Search PubMed⌕ Search

Biomedical subjects

H Iwase

Publications and source records attributed to H Iwase.

At least 91 records · Page 5Linked to original sources

[Creating language model of the forensic medicine domain for developing a autopsy recording system by automatic speech recognition].

For the purpose of practical use of speech recognition technology for recording of forensic autopsy, a language model of the speech recording system, specialized for the forensic autopsy, was developed. The language model for the forensic autopsy by applying 3-gram model was created, and an acoustic model for Japanese speech recognition by Hidden Markov Model in addition to the above were utilized to customize the speech recognition engine for forensic autopsy. A forensic vocabulary set of over 10,000 words was compiled and some 300,000 sentence patterns were made to create the forensic language model, then properly mixing with a general language model to attain high exactitude. When tried by dictating autopsy findings, this speech recognition system was proved to be about 95% of recognition rate that seems to have reached to the practical usability in view of speech recognition software, though there remains rooms for improving its hardware and application-layer software.

Autopsy↗

Clinical Significance of Estrogen Receptor Àin Breast Cancer.

To estimate the clinical significance of estrogen receptor (ER) beta in breast cancer we reviewed some reports and compared them with our preliminary results. The structure of ERbetais similar to that of ER alpha. The DNA binding domain of ER beta is 96% conserved compared with ER alpha, and the ligand binding domain shows 58% conserved residues, suggesting that both receptors can bind estrogen responsiveelements on target genes and that they may also bind similar ligand. The targettissues of ER beta such as testis, prostate, lung, brain, thymus, and ovary, are different from those of ER alpha, ovary, uterus, endometrium, and breast. Although the function of ER beta in breast cancer progression is not well understood, 30-50% of breast cancers may express ER beta mRNA signals. Additionally, ER beta may be auseful prognostic factor in patients with breast cancer, because tumors that co-expressed ER alpha and ER beta might be node positive and tend to be of higher grade.Further characterization of the function of ER beta and its isoforms in breast cancer is warranted.

Journal Article↗

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↗

Suppression of ING1 expression in sporadic breast cancer.

Down regulation of the ING1 candidate tumour suppressor promotes growth in soft agar and focus formation in vitro and tumour formation in vivo. ING1 encodes a nuclear, cell cycle-regulated protein, overexpression of which efficiently blocks cell growth and is capable of inducing apoptosis in different experimental systems. Here we present the first report of ING1 mutation and expression analysis in a total of 452 cancer samples. One germline missense alteration and three germline silent alterations were detected in 377 primary breast cancers while marked (2 - 10-fold) decreases in ING1 mRNA expression were seen in 44% of primary breast cancers and in ten of ten breast cancer cell lines examined. Furthermore, the majority of breast cancers (58%) showing decreased ING1 expression had metastasized to regional lymph nodes whereas only 9% of cancers with elevated ING1 expression, compared to adjacent normal tissues, were metastatic. Thus, ING1 mutation is very rare in breast or ovarian cancers, however, repression of ING1 expression frequently accompanies tumour development of breast cancer.

Adult↗

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↗

Consecutively Occurring Multiple Fibroadenomas of the Breast Distinguished from Phyllodes Tumors by Clonality Analysis of Stromal Tissue.

We present a woman with consecutively occurring multiple fibroadenomas of thebreast distinguished from phyllodes tumor by clonality analysis of stromal tissue. Fifty-three masses developed in her right breast in an 11.5 year period since first onset. A clonality analysis, performed by polymerase chain reaction (PCR), focused on the Hpa II site within exon 1 of the androgen receptor (AR) gene. Estrogen receptor (ER) alpha immunohistochemistry was performed with a specific polyclonal antibody against the hormone binding domain of the protein. Since all of the nodules were polyclonal in stromal tissues, they were hyperplastic rather than true neoplasms such as phyllodes tumors. The co-existence of abundant adenosisfoci and numerous sub-clinical small nodules in the adjacent breast tissue alsosuggested proliferative stimuli throughout the breast. ER alpha protein was expressed only in the nuclei of epithelial cells. The possible influence of ER positive epithelial cells on stromal cell growth is discussed.

Journal Article↗

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↗

Sarin-like and soman-like organophosphorous agents activate PLCgamma in rat brains.

