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Biomedical subjects

H Iwase

Publications and source records attributed to H Iwase.

At least 163 records · Page 9Linked to original sources
PubMed1996

Reactivity of glomerular and serum IgA1 to jacalin in IgA nephropathy.

To analyze O-linked oligosaccharides (O-glycans) in the hinge region of IgA1 in IgA nephropathy (IgAN), the reactivity of IgA1 to jacalin, which specifically binds to O-glycans, was investigated. Initially, renal biopsy specimens from 5 patients with IgAN and 3 patients with other renal diseases were investigated in an immunofluorescence study with jacalin, monoclonal antihuman IgA1 and IgA2 antibodies. All of the renal biopsy specimens of IgAN and none of other renal diseases were positively stained by both FITC-labeled jacalin and monoclonal anti-IgA1 antibody. The glomerular staining patterns of FITC-jacalin were similar to those of the monoclonal anti-IgA1 antibody. IgA2 was negative in all specimens. Based on the positive reactivity of deposited IgA1 to jacalin, the binding ability of serum IgA1 to jacalin was evaluated by inhibition assay using D-galactose in patients with IgAN (n = 58), other primary glomerulonephritides (PGN) (n = 41), and healthy controls (n = 52). The frequencies of the patients with serum IgA1 having a high affinity for jacalin were significantly greater in IgAN (19/58, 32.8%) compared with the healthy controls (2/52, 3.8%) and other PGN (4/41, 9.8%). These results suggested that the increased reactivity of O-glycan(s) in the IgA1 hinge region to jacalin is due to an unusual glycosylation of serum IgA1 in IgAN.

Adult↗
PubMed1996

Association of asialo-galactosyl beta 1-3N-acetylgalactosamine on the hinge with a conformational instability of Jacalin-reactive immunoglobulin A1 in immunoglobulin A nephropathy.

The O-glycans in Jacalin-binding immunoglobulin A1 (IgA1) were released by gas-phase hydrazinolysis and were fractionated by gel filtration and reversed-phase HPLC. Four peaks (P1 to P4) were obtained. There was a significant shift from Peak 2 (monosialylated Gal beta 1-3GalNAc) to Peak 4 (asialo-Gal beta 1-3GalNAc) in the IgA-nephropathy group compared with the negative control group (P < 0.05). One of the functions of the carbohydrate side chains is to stabilize the three-dimensional structure of the glycopeptides. In order to evaluate the stability of the Jacalin-binding IgA1 molecule, the increase in turbidity as a consequence of the increase of the aggregated IgA1 level under the condition of high temperature (63 degrees C) was observed. The increase in the turbidity was significantly higher in the IgA nephropathy group compared with the negative control group (21.7 vs. 5.9% at 150 min, P < 0.02). From a sample of IgA1 solution that had originated from a pooled normal serum, heat-tolerant (nonaggregated) and intolerant (aggregated) IgA1 molecules were separated by gel filtration. The heat-intolerant IgA1 had lower amounts of sialic acid (27.4 micrograms/mg IgA1) than the tolerant IgA1 (37.6 micrograms/mg IgA1). Further, the analysis of the O-glycans released from another IgA1 sample by the hydrazinolysis revealed that the ratio of the asialo-Gal beta 1-3GalNAc/total Gal beta 1-3GalNAc in the heat-in-tolerant IgA1 (27.2%) was increased compared with that in the heat-tolerant IgA1 (18.2%). From these results, it was suggested that unusual glycosylation on the hinge region of Jacalin-binding IgA1 induced an insufficient conformational stiffness to the hinge peptide, resulting in the aggregation of the IgA1 molecule in IgA nephropathy.

Acetylgalactosamine↗
PubMed1996

Neoadjuvant chemotherapy in scirrhous cancer of the stomach using uracil and tegafur and cisplatin.

