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Biomedical subjects

Y Hiki

Publications and source records attributed to Y Hiki.

At least 37 records · Page 2Linked to original sources
PubMed1999

Endoscopic diagnosis of mucosal cancer.

Now that minimally invasive treatment is performed more widely, it is important that more cases indicated for such treatment are diagnosed, i.e., microcancers that can be treated endoscopically should be accurately diagnosed. Since the diameter of early gastric cancer indicated for endoscopic treatment is generally less than 2.0 cm, detection of these microcancers is crucial and improvement in the endoscopic diagnosis is needed. We discuss the method for measuring lesion size, the procedure of dye scattering endoscopy, and the types of dyes used in this examination. In addition, we describe a method for increasing the diagnostic accuracy in the color of the vasoconstriction by the spraying of a drug that acts directly on the capillaries in the gastric mucosa. These basic aspects of endoscopic diagnosis of early gastric cancer will significantly assist gastroenterologists. We hope that these skills will be mastered and that endoscopic diagnosis, built on a firm foundation, will become even more widespread.

Capillaries↗
PubMed1999

Duodenoesophageal reflux induces apoptosis in rat esophageal epithelium.

The esophageal epithelial damage caused by duodenoesophageal reflux was examined by assessing histology, free radicals, and apoptosis in rats with an end-to-side esophagoduodenostomy (reflux group) or sham operation. Rats were sacrificed at 1, 6, or 12 weeks after surgery. Reflux-associated hyperplasia was noted in the reflux group at 6 and 12 weeks. The reflux group manifested glutathione (GSH) overproduction at one and six weeks. Apoptotic cells were detected by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling method. Significantly increased numbers of apoptotic cells were seen on the epithelial surface in the reflux group at 6 and 12 weeks. Duodenoesophageal reflux causes esophageal injury with hyperplasia. Early GSH overproduction indicated that reflux esophagitis may be partly mediated by free radicals. Increased apoptosis may counteract increased proliferation and may be a protective mechanism against increased genotoxic events.

Animals↗
PubMed1999

Exposed peptide core of IgA1 hinge region in IgA nephropathy.

BACKGROUND: The human IgA1 hinge region is a very unique O-linked glycopeptide, and its sialylation and galactosylation recently were reported to be defective in the serum IgA1 derived from patients with IgA nephropathy (IgAN). This study was performed to examine the underglycosylation of the IgA1 hinge region and consequent exposure of the peptide core in IgAN. METHODS: A polyclonal antibody against a synthetic human IgA1 hinge peptide, PVPSTPPTP SPSTPPTPSPS, (anti-sHP ab) was raised in rabbits and shown specifically to recognize the IgA1 which was treated with neuraminidase, beta-galactosidase and alpha-N-acetylgalactosaminidase. The reactivity of the anti-sHP ab against the purified serum IgA1 was compared among the following three groups: 39 patients with IgAN, 30 patients with other renal diseases (ORD) and 21 healthy controls (HC) using an enzyme-linked immunosorbent assay. RESULTS: The reactivity was significantly higher in the IgAN group (mean +/- SD of OD 490 nm: 0.327 +/- 0.059) than in the ORD group (0.274 +/- 0.043, P=0.0002) and in the HC group (0.265 +/- 0.037, P<0.0001). No significant difference was observed between the latter two groups. The frequency of positive cases (> mean +/- 2SD of HC) was 46.2% (18/39) in the IgAN group, 6.7% (2/30) in the ORD group and 0% (0/21) in the HC group. CONCLUSIONS: It was suggested that the peptide core of the IgA1 hinge region is exposed aberrantly by a defective N-acetylgalactosaminylation and plays a possible role in the pathogenesis of IgAN.

Adolescent↗
PubMed1999

Underglycosylation of IgA1 hinge plays a certain role for its glomerular deposition in IgA nephropathy.

