Biomedical subjects

Junichirou Nasu

Publications and source records attributed to Junichirou Nasu.

At least 19 recordsLinked to original sources

PubMed2006

Risk factors and indications for colectomy in ulcerative colitis patients are different according to patient's clinical background.

PURPOSE: Despite progress in medical treatment for ulcerative colitis, a considerable fraction of ulcerative colitis patients undergo colectomy. We analyzed the clinical variables of ulcerative colitis patients and determined the risk factors and indications for colectomy. METHODS: The clinical records of 981 consecutive Japanese patients with ulcerative colitis were reviewed both retrospectively and prospectively. RESULTS: Of 981 patients with ulcerative colitis, 85 patients underwent colectomy. Multivariate analysis indicated that male gender (risk ratio, 2.16; 95 percent confidence interval, 1.37-3.42), onset year during and after 2000 (risk ratio, 2.85; 95 percent confidence interval, 1.31-6.22), severe disease activity (risk ratio, 2; 95 percent confidence interval, 1.15-3.48), corticosteroid resistance (risk ratio, 7.05; 95 percent confidence interval, 4.29-11.59), and complications because of corticosteroid administration (risk ratio, 3.55; 95 percent confidence interval, 2.08-6.06) were significant risk factors for colectomy. In patients with disease duration of more than five years, only corticosteroid resistance and complications because of corticosteroid were significant risk factors for colectomy. When we stratified indications for colectomy for the 85 cases via patient disease duration, massive hemorrhage was a relatively frequent cause of colectomy in patients with a disease duration of less than five years (P = 0.091). On the other hand, colon dysplasia or cancer was a major cause for colectomy in patients with a disease duration of more than ten years (P = 0.0001). CONCLUSIONS: In ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patient's clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.

Adrenal Cortex Hormones↗

PubMed2006

[A case of gastric hamartomatous inverted polyp (submucosal tumor type) accompanied by gastric cancer].

Endoscopic examination of a 39-year-old woman revealed a flat-elevated submucosal tumor (SMT) in the upper third area of the stomach and a IIc lesion in the anterior wall of the lower third of the stomach. Endoscopic ultrasonography findings suggested an aberrant pancreas. Both lesions were resected by distal gastrectomy. Histological examination of the SMT revealed the dilated glands with cyst formation and proliferation of smooth muscle bundles in the submucosal layer, and it was diagnosed as a gastric hamartomatous inverted polyp. The IIc lesion was a signet ring cell carcinoma. Cases of gastric hamartomatous inverted polyps coexistent with gastric cancer have been rarely reported in Japan.

Adult↗

PubMed2005

A phase I study of doxifluridine combined with weekly paclitaxel for metastatic gastric cancer.

PURPOSE: Based on the synergistic effect in preclinical studies, a phase I clinical trial for the combination of paclitaxel and doxifluridine (an intermetabolite of capecitabine) was performed to determine the recommended dose for the treatment of patients with metastatic gastric cancer. METHODS: The dose of paclitaxel was increased from 60 mg/m2 at level 1 to 90 mg/m2 at level 5. It was administered as a 1-h infusion on days 1 and 8. The dose of doxifluridine was fixed at 600 mg/m2 per day up to level 3, and escalated to 800 mg/m2 per day at levels 4 and 5. It was administered orally for 2 weeks. The treatment was repeated every 3 weeks. RESULTS: A total of 28 patients were enrolled. No dose-limiting toxicity (DLT) was observed at levels 1 and 2 (paclitaxel 70 mg/m2). A DLT of grade 4 neutropenia lasting for more than 4 days was observed in one patient at level 3 (paclitaxel 80 mg/m2). In addition, the first five of six patients in this group experienced grade 3 neutropenia during the first treatment cycle. A further six patients were added in order to confirm the safety of this dosage level, and no more DLTs except for grade 3 nausea in one patient were observed in the second cohort. No DLT was seen in three patients at level 4 (paclitaxel 80 mg/m2). DLTs (grade 3 neuropathy in one patient and a treatment delay of the second cycle for more than 1 week due to grade 3 neutropenia in another) were observed in two out of six patients at level 5 (paclitaxel 90 mg/m2), and this dose level was determined as the maximum tolerated dose. The tumor response rate was 42% (95% confidence interval 20-67%) in 19 patients with measurable lesions. CONCLUSIONS: The recommended dose was determined as 80 mg/m2 of paclitaxel (days 1 and 8) and 800 mg/m2) of doxifluridine (days 1-14) every 3 weeks. The results of this phase I study are encouraging and a phase II trial is thus warranted.

