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Articles by K Yamaguchi
Total Records ( 6 ) for K Yamaguchi
  W Koizumi , T Akiya , A Sato , K Yamaguchi , T Sakuyama , N Nakayama , S Tanabe , K Higuchi , T Sasaki , T Sekikawa and The Tokyo Cooperative Oncology Group (TCOG GI Group)
  Objective

A multicenter trial was conducted to evaluate the efficacy and safety of paclitaxel every 2 weeks in patients with advanced or recurrent gastric cancer who had previously received fluoropyrimidine-based chemotherapy.

Methods

The subjects were patients with gastric cancer who had disease progression or recurrence while receiving fluoropyrimidine-based chemotherapy. All patients had adequate major organ functions with an Eastern Cooperative Oncology Group performance status (PS) of 0–2. Paclitaxel 140 mg/m2 was administered intravenously on days 1 and 15 of a 4-week cycle. The primary endpoint was the response rate. Secondary endpoints were progression-free survival (PFS), overall survival and safety.

Results

Response was assessable in 40 of 41 enrolled patients. Their median age was 63 (range: 48–77) years, and PS was 0 in 22 patients, 1 in 13 and 2 in 5. Previous treatment included S-1 (1 M tegafur–0.4 M gimestat–1 M otastat potassium) monotherapy in 32 patients and S-1-based combination therapy in 5. The median number of administered courses of paclitaxel was 3.5 (1–14). The response rate was 17.5% (95% confidence interval: 7.3–32.8%, partial response: 7, stable disease: 21, progressive disease: 10 and not evaluable: 2). The disease control rate was 70.0%, the median PFS was 111 days and the median overall survival was 254 days. Major adverse events of Grade 3 or 4 were neutropenia (27.5%), anemia (12.5%), diarrhea (2.5%) and sensory neuropathy (2.5%).

Conclusions

Biweekly paclitaxel seemed to be one of the useful chemotherapies after failure of fluoropyrimidine-based treatment in patients with advanced or recurrent gastric cancer.

  T Doi , N Boku , K Kato , Y Komatsu , K Yamaguchi , K Muro , Y Hamamoto , A Sato , W Koizumi , N Mizunuma and H. Takiuchi
  Objective

The addition of bevacizumab to fluoropyrimidine-based combination chemotherapy as first-line therapy for metastatic colorectal cancer results in clinically significant improvements in patient outcome. However, clinical trials have been conducted primarily in Caucasian patients with only a small proportion of Asian patients. This Phase I/II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab in Japanese patients with metastatic colorectal cancer.

Methods

Patients with previously untreated, measurable metastatic colorectal cancer received bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1000 mg/m2 twice daily on days 1–14, every 3 weeks. A three-step design evaluated in: step 1, initial safety of XELOX in six patients; step 2, initial safety of XELOX plus bevacizumab in six patients; and step 3, efficacy and safety in a further 48 patients. The primary study endpoints were safety and response rate.

Results

No dose-limiting toxicity occurred during Steps 1 and 2. Fifty-eight patients were enrolled in Steps 2 and 3 and received XELOX plus bevacizumab. In the 57 patients assessed for response, the overall response rate was 72% (95% confidence interval, 58.5–83.0). Median progression-free survival was 11.0 months (95% confidence interval, 9.6–12.5) and median overall survival was 27.4 months (95% confidence interval, 22.0–not calculated). Eight patients (14%) underwent surgery with curative intent. The most common grade 3/4 adverse events were neurosensory toxicity (17%) and neutropenia (16%).

Conclusions

XELOX plus bevacizumab is effective and has a manageable tolerability profile when given to Japanese patients with metastatic colorectal cancer.

  K Yamaguchi , K. i Suzuki and K. Tanaka
 

Electron staining reagents were examined to find a possible substitute for uranyl acetate (UA) in electron microscopy of bacterial ultrathin sections. Four kinds of stains, platinum blue (Pt-blue), oolong tea extract (OTE), potassium permanganate (KMnO4) and phosphotungstic acid (PTA), were examined in comparison with UA either with or without post-staining with lead citrate (Pb). Electron microscopy was performed on sections from Spurr-embedded cells of a Gram-positive bacterium, Bacillus cereus NBRC 13597, and a Gram-negative bacterium, Escherichia coli NBRC 3301. Both Pt-blue and OTE showed staining similar to each other and to that of double staining with UA and Pb in B. cereus, while in E. coli the cytoplasmic membrane appeared less dense when compared with UA and Pb. KMnO4 stained excessively to some extent, but showed images of the best contrast in the cytoplasmic membrane comparable with UA and Pb among the four reagents. PTA could stain the peptidoglycan layer but gave images of low quality for both bacteria. This study demonstrated that none of the reagents examined showed staining results of the same quality or better than the conventional method with UA and Pb. However, stains of Pt-blue, OTE and KMnO4 could possibly be an alternative candidate for the UA according to the structure in question.

