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Biomedical subjects

S Inoue

Publications and source records attributed to S Inoue.

At least 451 records · Page 25Linked to original sources

Superoxide formation and DNA damage induced by a fragrant furanone in the presence of copper(II).

2,5-Dimethyl-4-hydroxy-3(2H)-furanone (2,5-DMHF), a caramel-like fragrant compound found in may processed foodstuff, has been reported to be mutagenic. 4,5-Dimethyl-3-hydroxy-2(5H)-furanone (4,5-DMHF), which is a similar characteristic fragrant compound, has no report concerning its mutagenicity. DNA damage by 2,5-DMHF and 4,5-DMHF was investigated by using DNA fragments obtained from the p53 tumor suppressor gene. 2,5-DMHF induced DNA damage extensively in the presence of Cu(II), but only slightly in the presence of Fe(III). 4,5-DMHF did not cause metal-dependent DNA damage. Bathocuproine, a Cu(I)-specific chelator, and catalase inhibited DNA damage induced by 2,5-DMHF plus Cu(II), whereas free hydroxyl radical scavengers did not. The order of DNA cleavage sites was thymine, cytosine > guanine residues. The site-specific DNA damage and effects of scavengers show that DNA-copper-oxygen complex rather than free .OH are involved in the DNA damage. Formation of 8-oxodeoxyguanosine (8-oxodG) by 2,5-DMHF increased with its concentration in the presence of Cu(II), whereas 8-oxodG formation increased only slightly in the presence of Fe(III). Degradation of 2,5-DMHF was efficiently accelerated by Cu(II), but only slightly accelerated by Fe(III). The degradation of 4,5-DMHF was little even in the presence of metal ions. Examination using cytochrome c suggest that superoxide was generated from 2,5-DMHF. Stoichiometric study of Cu(II) reduction revealed that autoxidation of 2,5-DMHF could offer 4-electron reduction. These results suggest that, at least in vitro and in an acellular system, 2,5-DMHF generates superoxide and subsequently hydrogen peroxide to induce metal-dependent DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

Antifungal nickel(II) complexes derived from amino sugars against pathogenic yeast, Candida albicans.

Nickel(II) complexes containing N-glycosides derived from D-glucosamine (D-GlcN) and ethylenediamine (en) and trimethylenediamine (tn), [Ni(D-GlcN-en)2]Cl2.H2O (1) (D-GlcN-en = 1-¿(2-aminoethyl)amino¿-2-amino-1,2-dideoxy-D-glucose) and [Ni(D-GlcN-tn)2]Cl2.4H2O (2) (D-GlcN-tn = 1-¿(3-aminopropyl)amino¿-2-amino-1,2-dideoxy-D-glucose), are fairly stable in water at room temperature and showed effective antifungal activity against pathogenic yeast, Candida albicans, with the MIC (minimal concentration of inhibition) values of the complexes being 0.25 mM. The results obtained enzyme assays by using preparations of C. albicans chitinase fraction suggested that the sugar complexes 1 and 2 played a role of novel chitinase (chitin-degradation enzyme) inhibitor, where the modes of inhibition were competitive (Ki = 1.3 mM for 1, Ki = 1.8 mM for 2). The newly prepared nickel(II) complex 2 was characterized by elemental analysis, magnetic susceptibility, electronic absorption and circular dichroism spectroscopies, and an X-ray crystallographic analysis.

Antifungal Agents↗

Identification of oligo-N-glycolylneuraminic acid residues in mammal-derived glycoproteins by a newly developed immunochemical reagent and biochemical methods.