Adult↗

PubMed2005

Stool decay-accelerating factor as a marker for monitoring the disease activity during leukocyte apheresis therapy in patients with refractory ulcerative colitis.

BACKGROUND AND AIMS: We have shown previously that concentrations of stool decay-accelerating factor (DAF; CD55), a complement regulatory protein, in patients with ulcerative colitis (UC) are increased in relation to the severity of the colonic mucosal inflammation. In the present study, we evaluated the usefulness of stool DAF as a marker for monitoring disease activity in patients with steroid-resistant active UC being treated with leukocyte apheresis performed with a centrifugal cell separator. METHODS: Twenty-one patients with active and steroid-resistant UC were treated with leukocyte apheresis once a week for 4 weeks, and stool DAF concentrations were determined weekly by immunoassay. RESULTS: After treatment, 11 (52%) of the 21 UC patients went into remission. Stool DAF concentrations decreased promptly and steadily in the responsive group. The difference reached statistical significance as soon as after the second apheresis session (P < 0.003), compared with values before the therapy and corresponding values in the non-responsive group (P = 0.024). The reduction in stool DAF concentrations after the second apheresis session was significantly greater in the responsive group (median 90%, range 22-90%) than in the non-responsive group (median -13%, range -307-94%) (P = 0.008). Hematological tests, that is, white blood cell (WBC) count and C-reactive protein, declined significantly during the apheresis therapy, but not in relation to therapeutic response. CONCLUSION: Stool DAF concentration is a useful marker in the clinical response of UC patients to treatment with leukocyte apheresis.

Adolescent↗

PubMed2005

Treatment of elderly patients with early gastric cancer by endoscopic submucosal dissection using an insulated-tip diathermic knife.

OBJECTIVE: In recent years, the number of elderly patients with early gastric cancer (EGC) has steadily been increasing. In our institute, endoscopic submucosal dissection (ESD) involving the use of an insulated-tip diathermic knife (IT-ESD) was introduced for the treatment of mucosal gastric carcinoma in 1996. The purpose of this study was to evaluate the effectiveness of IT-ESD for the treatment of elderly patients with EGC. MATERIALS AND METHODS: A total of 144 patients with EGC were treated at Shikoku Cancer Center in the 5-year period from January 2000 to December 2004, including 53 patients over 75 years old. The performance status (PS) for all patients was less than 2. We compared patient's backgrounds, the one-piece resection rate, complete resection (CR) rate, operation time, bleeding rate, perforation rate, blood pressure, and peripheral oxygen saturation (SpO(2)) between patients over 75 years of age (elderly group) and the remaining 91 younger patients (non-elderly group). RESULTS: The rate of having underlying disease was significantly higher for the elderly group (p<0.05) and we found no significant difference for the one-piece resection rate, CR rate, operation time, bleeding rate, and perforation rate between the 2 groups. There were also no significant differences for the frequency of the use of oxygen, pressor and depressor between the 2 groups. CONCLUSION: There was no significant difference in the outcome resulting from ESD between the 2 groups. Our study proves that ESD is a feasible treatment for elderly patients with EGC PS of less than 2.

Adenocarcinoma↗

PubMed2005

Acute pancreatitis occurring in gastric aberrant pancreas treated with surgery and proved by histological examination.

