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Biomedical subjects

Y Hatanaka

Publications and source records attributed to Y Hatanaka.

At least 73 records · Page 4Linked to original sources
PubMed1997

Micellar electrokinetic capillary chromatography of benzodiazepine antiepileptics and their desmethyl metabolites in blood.

A fast and reliable method for the MEKC separation and determination of benzodiazepine antipileptics and their active metabolites in serum has been developed, using a separation buffer composed of borate (pH 9.5), SDS (18 mM), and acetonitrile (14%) as an organic modifier. The method is sensitive enough to be used clinically with a precision of less than 3% for the analysis of nitrazepam, clonazepam, clobazam, diazepam and their desmethyl metabolites in serum.

Anticonvulsants↗
PubMed1997

Characterization of sonographically indeterminate ovarian tumors with MR imaging. A logistic regression analysis.

PURPOSE: The goal of this study was to maximize the discrimination between benign and malignant masses in patients with sonographically indeterminate ovarian lesions by means of unenhanced and contrast-enhanced MR imaging, and to develop a computer-assisted diagnosis system. MATERIAL AND METHODS: Findings in precontrast and Gd-DTPA contrast-enhanced MR images of 104 patients with 115 sonographically indeterminate ovarian masses were analyzed, and the results were correlated with histopathological findings. Of 115 lesions, 65 were benign (23 cystadenomas, 13 complex cysts, 11 teratomas, 6 fibrothecomas, 12 others) and 50 were malignant (32 ovarian carcinomas, 7 metastatic tumors of the ovary, 4 carcinomas of the fallopian tubes, 7 others). A logistic regression analysis was performed to discriminate between benign and malignant lesions, and a model of a computer-assisted diagnosis was developed. This model was prospectively tested in 75 cases of ovarian tumors found at other institutions. RESULTS: From the univariate analysis, the following parameters were selected as significant for predicting malignancy (p< or =0.05): a solid or cystic mass with a large solid component or wall thickness greater than 3 mm; complex internal architecture; ascites; and bilaterality. Based on these parameters, a model of a computer-assisted diagnosis system was developed with the logistic regression analysis. To distinguish benign from malignant lesions, the maximum cut-off point was obtained between 0.47 and 0.51. In a prospective application of this model, 87% of the lesions were accurately identified as benign or malignant. CONCLUSION: Benign and malignant ovarian lesions can be distinguished in most sonographically indeterminate lesions by means of parameters obtained from contrast-enhanced MR imaging.

Contrast Media↗
PubMed1997

Induction of apoptotic cell death in human endothelial cells treated with snake venom: implication of intracellular reactive oxygen species and protective effects of glutathione and superoxide dismutases.

Human vascular endothelial cells play a pivotal role in atherosclerotic changes but are resistant to apoptotic inducers such as Fas ligand and it has been difficult to induce apoptosis. We developed an experimental model for the apoptosis in the endothelial cells by using snake venom treatment. Snake venom was found to generate intracellular reactive oxygen species (ROS) in the endothelial cells, which leads to apoptosis as judged by electron microscopy as well as by DNA cleavage. Buthionine sulfoximine (BSO) and diethyldithiocarbamate (DDC) accelerated the apoptosis, indicating intracellular glutathione and superoxide levels play a critical role. Pretreatment with tumor necrosis factor (TNF) or phorbol ester (TPA), which increases the Mn-SOD level, prevented the apoptosis. These data suggest that intracellular ROS enhances apoptosis whereas several anti-oxidants are protective in human endothelial cells. The induction of apoptosis by ROS of endothelial cells may be related to initiation of atherosclerotic changes.

Animals↗
PubMed1997

Result of long-term administration of L-threo-3,4-dihydroxyphenylserine in patients with pure akinesia as an early symptom of progressive supranuclear palsy.