The occurrence of the alpha2-->8-linked oligomeric form of N-glycolylneuraminic acid (oligo-Neu5Gc) residues in mammalian glycoproteins was unequivocally demonstrated using a newly developed anti-oligo/poly-Neu5Gc monoclonal antibody as well as by chemical and biochemical methods. First, the antibody, designated mAb.2-4B, which specifically recognized oligo/poly-Neu5Gc with a degree of polymerization of >2, was developed by establishing a hybridoma cell line from P3U1 myeloma cells fused with splenocytes from an MRL autoimmune mouse immunized with dipalmitoylphosphatidylethanolamine-conjugated oligo/poly-Neu5Gc. Second, oligo-Neu5Gc was shown to occur in glycoproteins derived from pig spleen by Western blot analysis using mAb.2-4B, which was also confirmed by fluorometric high performance liquid chromatographic analysis of the product of periodate oxidation/reduction/acid hydrolysis of the purified glycopeptide fractions and by TLC and 600-MHz 1H NMR spectroscopic analysis of their mild acid hydrolysates. Finally, the ubiquitous occurrence of oligo-Neu5Gc chains as glycoproteinaceous components in Wistar rat tissue was immunochemically indicated. This is the first example demonstrating the diversity in oligo/poly-Sia structure in mammalian glycoproteins, where only poly-N-acetylneuraminic acid is known to occur. Such diversity in oligo/poly-Sia structure also implicates a diverged array of biological functions of this glycan unit in glycoproteins.

Animals↗

Posterior extensions of the human compact atrioventricular node: a neglected anatomic feature of potential clinical significance.

BACKGROUND: Catheter ablation procedures have revived interest in the detailed anatomy of the specialized atrioventricular (AV) septal junctional area. The compact AV node usually is considered to have a blunt posterior end. The objective of this study was to reconstruct the human compact AV node in relation to the landmarks of Koch's triangle, with emphasis on its posterior extension. METHODS AND RESULTS: In 21 hearts obtained from autopsies, the AV nodal septal junctional area was removed en bloc, serially sectioned, and reconstructed. None of the hearts showed a blunt posterior ending of the compact AV node; 13 showed posterior extensions on both the right and left sides; 7 had a rightward posterior extension only; and 1 heart showed a single leftward extension. Hence, a rightward posterior extension was present in 20 of 21 hearts. Furthermore, in 16 of these 20 hearts, the rightward extension continued to the level of the coronary sinus ostium; in 7, the bundle extended beyond this anatomic landmark. The mean length of the right posterior extension was 4.4+/-2.0 mm; that of the leftward posterior extension was 1.8+/-0.9 mm. Superimposed onto the slope of the muscular AV septum, viewed from the right atrium, the rightward extension ran close to the tricuspid annulus with the leftward extension positioned superiorly. CONCLUSIONS: The human compact AV node contains rightward and leftward posterior extensions, with the right extension close to the tricuspid annulus. It is tempting to speculate that these extensions are involved in "slow pathway" conduction.

Adult↗

Clinical management of nonpalpable or small breast masses by fine-needle aspiration biopsy (FNAB) under ultrasound guidance.

BACKGROUND AND OBJECTIVES: Open breast biopsy of palpable breast masses is widely accepted. Now, the use of high-resolution, real-time ultrasound (US) makes it easy to detect nonpalpable or small breast nodules, as well as palpable breast masses. METHODS: We performed fine-needle aspiration biopsy (FNAB) under US guidance to manage the nonpalpable or small breast masses detected by US examination and to distinguish between benign and malignant tumors. To investigate the usefulness and sensitivity of FNAB under US guidance, we reviewed a total of 137 FNAB records for cases diagnosed between January 1993 and December 1994. RESULTS: Fifty-five cases were classified as benign, 70 as atypical/indeterminate, 1 as suspicious/probably malignant, 6 as malignant, and 5 as unsatisfactory. Of these, five cases were confirmed as malignant, but one case showed no malignancy at surgery. Four cases were nonpalpable breast cancer, two were in stage 0, and two were in stage I. One case in the suspicious/probably malignant group on the initial FNAB was shown to be malignant by re-aspiration on follow-up study. The sensitivity of FNAB under US guidance was 83.3% (5/6) and the specificity was 99.2% (125/126). The diagnostic accuracy was 83.3% (5/6) and the negative predictive value was 99.2% (125/126). CONCLUSIONS: FNAB under US guidance is useful for the management of nonpalpable or small breast masses; it is sensitive for distinguishing between benign and malignant tumors and may reduce unnecessary surgical procedures and replace conventional manual aspiration biopsy.

Adult↗

Altered regulation of Src tyrosine kinase by transforming growth factor beta1 in a human hepatoma cell line.