We describe a case of gastric aberrant pancreas with acute pancreatitis. Barium meal examination, endoscopic examination and computed tomography of a 32-year-old man with abdominal pain revealed a submucosal tumor, about 3.5 cm in diameter, at the angulus of his stomach. Endoscopic ultrasonography revealed a hypoechoic mass with anechoic capillary areas. His serum amylase level was high at 262 IU/l. Laparoscopy-assisted local resection was carried out. The resected tumor revealed pancreatic tissue with extensive neutrophil infiltration in the gastric wall and fat necrosis in the subserosa. There are few cases of histologically proven acute pancreatitis in gastric aberrant pancreatic tissue.

Adult↗

PubMed2005

Gastritis cystica polyposa concomitant with gastric inflammatory fibroid polyp occurring in an unoperated stomach.

The endoscopic examination of a 61-year-old male patient revealed a protruding lesion in the greater curvature of the lower third area of the stomach. The lesion, 17 mm in size, was resected completely with endoscopic submucosal dissection using an insulated-tip diathermic knife (IT-ESD). Histological examination of the protruding lesion revealed proliferation of fibroblasts and infiltration of inflammatory cells in the mucosa and submucosa, and it was diagnosed as an inflammatory fibroid polyp (IFP). Gastritis cystica polyposa (GCP) was presented adjacent to the IFP. This may be the first report of GCP concomitant with gastric IFP occurring in an unoperated stomach.

Comorbidity↗

PubMed2004

Increased serum concentrations and surface expression on peripheral white blood cells of decay-accelerating factor (CD55) in patients with active ulcerative colitis.

Inflammatory stimuli induce expression and release of decay-accelerating factor (DAF), a complement-regulatory protein present on peripheral-blood cells. Therefore, in ulcerative colitis (UC), an inflammatory colonic disease in which activated leukocytes are involved, DAF may be released from leukocytes into the circulation. In this study we compared serum DAF concentrations and surface DAF expression on peripheral-blood cells in patients with UC with disease activity. Peripheral-blood samples were obtained from 60 patients with UC (30 with active and 30 with inactive disease) and 19 healthy volunteers. Serum DAF concentrations were determined by means of immunoassay, and surface DAF expression on blood cells was examined with the use of flow cytometry. Serum DAF concentrations in patients with active disease (mean 48.6 ng/mL) were significantly higher than those in patients whose disease was in remission (33.3 ng/mL; P =.0003) and those in healthy controls (32.3 ng/mL; P =.0007). Surface DAF expression on neutrophils, CD14+ monocytes, and subsets of lymphocytes in patients with active UC was significantly increased compared with that in patients with UC in remission and in healthy controls. The increased serum DAF concentrations and surface DAF expression on leukocyte fractions in patients with active disease fell to significantly lower levels when the disease had gone into remission after medical therapy. Serum DAF concentrations are increased in UC patients in relation to disease activity. The likely source of increased DAF concentrations is peripheral-blood leukocytes that have been activated as part of the UC disease process.

Adult↗

PubMed2004

Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

Adenocarcinoma↗

PubMed2004

Enhanced expression of decay-accelerating factor, a complement-regulatory protein, in the specialized intestinal metaplasia of Barrett's esophagus.

Intestinal-type epithelium in Barrett's esophagus, so-called specialized intestinal metaplasia (SIM), is a risk factor for the development of esophageal adenocarcinoma. Surface expression of decay-accelerating factor (DAF), a complement-regulatory protein, is markedly enhanced in intestinal metaplasia of the gastric mucosa. We therefore examined DAF expression in areas of SIM in Barrett's esophagus in an attempt to determine whether DAF is a biomarker of SIM. We obtained 53 endoscopic biopsy specimens from the esophageal columnar mucosae of 45 patients. We immunohistochemically examined the distribution of DAF and 2 other complement-regulatory proteins: homologous restriction factor-20 and membrane cofactor protein. We also examined the expression of DAF messenger RNA in SIM with the use of laser-capture microdissection and reverse transcription-polymerase chain reaction. Of the 53 specimens, 10 were found histologically to involve areas of SIM, 41 were SIM-negative epithelium, and 2 comprised areas of SIM and SIM-negative epithelium. DAF staining was negligible in 35 of 43 specimens of the SIM-negative columnar epithelium, but DAF was strongly stained on the apical surface in all 12 SIM-positive specimens (P <.0001). In the 2 biopsy specimens in which both SIM and SIM-negative columnar epithelium were present, DAF staining was confined to the area of SIM. The expression of DAF messenger RNA was detected significantly more often in SIM than in SIM-negative columnar epithelium (P =.022). We conclude that DAF may be a surface marker for SIM and therefore useful in the identification of areas of the mucosa at risk for the development of adenocarcinoma in Barrett's esophagus.