Results of long-term administration of L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic precursor of noradrenaline, in a patient with freezing gait and pure akinesia are reported. Effects were temporal and disappeared during a 16-month treatment period. It was recognized that pure akinesia is an early symptom of progressive supranuclear palsy (PSP). Previously, we reported results of short-term (4 weeks) administration of L-DOPS in this patient. We present the further clinical course of the patient, along with results of long-term (16 months) administration of L-DOPS.

Antiparkinson Agents↗
PubMed1997

Nitric oxide and aneurysm formation in Kawasaki disease.

The objective of this study is to show that nitric oxide plays a role in the development of coronary artery abnormalities in Kawasaki disease. We examined nitrite+nitrate, biopterin and neopterin in 316 urine samples of 34 patients with Kawasaki disease, those of 24 patients with other diseases, and those of 25 healthy children acting as a control group, because urinary nitrite + nitrate are reportedly useful as markers of nitric oxide generation in vivo, and pathways for neopterin-biopterin synthesis and nitric oxide generation are tightly coupled. In our study, the children with Kawasaki disease excreted more urinary nitrite + nitrate and neopterin than did the healthy control group children and excreted abnormally high quantities more often than did the patients with other diseases. Good relationships were found between the urinary nitrite + nitrate levels and the urinary biopterin levels, and between these biopterin levels and the urinary neopterin levels. Nitric oxide is therefore thought to be generated in abnormally high quantities, and to be closely related to the pathology of Kawasaki disease and to the development of coronary artery abnormalities. The role of nitric oxide in Kawasaki disease should be further studied to elucidate the pathophysiology of the disease and to aid in the development of new treatments.

Biomarkers↗
PubMed1996

A role of peroxides in Ca2+ ionophore-induced apoptosis in cultured rat cortical neurons.

The implication of reactive oxygen species for the Ca2+ ionophore ionomycin-induced apoptosis was investigated in cultured cortical neurons from embryonic rats. Ionomycin increased the production of intracellular peroxides as measured by flow cytometric analysis with 6-carboxy-2'7'-dichorodihydrofluorescein diacetate, di(acetoxymethyl ester). Low doses of ionomycin increased the level of manganese-superoxide dismutase (Mn-SOD). In addition, N-acetyl-L-cysteine prevented apoptotic neuronal death induced by ionomycin in a dose-dependent manner. Buthionine sulfoximine suppressed the effect of N-acetyl-L-cysteine. These results suggest that peroxides and redox-regulation play an important role in the apoptosis of neurons induced by elevation of intracellular Ca2+ concentration.

Acetylcysteine↗
PubMed1996

Enhanced expression of the protein kinase substrate annexin in human hepatocellular carcinoma.

Annexin (AX) constitutes a new family of Ca2+-dependent membrane-binding proteins; 13 of them have been described. Among these, annexin-1 (AX-I) has displayed many biological functions in vitro. Its actual role in vivo, however, remains unknown. We already reported that AX-I was expressed in proliferating (regenerating) hepatocytes at both protein and messenger RNA (mRNA) levels. The role of AX-I in human hepatocellular carcinoma (HCC) remains obscure. In this study, the amounts of AX-I at protein and mRNA levels, as well as its localization, have been determined in the normal human liver, chronic hepatitis liver, and nontumorous and tumorous portions of HCC. AX-I was rarely found in normal and chronic liver tissues, whereas it is overexpressed at both the transcriptional and translational levels in tumorous and nontumorous regions of HCC. In addition, more AX-I was expressed in the tumorous portion than the nontumorous portion of HCC. AX-I was present in the hepatocytes and HCC cells, localized mainly in the cytoplasm. AX-I was expressed in poorly differentiated cancer cells. Furthermore, AX-I was tyrosine-phosphorylated in HCC. We also found that some of the AX-I- positive hepatocytes in the nontumorous tissues were derived from a particular subset of parenchymal cells (stem or oval cells). These results indicate that AX-I plays an important role in the malignant transformation process leading to HCC and that it is closely related to the histological grade of HCC. HCC would offer a novel tool with which to study the function of AX-I in malignant transformation.