This study was performed to isolate and investigate the IgA1 that could accumulate in glomeruli (glomerulophilic IgA1). IgA1 was fractionated by the electric charge and the reactivity to Jacalin. Serum IgA1 of IgA nephropathy patients was separated and fractionated using a Jacalin column and subsequent ion-exchange chromatography. The fractions were divided into three groups of relatively cationic (C), neutral (N), and anionic (A). IgA1 was also divided into Jacalin low (L), intermediate (I), and high (H) affinity fractions by serial elution using 25, 100, and 800 mM galactose. The left kidneys of Wistar rats were perfused with 2, 5, or 10 mg of each group of IgA1. The rats were sacrificed 15 min, 30 min, 3 h, or 24 h after the perfusion. The accumulation of each IgA1 in the glomeruli was then observed by immunofluorescence. The IgA1 of the fractions N and H separated by the two methods was definitely accumulated in the rat glomeruli with a similar pattern. The electrophoresis revealed that the macromolecular IgA1 was increased in fraction H compared with other fractions. Therefore, Jacalin high-affinity IgA1(fraction H) was applied on a diethylaminoethyl column and divided into electrically cationic (HC), neutral (HN), and anionic (HA). Only the asialo-Galbeta1,3GalNAc chain was identified in the fraction HN IgA1 by gas-phase hydrazinolysis. Furthermore, the IgA1 fraction was strongly recognized by peanut agglutinin, Vicia Villosa lectins, and antisynthetic hinge peptide antibody. These results indicated that the IgA1 molecules having the underglycosylated hinge glycopeptide played a certain role in the glomerular accumulation of IgA1 in IgA nephropathy.

Animals↗
PubMed1999

[Combination of 5'-DFUR and MMC for recurrent rectal cancer with pulmonary metastasis].

We report a 68-year-old man with rectal cancer and recurrent pulmonary metastasis treated with concomitant 5'-DFUR + MMC, which resulted in an extreme reduction of the lesion. The initial pulmonary metastases were treated by pneumonectomy, but 32 months later the patient again showed a pulmonary metastasis. Thus, from July 1997, he was treated with 5'-DFUR (800 mg/day) + MMC (4 mg/2 weeks). After 3 months of therapy, the chest CT examination showed an extreme reduction of the pulmonary lesion, and at 5 months the lesion was even smaller. Presently, after 7 months of therapy, the lesion remains stable. His CEA level is 1.0-2.6 ng/ml. After 4 months of treatment he had mild anorexia, which was alleviated by reducing the 5'-DFUR to 600 mg/day. No other adverse reaction was observed; the therapy was safely conducted on an outpatient basis.

Adenocarcinoma↗
PubMed1998

Application of matrix-assisted laser desorption ionization time-of-flight mass spectrometry to the analysis of glycopeptide-containing multiple O-linked oligosaccharides.

In our previous report [Iwase et al., J. Biochem., 120 (1996) 393], the number of O-linked oligosaccharide chains on the hinge region of IgA1 was estimated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS). In this experiment, the number of non-substituted N-acetylgalactosamines and Galbeta1,3GalNAc residues, as the core O-linked oligosaccharide structure per heavy chain of normal human serum IgA1, was estimated by digestion of the asialo-hinge glycopeptide with alpha-N-acetylgalactosaminidase (GalNAc-ase) or endo-alpha-N-acetylgalactosaminidase (endo-GalNAc-ase). GalNAc-ase treatment of the asialoglycopeptide produced two major peaks, one being a glycopeptide containing four GalNAc and four Gal residues, and the other contained three GalNAc and three Gal residues. Treatment with endo-GalNAc-ase also produced a nearly equal amount of the two peaks, with the naked hinge peptide and the peptide having one GalNAc residue. From those results, we concluded that the asialo-hinge glycopeptide was composed of three components bearing four Galbeta1,3GalNAc and one GalNAc, only four Galbeta1,3GalNAc, and three Galbeta1,3GalNAc and one GalNAc, respectively. This method was useful for determining the glycoforms on the IgA1 molecule with respect to the core O-linked oligosaccharide structure.

Carbohydrate Conformation↗
PubMed1998

Evidence for a site-specific fucosylation of N-linked oligosaccharide of immunoglobulin A1 from normal human serum.

Glycopeptides containing the N-linked oligosaccharide from human serum IgA1 were analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS). Two glycopeptides, GP1 and GP2, prepared from the endoproteinase Asp-N digest of the IgA1 heavy chain, were derived from the CH2 domain (N-glycan site at Asn263) and the tailpiece portion (N-glycan site at Asn459), respectively. The structure of the attached sugar chain was deduced from the mass number of the glycopeptide and confirmed by a two-dimensional mapping technique for a pyridylaminated oligosaccharide. GP1 was composed of two major components having a fully galactosylated bianntena sugar chain with or without a bisecting N-acetylglucosamine (GlcNAc) residue. On the other hand, the GP2 fraction corresponded to the glycopeptides having a fully galactosylated and fucosylated bianntena sugar chain partly bearing a bisecting GlcNAc residue. Thus, the site-specific fucosylation of the N-linked oligosaccharide on the tailpiece of the alpha1 chain became evident for normal human serum IgA1.

Amino Acid Sequence↗
PubMed1998

Low levels of apoptosis and proliferative activity in colorectal villous tumors: comparison with tubular tumors.