We report that there is a time-related change in the phospholipase C (PLC) activities of rat brain cytosol and membrane fractions after iv injection of a soman-like or a sarin-like organophosphorous agent (bis(isopropyl methyl)phosphonate [BIMP] and bis(pinacolyl methyl)phosphonate [BPMP]). PLCgamma was activated in the brain cytosol fraction from BPMP-injected rats. The phosphorylating activity of rat brain membrane fractions were enhanced by BPMP treatment. The brain membrane fractions from BPMP-treated rats phosphorylated several proteins, including supposedly PLCgamma in the brain cytosol fraction from control rats in vitro. These results suggest that soman and sarin may stimulate a membrane tyrosine kinase, including growth factor receptors, directly or indirectly.

Animals↗

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↗

Identification of cis-9,10-methylenehexadecanoic acid in submitochondrial particles of bovine heart.

Submitochondrial particles of bovine heart were hydrolyzed by phospholipase A2 and the products were analyzed by liquid chromatography electrospray ionization-mass spectrometry. We found a fatty acid with a molecular mass of 268 Da and a retention time longer than that of linoleic acid. Next, we synthesized organically cis-9,10-methylenehexadecanoic acid, which has a molecular mass similar to that of the extracted fatty acid, and characterized its high performance liquid chromatography and gas chromatography-mass spectrometry profiles. Using these data we were able to identify endogenous cis-9,10-methylenehexadecanoic acid in rat and human heart and liver tissues that had been hydrolyzed by phospholipase A2. This fatty acid was not detected in tissue extracts that had not been hydrolyzed by phospholipase A2. Similar amounts of cis-9, 10-methylenehexadecanoic acid were measured in tissue extracts after total hydrolysis. These results suggest that cis-9, 10-methylenehexadecanoic acid is a fatty acid component, in the sn-2 position, of phospholipids in some mammalian tissue.

Animals↗

Which technique, circular stapled anastomosis or double stapling anastomosis, provides the optimal size and shape of rectal anastomotic opening?

BACKGROUND: Two types of end-to-end colorectal anastomosis using a circular stapler, circular stapled anastomosis(CSA) and double stapling anastomosis(DSA), have become the standard technique. The possibility of anastomotic openings of the DSA being smaller and somewhat distorted, because of some portion of the stapled rectal stump not being included in the anastomotic opening, was examined. METHODS: Anastomotic openings created by CSA and DSA were photographed through a sigmoidoscope, and the maximal and minimal diameters and the areas of the anastomotic openings were measured and calculated with an image analyzer. They were examined in the swine rectum immediately after surgery and were also examined in the randomized clinical cases 3 or more months after surgery. RESULTS: It was found that larger anastomotic openings could be created as the diameter of the anastomosed intestine and the cartridge size became wider in both methods immediately after surgery. The shape of anastomotic opening created by DSA was observed to be more oval than round immediately after surgery. The anastomotic stenosis occurred in a small number of patients in both methods within 3 months after surgery. The area of the anastomotic opening created by CSA was about 25% larger than that by DSA immediately after surgery and about 30% larger 3 or more months after surgery. CONCLUSION: CSA provides a larger anastomotic opening than DSA. Anastomotic stenosis occurred in a small number of patients in both methods.

Aged↗

Does the sequence of onset of rigor mortis depend on the proportion of muscle fibre types and on intra-muscular glycogen content?

We examined the postmortem changes in the levels of ATP, glycogen and lactic acid in two masticatory muscles and three leg muscles of rats. The proportion of fibre types of the muscles was determined with NIH image software. The ATP levels in the white muscles did not decrease up to 1 h after death, and the ATP levels 1 and 2 h after death in the white muscles were higher than those in the red muscles with a single exception. The glycogen level at death and 1 h after death and the lactic acid level 1 h after death in masticatory muscles were lower than in the leg muscles. It is possible that the differences in the proportion of muscle fibre types and in glycogen level in muscles influences the postmortem change in ATP and lactic acid, which would accelerate or retard rigor mortis of the muscles.

Adenosine Triphosphate↗

A 'keyhole lesion' gunshot wound in an adipocere case.

A corpse completely converted into adipocere and showing two adjacent bone defects--a typical gunshot entrance wound and a keyhole lesion--is reported. Postmortem changes, a comminuted fracture of the cranial base, and destruction of the bullets made it impossible to determine the direction of fire through the keyhole lesion. Gunshot wounds may show various atypical forms, including keyhole lesions, and especially in old corpses, the distinction between an entrance wound and an exit wound can be very difficult, even if a careful complete autopsy is performed.

Journal Article↗

DNA methylation analysis at distal and proximal promoter regions of the oestrogen receptor gene in breast cancers.