Annexin A1↗
PubMed1996

Detection of hepatocellular carcinoma by intraarterially enhanced ultrasonography with CO2 microbubbles. Comparison with DSA, dynamic CT, and Lipiodol CT.

PURPOSE: To evaluate the diagnostic value of contrast-enhanced US with CO2 microbubbles (EU) for HCCs. Detectability was compared with DSA, dynamic CT, and Lipiodol CT. MATERIAL AND METHODS: Forty-seven histologically proven HCCs detected with US were evaluated with EU, DSA, and dynamic CT. In 23 patients (35 lesions), Lipiodol CT was also performed. The size of the tumors ranged from 8 to 71 mm (average 28.1 mm); 24 lesions were smaller than 20 mm and 23 lesions were larger than 20 mm. RESULTS: Overall detection was possible in 40 of 47 lesions (85%) by EU, in 32 of 47 (68%) by DSA, in 33 of 47 (74%) by dynamic CT, and in 27 of 35 (77%) by Lipiodol CT. In tumors smaller than 20 mm, detection was possible in 21 of 24 lesions (88%) by EU, 14 of 24 (58%) by DSA, 14 of 24 (58%) by dynamic CT, and 11 of 17 (65%) by Lipiodol CT. CONCLUSION: EU has significant diagnostic value for detection of HCCs, particularly tumors smaller than 20 mm.

Angiography, Digital Subtraction↗
PubMed1996

Synthesis and characterization of a carbene-generating biotinylated lactosylceramide analog as a novel chromogenic photoprobe for GM3 synthase.

A new biotinylated lactose derivative bearing a nitro-substituted chromogenic diazirine was synthesized. The biotinyl group within the structure enabled the performance of a convenient assay of GM3 synthase based on avidin-biotin technology, and the Km values of this biotinylated photoprobe were determined as 40 and 47 microM using bovine brain and rat liver Golgi as enzyme sources, respectively. Furthermore, the sialylation of lactosylceramide, a natural acceptor substrate for GM3 synthase, was competitively inhibited by this synthetic analog. The reagent could be a useful chromogenic photoprobe for GM3 synthase.

Animals↗
PubMed1996

Studies on metabolites of mycoparasitic fungi. V. Ion-spray ionization mass spectrometric analysis of trichokonin-II, a peptaibol mixture obtained from the culture broth of Trichoderma koningii.

The sequence of a peptide, trichokonin-II (TK-II), obtained from the culture broth of Trichoderma koningii OUDEMANS, was examined by ion-spray ionization mass spectrometry (ISI-MS), including the collision-induced dissociation (CID) technique. TK-II was concluded to be a mixture of three peptaibols, TK-IIa, TK-IIb, and TK-IIc.

Alamethicin↗
PubMed1996

Short communication: the value of embolization therapy in painful osseous metastases from hepatocellular carcinomas; comparative study with radiation therapy.

We evaluated the therapeutic effect of transcatheter arterial embolization therapy (TAE) for painful osseous metastases from hepatocellular carcinoma (HCC) in comparison with radiation therapy (RT). TAE using gelatin sponge particles was performed for seven lesions in seven patients. Selective catheterization and embolization were successfully performed in all lesions. Within 10 days after TAE, complete pain relief (CR), partial relief (PR) and no relief (NR) were attained in 57%, 29% and 14%, respectively. RT was used to treat 34 lesions in 22 patients. The dose fractionation schedules were in the range 28.0-50.4 Gy, with 1.8-4.0 Gy per fraction. CR, PR and NR were attained in 47%, 47% and 6%, respectively. There were no serious complications related to these treatments. Both TAE and RT are effective and the treatment of choice should be selected on an individual basis.

Bone Neoplasms↗
PubMed1996

[MR appearance of fat distribution in ovarian teratoma: pathologic correlation].

