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Biomedical subjects

Y Hiki

Publications and source records attributed to Y Hiki.

At least 19 recordsLinked to original sources
PubMed2001

Identification of N(omega)-carboxymethylarginine, a new advanced glycation endproduct in serum proteins of diabetic patients: possibility of a new marker of aging and diabetes.

A new advanced glycation end product (AGE), N(omega)-carboxymethyl-arginine (CMA), was found in acid-soluble skin collagen of a newborn bovine prepared by in vitro glycation with 1 M glucose incubation at 37 degrees C for about 30 days [ 1 ]. CMA production was increased with incubation time in parallel, and after 30 days incubation the yield was 100 times higher than that of pentosidine [ 1 ]. This result suggested the importance of CMA as a major AGE in collagen. We have detected and measured the CMA level in human serum proteins by electrospray ionization/liquid chromatography/mass spectrometry (ESI/LC/MS), using CMA standard concentration curve. In this report, we first show the existence of CMA in vivo, and its serum level is significantly elevated in diabetic serum proteins, compared to age-matched control serum proteins. These results provide strong evidence that CMA is a new diagnostic marker of glycation in diabetes.

Aging↗
PubMed2001

Analysis of the microheterogeneity of the IgA1 hinge glycopeptide having multiple O-linked oligosaccharides by capillary electrophoresis.

It was found that the self-aggregation of IgA1 was closely connected with the glycoform of a mucin-type sugar chain on its hinge portion. In this report, normal human serum IgA1 was separated into two subfractions by a jacalin column. The elution condition, 25 mM galactose, used here was similar to that reported for the glycoprotein with a single mucin-type sugar chain per molecule. The IgA1 eluted under this condition was substantially the monomeric form. In contrast, the remaining IgA1 eluted from the column with 0. 8 M galactose was substantially the aggregated form. An analytical method for the microheterogeneity of the IgA1 hinge glycopeptide (HGP33) was developed to determine the difference between these IgA1 fractions by capillary electrophoresis (CE). Native HGP33 from both IgA1 fractions was separated into peaks 1-11, depending on their glycoforms. Because the sialic acid-rich component migrated slowly on CE, the 25 mM fraction was abundant in the sialic acid-rich components (peaks 7-11), but the 0.8 M fraction was abundant in the sialic acid-poor components (peaks 1-4). Comparison of the number of sugar chains per hinge peptide indicated that the 25 mM fraction was relatively well glycosylated. Thus, application of CE analysis to the HGP33 indicated that the monomeric IgA1 was composed of a relatively complete molecule with respect to the glycoform rather than the aggregated IgA1.

Chromatography, Affinity↗
PubMed2001

Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy.

BACKGROUND: The IgA1 molecule, which is predominantly deposited in glomeruli in IgA nephropathy (IgAN), is a unique serum glycoprotein because it has O-glycan side chains in its hinge region. Our study was conducted to investigate the O-glycan structure in the glomerular IgA1 in IgAN. METHODS: The IgA1 was separated from 290 renal biopsy specimens of 278 IgAN patients and from four serum IgA1 samples (IgAN, 2; control, 2). The variety of O-glycan glycoform was determined by estimating the precise molecular weights of the IgA1 hinge glycopeptides using matrix-assisted laser desorption ionization time of flight mass spectrometry. RESULTS: The peak distribution of IgA1 hinge glycopeptides clearly shifted to lesser molecular weights in both glomerular and serum IgA1 in IgAN compared with the serum IgA1 of controls. In the five major peaks of IgA1 hinge glycopeptides in each sample, the numbers of carbohydrates composing O-glycans (GalNAc, Gal, and NANA) in the deposited and serum IgA1 in IgAN patients were significantly fewer than those in the serum IgA1 in the control groups. CONCLUSION: The O-glycan side chains in the hinge of the glomerular IgA1 were highly underglycosylated in IgAN. These results indicate that the decreased sialylation and galactosylation of the IgA1 hinge glycopeptides play a crucial role in its glomerular deposition in IgAN.

Adult↗
PubMed2001

[Combination chemotherapy of doxifluridine plus mitomycin C for colorectal lung metastasis--phase II study].