We administered a mixture of uracil and tegafur (UFT)/cisplatin (CDDP) chemotherapy in 28 patients with scirrhous gastric cancer. In the regimen, UFT was orally administered at a dose of 200 mg/m2 twice a day. The CDDP was administered at a dose of 90 mg/m2 by 24-hour continuous infusion every 4 weeks. As a result, antitumor effects for primary gastric foci were achieved in 14 of the 28 patients (50%). Ascites from peritoneal dissemination disappeared completely in eight of 13 patients (62%). Total gastrectomy was performed in ten patients after 2 to 3 courses of chemotherapy. Histological response grades assessed on the resected specimen were Grade 2 in four, Grade 1b in three, Grade 1a in one and Grade 0 in two patients. Neoadjuvant chemotherapy is feasible against scirrhous gastric cancer and a subsequent prospective randomized trial should be prepared to clarify the survival benefit of the treatment.

Adenocarcinoma, Scirrhous↗
PubMed1996

[Molecular analysis of the estrogen receptor (ER) gene in association with ER negativity in breast cancer].

DNA from ninety-eight primary breast cancer biopsies has been examined for loss of heterozygosity (LOH). Thirteen of seventy-two informative cases (18.1%) were positive for LOH, which correlated with age at operation but not with ER status. This result suggests that LOH of the ER gene does not have an important role in the lack of ER function in breast cancer tissues. Thirteen breast cancers with ER negative/progesterone receptor (PgR) positive were screened for mutation analysis of the ER gene using single strand conformational polymorphism (SSCP). We found 2 polymorphisms in codon 10 (C to G) codon 325 (C to T), although neither germline nor somatic mutation was detected. Since the sequence variant of codon 325 tends to be more frequently seen in ER negative/PgR negative breast cancer patients than non-cancer control patients, it is suggested that this polymorphism was related to negativity and function of ER in breast cancer tissues.

Breast Neoplasms↗
PubMed1995

Establishment of a monoepoxide (leukotoxin and its isomer) producing system using a hydrogen peroxide-generating system.

We established an effective monoepoxide-generating system by combining cytochrome-c (Cyt-c) with a hydrogen peroxide (H2O2)-generating system comprising hypoxanthine (HX), xanthine oxidase (XO) and superoxide dismutase (SOD; HX-XO-SOD-Cyt-c system). Using this and the H2O2-Cyt-c system, we proved that monoepoxide production from linoleic acid was due to hydroxy radical formation by the reaction of Cyt-c with H2O2 and not to the formation of other active oxygen species.

Benzoates↗
PubMed1995

pH dependent alterations of monoepoxides and monochlorohydrins of linoleic acid, and their existence in vivo.

Some monoepoxides of linoleic acid (LA) were converted to monochlorohydrins in low-pH solutions containing chloride ions (Cl-). Conversely, monochlorohydrins of LA were converted to monoepoxides in high-pH solutions. We attempted to determine whether these monochlorohydrins and monoepoxides were produced from LA by the cytochrome-c-H2O2-and/or myeloperoxidase-H2O2-system. The existence of monoepoxides and monochlorohydrins of LA in leukocytes was confirmed by high-performance liquid chromatography (HPLC). Furthermore, leukotoxin in human leukemia cells (THP-1) was stained immunohistochemically by a monoclonal anti-leukotoxin antibody.

Animals↗
PubMed1995

The presence of 2-keto-3-deoxygluconic acid and oxoaldehyde dehydrogenase activity in human erythrocytes.

2-Keto-3-deoxygluconic acid (3-DGA) is produced from 3-deoxyglucosone (3-DG:a highly reactive glycation intermediate) through oxidation by the enzyme oxoaldehyde dehydrogenase (OAD) in animals. We developed a specific assay method for 3-DGA using high-performance liquid chromatography [Fujii, E. et al. (1994) J. Chromatogr. B 660, 265-270] and measured it in the hemolysate and plasma of diabetic patients and healthy subjects. Both human erythrocytes and plasma contained considerable amounts of 3-DGA. However, human erythrocyte contained about 30-50 times higher 3-DGA than human plasma did and also had the same ability to convert 3-DG to 3-DGA as OAD had. Erythrocyte 3-DGA levels of diabetic patients were 990 +/- 370 nmol/gHb (n = 57, Mean +/- SD) and were significantly higher compared with healthy subjects (527 +/- 194 nmol/gHb, n = 7, p < 0.01). In all diabetic patients and healthy subjects (n = 64), there was only one patient who had a very low level of erythrocyte 3-DGA and lacked the ability to convert 3-DG to 3-DGA. When erythrocytes were incubated at 37 degrees C for 8 hours in phosphate buffer containing 0.35 mM 3-DG, 3-DG was easily taken into the erythrocytes and was converted to 3-DGA. Our results suggest the contribution of OAD not only to the prevention of glycation of hemoglobin but also to that of blood vessels by scavenging plasma 3-DG into erythrocytes.