Magnetic resonance (MR) imaging was performed in 45 patients with 52 surgically proved ovarian teratomas. MR findings of these tumors were classified into three types depending on the degree of fatty proportions in the tumor. The majority of teratomas were filled with fatty tissue in the cystic cavity (n = 43, 82.7%). In 5 tumors (9.6%), fatty tissue was seen at the edge or within the cyst wall. Fatty tissue could not be seen in any part of the tumor in 4 cases (7.7%). The tumors without a fatty component on MR images tend to have fewer sebaceous glands and less fatty tissue within the cyst wall than tumors with an abundant fatty component. Demonstration of fatty tissue is pathognomonic for these tumors. However, tumors with a small amount of fatty tissue may be indistinguishable from cystic ovarian tumors on MR images.

Adipose Tissue↗
PubMed1996

Structure and function of the N-linked carbohydrate chains of pig zona pellucida glycoproteins.

The N-linked carbohydrate chain of the PZP3 glycoprotein family of pig zona pellucida is shown by competition assay to possess sperm receptor activity. Structural analysis reveals that the N-linked chains comprise neutral and acidic complex-type chains. The tri- or tetra-antennary fraction in the neutral chains possesses the sperm receptor activity, but the activity is markedly reduced compared with that of PZP3, suggesting that the protein moiety participates in the maintenance of proper orientation of the active chain. Two components in the PZP3 family can be separated by reverse-phase HPLC after endo-beta-galactosidase (E beta G) digestion and one of the digests, E beta G-PZP3 alpha, possesses the sperm receptor activity. E beta G-PZP3 alpha deprived of O-linked chains by treatment with alkali retains the activity comparable with E beta G-PZP3 alpha, while E beta G-PZP3 alpha deprived of N-linked chains by N-glycanase digestion loses the activity. Furthermore, competition assay of the digests of E beta G-PZP3 alpha with lysyl-endopeptidase indicates that the active chain is linked to Asn67 or Asn84 of PZP3 alpha or to both residues. We conclude that sperm-egg binding in pigs is mainly mediated by tri- or tetra-antennary, neutral, complex-type N-linked carbohydrate chain(s) localized in the N-terminal region of PZP3 alpha protein.

Animals↗
PubMed1995

Involvement of N-linked carbohydrate chains of pig zona pellucida in sperm-egg binding.

The sperm receptor activity of pig zona pellucida has been previously shown to exist in one of the components, pig zona protein 3 alpha (PZP3 alpha), that can be purified after the removal of sialylated and/or sulfated N-acetylpoly(lactosamine) by digestion with endo-beta-galactosidase. In this study, we examined whether N-linked or O-linked carbohydrate chains are involved in the sperm receptor activity of pig zona pellucida. The elimination of N-linked carbohydrate chains from endo-beta-galactosidase-digested PZP3 alpha by digestion with N-glycanase markedly reduced its inhibitory effect on sperm-egg binding in an in vitro competition assay, whereas the elimination of O-linked carbohydrate chains by alkali treatment hardly reduced the inhibitory effect. These results indicate that N-linked carbohydrate chains of PZP3 alpha play a major role in mediating the sperm binding of zona pellucida in pig.

Amidohydrolases↗
PubMed1995

Identification of the electrophilic substrate-binding site of glutathione S-transferase P by photoaffinity labeling.

We determined the electrophilic substrate-binding site of rat glutathione S-transferase P (GST-P) by photoaffinity labeling using the photosensitive compound S-[2-(2-fluoro-4-nitrophenoxy)ethyl]glutathione. This photosensitive glutathione analogue inhibited the catalytic activity in a competitive manner against both glutathione and 1-chloro-2,4-dinitrobenzene, a putative electrophilic substrate. The enzyme kinetics indicated that the photoactivatable glutathione analogue was specifically bound at the active site, which consisted of glutathione-binding (G-site) and the electrophilic substrate-binding (H-site) regions. The procedure involved the following steps: S-[2-(2-fluoro-4-nitrophenoxy)ethyl]glutathione was photochemically reacted with a purified recombinant GST-P expressed in Escherichia coli using ultraviolet irradiation for 30 min on ice. After the reaction, only the GST-P complexed with the glutathione analogue was prepared with glutathione-immobilized agarose. The GST-P covalently bound with the analogue was digested with lysyl endopeptidase (Achromobacter protease I), and the peptides were separated by high-performance liquid chromatography. Only a single major peak with appreciable absorbance at 340 nm was observed by peptide mapping. The peptide was collected and analyzed using an automated peptide sequencer (ABI 477A). Amino acid sequence analysis showed that this peptide consisted of seven amino acid residues corresponding to the sequence at positions 122-128 of GST-P (Ala-Leu-Pro-Gly-Xaa-Leu-Lys). No appreciable phenylthiohydantoin-amino acid was detected at the fifth cycle, which indicated that His126 was chemically labeled with the photosensitive glutathione analogue. It was concluded that His126 was one of the amino acid residues forming the electrophilic substrate-binding site of GST-P.