PURPOSE: We conducted a multi-center study to investigate the usefulness of a combination drug therapy with doxifluridine (5'-DFUR) and mitomycin C (MMC) in colorectal cancer patients with lung metastasis. PATIENT AND METHODS: Subjects were advanced/recurrent colorectal cancer patients with lung metastasis, who underwent concomitant drug administration with 533 mg/m2/day of 5'-DFUR orally and 4 mg/m2/day of MMC every 2 weeks intravenously. RESULTS: Of 84 patients registered, 54 patients who were evaluable for tumor response showed results such as: complete response, one; partial response, 4; no change, 30; and progressive disease, 19, corresponding to a response rate of 9.3%. The median survival period of 54 patients was long at 473 days. The median administration days of 5'-DFUR was 201.5 days and the median number of MMC administrations was 14, indicating a long administration period of the combined therapy. The incidence of adverse drug reactions (ADRs) was 37.2% which included thrombocytopenia, 16.7%, and leukocytopenia, 11.5%; only a few ADRs were grade 3 or over. CONCLUSIONS: While combined therapy with 5'-DFUR and MMC resulted in a low response rate, the regimen suggested a survival effect in the patients.

Adult↗
PubMed2000

Direct evidence for decreased sialylation and galactosylation of human serum IgA1 Fc O-glycosylated hinge peptides in IgA nephropathy by mass spectrometry.

Human serum immunoglobulin IgA1 is produced in bone marrow and interacts with specific cellular receptors that mediate biological events. In this study, we have analyzed the detailed glycoform structure of the human serum IgA1 Fc O-glycosylated hinge region by electrospray ionization liquid mass spectrometry. The IgA1 fragments containing the hinge glycopeptide were separated from 4 IgA nephropathy patient (IgAN) pooled sera, 10 non-IgAN pooled sera with other primary glomerulonephritides, and 5 healthy control subject pooled sera by trypsin treatment and Jacalin affinity chromatography. The molecular weights of IgA1 hinge glycopeptide were estimated using mass spectrometry, and 13 sialo and 8 asialo glycopeptide groups were identified. The results obtained clearly showed a decrease of GalNAc, Gal, and sialic acid in IgAN compared with non-IgAN and normal controls, and those strongly suggested the possibility that the decreased galactosylation and sialylation of the IgA1 hinge result in its glomerular deposition in IgAN.

Adult↗
PubMed2000

[Combined laparoscopic-endoscopic procedure in stomach carcinoma].

The purpose of this review is to outline the laparoscopic-endoscopic procedures that we perform for early gastric cancer. These procedures were applied to 29 patients. Preoperative work-up included gastric endoscopy, barium X-ray examination, endoscopic ultrasonography, and histological examination, and surgery was performed in patients diagnosed as having mucosal gastric cancer for which endoscopic mucosal resection (EMR) was difficult. Laparoscopic wedge resection of the stomach using the lesion-lifting method, by which a wedge resection is made while pulling up the full-thickness gastric wall, was carried out in the 16 patients with lesions of the anterior wall, lesser curvature, and greater curvature of the stomach. On pathological examination of resected specimens, the surgical margin and lymphatic or venous invasion were negative in all these patients. The histological depth of the lesions was m (mucosal cancer) in 15 patients and sm1 (slight cancer infiltration into the submucosal layer) in one. This one patient later underwent gastrectomy but no lymph node metastases were found. Oral nutrition was resumed for a mean (+/- SD) of 2.9 +/- 0.8 days after operation, and the duration of hospitalization after operation was 12.3 +/- 3.4 days. The 13 patients with lesions of the posterior wall of the stomach and near the cardia or the pylorus received laparoscopic intragastric mucosal resection. Laparotomy was required in 1 of these patients due to intraoperative hemorrhage. The surgical margins were negative in all 12 patients in whom laparoscopic intragastric mucosal resection was successful. Lymphatic or venous invasion was positive in 2, both of whom had sm1 cancer lesions of both of these patients were located in the cardiac region, total gastrectomy was avoided, and careful observation is continued. Oral nutrition was resumed 4.0 +/- 1.6 days after operation, and the duration of hospitalization after operation was 12.0 +/- 3.5 days. In addition, no postoperative complication was noted after either procedure, and all patients have been recurrence free for a follow-up period of 460 months. Selected properly, these laparoscopic endoscopic procedures are considered to be curative and minimally invasive treatments for early gastric cancer.