Oestrogen receptor alpha (ER-alpha) gene has two specific promoters, distal (P0) and proximal (P1), which induce almost identical transcripts in size due to different splicing. We examined the methylation at both promoter regions of the ER-alpha gene using HpaII, a methylation-sensitive restriction enzyme, prior to polymerase chain reaction (PCR) amplification. To confirm the results of PCR-based methylation analysis, Southern hybridization was also performed. Twenty of 29 patients with ER-alpha-positive tumours and five of 27 with ER-alpha-negative tumours were unmethylated at the P1 promoter region of the ER-alpha gene. The incidence of methylation was highly negatively correlated with ER-alpha expression (P = 0.0002). A similarly negative correlation was observed at the P0 promoter region of the ER-alpha gene (P = 0.0154). Additionally, the tumours with the ER-alpha gene hypermethylated at both promoter regions had definitely negative ER-alpha values. It was suggested that this epigenetic change might control ER-alpha expression, and might play an important role in the loss of hormone-dependence in breast cancer.

Breast Neoplasms↗

In vivo metabolism of aloemannan.

The metabolism of fluoresceinyl isothiocyanate labeled aloemannan (FITC-AM) was examined by p.o. and i.v. administration in mice at a dose of 120 mg/kg. Analysis of FITC-AM in urine and feces showed that FITC-AM (MW 500 KD) was metabolized into smaller molecules that mainly accumulated in the kidneys. AM was catabolized by the human intestinal microflora to catabolites 1 and 2 with molecular weights of 30 and 10 KD, respectively. Hydrolysis of AM showed hexosamine peaks on HPAE. The findings suggest that the immunomodulation of AM may come from not only neutral polysaccharides but also contaminated hexosamine in AM.

Adjuvants, Immunologic↗

Misery perfusion caused by cerebral hypothermia improved by vasopressor administration.

Therapeutic cerebral hypothermia is widely used for the treatment of severe head injury and cerebral ischemia. The effects of cerebral hypothermia on the cerebral blood flow (CBF) and metabolism, and cerebral vasculature in the normal brain were investigated. Thirty-four adult cats were divided into four groups. CBF was monitored by hydrogen clearance. Arteriovenous oxygen difference (AVDO2) and cerebral venous oxygen saturation (ScvO2) were measured in blood samples from the superior sagittal sinus. The cerebral metabolic rate of oxygen (CMRO2) and cerebral vascular resistance (CVR) were calculated. The cerebral blood volume (CBV) was measured using technetium-99m-labeled human serum albumin in 12 cats. Deep cerebral temperature was cooled from 37 degrees C to 25 degrees C using a water-circulating blanket. In the hypothermia group (Group A: n = 10), CBF (51.2 +/- 8.3 ml 100 g-1 min-1 at 37 degrees C) decreased with lower brain temperature (6.1 +/- 2.7 at 25 degrees C). CMRO2 (2.24 +/- 0.75 ml 100 g-1 min-1 at 37 degrees C) was also decreased (0.52 +/- 0.20 at 25 degrees C). AVDO2 (4.3 +/- 1.0 ml 100 g-1 min-1 at 37 degrees C) increased significantly at 31 degrees C (6.6 +/- 1.8; p < 0.05) and ScvO2 (67.8 +/- 7.9% at 37 degrees C) decreased significantly at 29 degrees C (53.7 +/- 9.7; p < 0.05). CBV (5.3 +/- 1.2% at 37 degrees C) decreased significantly at 29 degrees C (3.7 +/- 1.0; p < 0.05) and CVR (3.2 +/- 0.7 mmHg ml-1 100 g-1 min-1 at 37 degrees C) increased significantly at 29 degrees C (13.8 +/- 5.2; p < 0.01). The combined effect of hypothermia with vasopressor (noradrenalin) (Group B: n = 6) or barbiturate (thiopental) administration (Group C: n = 6) on the cerebral metabolic parameters were also examined. Hypothermia with noradrenalin administration significantly improved the ischemic parameters (AVDO2 was 4.7 +/- 1.4 ml 100 g-1 min-1 at 31 degrees C and ScvO2 was 72.2 +/- 6.4% at 29 degrees C). However, hypothermia with barbiturate administration did not improve these metabolic parameters. These results suggest that hypothermia may cause vasoconstriction and misery perfusion in the brain. This potential risk of relative ischemia can be avoided by combination with vasopressor administration.

Analysis of Variance↗

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↗

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↗