Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 37 records · Page 2Linked to original sources

PubMed2000

Syntheses of 4'-C-ethynyl-beta-D-arabino- and 4'-C-ethynyl-2'-deoxy-beta-D-ribo-pentofuranosylpyrimidines and -purines and evaluation of their anti-HIV activity.

4'-C-Ethynyl-beta-D-arabino- and 4'-C-ethynyl-2'-deoxy-beta-D-ribo-pentofuranosylpyrimidine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabinopyrimidine derivatives were prepared from the corresponding ribo derivatives via O(2),2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC(50) values ranging from 0.0003 to 0. 03 microM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC(50) values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2, 6-diamino-2'-deoxypurine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2'-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.

Anti-HIV Agents↗

PubMed2000

Reduced ventricular response irregularity is associated with increased mortality in patients with chronic atrial fibrillation.

BACKGROUND-Variations in the ventricular response interval (VRI) during atrial fibrillation (AF) may be reduced in patients with adverse clinical outcomes. The properties of VRI dynamics associated with prognosis remain undetermined. METHODS AND RESULTS-In 107 patients with chronic AF (age, 64+/-9 years), we analyzed a 24-hour ambulatory ECG for VRI variability (SD, SD of successive differences, and SD of 5-minute averages) and VRI irregularity (Shannon entropy of histogram, symbolic dynamics, and approximate entropy of beat-to-beat and minute-to-minute fluctuations [ApEn(b-b) and ApEn(m-m)]). During a follow-up period of 33+/-16 months, 18 patients died (17%), 9 from cardiac causes, 7 from fatal strokes, and 2 from malignancies. Reductions in all VRI variability and irregularity measures were associated with an increased risk for cardiac death but not for fatal stroke. A significant association with cardiac death was also found for ejection fraction (relative risk, 1.10; 95% confidence interval [CI], 1.04 to 1.17, per 1% decrement) and ischemic AF (relative risk, 6.52; 95% CI, 1.62 to 26. 3). After adjustment for these clinical variables, all irregularity measures except symbolic dynamics had predictive value (relative risks [95% CIs] per 1SD decrement: Shannon entropy of histogram, 2. 03 [1.14 to 3.61]; ApEn(b-b), 1.72 [1.14 to 2.60]; and ApEn(m-m), 1. 90 [1.03 to 3.52]); however, the predictive power of variability measures was no longer significant. When the patients were stratified with the 33rd and 67th percentile values of ApEn(b-b) (1. 83 and 1.94, respectively), the 5-year cardiac mortality rates for the upper, middle, and lower tertiles were 0%, 13%, and 43%, respectively (log-rank test, P=0.04). CONCLUSIONS-Reduced VRI irregularity in a 24-hour ambulatory ECG has an independent prognostic value for cardiac mortality during long-term follow-up in patients with chronic AF.

Adult↗

PubMed2000

Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors.

Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-100-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography studies suggest that the 2-substituent may have a conformational effect favoring the extended binding conformation.

Anticoagulants↗

PubMed2000

The clinicopathological significance of preoperative serum-soluble interleukin-2 receptor concentrations in operable non-small-cell lung cancer patients.

BACKGROUND: Serum-soluble interleukin-2 receptor (IL-2R) concentrations have been found to be elevated in cancer patients. However, the importance of this finding in patients with non-small-cell lung cancer (NSCLC) has not been previously established. METHODS: Preoperative serum-soluble IL-2R concentrations were determined in 65 consecutive patients with operable NSCLC. The correlation of preoperative serum-soluble IL-2R concentrations with various clinicopathological features of this cancer was evaluated to clarify the clinical significance of this parameter. RESULTS: Although serum-soluble IL-2R concentrations were not significantly higher in operable NSCLC patients than in normal controls (P = .1180), serum-soluble IL-2R concentrations were significantly higher in patients with stage IIIB or IV disease than in normal controls (P = .0001). The presence of intrapulmonary metastasis was the only clinicopathological feature that was significantly correlated to serum-soluble IL-2R concentration (P = .0004). The sensitivity of serum-soluble IL-2R concentration in identifying the presence of intrapulmonary metastasis was 87.5%; specificity was 75%. CONCLUSIONS: Elevated preoperative serum-soluble IL-2R concentrations in patients with operable NSCLC reflect the occurrence of intrapulmonary metastasis. Preoperative examination of serum-soluble IL-2R concentrations may be valuable in the detection of the intrapulmonary metastasis preoperatively.

Aged↗

PubMed2000

Assessment of the geometry of human finger phalanges using quantitative ultrasound in vivo.