Gastric Mucosa↗
PubMed2000

Measuring the tumor volume of gastric carcinoma by computer image analysis: clinical significance.

The tumor diameter of gastric carcinoma, measured by gross or histologic examination, is a rough indicator of actual tumor size. Therefore we investigated the utility of three-dimensional reconstruction of tumors in gastric carcinoma. Altogether 105 primary gastric carcinoma lesions, consisting of 16 advanced and 89 early carcinomas, were analyzed. A total of 942 lesion tissue sections, comprising 2 to 37 sections per lesion (mean 9 sections), were examined histologically. Surface rendering using a computer graphics analysis program was then performed from serial sections to create a three-dimensional reconstruction of tumor morphology from which to measure tumor volume. For the 105 lesions the tumor diameter ranged between 4 and 106 mm (average +/- SE: 32.4 +/- 2.0 mm), and tumor volume ranged between 4 and 5853 mm3 (average +/- SE: 773.0 +/- 104.6 mm3). A significant correlation was found between tumor diameter and the log of the tumor volume (r = 0.733, p < 0.0001). Although the logs of tumor volume for advanced carcinomas were all > 2.5, in 11 of these 16 patients (66%) the tumor diameter was < 4 cm, and in one patient < 2 cm. In addition, tumor diameter did not differ significantly between the 16 advanced and the 89 early gastric carcinomas (p = 0.114), whereas the log of the tumor volume did (p < 0.0001). In conclusion, conventional measurements of tumor diameter as a rough indicator of tumor size can predict the actual tumor size of a gastric carcinoma. Three-dimensional reconstruction using computer graphics provides a better estimation of true tumor size and extent of progression than tumor diameter.

Adult↗
PubMed2000

Feasibility of a novel weekday-on/weekend-off oral UFT schedule as postoperative adjuvant chemotherapy for colorectal cancer. UFT Compliance Study Group, Kanagawa, Japan.

PURPOSE: When oral anticancer agents are used for adjuvant chemotherapy of colorectal cancer, compliance and feasibility become issues because of the long treatment time. Appropriate studies of these issues are lacking. We investigated compliance and feasibility during a weekday-on/weekend-off schedule of oral UFT (uracil-tegafur) over a period of 1 year administered as adjuvant chemotherapy to patients with colorectal cancer. PATIENTS AND METHODS: A UFT dose of 600 mg/day was prescribed according to a weekday-on/weekend-off schedule to 87 patients after potentially curative resection. Compliance was investigated in three ways: physician interview, patient self-report, and chemical analysis of urine. The results were compared with the dose prescribed. Feasibility was evaluated on the basis of two indices: relative performance (RP), which was the ratio of the actual total dose taken to the total dose planned, and individual dose intensity (IDI), which was the ratio of the actual dose taken to the dose planned during a given period. RESULTS: The compliance assessed by physician interview and by patient self-report conformed well with the prescribed dose, the rate of agreement among the three compliance measures being more than 94%. Chemical analysis of urine in 38 of the patients revealed that they were actually taking the drug. The RP was 0.72, and the IDI was 0.8. CONCLUSION: From these results, the feasibility of the weekday-on/weekend-off schedule was judged to be good. It is suggested that the feasibility would be even better if the dose of UFT was set according to body surface area.

Administration, Oral↗
PubMed2000

Tumor volume: a novel prognostic factor in patients who undergo curative resection for gastric cancer.

BACKGROUND AND AIMS: The present study evaluates the significance of tumor volume as a prognostic factor in gastric cancer. PATIENTS/METHODS: Tumor volume was measured from serial tissue sections of 101 patients who had undergone curative resection for solitary carcinoma of the stomach using a computer graphics analysis program. These patients were analyzed with respect to survival based on univariate and multivariate analyses of clinicopathological factors, including tumor volume, to determine an independent prognostic factor. RESULTS: Significant differences in survival were found with respect to depth of tumor invasion (P=0.001), status of lymph-node metastasis (P=0.018), tumor diameter (P=0.005), and tumor volume (P<0.0001) based on univariate analysis. However, multivariate analysis indicated only tumor volume as a valid factor in determining prognosis among the nine variables and was significantly associated with the prognosis (P=0.0005; relative risk 18.23; 95% confidence interval 3.52-94.37). CONCLUSION: The present findings indicate that tumor volume is an important prognostic factor in patients who undergo curative resection for gastric cancer and may be an alternative to conventional factors, thus providing a novel independent prognostic factor in gastric cancer.