Amino Acid Sequence↗
PubMed1995

Synthesis of nitrodiazirinyl derivatives of neurotoxin II from Naja naja oxiana and their interaction with the Torpedo californica nicotinic acetylcholine receptor.

Five singly modified nitrodiazirine derivatives of neurotoxin II (NT-II) from Naja naja oxiana were obtained after NT-II reaction with N-hydroxysuccinimide ester of (2-nitro-4-[3-(trifluoromethyl)-3H-diazirin-3yl]phenoxy)acet ic acid followed by chromatographic separation of the products. To localize the label positions, each derivative was first UV-irradiated and then subjected to reduction, carboxymethylation, and trypsinolysis. Tryptic digests were separated by reversed phase-HPLC, the labeled peptides being identified by mass spectrometry. The derivatives containing the photolabel at the position Lys 25, Lys 26, Lys 44, or Lys 46 were [125I]iodinated by the chloramine T procedure. Each iodinated derivative was found to form photoinduced cross-links with the membrane-bound nicotinic acetylcholine receptor (AChR) from Torpedo californica. The pattern of labeling the receptor's alpha, beta, gamma, or delta subunits was dependent on the photolabel position in the NT-II molecule and differed from that obtained earlier with an analogous series of p-azidobenzoyl derivatives of NT-II. The results obtained indicate that (i) different sides of the neurotoxin molecule are involved in the AChR binding, and (ii) fragments of the different AChR subunits are located close together at the neurotoxin-binding sites.

Affinity Labels↗
PubMed1995

Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury.

In the kidneys of anti-glomerular basement membrane (anti-GBM) antibody disease, binding of antibodies to tubular basement membrane (TBM) is often observed. The present work was performed to explore the mechanisms of binding of anti-GBM antibodies to TBM in vivo with special reference to 5I2Ag, a rat membrane inhibitor of complement which regulates complement activation at C3 convertase level. To suppress functions of renal 5I2Ag, F(ab')2 fragment of 5I2 (a neutralizing mAb against 5I2Ag) was perfused in the left kidney and then blood circulation was restored. Mild proteinuria ( < 10 mg/16 hr) was observed during first several days. Five days later, there were tubulointerstitial injuries defined by tubular vimentin staining and leukocyte infiltration. Significant deposition of C3 was observed in the capillaries and in TBM. In rats intravenously injected with rabbit anti-rat GBM antibodies five minutes after kidney perfusion with 5I2, strong binding of rabbit IgG to TBM was observed at one and five days after injection. Although these rats showed mild proteinuria comparable to those perfused with 5I2 and those injected with normal rabbit serum, tubulointerstitial injury was significantly enhanced at Day 5. In contrast, rats perfused with irrelevant mAb and injected with anti-GBM antibodies did not show any significant binding of antibodies to TBM nor tubulointerstitial injury. Furthermore, rats which were made proteinuric by puromycin aminonucleoside and injected with anti-GBM antibodies did not show any significant binding of rabbit IgG to TBM. These results indicate that 5I2Ag, a rat membrane inhibitor of complement at the C3 convertase level, regulates vascular permeability in the living kidney, and that dysfunction or decreased expression of this molecule leads to increased accessibility of anti-GBM antibodies to TBM.

Albuminuria↗