Biomedical subjects

Masafumi Noda

Publications and source records attributed to Masafumi Noda.

At least 19 recordsLinked to original sources

PubMed2006

Identification and kinetic study of tyrosinase inhibitors found in sake lees.

The present study found that the n-hexane extract of freeze-dried sake lees inhibits tyrosinase activity and showed that the constituents isolated from the n-hexane extract are the mixture of triacylglycerols. The inhibitory effects of triolein and trilinolein found as the triacylglycerols were examined using tyrosinases from mushroom and Streptomyces castaneoglobisporus. The IC50 values of the triacylglycerol mixture for the oxidase activity on mushroom and Streptomyces tyrosinases were 20 and 0.14 microg/mL, respectively. The IC50 values of trilinolein for the oxidase activity on mushroom and Streptomyces tyrosinases were 8.4 and 0.1 microM, respectively. However, the inhibitory effect of triolein (IC50=30 microM) was lower than that of trilinolein, even when the Streptomyces tyrosinase was used for the assay. Kinetic analyses indicate that both trilinolein and triolein inhibit the tyrosinase activity noncompetitively. When transformed with a plasmid carrying the Streptomyces tyrosinase gene, the melanin-synthesizing ability of the transformed Escherichia coli host was dose-dependently interfered with by trilinolein.

Agaricales↗

PubMed2006

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer.

AIM: To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC). METHODS: Firstly, we used protein microarrays to analyze the in vitro expression profiles of potential PSK-related markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we investigated the clinical implications of these markers in the prognosis of CRC patients. RESULTS: ECA39, a direct target of c-Myc, was identified as a candidate protein affected by the anti-metastatic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P<0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value: 86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P<0.05). CONCLUSION: Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in patients with advanced CRC and that its suppression by PSK might represent a useful application of immunotherapy as part of a program of integrated medicine.

Adenocarcinoma↗

PubMed2006

Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis.

We experienced a very rare case of ulcerative colitis (UC) accompanied with analogous lesions in the stomach, duodenum, and ileal J-pouch. Ileal J-pouch anal anastomosis was performed on a 29-year old woman in 1996. Six years later, she was admitted again to our hospital because of epigastralgia, nausea, watery diarrhea and low fever. Based on the results of endoscopic examination, we diagnosed it as pouchitis. Moreover, on hypotonic duodenography, expansion of the duodenal bulb and the descending portion were poor. Kerckring folds disappeared with typical lead-pipe appearance. The pathogenesis of the gastric and duodenal lesion in this patient was similar to that of the colonic lesions of UC. For the gastroduodenal lesions in this patient, symptomatic remission was obtained following administration of crushed mesalazine tablets (1500 mg/d) for 14 d with continuous administration of omeprazole. Firstly we used ciprofloxacin to treat pouchitis. On the fifth day, she got a fever because of catheter infection. In the catheter culture, methicillin-resistant Staphylococcus aureus (MRSA) was detected. Therefore we changed ciprofloxacin to vancomycin hydrochloride (Vancomycin). Vancomycin was very effective, and the stool frequency dramatically improved in three days. Now she continues to take mesalazine, but her condition is stable and there has been no recurrence of pouchitis.

Adult↗

PubMed2006

Incidence of and risk factors for dysplasia in mucosectomy area in ulcerative colitis patients undergoing restorative proctocolectomy.