Quantitative Ultrasound (QUS) methods have been shown to be useful in the assessment of bone status. Nevertheless, ultrasound transmission depends on a variety of skeletal parameters, and a detailed understanding of ultrasound propagation through bone is important for the accurate interpretation of QUS results. In this study we wanted to elucidate the pathways of an ultrasound wave through finger phalanges and determine correlations between geometric and QUS parameters. Phalanges of a subject group were measured using QUS and magnetic resonance imaging (MRI). MRI was used for the derivation of the geometric parameters. Similar assessments were performed on cylindrical tubes and with a simulation program. New parameters related to speed of sound (SOS) and amplitude of the wave (A2P) were calculated. Strong correlations between QUS parameters and morphologic cross-sectional areas were observed in vivo and in phantoms. Similar correlations could be found in the calculations using the simulation software. Cross-sectional cortical area, medullary canal area and relative cortical area could be calculated from the QUS parameters (subjects: R2 = 0.71 for cortical area, R2 = 0.45 for medullary canal area and R2 = 0.61 for relative cortical area; phantoms: R2 = 0.98 for cortical area, R2 = 0.78 for medullary canal area and R2 = 0.77 for relative cortical area). In vivo, phantom and simulation results consistently showed that SOS was correlated with cortical area but not with medullary canal area while the opposite was found for A2P. Pathways of the ultrasound wave through solid cortical bone and the medullary canal could be identified and the propagation of the wave could be depicted. These results help to interpret QUS findings and provide information that may be helpful in improving the performance of QUS.

Adult↗

PubMed2000

Thoracoscopic treatment of primary chylopericardium.

The development of video-assisted thoracoscopy has changed the practice of thoracic surgery. This report describes a 20-year-old man who successfully underwent thoracoscopic thoracic duct ligation and partial pericardiectomy for primary chylopericardium. We recommend a right-sided thoracoscopic approach to the thoracic duct in the lower thoracic cavity.

Adult↗

PubMed2000

Event-related potentials elicited by wrong terminal notes: effects of temporal disruption.

Wrong terminal notes of familiar musical phrases are known to elicit a large positive deflection of the event-related potential (ERP). The present study examined whether the effect of wrong terminal notes on ERP was modulated by the timing of their occurrence. Sixteen non-musicians were asked to rate the congruity of the endings of 50 well-known musical phrases. Four different types of endings were made for each phrase by manipulating the timing (well-timed vs. delayed for 750 ms) and pitch (correct vs. wrong) of the last note orthogonally. These ending patterns were presented equiprobably in an unpredictable order. Wrong notes elicited large late positive waves irrespective of the timing of occurrence. When the notes were delayed, however, the positive waves were reduced in amplitude to about 50% of those elicited by well-timed notes. These results suggest that the temporal (rhythmic) structure of musical phrases strongly influences the processing of melodic information.

Adult↗

PubMed2000

Synthesis and biological activities of 2'-deoxy-2'-fluoro-4'-thioarabinofuranosylpyrimidine and -purine nucleosides.

As part of our ongoing investigation of the synthesis of biologically interesting 2'-modified-4'-thionucleosides, we synthesized 2'-deoxy-2'-fluoro-4'-thioarabinofuranosylpyrimidine and -purine nucleosides, and evaluated their antiviral and antitumor activities. In the pyrimidine series, beta-anomers of 5-ethyluracil, 5-iodouracil, 5-chloroethyluracil, and 5-iodocytosine derivatives showed potent and selective anti-HSV-1 and HSV-2 activities in vitro. In the purine series, guanine and 2,6-diaminopurine derivatives showed prominent antiviral activities with slight cytotoxicity. On the other hand, the 5-fluorocytosine derivative (5F-4'-thioFAC) showed potent antitumor activity against both leukemia and solid tumor. Its antitumor spectrum against 14 human solid tumor and one leukemic cell lines was compared with that of 4'-thioFAC. The results showed that 5F-4'-thioFAC had an antitumor spectrum similar to that of 4'-thioFAC. However, 5F-4'-thioFAC was about 10 times less active than 4'-thioFAC.

Antineoplastic Agents↗

PubMed2000

Comparison of two automatic staplers for closing the bronchial stump after pulmonary resection.