In order to clarify the cell kinetics of colorectal villous tumors (VT), 21 villous adenomatous areas and 12 carcinomatous areas within villous adenomas were investigated for proliferative activity and apoptosis and compared with a series of 41 tubular tumors (TT), demonstrating elements of intramucosal carcinomas as well as tubular adenomas (so-called carcinoma in tubular adenoma). Proliferation was estimated in terms of Ki-67 labeling indices and mitotic indices, and apoptosis was assessed by DNA nick-end labeling to give apoptotic indices. Apoptotic indices of villous adenomatous and carcinomatous regions were significantly lower than the values for their tubular counterparts. Ki-67 labeling indices were also significantly lower for adenoma components. Apoptotic indices, Ki-67 labeling indices and mitotic indices increased with atypia raised in tubular adenoma components. Correlations of mitotic indices with apoptotic indices, Ki-67 labeling indices with apoptotic indices and mitotic indices with Ki-67 labeling indices were found for each villous tumor group and tubular tumor group, and the apoptosis and proliferation ratios for villous tumors were relatively low, suggesting a tendency for greater growth due to less cell deletion. Although this is only one of the biological features of villous tumor groups, it might play a major role in generation of malignancy.

Adenocarcinoma↗
PubMed1998

Protective role of IgA1 glycans against IgA1 self-aggregation and adhesion to extracellular matrix proteins.

The aim of this study was to investigate the role of carbohydrate moieties attached to IgA1 hinge region in IgA1 self-aggregation and adhesion to extracellular matrix (ECM) proteins previously reported in IgA nephropathy. Serum IgA1 samples isolated from healthy individuals were digested with neuraminidase (NA), NA + beta-galactosidase, and NA + beta-galactosidase + alpha-N-acetylgalactosaminidase to remove the carbohydrates from the hinge region and were named asialo, agalacto, and naked IgA1, respectively. First, polyacrylamide gel electrophoresis was performed under the native condition, and consequently, a broad band indicating IgA1 self-aggregation was clearly observed in asialo, agalacto, and naked IgA1, but not in native IgA1. However, the broad band disappeared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the nonreducing condition. Second, it was shown that IgA1 adhesion activities to type IV collagen, fibronectin, and laminin were significantly higher in asialo, agalacto, and naked IgA1 than in native IgA1, using enzyme-linked immunosorbent assay (asialo, agalacto, and naked versus native: P < 0.01). In addition, agalacto IgA1 had the highest affinity for all of the ECM proteins among the deglycosylated IgA1 (agalacto versus asialo and naked, P < 0.05). These results indicated that the removal of carbohydrates from the IgA1 molecule resulted in noncovalent self-aggregation and a significant increase in adhesion to the ECM proteins. It was therefore suggested that the IgA1 glycans played a protective role against aggregation and adhesion and that the underglycosylation of the IgA1 molecule found in IgA nephropathy could be involved in the nonimmunologic glomerular accumulation of IgA1.

Electrophoresis, Polyacrylamide Gel↗
PubMed1998

Analyses of IgA1 hinge glycopeptides in IgA nephropathy by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

This study was performed to analyze the structural variety of O-glycans on the IgA1 hinge in IgA nephropathy (IgAN). The IgA1 fragments containing the hinge glycopeptide (33-mer hinge peptide core (HP) + O-glycans) were separated from 13 IgAN patients, eight healthy control subjects, and 11 patients with other primary glomerulonephritides by pyridylethylation, trypsin treatment, and Jacalin affinity chromatography. Because of the use of Jacalin, only the Gal beta 1-3GalNAc residue containing IgA was analyzed. The molecular weights (MW) of the IgA1 fragments treated by the following sequential treatment by exoglycosidases were estimated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: (1) Sialidase treatment: the MW of the two observed peaks A and B were compatible with (A) HP + 4GalNAc + 4Gal and (B) HP + 5GalNAc + 4Gal. (2) Sialidase and galactosidase: the MW of the two identified peaks a and b were consistent with (a) HP + 4GalNAc and (b) HP + 5GalNAc. (3) Sialidase, galactosidase, and alpha-N-acetylgalactosaminidase. All subjects revealed one peak, indicating the 33-mer IgA1 hinge peptide core. The intensity rate of peak B/A was significantly decreased in the IgAN group (mean +/- SD, 1.01 +/- 0.08) compared with the negative control subjects (healthy group, 1.15 +/- 0.06, P = 0.0048; other glomerulonephritis group, 1.13 +/- 0.10, P = 0.0049; Scheffe's F test). These results suggested the presence of a defect in the Gal and/or GalNAc residues in the IgA1 hinge glycopeptides in IgAN.