BACKGROUND AND AIMS: We evaluated the incidence of dysplasia in the mucosectomy area using resected specimens to determine preoperative risk factors for the occurrence of dysplasia in this area. PATIENTS AND METHODS: We prospectively studied a consecutive series of 137 patients, each of whom underwent a restorative proctocolectomy with a mucosectomy and hand-sewn ileal J-pouch anal anastomosis between January 2003 and December 2004. Sections from the anal transitional zone mucosa were taken from the dentate line to 2.5 cm above the resected line and stained with hematoxylin and eosin then characterized as indefinite for dysplasia, low-grade dysplasia, and high-grade dysplasia based on the criteria of an international working group for rectal mucosal atypia. RESULTS: Dysplasia of the mucosectomy area was present in six (4.4%) of the patients, including one with low-grade and five with high-grade dysplasia. A multivariate analysis showed relations between age at time of surgery (>or=40 years) and duration of disease (>or=10 years) with a risk for development of mucosectomy area dysplasia. CONCLUSION: The incidence of dysplasia of the mucosectomy area was 4.4%, and preoperative risk factors were shown to be duration of disease and age at time of surgery.

Adolescent↗

PubMed2006

Postoperative joint symptoms: a risk factor for pouchitis in ulcerative colitis patients.

BACKGROUND: The prevalence and significance of joint symptoms appearing in patients with ulcerative colitis (UC) following a colectomy are unclear. AIM: We investigated the relationship between joint symptoms during steroid tapering following an ileal pouch-anal anastomosis (IPAA) and the cumulative risk for developing pouchitis. PATIENTS AND METHODS: The medical records of 571 patients who underwent an IPAA with a mucosectomy were retrospectively reviewed to evaluate their joint symptoms. A diagnosis of pouchitis was obtained using the Pouchitis Disease Activity Index (PDAI) and the cumulative risk of pouchitis was estimated using a Kaplan-Meier life table analysis. RESULTS: Joint symptoms during steroid tapering were reported by 126 (22.0%) of the UC patients and each of those had involvement of the small joints of the hand. The main symptoms were pain and stiffness, especially in the morning. The cumulative risk for developing pouchitis after 10 years was found to be 20% in patients who experienced joint symptoms during steroid tapering and 10% in those without those symptoms (p = 0.001). CONCLUSION: The presence of joint symptoms during steroid tapering is a significant risk factor for the development of pouchitis in patients who have undergone an IPAA for UC.

Adolescent↗

PubMed2006

Successful chemotherapeutic modality of doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis.

PURPOSE: Desmoid tumors are locally aggressive and can be fatal in familial adenomatous polyposis (FAP) patients if they are not suitable for surgery or radiation therapy. Here, we prospectively investigated the efficacy of a chemotherapeutic regimen involving doxorubicin (DOX) and dacarbazine (DTIC) for inoperable FAP-associated desmoid tumors. PATIENTS AND METHODS: From an initial group of 120 FAP patients, seven of the 11 individuals with symptomatic unresectable desmoid tumors that were unresponsive to conventional hormone therapy were enrolled onto this study. The general chemotherapy regimen comprised four or five cycles of DOX (20 mg/m2 daily) plus DTIC (150 mg/m2 daily) throughout 4 days of drip intravenous infusion (day 1 through 4) every 28 days, followed by the cyclooxygenase-2 inhibitor meloxicam (10 mg/m2). The primary end point was relapse-free survival. The secondary end points included toxicity, clinical improvement, and tumor regression according to computed tomography. RESULTS: Significant tumor regression was observed clinically and radiologically in all seven patients. Three patients showed a complete response. The average progression-free survival period was 74.0 months (range, 32.5 to 107.5 months). Three patients showed grade 3 adverse events with no treatment-related mortality. All seven patients survived and remained without tumor progression. An adenomatous polyposis coli germline-mutation analysis revealed no mutations in the specified regions. CONCLUSION: A chemotherapeutic regimen of DOX plus DTIC followed by meloxicam is an effective and safe treatment for FAP-associated desmoid tumors. This modality should be considered for use as first-line chemotherapy in symptomatic desmoid tumors that are unresponsive to conventional medical therapy, due to the absence of useful presymptomatic markers.

Adenomatous Polyposis Coli↗

PubMed2006

Leukocyte removal therapy for ulcerative colitis does not affect postoperative complications.