The incidence of complications following pulmonary resection using an automatic stapler was studied in 348 consecutive patients. A parallel-jaw stapler with two staple lines was used in group A (133 males, 101 females, mean age 66 years) between 1990 and 1995, and a hinged-jaw stapler with three staple lines in group B (70 males, 44 females, mean age 67 years) in 1995-1997. The incidence of bronchopleural fistula was 0.4% (1 patient) in group A and nil in group B. The incidence of intraoperative air leak requiring interrupted suture closure was 4.7% (11 patients) in group A and nil in group B (p < 0.05). Postoperative bronchopleural fistula did not develop in any of the cases, and there was no mortality. For management of the bronchial stump after pulmonary resection, the newer device firing three rows of staples is superior to the two-row device.

Adult↗

PubMed2000

Synthesis of 4'-ethynyl-purine nucleosides possessing anti-HIV activity.

Searching for more effective anti-HIV agents, we have prepared 4'-ethynyl-purine nucleosides. They were derived in several steps from 4-C-triethylsilylethynyl ribose, which was used as an intermediate in the synthesis of pyrimidine nucleosides. The adenine derivative exhibited significant anti-HIV activity and favorable cytotoxicity profile in vitro.

Anti-HIV Agents↗

PubMed2000

Increase in O(2) delivery with hyperoxia does not increase O(2) uptake in tetanically contracting dog muscle.

We investigated the influence of hyperoxia on O(2) uptake in tetanically contracting canine gastrocnemius. Hyperoxia showed neither increase in O(2) uptake nor decrease in lactate release, irrespective of increased O(2) supply, venous Po(2) and vascular resistance, as compared to normoxia, suggesting that hyperoxia decreases O(2) diffusion conductance and/or effective O(2) supply probably due to arteriovenous O(2) diffusion shunt.

Anaerobic Threshold↗

PubMed2000

Correlation between erythropoietin and lactate in humans during altitude exposure.

The plasma concentrations of both immunoreactive erythropoietin (EPO) and lactate were determined in four healthy untrained subjects at sea level and on the 2nd or 3rd day at altitudes (1,300 and 3,500 m). The mean plasma EPO (18.8 +/- 1.6 mU/ml at sea level) increased significantly on the 3rd day at 1,300 m (25.5 +/- 2.0 mU/ml, p < 0. 05) and showed an almost three-fold increase on the 2nd day at 3,500 m (53.5 +/- 3.7 mU/ml, p < 0.001). Likewise, the mean plasma lactate at 3,500 m (3.98 +/- 0.27 mmol/l) was 3.6 times as high as that at sea level (1.11 +/- 0.05 mmol/l) (p < 0.001). The plasma EPO concentrations were found to correlate well with the lactate concentrations at sea level and altitudes (r = 0.86, p < 0.01). These results are consistent with the well-known EPO/lactate response to altitudes and suggest that the circulating EPO concentration as well as blood lactate concentration can be used as an index of anaerobic condition.

Adult↗

PubMed2000

Postoperative oxygenation following coronary artery bypass grafting. A multivariate analysis of perioperative factors.

BACKGROUND: Pulmonary oxygenation is generally temporarily impaired following cardiac surgery. We studied the factors influencing postoperative oxygenation using multivariate analysis. METHODS: This study was retrospectively performed in University hospital. Fifty patients undergoing solitary coronary artery bypass grafting were included in this study. Patients were divided into two groups by mean age; older group (n=25) and younger group (n=25). Alveolar-arterial oxygen difference (A-aDO2) and respiratory index (RI) were measured at 3 hours after surgery and on postoperative day 1. Statistical analysis was performed using forward selection stepwise regression of 12 perioperative variables. RESULTS: In all patients, A-aDO2 and RI significantly (p<0.01) increased after surgery and remained high on POD1. In stepwise regression analysis, preoperative A-aDO2 and RI were significant factors in the equations for postoperative A-aDO2 and RI in general, which was the most important factor in the older group. In the older group, preoperative A-aDO2 or RI and water balance were significant (p<0.05) factors which were responsible for half the oxygenation impairment just after surgery, and PCWP showed a significant (p<0.01) negative correlation with both A-aDO2 and RI on POD1. In the younger group, PCWP was a significant (p<0.01) factor for A-aDO2 and CVP and CI were significant for RI on POD1. CONCLUSIONS: Postoperative oxygenation was mainly influenced by the preoperative respiratory condition, especially in old patients, indicating that preoperative management by a physiotherapist may be necessary. Pleurotomy also had a negative influence. Careful intraoperative and postoperative volume control is important in old patients.

Adult↗

PubMed2000

[Surgical treatment of bronchial carcinoid: report of seven cases].