Amino Acid Sequence↗
PubMed1997

Evidence for involvement of IgA1 hinge glycopeptide in the IgA1-IgA1 interaction in IgA nephropathy.

The study was performed to investigate the role of the IgA1 hinge region in the IgA1-IgA1 interaction, which was observed previously in IgA nephropathy. The competitive inhibition assays of the IgA1-IgA1 binding were performed using the following candidates for inhibitors: native IgA1 hinge glycopeptide (nHGP), IgA1, IgA2, and IgG. The IgA1-IgA1 binding was definitely inhibited by the nHGP and the IgA1 (maximum of percent inhibition: 66.1 and 60.5%, respectively). There was no obvious inhibition in the IgA2 and the IgG. The inhibition curves of the nHGP and the IgA1 were significantly different from that of the IgG (P < 0.01, respectively). Furthermore, to reveal the detailed binding sites in the interaction, the same inhibition assays were performed using the following substances composing the IgA1 hinge glycopeptide: galactose (Gal), N-acetyl-galactosamine (GalNAc), Gal beta 1-3GalNAc, sialic acid, tetrapeptide PTPS, and synthesized hinge proline-rich peptide PVPSTPPTPSPSTPPTPSPS (sHP). sHP, Gal beta 1-3GalNAc, Gal, and GalNAc inhibited the binding (69.3, 34.1, 14.9, 14.6%, respectively). No obvious inhibition was observed in sialic acid and tetrapeptide PTPS. The inhibition curve of sHP was significantly different from that of the PTPS (P < 0.05). Those of Gal beta 1-3GalNAc, Gal, and GalNAc were also significantly different from that of sialic acid (P < 0.05, respectively). These results suggested that the IgA1-IgA1 interaction could be mediated by the core structure including the peptide and the sugars, except for sialic acid in the hinge region, resulting in the formation of the circulating macromolecular IgA1 in IgA nephropathy.

Adult↗
PubMed1996

Cooperative clinical trial of photodynamic therapy with photofrin II and excimer dye laser for early gastric cancer.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is a recently developed endoscopic method for treating malignant tumors. For obtaining more photodynamic action with less thermal effect, we employed as the excitation light source for PDT an excimer dye laser, which is a pulsed laser with extremely high peak power, instead of an argon dye laser, which is a continuous wave laser and has been used conventionally. STUDY DESIGN/MATERIALS AND METHODS: The effect of PDT using Photofrin II and the excimer dye laser was evaluated in 27 patients with early gastric cancer. RESULTS: Complete responses (CR) were obtained in 88% of 24 assessable patients and the response rate was 100%. CR was observed in all cases of lesions of superficial depressed type without ulceration and/or with tumor diameter less than 2 cm. Regarding toxicity, mild cutaneous reaction and photosensitivity were seen and lasted several weeks. There were no serious abnormalities in laboratory tests. CONCLUSION: We conclude that PDT is a promising modality for early gastric cancer.

Aged↗
PubMed1996

Thoracoscopic splanchnicectomy for the relief of intractable abdominal pain.

Video-thoracoscopic transthoracic splanchnicectomy has been applied to patients in the end stage of pancreas cancer who had intractable pain mediated through the splanchnic nerve in the left upper quadrant. The procedure is performed under general anesthesia in a right hemilateral position. Following the establishment of access to the thoracic cavity, the left splanchnic nerve is cut off at the level immediately above the aortic hiatus, through a small opening made in the pleura between the descending aorta and the vertebrae. All patients had immediate and complete relief of pain postoperatively. Only a transient drop in the mean arterial pressure was observed immediately after cutting off the nerve. No other detrimental effect of the procedure on the general condition was observed. No patients developed postoperative complications. The present method may, thus, be a treatment of choice directed toward the relief of intractable abdominal pain in selected patients with pancreatic cancer.

Abdominal Pain↗
PubMed1996

Abundance of Gal beta 1,3GalNAc in O-linked oligosaccharide on hinge region of polymerized IgA1 and heat-aggregated IgA1 from normal human serum.

Gas-phase hydrazinolysis was used to analyze the glycoform of the O-linked oligosaccharide of human serum IgA1. In our previous report, only one glycoform was obtained from the IgA1 of healthy individuals. However, it was found to be composed of heterogeneous IgA1 components having mutually different glycoforms. First, the IgA1 was separated into two subfractions having different affinities toward jacalin. Among them, the high-affinity subfraction was mainly composed of polymerized IgA1. Comparative study of the carbohydrate chain showed a relative abundance of Gal beta 1,3GalNAc in the polymerized form. A simultaneous analysis of the N-glycan of these subfractions was also carried out. Three major components, two biantennary and one triantennary oligosaccharides, were obtained from both subfractions and the relative contents of these components were almost the same. On the other hand, IgA1 was artificially polymerized by heating at 63 degrees C for 2 h. The heat-stable IgA1 was separated from the heat-aggregated material on a Sephacryl S-300 column. The obtained heat-stable IgA1 (approximately 20%) was not further aggregated by more heating under the same conditions. The heat-stable IgA1 contained a much higher amount of the sialylated Gal beta 1,3GalNAc. Thus, it was shown that the degree of completeness of the hinge O-linked oligosaccharide might be correlated with the stability and polymerization process of the IgA1 molecule.