BACKGROUND: We investigated the incidence of postoperative complications in patients treated with or without preoperative leukocyte removal therapy (LRT). METHODS: The case notes of 387 patients with ulcerative colitis (UC) who underwent surgical intervention were retrospectively reviewed. One hundred nine patients were treated with LRT within 8 weeks before surgery (LRT group), and 278 had not received LRT since at least 8 weeks before surgery (without LRT group). We reviewed the postoperative complications according to type of initial operation. RESULTS: Of the patients who underwent an ileal J-pouch anal anastomosis (IPAA) without an ileostomy, 3 (6.5%) in the LRT group developed pouch-related complications (PRC), while 11 (7.5%) in the without LRT group developed PRC. The overall postoperative complication rates were 28.3% in the LRT group and 21.8% in the without LRT group. For patients who underwent an IPAA with an ileostomy, the overall rates of postoperative complications were 39.1% in the LRT group and 31.8% in the without LRT group. Among those undergoing a total colectomy, 33.3% in the LRT group and 18.2% in the without LRT group had postoperative complications. No statistically significant differences were demonstrated between the two groups with respect to postoperative complications. CONCLUSIONS: Our results suggest that preoperative LRT does not influence the rate of postoperative complications in UC patients.

Adolescent↗

PubMed2006

[Bronchoplasty without lung resection for the complete transection of the left main bronchus due to blunt trauma].

Blunt bronchial injury is rare but crucial injury. A 17-year-old female was admitted due to traumatic injury. She was diagnosed with bilateral lung contusion, multiple rib fractures, spleen damage and the suspicion about the complete transection of the left main bronchus on X-ray and computed tomography (CT). She was brought to our hospital at 30 hours later from injury. Bronchoscopy revealed the complete transection and the edema of the left main bronchus. She underwent a resection of the disrupted portion and end-to-end anastomosis of left main bronchus without lung resection. We should be an immediate and accurate diagnosis of tracheobronchial disruption by X-ray, CT and bronchoscopy whenever we evaluate patients with blunt chest trauma.

Adolescent↗

PubMed2005

A novel assay method for an amino acid racemase reaction based on circular dichroism.

We have established a novel assay method based on circular dichroism that can be used for the kinetic study of the activity of amino acid racemases, such as ALR (alanine racemase). Although an enzyme-coupled assay method has been used to measure racemase activity, the CD method is superior to the enzyme assay because it can accurately determine the immediate changes of an enantiomer on racemization between its L- and D-forms. The enzyme-coupled assay requires D-amino acid oxidase, which is inactivated by an inhibitor of ALR, D-cycloserine. This indicates that the inhibitory kinetic study for ALR with D-cycloserine by the enzyme-coupled assay method is restricted to the analysis of only the reaction resulting in the formation of L-Ala from D-Ala. However, since the CD assay does not require the coupled enzyme, it can be used to comprehensively evaluate the reactions that result in the formation both of D-Ala from L-Ala and of L-Ala from D-Ala at several substrate concentrations. Streptomyces ALR also catalyses the formation of D-Ser from L-Ser and of L-Ser from D-Ser, but the catalytic constants (kcat) are 4- and 10-fold lower than those for the formation of D-Ala from L-Ala and of L-Ala from D-Ala respectively.

Alanine↗

PubMed2005

Bioresorbable hyaluronate-carboxymethylcellulose membrane (Seprafilm) in surgery for rectal carcinoma: a prospective randomized clinical trial.