Seven patients with pulmonary carcinoid including three with typical carcinoid and four with atypical carcinoid were reported. There were 3 males and 4 females, with an age range of 37 to 80 years. All patients with typical carcinoid had pathological stage I. Of the patients with atypical carcinoid, one patient had stage I, two stage IIIA and one stage IIIB. All but two patients underwent lobectomy and mediastinal lymph node dissection. Bronchoplastic operation or right pneumonectomy were performed in the two patients. All but one patient underwent absolute or relative curative operation. Only one patient died on the 4th postoperative day. One patient with atypical carcinoid died of cancer recurrence 4 years after surgery. One patient died of breast cancer. One patient underwent surgery for metachronous multiple lung cancer, and he is doing well without recurrence. In conclusion, a limited operation is thought to be acceptable only in patients with typical carcinoid in a peripheral lesion without lymph node metastasis. Lobectomy and mediastinal lymph node dissection is necessary for the atypical carcinoid case.

Adult↗

PubMed2000

[Evaluation of TNM classification for lung carcinoma with satellite nodules in the same lobe as the primary].

We conducted a validation of the treatment of satellite nodules in the UICC TNM classification of 1997. Over the past 17 years (1981 to 1997), 29 patients underwent complete pulmonary resection for primary lung cancer accompanied by satellite nodules in the same lobe as the primary. All these patients were categorized as stage IIIB according to the current staging system. The five-year survival rate of all patients was 40% and the figure was unduly better for stage IIIB patients. The three-year survival rate of 20 patients having lymphatic involvement were 18%, but those of 9 patients without it was 89%. Outcome was significantly influenced on their presence or absence of lymph node metastases. The current staging system for patients with satellite lesions in the same lobe appears to be unacceptable because they provide the different influences on prognosis and selecting treatment modality according to the N status.

Adult↗

PubMed2000

Management of ipsilateral intrapulmonary metastases in the new TNM system for non-small cell lung cancer.

BACKGROUND: Recently, the Union Internationale Contre le Cancer and American Joint Committee on Cancer reclassified not only TNM staging but also ipsilateral intrapulmonary metastases (PM) as T4 in a same lobe or M1 in different lobes. To determine whether the new PM staging is appropriate, we studied the prognosis of PM. METHODS: From January 1981 to October 1997, we performed a lobectomy or pneumonectomy with mediastinal lymph node dissection, and had 42 patients with PM. We analyzed the postoperative prognosis of the patients with ipsilateral PM compared with the same stage group without PM (the non-PM). RESULTS: In the previous classification of PM (the old PM), 2 patients were categorized as stage IIA, 9 as IIB, 17 as IIIA, and 14 as IIIB. After reclassification (the new PM), 37 patients were categorized as stage IIIB, and 5 as IV. The old PM stage IIIA group had a significantly poor prognosis compared with the non-PM stage IIIA. However, the prognosis of the new PM group was compatible with that of the non-PM. None of the other staging group had a significant difference in the prognosis. CONCLUSIONS: The management of PM in the new TNM system for non-small cell lung cancer is appropriate.

Adenocarcinoma↗

PubMed1999

Vinexin: a novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization.

Using the yeast two-hybrid system and an in vitro binding assay, we have identified a novel protein termed vinexin as a vinculin-binding protein. By Northern blotting, we identified two types of vinexin mRNA that were 3 and 2 kb in length. Screening for full-length cDNA clones and sequencing indicated that the two mRNA encode 82- and 37-kD polypeptides termed vinexin alpha and beta, respectively. Both forms of vinexin share a common carboxyl-terminal sequence containing three SH3 domains. The larger vinexin alpha contains an additional amino-terminal sequence. The interaction between vinexin and vinculin was mediated by two SH3 domains of vinexin and the proline-rich region of vinculin. When expressed, vinexin alpha and beta localized to focal adhesions in NIH 3T3 fibroblasts, and to cell-cell junctions in epithelial LLC-PK1 cells. Furthermore, expression of vinexin increased focal adhesion size. Vinexin alpha also promoted upregulation of actin stress fiber formation. In addition, cell lines stably expressing vinexin beta showed enhanced cell spreading on fibronectin. These data identify vinexin as a novel focal adhesion and cell- cell adhesion protein that binds via SH3 domains to the hinge region of vinculin, which can enhance actin cytoskeletal organization and cell spreading.

3T3 Cells↗

PubMed1999

Basaloid carcinoma of the thymus.

A 58-year-old man was found to have a basaloid carcinoma of the thymus, initially detected as an abnormal shadow on chest radiograph. The patient underwent resection followed by radiotherapy, and has survived 25 months without recurrence. Although this rare tumor may be related to multilocular thymic cyst, its pathogenesis is obscure. We discuss clinicopathologic features of our case and others.

Carcinoma, Transitional Cell↗