Adult↗
PubMed1995

Determination of amino acids in human plasma by liquid chromatography with postcolumn ninhydrin derivatization using a hydroxyapatite cartridge for precolumn deproteination.

Amino acids in human plasma were determined by liquid chromatography with postcolumn ninhydrin derivatization using a hydroxyapatite cartridge for precolumn deproteination. S-Carboxymethyl-L-cysteine, D-phenylglycine and S-aminoethyl-L-cysteine were found to be suitable internal standards. The proposed method is simple, rapid (deproteination time less than 1 min) and reproducible [relative standard deviation below 3% except for low-level aspartic acid (n = 3)]. The average recovery of 25 amino acids was above 90%. The elution time of amino acids in human plasma was approximately 2 h. Protein binding of tryptophan was also determined by the proposed method. The analytical data for amino acids in human plasma deproteinated using the proposed and published methods (5-sulphosalicylic acid and ethanol) were compared.

Amino Acids↗
PubMed1995

Clinical significance of cathepsin D assay in breast cancer tissues.

Cathepsin D was assayed in 74 primary breast cancer specimens by enzyme immunoassay (EIA) and immunohistochemical assay (ICA). Of the 74 specimens, 38 (51.4%) were scored positive by ICA, and 25 (33.8%) were scored positive by EIA. The coincidence rate between ICA and EIA was 71.6% (53/74). There was no significant correlation between cathepsin D and menopausal status, tumor size, number size, number of metastatic lymph nodes, histological type of the tumor, or steroid receptor status. Cathepsin D status designated by EIA or ICA predicted neither disease-free survival (DFS) nor overall survival (OAS). Subject analysis with estrogen receptor, menopausal, and lymph node status revealed no association between cathepsin D and DFS or OAS. Therefore, cathepsin D is not an independent prognostic factor in breast cancer.

Adult↗
PubMed1995

Evaluation of serum tumor markers in patients with advanced or recurrent breast cancer.

Serum CA15-3, CEA, and BCA225 concentrations were determined in 98 patients with advanced or recurrent breast cancer in an attempt to correlate elevation with clinical status. The rate of serum positivity was 68.4% (67/98), 55.1% (54/98), and 43.9% (43/98) for CA15-3, CEA, and BCA225, respectively. After a 4 weeks-interval, a 20% change of tumor marker concentration from the preceding assay correlated significantly with clinical findings. Significant elevation was predictive of new recurrence or tumor regrowth after complete remission, especially in patients with bone metastasis. The 20% change in concentration at 4 weeks was also useful in patients with tumor marker concentrations persistently beneath the cut-off level for positive. Serological evaluation of tumor markers in patients with advanced or recurrent breast cancer should seek to document 20% changes over a 4 week interval.

Biomarkers, Tumor↗
PubMed1995

Immunohistochemical dynamics of leukotoxin (9,10-epoxy-12-octadecenoic acid) in lungs of rats.

This paper investigates the immunohistochemical dynamics of leukotoxin (9,10-epoxy-12-octadecenoic acid, LTx) in the lungs of rats exposed to hyperoxia with or without paraquat. The rats were treated with 100% oxygen or ambient air for 24, 48, 72 and 96 h in the presence or absence of a low or high dose paraquat (1,1'-dimethyl-4,4'-bipyridinium, PQ) injection. Immunostaining for LTx demonstrated positive reactions in the neutrophils that showed a progressive increase in intensity of staining with time in all groups exposed to 100% oxygen and in the group with high dose PQ, but the positive findings were weak in the group injected with low dose PQ only. We found the positive immunostaining reaction not only in neutrophils but also in alveolar macrophages. This indicates that LTx is produced by alveolar macrophages as well as by neutrophils depending on the treatment period under hyperoxic conditions, suggesting that LTx is an important chemical mediator in pulmonary diseases.