PURPOSE: To evaluate the effectiveness of Seprafilm in preventing abdominal adhesions after radical resection of rectal carcinoma, and to observe whether Seprafilm had any adverse effects in patients treated with radiotherapy and chemotherapy. METHODS: A total of 62 patients participated in this prospective randomized clinical study, which was conducted to compare the outcomes of patients operated on with Seprafilm (SEPRA+) with those operated on without Seprafilm (SEPRA-). All patients received preoperative radiotherapy, followed by a two-stage operation, and 5-fluorouracil (5-FU)-based systemic chemotherapy. The primary endpoint of severity and extent of adhesions were evaluated at the time of ileostomy closure. The secondary endpoint included the recurrence of tumors, late complications, and outcome. RESULTS: Seprafilm significantly reduced the adhesions in both the midline incision area and peristomal area. This in turn reduced the operation time, blood loss, and extent of the incision at ileostomy closure. Seprafilm was not associated with any postoperative complications or chemoradiation-related toxicity, nor did it affect recurrence or survival rates. CONCLUSION: Seprafilm effectively reduced abdominal adhesions in chemoradiated patients, and had no adverse effects on the oncologic results of fully introduced adjuvant therapy. Thus, Seprafilm is a safe and effective tool for use in rectal carcinoma surgery.

Absorbable Implants↗

PubMed2005

Safety of one-stage restorative proctocolectomy for ulcerative colitis.

PURPOSE: The aim of this study was to compare clinical outcomes in patients with ulcerative colitis who underwent restorative proctocolectomy with and without diverting ileostomy. METHODS: A series of 245 consecutive patients who underwent ileal pouch anal anastomosis with mucosectomy with an ultrasonically activated scalpel (harmonic scalpel) was studied. Of these patients, 92 patients had a diverting ileostomy and 150 selected patients did not. The decision for or against an ileostomy was made at the end of the operation. RESULTS: Twelve patients (8 percent) in the group without ileostomy had pouch-related complications, which necessitated secondary ileostomy in five patients (3.3 percent). Intestinal obstruction developed in 17 patients (11.3 percent) who had no ileostomy and in 12 patients (13.0 percent) who underwent ileostomy. Two of 17 patients who had no ileostomy and 1 of 12 patients with ileostomy required laparotomy with division of adhesions, whereas the remaining patients responded to conservative measures. There were no significant differences in the incidence of postoperative complications after the initial operation between the two groups. In the group with ileostomy, the morbidity rate for ileostomy was 12.1 percent, and that for ileostomy closure was 18.7 percent. The total postoperative complication rate for the group with ileostomy was significant higher than that for the group without ileostomy. CONCLUSION: We conclude that restorative proctocolectomy with mucosectomy by use of an ultrasonically activated scalpel and without diversion is a superior therapeutic choice for selected patients.

Adolescent↗

PubMed2005

[Schwannoma arising from brachial plexus with intrathoracic extension; report of a case].

We report a case of schwannoma arising from brachial plexus with intrathoracic extension. An 18-year-old man demonstrated a tumor shadow at the right pulmonary apex area. In the 2-months of follow-up, tumor size had been growing rapidly. Chest computed tomography (CT) and magnetic resonance imaging (MRI) revealed a giant tumor mass infiltrated right lung. We perfomed operation under the posterolateral incision approach. The pathological diagnosis was schwannoma. We resected this tumor safely and conserved with the seventh, eighth cervical nerve of the brachial plexus under posterolateral incision approach.

Adolescent↗

PubMed2005

Venous thromboembolism in colorectal cancer patients with central venous catheters for 5-FU infusion-based pharmacokinetic modulating chemotherapy.

