomy, survival in those with node-negative disease was better than in those with node-positive disease (94% vs. 44%, p < 0.01). CONCLUSIONS: Lymph node involvement, especially in tumors with pleural involvement, is not uncommon, even when tumors are 2.0 cm or less in diameter. Systemic hilar and mediastinal dissection is therefore required for disease staging and treatment.

Aged↗
PubMed2000

Evaluation of the malignant grade of thymic epithelial tumors according to the epithelial subclassification.

We investigated the clinicopathological correlations among 49 surgically resected thymic epithelial tumors (TET), which were subclassified according to the six subtypes established by the Marino, Kirchner, and Müller-Hermelink system, which were renamed as follows: spindle cell type (medullary thymoma), mixed spindle and polygonal cell type (mixed medullary and cortical thymoma), small polygonal cell type (predominantly cortical thymoma), large polygonal cell type (cortical thymoma), atypical type (well differentiated thymic carcinoma), and cytologically malignant type (high-grade thymic carcinoma). The related categories were grouped for statistical analysis as follows: group 1, spindle cell type and mixed type; group 2, small polygonal cell type and large polygonal cell type; group 3, atypical type; group 4, cytologically malignant type. The association of each group with the presence of myasthenia gravis, tumor stage, and the length of survival was studied. Myasthenia gravis was significantly present in patients with small polygonal type, large polygonal type, and atypical type tumors (groups 2 and 3) (P = 0.003). The tumors in group 1 showed the lowest tumor stage while those of group 4 had the most advanced tumor stage (P = 0.002). The patients in group 4 had the worst prognosis, followed by those in group 3, 2, and 1, in that order. The differences among these groups were statistically significant (P = 0.0003). From our results, we determined that TET can be separated into an extremely low-grade malignancy group (group 1), a low-grade malignancy group (group 2), an intermediate malignancy group (group 3), and a high-grade malignancy group (group 4).

Epithelial Cells↗
PubMed2000

Isolation of proteoglycan (versican) aggregate from rat dental pulp.

Versican is a large interstitial proteoglycan that is believed to be able to bind hyaluronan to form large aggregate structures, but no study has isolated native versican aggregates from any tissue. In this study, ternary aggregate structures consisting of versican, hyaluronan, and link protein were isolated from rat dental pulp by associative extractions followed by caesium sulphate rate zonal sedimentation centrifugation. Fractions from the centrifugation were analysed by dot blot and Western blot using monoclonal antibodies and hyaluronan-binding protein. About 60% of the hexuronic acid was extracted by associative extractions. Positive reactions for versican, hyaluronan and link protein were clearly detected in the bottom fractions from the centrifugation, but were barely detectable in the top fractions. These results suggest that the majority of the versican, hyaluronan, and link protein forms ternary aggregate structures in the rat dental pulp.

Animals↗
PubMed2000

New method for evaluating intestinal contractions in guinea pig by curve fitting.

Using a "hybrid logistic function," we attempted to develop a new approach for a quantitative and comprehensive evaluation of the force-time curve of guinea pig gut contractions. We recorded ileum twitch and proximal colon spontaneous isometric longitudinal contractions because of their high regularities. We digitized the force-time curves of both contractions and performed curve fitting to them by hybrid logistic functions with a personal computer. We found that the fitness of these functions to both contractions was excellent. The respective best-fit parameters of these functions were closely correlated with the observed mechanical indexes, all of which are physiologically meaningful. This result suggests the possibility that these parameters can characterize the magnitudes and time courses of F(t) curves of the intestinal contractions. Furthermore, it might be able to show an effect of a pharmacological agent specifically either on the contraction phase, the relaxation phase, or other parameters of each. Therefore, we insisted that the present new approach for evaluating gut motility is promising for clinical application.

Animals↗
PubMed2000

Intermediate state during the crystal transition in aspartame, studied with thermal analysis, solid-state NMR, and molecular dynamics simulation.

Aspartame (L-alpha-aspartyl-L-phenylalanine methyl ester) is a dipeptide sweetener about 200 times as sweet as sugar. It exists in crystal forms such as IA, IB, IIA, and IIB, which differ in crystal structure and in the degree of hydration. Among these, IIA is the most stable crystal form, and its crystal structure has been well determined (Hatada et al., J. Am. Chem. Soc., 107, 4279-4282 (1985)). To elucidate the structural factors of thermal stability in the IIA form of aspartame and to examine the physical process in the crystal transformation between the IIA and IIB forms, we performed a thermal analysis and solid-state NMR measurements. We found that a quasi-stable intermediate state exists in the transformation, and it has the same crystal lattice as the usual IIA form, despite the dehydration from 1/2 mol to 1/3 mol per 1 mol of aspartame. The results of the energy component analysis and the molecular dynamics simulation suggest that the entropic effect promotes the generation of the intermediate state, which is presumably caused by the evaporation of the water of crystallization and the increase of molecular motion in aspartame. Thus, the thermal stability of the IIA form is attributable to a structural property, i.e., the crystal lattice itself is retained during the above dehydration. Moreover, the molecular dynamics simulations suggest that the aspartame molecules have two kinds of conformational flexibility in the intermediate state.

Aspartame↗
PubMed2000

[Clinical evaluation of VATS lobectomy for lung cancer].

Thoracoscopic lobectomy is now recognized as a possible less invasive surgical option for stage I primary non-small cell lung cancer. We have widely used thoracoscopic procedure for surgical diagnosis of lung nodules especially in lung peripheral region as well as resection of primary lung cancer. Results of 47 thoracoscopic lobectomy during last 5 years were compared with 24 standard lobectomy under postero-lateral thoracotomy. There were no significant differences in the duration of surgery, post-operative hospital stay, intraoperative blood loss and post-operative survival. All but three patients who were diagnosed as n 2 disease or tumor with extrapulmonary extension post-operatively are surviving at the time of survey. We conclude that thoracoscopic lobectomy is safe and less invasive procedure compared to standard thoracotomy. We believe it can provide sufficient outcome for stage I non-small cell lung cancer.

Aged↗