Adult↗
PubMed2000

Benign esophageal schwannoma: report of a case.

We report herein the case of an otherwise asymptomatic 62-year-old woman who was found to have an incidental esophageal lesion during endoscopic follow-up of an unrelated disorder. An esophageal submucosal tumor was diagnosed, and the patient was subsequently monitored on a regular yearly basis. As the diameter of the tumor doubled over a 4-year period, the possibility of a malignant lesion could not be excluded, and she was admitted to our hospital for further investigations. Esophagography, endoscopy, endoscopic ultrasonography, and computed tomography confirmed a submucosal tumor, 35 mm in length, in the thoracic midesophagus. A leiomyoma or leiomyosarcoma was suspected based on the known incidence of such tumors, and tumor enucleation was performed. Gross inspection revealed a solid tumor arising from the wall of the esophagus. Histopathologic examination showed intertwined bundles of spindle cells with spiral-like proliferation, and immunohistochemical studies were positive for S-100 protein, whereby a diagnosis of esophageal schwannoma was established. The patient experienced no postoperative complications, and her clinical course to date has been satisfactory. To date, 2 years 8 months after surgery, she has shown no sign of tumor recurrence and remains in good health.

Esophageal Neoplasms↗
PubMed2000

Preoperative evaluation to predict technical difficulties of laparoscopic cholecystectomy on the basis of histological inflammation findings on resected gallbladder.

BACKGROUND: No papers have heretofore documented histological studies of cases involving the inflammation of resected gallbladder or examined surgical difficulties on the basis of pathological findings. METHODS: On the basis of the histological inflammation findings on the resected gallbladders of 437 patients who underwent laparoscopic cholecystectomy (LC), the factors affecting the technical difficulty of the operation were examined through preoperative clinical findings (13 items), diagnostic imaging (22 items), and blood test findings (6 items), using multivariate analysis. RESULTS: In accordance with the four-stage classification of inflammation findings for the resected gallbladder, the inflammation findings on the resected gallbladder indicated a higher correlation with the time required for gallbladder dissection (30.2 +/- 16.3 minutes) than with the operation time (77.6 +/- 32.7 minutes). Thus, the technical difficulty of the operation was judged according to the time required for gallbladder dissection. For the preoperative findings on 418 patients who underwent successful LC, the most influential factors on the time required for gallbladder dissection were the presence of abnormal findings on computed tomography, the degree of fever, obesity index, nonvisualized gallbladder cholangiography, and cystic duct length. According to the multiple regression equation of these five factors, the gallbladder dissection for the 19 patients who underwent conversion to open cholecystectomy (OC) due to extreme inflammation was calculated to require 61.9 +/- 12.3 minutes, and the patients who showed a gallbladder dissection time longer than 49.6 minutes were judged to have high technical difficulty predicted from the preoperative evaluation. In the preoperative evaluation, sensitivity was 79.6%, specificity was 97.6%, accuracy was 95.0%, positive predictive value was 85.0%, and negative predictive value was 96.6%. Next, each finding was scored on the basis of a multiple regression equation of five factors, and the technical difficulty of the operation was quantified using these scores. The score of the patients who underwent conversion to OC was 8.0 +/- 2.0, and the patients who showed a score higher than 6 were judged to have high technical difficulty. Almost the same results as in the aforementioned preoperative evaluation were obtained using these scores. CONCLUSION: The judgment using the scores was satisfactory in terms of the simplicity of evaluating the technical difficulties associated with each patient and the ease of obtaining information for each factor. The quantification of technical difficulty using the scores is useful for preoperative prediction of which patients will have difficulties in gallbladder dissection and the conversion to OC in LC. Our results suggest that the consideration of technical difficulties is important for conducting safe operations with avoiding intraoperative complications.