Colorectal cancer patients with central venous catheters (CVC) for pharmacokinetic modulating chemotherapy (PMC) have a substantial risk of venous thromboembolism (VTE). PMC, designed as a hybrid of lower metronomic and higher shorter plasma 5-FU concentrations, has been clinically successful. To determine the effectiveness and safety of D-dimer tests and multidetector-row CT (MDCT) for diagnosis in cancer patients with suspected VTE, we carried out a clinical outcome study on PMC outpatients. Patients received a D-dimer test before and after commencing the PMC regimen. MDCT was performed additionally if the D-dimer test appeared positive or showed signs of VTE. When CT results were positive for thromboembolism, anticoagulation was started. The overall prevalence of VTE in PMC patients was 2.0% (7 of 350 patients). In this study, 34 out of 102 colorectal cancer patients gave a positive D-dimer test (33.3%). CT identified venous thrombi in 2 of the 102 patients (2.0%), mural thrombosis on catheterized veins in another 3 patients (2.9%), and endothelial hyperplasia on catheterized veins in 8 patients (7.8%). The catheters of these patients did not show any significant abnormalities. Patients with negative D-dimer tests showed no signs or symptoms of VTE. In colorectal cancer patients receiving continuous 5-FU infusion via CVC, a D-dimer test can be safely used as the primary diagnostic test for ruling out VTE. We suggest 7.0 microg/ml as the D-dimer cut-off value. Thromboprophylaxis should be considered in the patients showing values >7.0 microg/ml.

Adult↗

PubMed2004

Self-protection mechanism in D-cycloserine-producing Streptomyces lavendulae. Gene cloning, characterization, and kinetics of its alanine racemase and D-alanyl-D-alanine ligase, which are target enzymes of D-cycloserine.

An antibiotic, D-cycloserine (DCS), inhibits the catalytic activities of alanine racemase (ALR) and d-alanyl-d-alanine ligase (DDL), which are necessary for the biosynthesis of the bacterial cell wall. In this study, we cloned both genes encoding ALR and DDL, designated alrS and ddlS, respectively, from DCS-producing Streptomyces lavendulae ATCC25233. Each gene product was purified to homogeneity and characterized. Escherichia coli, transformed with a pET vector carrying alrS or ddlS, displays higher resistance to DCS than the same host carrying the E. coli ALR- or DDL-encoded gene inserted into the pET vector. Although the S. lavendulae DDL was competitively inhibited by DCS, the K(i) value (920 microM) was obviously higher (40 approximately 100-fold) than those for E. coli DdlA (9 microM) or DdlB (27 microM). The high K(i) value of the S. lavendulae DDL suggests that the enzyme may be a self-resistance determinant in the DCS-producing microorganism. Kinetic studies for the S. lavendulae ALR suggest that the time-dependent inactivation rate of the enzyme by DCS is absolutely slower than that of the E. coli ALR. We conclude that ALR from DCS-producing S. lavendulae is also one of the self-resistance determinants.

Alanine Racemase↗

PubMed2004

Structural evidence that alanine racemase from a D-cycloserine-producing microorganism exhibits resistance to its own product.

Alanine racemase (ALR), an enzyme that catalyzes the interconversion of Ala enantiomers, is essential for the synthesis of the bacterial cell wall. We have shown that it is harder to inhibit the catalytic activity of ALR from D-cycloserine (DCS)-producing Streptomyces lavendulae than that from Escherichia coli by DCS. To obtain structural evidence for the fact that Streptomyces ALR displays resistance to DCS, we determined the precise nature of the x-ray crystal structures of the cycloserine-free and cycloserine enantiomer-bound forms of Streptomyces ALR at high resolutions. Streptomyces ALR takes a dimer structure, which is formed by interactions between the N-terminal domain of one monomer with the C-terminal domain of its partner. Each of the two active sites of ALR, which is generated as a result of the formation of the dimer structure, is composed of pyridoxal 5'-phosphate (PLP), the PLP-binding residue Lys(38), and the amino acids in the immediate environment of the pyridoxal cofactor. The current model suggests that each active site of Streptomyces ALR maintains a larger space and takes a more rigid conformation than that of Bacillus stearothermophilus ALR determined previously. Furthermore, we show that Streptomyces ALR results in a slow conversion to a final form of a pyridoxal derivative arising from either isomer of cycloserine, which inhibits the catalytic activity noncompetitively. In fact, the slow conversion is confirmed by the fact that each enzyme bound cycloserine derivative, which is bound to PLP, takes an asymmetric structure.