Acetylgalactosamine↗
PubMed1996

Estimation of the number of O-linked oligosaccharides per heavy chain of human serum IgA1 by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis of the hinge glycopeptide.

In our previous study, gas-phase hydrazinolysis was used to analyze the glycoform of the O-linked oligosaccharide of human serum IgA1. All O-linked oligosaccharide chains are known to be present in the hinge portion. However, the number of O-linked oligosaccharide chains on IgA1 remained unclear. In order to determine the number of linked sugar chains, we applied matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) to the hinge glycopeptide prepared from human serum IgA1. MALDI-TOFMS did not show clear peaks, probably due to the microheterogeneity of the structure of each sugar chain. However, elimination of peripheral sialic acid and galactose residues by sequential treatment with neuraminidase and beta-galactosidase gave clear mass spectra with several sharp peaks. On the basis of these spectra, we conclude that IgA1 prepared from normal human serum carries different numbers of sugar chains. There are two major populations, one contains five GalNAc residues and the other four GalNAc residues. On the other hand, the hinge glycopeptide prepared from myeloma IgA1 was composed mainly of one population containing four GalNAc residues. Earlier, we reported incomplete glycosylation of IgA1 isolated from the serum of an IgA1 myeloma patient. In this experiment, the presence of four O-linked oligosaccharides per heavy chain of IgA1 from a myeloma patient was found. The reason why only four out of five sites on the hinge glycopeptide were fully glycosylated in the IgA1 from the IgA1 myeloma patient is not clear.

Amino Acid Sequence↗
PubMed1996

Apoptosis of colon cancers assessed by in situ DNA nick end-labeling method.

Apoptosis in colon cancers was investigated using in situ DNA nick end-labeling. Seventy-six colon cancer cases were divided according to histologically defined malignant grading, degree of invasion and other pathologic indicators. The apoptotic labeling index (ALI) was highest in cases with invasion limited to the submucosa, the difference as compared to other stages being statistically significant, while no correlation was noted between ALI and histological type. ALI significantly decreased with lymph node involvement of cancers. In contrast, there appeared to be no link with vessel invasion. ALI was significantly higher in lesions smaller than 2 cm in diameter. These results indicate that apoptosis in colon cancers is more frequent at a relatively early stage when the lesions are small, and suggest that the apoptotic phenomenon may play some role in regulating the size and progression of such tumors.

Adenocarcinoma↗
PubMed1996

Steroid therapy during the early stage of progressive IgA nephropathy. A 10-year follow-up study.

This study was undertaken to clarify the effect of corticosteroids on the long-term clinical course of the early stage of progressive IgA nephropathy. The early stage of progressive IgA nephropathy was defined as having moderate proteinuria between 1 and 2 g/day, creatinine clearance values of 70 ml/min or more, and a histological severity score of 7 or more. The number of patients who fulfilled these three conditions during 12 years from 1972 and then were continuously followed up for 10 years or more in our renal unit was 46. Twenty of them received steroid treatment for an average period of 18 months, and the remaining 26 patients had no steroid treatment. The initial data of proteinuria, creatinine clearance values, frequency of hypertensive cases, and histological scores of 7 or more were not different between the two groups: 1.4 +/- 0.4 vs. 1.3 +/- 0.3 g/day, 85 +/- 14 vs. 88 +/- 13 ml/min, 25 vs. 38%, and 10.7 +/- 2.5 vs. 11.0 +/- 3.0, respectively. During the follow-up period of 10 years, the renal survival rate was significantly different between the two groups (100 vs. 84% 5 years after starting therapy and 80 vs. 34% 10 years later; p < 0.001). The final creatinine clearance values were significantly different between the two groups (54 +/- 35 vs. 20 +/- 29 ml/min; p < 0.005). On the other hand, the patient groups with mild histological changes or decreased renal function due to moderate proteinuria showed no significant differences in the final outcome. These results indicate that corticosteroids are beneficial in stabilizing the renal function for a long time during the early stage of progressive IgA nephropathy, although this study was not a randomized one.

Adult↗