Animals↗
PubMed1995

Loss of heterozygosity of the oestrogen receptor gene in breast cancer.

DNA from 67 primary breast carcinoma biopsies has been examined for loss of heterozygosity (LOH) using the microsatellite (TA)n repeat marker positioned 1 kb upstream of the oestrogen receptor (ER) gene. Forty-seven (70.1%) of the cases were informative; nine of these (19.1%) were positive for LOH. In three of the nine cases, there was total loss, and in the other six cases there was a marked reduction in the intensity of signal from one allele. LOH correlated weakly with histological grade and age, but not with ER status. This result suggests that LOH of the ER gene does not have an important role in the lack of ER function in breast cancer tissues.

Base Sequence↗
PubMed1995

Higher dopamine level in lymph from the cervical lymph trunk than in plasma following intravenous bolus injection of L-dopa in rats.

To clarify the mechanism(s) responsible for nausea and vomiting induced by L-dopa administration, dopamine levels in the plasma and lymph of rats were investigated in the 60-min period following an intravenous bolus of L-dopa (2.5 mg/kg body weight). The dopamine level in plasma from the femoral artery was the highest at 5 min immediately after the L-dopa injection, and was eliminated thereafter. Showing the same tendency as the plasma, the lymph from the thoracic duct showed a maximal increase of dopamine at 0 to 10 min, and a rapid decrease later. In contrast, the dopamine level in the lymph from the cervical lymph trunk increased, peaked at 10 to 20 min, and fell gradually thereafter. The dopamine level in the cervical lymph was higher than that in the thoracic lymph. When these data were kinetically analyzed, the cervical lymph had a larger area under the dopamine concentration-time curve than the thoracic lymph. Both the cervical lymph and the thoracic lymph had longer values of dopamine mean residence time than the plasma. Our findings revealed that when L-dopa was administered with an intravenous bolus, dopamine was higher and remained longer in the cervical lymph than in the rest of the body.

Animals↗
PubMed1995

[Binding of IgA1 to monocyte/macrophage cell lines (THP-1, U937) in IgA nephropathy--a possible role of O-glycan in the IgA1 molecule].

IgA1 is an exceptional serum glycoprotein because it has O-glycans in the hinge region. It has been observed that the monocyte/macrophages infiltrate within the glomeruli in IgA-N. On the other hand, it is well established that the carbohydrate side chains (N-glycans) of the IgG molecule play a role in the binding of IgG to Fc receptors. Therefore, the binding of IgA1 to monocyte/macrophage cell lines was observed with the aim of clarifying the role of the O-glycan side chains in IgA-N in the initial mechanism of glomerular damage due to the interaction between the O-glycan chains on the IgA1 molecule and infiltrating monocyte/macrophages. Two human myelomonocytic cell lines, THP-1 and U-937, were activated and incubated with separated IgA1 (IgA-N, n = 16; other glomerulonephritides (other GN), n = 15; healthy controls, n = 9). The binding attitude of IgA1 to the cell lines was observed by flow immunofluorometry using a FACScan. FACScan showed that the binding of IgA1 to both of the stimulated monocyte/macrophage cell lines was increased in IgA-N compared to the normal controls and other GN. The binding of IgA1 to THP-1 was partially, but definitely inhibited by adding 100 mM melibiose (19.6 +/- 7.7%) and galactose (13.1 +/- 2.9%), but not glucose (2.9 +/- 2.2%), lactose (4.7 +/- 4.7%) and mannose (3.3 +/- 3.3%). These results suggested that THP-1 had a receptor that recognized the O-glycan in the IgA1 hinge region.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗
PubMed1995

[Expression of E-cadherin in thyroid neoplastic tissues and its correlation with malignant and metastatic potential].

Cadherin is an Ca2+ dependent adhesion molecules, which contribute to cell-cell adhesion and maintenance of tissue structures. Its decrease or functional abnormality plays an important vole in cancer invasion and metastasis. We investigate the expression of E- cadherin in thyroid neoplasms (papillary cancer, follicular cancer, medullary cancer anaplastic cancer and follicular adenoma) and normal thyroid. The decrease of E-cadherin expression in thyroid cancer correlates with its malignancy and metastatic potentiality.

Adenocarcinoma, Follicular↗