Adult↗
PubMed2000

[Problems concerning the prices of surgical operations in Japan. Union of Social Medical Insurance Committee Members of Surgical Societies in Japan].

The Union of Social Medical Insurance Committee Members of Surgical Societies in Japan was established in 1967. The union has tried to develop scientific methods to assess the price of surgical operations in Japan and proposed a tentative plan for the assessment of the price of operations. The price of an operation includes personnel expenses and other costs such as the prime costs to repay loans for land and buildings, and taxes. Personnel expenses are calculated by the grade of technical difficulties, the number of doctors and nurses and the duration of the operation. A more precise method to judge the difficulties of the operation seems to be necessary. To examine the recent increase in expenses for surgical materials, the cooperation of main hospitals authorized by surgical societies will be necessary. The prices of surgical operations presented by the Ministry of Health and Welfare of Japan correlated well with the prices proposed by the Union.

Fee-for-Service Plans↗
PubMed2000

[Optimal dosage of UFT in a weekday-on/weekend-off schedule as a postoperative adjuvant chemotherapy for colorectal cancer].

In evaluations of adjuvant chemotherapy with oral anticancer agents, compliance in taking the drug as prescribed (compliance), adverse reactions, and feasibility are important factors in setting the dose. A weekday-on/weekend-off schedule, in which 600 mg/day of UFT was taken for 5 consecutive days and not taken on the following 2 days, was carried out as a postoperative adjuvant chemotherapy for one year in 87 patients with colorectal cancer who had undergone potentially curative resection. The prescribed dose and the dose of ingestion confirmed by physician interview were both highly consistent with the dose of ingestion according to the patients' self reports, with consistency rates of more than 94% for both. Relative performance (RP) yielded a value of 0.72, and individual dose intensity (IDI) yielded 0.8 on average. Female gender, low body weight, and low body surface area were factors that negatively affected feasibility. None of the adverse reactions was serious. Based on the feasibility and adverse reactions, the dosage of UFT should be set according to the body surface area at 375-425 mg/m2/day. When this schedule is used as one arm of a controlled study, it is suggested that the dose should be decided with 400 mg/m2 as a guideline.

Adult↗
PubMed1999

Human serum immunoglobulin G3 subclass bound preferentially to asialo-, agalactoimmunoglobulin A1/Sepharose.

As we reported before, exoglycosidase treatment of human serum IgA1 changed it to a sticky molecule. In order to examine the presence of the specific binding protein to the sticky IgA1 in human serum, IgA1, asialo-IgA1 (IgA1-S) and asialo-, agalacto-IgA1 (IgA1-SG)/Sepharose column chromatography of normal human serum was carried out. Purified hinge glycopeptide (HGP33) prepared from IgA1 was used for the preparation of HGP/Sepharose. A portion of the serum protein was bound to those columns and eluted with the buffer containing 1.0 M NaCl. About four times the amount of protein was eluted from the IgA1-SG/Sepharose column than that from IgA1/Sepharose. Most of the eluted protein was IgG, and the IgG1 and IgG3 subclasses but neither IgG2 nor IgG4 was dominant. Under the lower salt concentration, a portion of IgG was also bound to the HGP-SG/Sepharose column. The obtained results coincide well with the previous report of the co-present of IgG1 and IgG3 with deposited IgA1 in IgA nephropathy patients (Aucouturier, P., et al. (1989) Clin. Immunol. Immunopathol. 51, 338-347). Thus, the results solved the question of why the IgG3 was co-present with deposited IgA1 in IgA nephropathy patients.

Chromatography, Liquid↗
PubMed1999

Study of the relationship between sticky human serum IgA1 and its O-glycan glycoform.