  K Hara , T Mochizuki , I Sekiya , K Yamaguchi , K Akita and T. Muneta
  Background

Double-bundle anterior cruciate ligament (ACL) reconstruction has several potential advantages over single-bundle reconstruction with hamstring tendons. However, there are still controversies regarding tunnel placement in tibial and femoral attachments.

Hypothesis

The macroscopically normal ACL consists of small bundles about 1 mm in diameter. Detailed observation of the divided smaller bundles will achieve better understanding of the tunnel placement in anatomic ACL reconstruction.

Study Design

Descriptive laboratory study.

Methods

This study used 20 cadaveric knees. The ACL was divided into anteromedial and posterolateral bundles, then separated into 10 small bundles of 2-mm diameters, with preservation of their attachment sites marked with color markers. The positional relationship between the femoral and tibial attachments of each small bundle was investigated.

Results

A layered positional correlation of small bundles was found between the tibial and femoral attachments. Small bundles aligned in the anterior-posterior direction in the tibia corresponded to the bundles aligned in a high-low direction in the femur in flexion. The femoral attachment pattern was relatively similar in each specimen; however, the tibial attachment showed 2 patterns: an oblique type (12 of 20) and a transverse type (8 of 20). The posterior portion of the posterolateral bundle was separately attached to the medial and lateral portions of the tibial attachment. There was no fibrous insertion in the center of the posterior portion of the ACL tibial attachment in any specimen. In this bare area, there was fat tissue and vascular bundles.

Conclusion

Small bundles constituting the ACL showed a relatively layered arrangement between 2 attachments. The tibial attachment showed 2 patterns of oblique and transverse types, and the vascular bundles were located in the center of the posterolateral bundle.

Clinical Relevance

The results of this study of the normal ACL will provide insights for surgeons when placing grafts during anatomic ACL reconstruction.

  T Yamanishi , T Hatakeyama , K Yamaguchi and T. Oda
 

We found that CEL-I, a GalNAc-specific C-type lectin isolated from the marine invertebrate Holothuroidea (Cucumaria echinata), induces inducible nitric oxide synthase (iNOS) expression and NO production in RAW264.7 cells. The NO production was inhibited by an iNOS inhibitor, L-NAME, but was not by a lipopolysaccharide (LPS) inhibitor, polymyxin B. In the presence of 0.1-M GalNAc, increased NO production by CEL-I-treated RAW264.7 cells was observed rather than the inhibition. Bovine serum albumin (BSA) significantly inhibited the CEL-I-induced NO production as well as the binding of FITC-labelled CEL-I on RAW264.7 cells. Three MAP kinase inhibitors (specific to extra-cellular regulated kinase, c-jun NH2-terminal kinase and p38 MAP kinase) inhibited CEL-I-induced NO production with different extents. Heat-treatment of CEL-I resulted in a decreased activity of CEL-I depending on the temperature. These results suggest that CEL-I induces NO production in RAW264.7 cells through the protein–cell interaction rather than the binding to the specific carbohydrate chains on the cell surface.

  M Kiyohara , K Sakaguchi , K Yamaguchi , T Araki and M. Ito
 

β-1,3-Xylanase from Vibrio sp. strain AX-4 (XYL4) is a modular enzyme composed of an N-terminal catalytic module belonging to glycoside hydrolase family 26 and two putative carbohydrate-binding modules (CBMs) belonging to family 31 in the C-terminal region. To investigate the functions of these three modules, five deletion mutants lacking individual modules were constructed. The binding assay of these mutants showed that a repeating unit of the CBM was a non-catalytic β-1,3-xylan-binding module, while the catalytic module per se was not likely to contribute to the binding activity when insoluble β-1,3-xylan was used for the assay. The repeating CBMs were found to specifically bind to insoluble β-1,3-xylan, but not to β-1,4-xylan, Avicel, β-1,4-mannan, curdlan, chitin or soluble glycol-β-1,3-xylan. Both the enzyme and the binding activities for insoluble β-1,3-xylan but not soluble glycol-β-1,3-xylan were enhanced by NaCl in a concentration-dependent manner, indicating that the CBMs of XYL4 bound to β-1,3-xylan through hydrophobic interaction. This property of the CBMs was successfully applied to the purification of a recombinant XYL4 from the cell extracts of Escherichia coli transformed with the xyl4 gene and the detection of β-1,3-xylan-binding proteins including β-1,3-xylanase from the extract of a turban shell, Turbo cornutus.

 
 
 
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