Adult↗

PubMed2004

Complement regulatory proteins in normal human esophagus and esophageal squamous cell carcinoma.

BACKGROUND: Altered expression of three complement regulatory proteins, decay-accelerating factor (CD55), membrane cofactor protein (CD46) and homologous restriction factor 20 (CD59) has been identified in human gastrointestinal malignancies, but their expression in esophageal cancer has not been described. Therefore the purpose of the present paper was to study the distribution of these proteins in human normal and malignant esophageal mucosa. METHODS AND RESULTS: In the normal esophageal mucosa, CD55 predominantly stained on the cell membrane of squamous epithelium in the superficial and prickle cell layers, whereas CD46 most intensely stained on the cell membrane in the basal and parabasal cell layers. In contrast to this reciprocal expression of CD55 and CD46, CD59 was broadly distributed on the cell membrane in all layers. In the esophageal squamous cell carcinoma, CD55 staining was intense in the stroma but was negligible in the cancer cells. In contrast, CD46 and CD59 stained almost uniformly on the tumor cell membrane. There was a significant difference in the intensity of the staining of CD55 and CD46 among cells in various layers of normal esophageal mucosa and esophageal carcinoma cells, but not in the staining of CD59. Similar expression patterns of the three complement regulatory proteins in carcinoma cells and in normal epithelium in the basal and parabasal cell layers were observed. CONCLUSIONS: These observations on the expression of the three complement regulatory proteins would help understanding of the host immune responses involving the complement system against esophageal squamous cell carcinoma.

Antigens, CD↗

PubMed2004

[Clinical study of irinotecan therapy in patients with fluoropyrimidine-resistant advanced colorectal cancer].

The clinical efficacy and safety of irinotecan (CPT-11) therapy were studied retrospectively in patients with fluoropyrimidine-resistant advanced colorectal cancer. The subjects were 44 patients who were treated with CPT-11 alone or with a combination of CPT-11 and mitomycin C (MMC) at our institute from April 1999 to March 2003. CPT-11 (120-150 mg/m2) alone or CPT-11 with MMC (5 mg/m2) was administered every 2 weeks. The objective overall response rate was 11% (95% confidence interval, 3.8-25%). In 38 patients who were treated until October 2002, the median survival time was 12 months. Two-year survival rate was 13%. Grade 3 anorexia or diarrhea occurred in 6 patients (14%) and 5 patients (11%), respectively. There was no treatment-related death or early death within 30 days from the last administration of CPT-11 (+MMC). This retrospective study demonstrated the reproducible activity and safety of CPT-11 for the treatment of fluoropyrimidine-resistant advanced colorectal cancer in clinical practice.

Adenocarcinoma↗

PubMed2004

[Clinical study of gemcitabine therapy for recurrent or metastatic pancreatic cancer].

The clinical efficacy and safety of gemcitabine (GEM) monotherapy were studied retrospectively in the patients with recurrent or metastatic pancreatic cancer. The subjects were 30 patients who were treated with GEM at our center between May 2001 and August 2003. The objective overall response rate was 11% (3/28; 95% confidence interval, 2.3-28%). The disease control rate (CR+PR+SD) was 54%. Grade 3 or 4 neutropenia was most frequently seen in 46%. Non-hematological toxicities were mild. The median survival time was 4.8 months. One-year survival rate was 15%. This study showed the reproducible activity and safety of GEM in practice.