The high-affinity IgA1 toward jacalin was mostly composed of aggregated IgA1 and abundantly contained the asialo disaccharide, Galbeta1,3GalNAc, in the O-linked oligosaccharide in the hinge region [Journal of Biochemistry 120, 92-97 (1996)]. Meanwhile, the removal of sialic acid from IgA1 accelerated the aggregation of the IgA1 molecule [J. Am. Soc. Nephrol. 9, 2048-2054 (1998)]. In order to examine the nature of such a sticky IgA1, affinity chromatography using asialo-IgA1 (deSIgA1)-Sepharose was carried out. Seventeen percent of normal human serum IgA1, 27% of asialo-IgA1 (IgA1-S), and 48% of asialo-, agalacto-IgA1 (IgA1-SG) were bound to the column. Removal of the N-acetylgalactosamine residue from IgA1-SG resulted in a decreasing affinity toward deSIgA1-Sepharose. Thus, the binding ability toward the column was the highest for the IgA1-SG among the deglycosylated IgA1s. On the other hand, heat treatment of IgA1 accelerated the aggregation but decreased its binding ability toward the column. Such heat denaturation probably destroys the structure of the binding site. Since the enzymatic removal of the N-glycan sugar chains did not induce the aggregation and exhibited no effect on the binding, the incomplete O-linked sugar chain on the hinge portion should be directly related to the sticky characteristics of the IgA1 molecule. The binding was non-covalent and not strong because the asialo-, agalacto-hinge glycopeptide was eluted slightly slower than the native one from the column and the bound IgA1 was dissociated in the presence of 1 M NaCl.

Chromatography, Affinity↗
PubMed1999

Mutual separation of hinge-glycopeptide isomers bearing five N-acetylgalactosamine residues from normal human serum immunoglobulin A1 by capillary electrophoresis.

Immunoglobulin A1 (IgA1) from normal human serum is known to have O-linked sugar chains, sialylated Galbeta1,3GalNAc, in the hinge portion. In order to reduce the microheterogenity of the sugar chain, the hinge glycopeptide prepared from IgA1 was sequentially treated with neuraminidase and beta-galactosidase. The asialo-, agalacto-hinge glycopeptide (HGP-SG) composed of a 33-mer peptide (HP33) and N-acetylgalactosamine (GalNAc) residues was obtained. The HGP-SG was separated into three major peaks, A, B and C, by high-performance liquid chromatography (HPLC). Each glycopeptide fraction was further separated by capillary electrophoresis (CE). Peaks A, B and C with HPLC abundantly contained HP33 bearing five and six N-acetylgalactosamine residues (HGP33-5,6GN), HGP33-4,5GN and HGP33-3,4GN, respectively. Among these glycopeptide peaks, only the HGP33-5GN peak was partly split into two peaks based on the CE analysis - HGP33-5GN-alpha and -beta. The glycopeptide, HGP25-5GN shortened by the thermolysin digest of HGP33-SG was also well separated into the alpha and beta forms by CE analysis. No differences in their mass and peptide portion were observed between HGP25-5GN-alpha and -beta. Therefore, the obtained result might indicate that HGP25-5GN-alpha was an isomer of HGP25-5GN-beta differing in its stereospecific structure of the peptide portion and/or the attachment site of the GalNAc residue.

Acetylgalactosamine↗
PubMed1999

Aggregated human serum immunoglobulin A1 induced by neuraminidase treatment had a lower number of O-linked sugar chains on the hinge portion.

A part of human serum immunoglobulin A1(IgA1) was aggregated by treatment with neuraminidase. Aggregated IgA1 was separated from non-aggregated IgA1 by gel permeation chromatography. The prepared asialo-hinge glycopeptide (asialo-HGP) from both IgA1 subfractions was treated with beta-galactosidase to determine the number of beta-linked sugar chains attached on the hinge region. Removal of the galactose residue from asialo-HGP resulted in the HPLC separation of three major peaks. MALDI-TOFMS analysis of the glycopeptides also indicated the presence of three HGP components with three, four and five N-acetylgalactosamine (GalNAc) residues, respectively. Comparison of their relative content among the glycopeptide components showed a higher content of the HGP component with a lower number of GalNAc residues on aggregated IgA1. Thus, asialo-HGP prepared from aggregated IgA1 induced by neuraminidase treatment had an incomplete core structure of O-linked oligosaccharides. Especially, the result suggested that the reduced number of the attached O-linked oligosaccharides on IgA1 take part in phenomena such as self-aggregation of asialo-IgA1.

Amino Acid Sequence↗