Alanine Racemase↗

PubMed2004

Incidence and therapeutic outcome of pouchitis for ulcerative colitis in Japanese patients.

AIM: The aim of this study was to examine the cumulative risk of pouchitis following restorative proctocolectomy for UC and FAP in Japanese patients, and to assess the response to medical treatment and its outcome. PATIENTS AND METHODS: 521 patients with UC and 117 FAP patients underwent proctocolectomy and received a J-shaped IPAA at our department of surgery. We investigated these patients using PDAI for the diagnostic criteria of pouchitis. RESULTS: Pouchitis occurred in only 32 UC patients (6.1%). The cumulative risk of developing pouchitis for a UC patient was 7% at 5 years after and 12% at 10 years after surgery. The medical treatment of acute pouchitis was usually oral metronidazole (250 mg twice daily) for 2 weeks or oral ciprofloxacin (200 mg thrice daily) in patients who could not tolerate metronidazole. Single episodes of pouchitis occurred in 21 patients (65.6%) and chronic or frequent relapses of pouchitis in 11 patients (34.4%). Three patients (9.4%) required re-ileostomy. Two patients (6.3%) required pouch excision. There were no patients with complicated dysplasia. CONCLUSION: The cumulative risk of pouchitis in Japanese UC patients is lower than that of western countries.

Adenomatous Polyposis Coli↗

PubMed2004

Gene expression in response to anti-tumour intervention by polysaccharide-K (PSK) in colorectal carcinoma cells.

Distant metastasis is one of the major problems in treatment for advanced colorectal cancer. Polysaccharide-K (PSK), or Krestin, a mushroom ingredient, has been used as a chemoimmunotherapeutic agent for the treatment of cancers in Asia for over 30 years. Some studies have reported that PSK prevent distant metastases and improve survival rates by 10-20% in colorectal cancer. However, the mechanism of the interrelated immunomodulatory and direct anti-cancer cell activities of PSK has yet to be elucidated. To investigate the direct effect, we used cDNA microarrays to analyse expression profiles in a human colorectal adenocarcinoma cell line, HCT116, containing the wild-type p53 gene. Expression of 453 genes was significantly altered (142 up-regulated and 311 down-regulated) after 96 h exposure to 500 microg/ml PSK. Under more stringent conditions, 9 genes were up-regulated and 36 down-regulated. We then examined the expression of candidate genes in two cell lines, HCT116, and SW480, a cell line with a mutant p53 gene. Our results suggest that PSK may augment anti-tumour action via genes including multidrug resistance protein 3 (MRP3), lymphotactin (Lptn), transgelin (TAGLN), and Pirin, without disturbing cell-cycle progression, and may deserve a large clinical trial in cancer therapy.

Antibiotics, Antineoplastic↗

PubMed2003

Clinical results after restorative proctocolectomy without diverting ileostomy for ulcerative colitis.

BACKGROUND AND AIMS: This study evaluated the postoperative complications and clinical results of restorative proctocolectomy without diverting ileostomy for ulcerative colitis. PATIENTS AND METHODS: One hundred selected patients had a hand-sewn ileal J-pouch anal anastomosis with mucosectomy using an ultrasonically activated scalpel. RESULTS: Three patients with pouch-related complications who needed diverting ileostomy. Five patients showed intestinal obstruction; two of the five needed relaparotomy and division of adhesions. The median number of bowel movements per 24 h was 6.5 (2-13) at 3 months and 5 (3-10) at 12 months. The corresponding nightly frequencies were 0 (0-5) at 3 months and 0 (0-3) at 12 months. After 3 months 82% of patients had no soiling during the daytime, and 45% were fully continent day and night. After 3 months 89% had recovered the ability to distinguish flatus from feces. CONCLUSION: Ileal pouch anal anastomosis can be performed safely without diverting ileostomy using an ultrasonically activated scalpel. The postoperative functional result was stabilized 3 months after the operation.

Adolescent↗