Adult↗

PubMed2003

Release of decay-accelerating factor into stools of patients with colorectal cancer by means of cleavage at the site of glycosylphosphatidylinositol anchor.

The expression of decay-accelerating factor (DAF), a cell-membrane-complement regulator, is enhanced in colorectal cancer, and DAF is detected in the stools of patients with colorectal cancer. In this study, to elucidate mechanisms whereby DAF is released into the colonic lumen, we analyzed and compared the properties of DAF in stools and colorectal-cancer tissues. Stool specimens taken before surgery and tissue samples from surgically resected colorectal cancers were obtained from 21 patients. We analyzed DAF in stool and tissue specimens using immunoblotting, ultracentrifugation, and phase separation with Triton X-114. We analyzed the expression profile of DAF mRNA in cancer tissues using reverse transcription-polymerase chain reaction to determine whether DAF transcripts for a secretory form of DAF were present. With the use of immunoblotting, stool DAF was detected as a broad band with a molecular weight of around 70,000 kDa that migrated slightly more slowly than cancer-tissue DAF. About 90% of stool DAF was present as a soluble form that remained in the 100,000 g supernatant after ultracentrifugation. On phase separation with Triton X-114, the soluble stool DAF was partitioned mainly into the aqueous phase, indicating its hydrophilic nature and lack of the fatty-acid glycosylphosphatidylinositol anchor component. In colorectal cancer tissues, reverse transcription-polymerase chain reaction experiments revealed a nonspliced DAF messenger RNA that encodes a secretory form of DAF in just 2 of the 21 specimens examined. These data suggest that DAF is released from colorectal cancer cells by way of cleavage of membrane-bound DAF at the site of the glycosylphosphatidylinositol anchor.

Adult↗

PubMed2003

A monoclonal antibody to rat asialoglycoprotein receptor that recognizes an epitope specific to its major subunit.

We previously developed three mouse monoclonal antibodies (MoAbs) identifying the domain-specific plasma membrane proteins of rat hepatocytes. Based on the results of immunohistochemical and immunoblot analysis, one of them, clone 8D7, likely recognizes the rat asialoglycoprotein receptor (ASGPR), which consists of three polypeptide subunits: rat hepatic lectin (RHL)-1, RHL-2 and RHL-3. In this study, we examined the reactivity of MoAb 8D7 with these subunits in order to identify specifically the protein it recognizes. RHL-1 and RHL-2/3 were expressed in COS-1 mammalian kidney cells transfected with cloned cDNAs. Reactivity of MoAb 8D7 with these proteins was examined by flow cytometry, immunoblotting, and an immunofluorescence staining. By flow cytometry, MoAb 8D7 reacted with cell surface proteins on the COS-1 cells transfected with RHL-1 cDNA but not with RHL-2/3 cDNA. By immunoblotting, the antibody recognized proteins (molecular weights 45 and 96 kDa) in RHL-1-expressing cells but not in the RHL-2/3 cDNA-transfected cells. Immunoreactive staining with MoAb 8D7 was observed on the cell surface and in the cytoplasm of RHL-1-transfected COS-1 cells but not in cells expressing RHL-2/3. These findings indicate that MoAb 8D7 recognizes a subunit-specific epitope on RHL-1 of rat ASGPR.

Journal Article↗

PubMed2003

Testing of multiple samples increases the sensitivity of stool decay-accelerating factor test for the detection of colorectal cancer.

OBJECTIVES: We previously reported that the measurements of stool decay-accelerating factor (DAF), a membrane-bound, complement regulatory protein, may be valuable for the detection of colorectal cancer. Recently we have refined the immunoassay for stool DAF. In the present study, using the refined assay, we measured stool DAF concentrations in multiple samples from patients with colorectal cancer and in healthy controls to determine whether testing of multiple samples would increase the sensitivity of the stool DAF test. METHODS: DAF was measured in three spontaneously passed stool samples from each of 100 patients with colorectal cancer and 100 control subjects without apparent colorectal disease. RESULTS: The stool DAF concentrations in the patients with colorectal cancer (median 11.1 ng/g stool; interquartile range 2.9-32.7 ng/g) were significantly higher than concentrations in the subjects without colorectal diseases (median 1.6 ng/g stool; interquartile range 0.4-3.4 ng/g) (p<0.0001). Testing of two samples from each patient significantly increased the sensitivity (72%) of the stool DAF test without significantly decreasing its specificity (92%). The stool DAF test was positive in more than one half of patients with colorectal cancer at a relatively early TNM stage or with negative fecal occult blood test. CONCLUSIONS: These findings suggest that stool DAF is a marker of colorectal cancer independent of fecal occult blood and testing of two samples increases the sensitivity of the stool DAF test. Measurement of stool DAF now seems worthy of further consideration as a noninvasive method for the detection of colorectal cancer.

Adult↗

PubMed2003

[Clinical study of TS-1 therapy for inoperable and recurrent gastric cancer].

The clinical efficacy and safety of TS-1 therapy were studied retrospectively in patients with inoperable and recurrent gastric cancer. The subjects were 45 patients who were treated with TS-1 for more than 4 weeks at our center between May 1999 and July 2002. The objective overall response rate was 32% (14/44; 95% confidence interval, CI, 19-48). The response rate in the chemo-naive patients was 44% (11/25; 95% CI, 24-65), and that in the patients with previous chemotherapy was 16% (3/19; 95% CI, 3.4-40). Although doses or durations of TS-1 administration were reduced in 22 patients (reduction group) due to adverse effects or poor performance status, they achieved a fairly high response rate of 38% (8/21). For primary lesions, the response rate was 30% (8/27). The prevalence of adverse reactions with a grade of 3 or 4 was 36%. However, the prevalence of each grade 3 or 4 adverse effect was relatively low, at 13% for neutropenia, and around 5% for anorexia, nausea, vomiting, and diarrhea. The median administration period was 10 weeks (4-47 weeks) in all patients and 11 weeks (6-47 weeks) in the reduction group. The relative dose intensity was 0.89 in all patients and 0.81 in the reduction group. In patients who were treated until August 2001, the median survival time (MST) was 13 months with 1-year and 2-year survival rates of 53% and 14%, respectively. These results were similar to those reported in the phase II study for the new drug approval. This study demonstrated the reproducible activity and safety of TS-1 in practice.

Adenocarcinoma↗

PubMed2002

Identification of a target antigen recognized by a mouse monoclonal antibody to the bile canalicular surface of rat hepatocytes with a random phage display library.

We developed a monoclonal antibody (MoAb) (clone 5E8) against an antigen on the bile canalicular membrane of rat hepatocyte. By immunoblotting, MoAb 5E8 detected a band of 110 kD. In this study, we used the phage display technique to identify the target antigen recognized by MoAb 5E8. We screened a random phage display library expressing 12-mer peptide sequences and identified a peptide sequence, FHFNPYTGHPLT, as an epitope. We compared this peptide sequence with those of dipeptidyl peptidase IV (DPP IV, E.C.3.4.14.5) and Cell-CAM105, which proteins were located by a database search based on the information of tissue localization and approximate molecular weight of the MoAb 5E8 antigen, and sequence similarity with a region in DPP IV (amino acids 225-233) but not with Cell-CAM105 was found. In addition, we immunohistochemically stained various tissues (liver, small intestine, and kidney) of Japanese Fischer 344 rats, known to be deficient for DPP IV, with MoAb 5E8 and showed that the expression of MoAb 5E8 antigen was negligible or weak. In contrast, tissues sampled from the same organs of Sprague-Dawley rats, known to express DPP IV, were positively stained. These findings suggest that the antigen recognized by MoAb 5E8 is DDPIV and its major epitope is located in amino acids at positions 225-233.

Amino Acid Sequence↗