Transforming growth factor betas (TGF-betas) are the potent growth inhibitors for various cell types. Certain transformed cells, however, show poor response to TGF-beta-induced growth inhibition, which contributes to their uncontrolled proliferation. Recently, we have reported that TGF-beta1 induces degradation of activated Src tyrosine kinase in rat fibroblasts. To elucidate the alteration in TGF-beta signaling pathway in tumor cells that cannot respond to the cytokine, we compared the effects of TGF-beta1 on Src kinase in two human hepatoma cell lines, TGF-beta1-insensitive Mahlavu cells and TGF-beta1-sensitive HepG2 cells. TGF-beta1 decreased Src kinase activity in HepG2 cells, but increased cellular Src levels and Src kinase activity in Mahlavu cells. Co-incubation of Mahlavu cells with TGF-beta1 and 12-O-tetradecanoyl phorbol 13-acetate (TPA) decreased Src protein levels and Src kinase activity, inducing TGF-beta1 sensitivity. TGF-beta1 induced tyrosine dephosphorylation of Ras guanosine triphosphatase-activating protein (Ras-GAP) and Ras inactivation in HepG2 cells, but induced Ras-GAP phosphorylation and Ras activation in Mahlavu cells. The Src kinase inhibitor abolished the increase of Src kinase activity in TGF-beta1-treated Mahlavu cells, and induced TGF-beta1 sensitivity. These findings suggest that regulation of Src kinase by TGF-beta1 is altered in Mahlavu cells. The altered regulation of Src may contribute to TGF-beta1 insensitivity in this cell line, at least in part through activation of Ras.

Animals↗

[Intraabdominal organ injury due to blunt chest trauma--report of two cases].

Two cases of intraabdominal organ injuries due to blunt chest trauma are reported. A 58-year-old man was admitted to our hospital with multiple rib fractures, hemopneumothorax and left flail chest. An emergency operation was performed and intraoperative findings revealed that the fractured rib was penetrating through the diaphragm to the stomach. A 52-year-old woman was admitted to our hospital with left multiple rib fractures and hemopneumothorax. Her treatment included chest tube drainage, but a week after admission, intraabdominal bleeding occurred due to a ruptured spleen, necessitating an emergency operation (splenectomy). Blunt chest trauma injury is usually accompanied by multisystem injury. Therefore, it is important to detect intraabdominal injury during an emergency operation and the follow-up period.

Emergencies↗

Giant hamartoma of the lung.

In the following case of giant pulmonary hamartoma, a 62-year-old woman exhibited a huge tumor shadow in the right lung field, whilst remaining asymptomatic. A thoracotomy revealed a solid intrapulmonary mass histologically diagnosed as a cartilaginous hamartoma with no evidence of malignancy. The tumor was resected by enucleation and there has been no recurrence for 40 months since surgery. Parenchyma-saving enucleation or excision is a safe and sufficient procedure for peripheral hamartomas of any size.

Female↗

Polymorphism of insulin-like growth factor I gene and bone mineral density.

The polymorphism of insulin-like growth factor-I (IGF-I) gene was examined in Japanese postmenopausal women to analyze the genetic background for osteoporosis. In this study, the dinucleotide (cytosine-adenine; CA) repeat sequence lying upstream of the transcription initiation site of this gene was examined. We named the most frequent allele including (CA) 19 as J allele. There were 6 alleles (J-4 containing 17 CA repeats: (CA)17, [J-2 (CA)18, J (CA)19, J + 2 (CA)20, J + 4 (CA)21, J + 6 (CA)22]) in the Japanese population. The genotype distribution was different from that of Caucasians. There was no different in bone mineral density (BMD) between the group with one or two alleles of each genotype and that without that genotype. When we separate the subjects into three groups having two alleles, one allele, and no alleles, the three subjects who possess the allele 'J-2' in both strands had low BMD (Z score of L2-4; -1.24 +/- 0.56, total body; -0.943 +/- 0.59, mean +/- SE). On the other hand, sequence of IGF-I gene in this study was different from reported sequence of IGF-I gene; that was 2 base pair (bp) deletion following 3'end of CArepeat (-645adenine/-646guanine). The present study showed that there was no association between the microsatellite polymorphism of IGF-I gene and BMD in Japanese postmenopausal women, but some possibility remains that the microsatellite polymorphism of IGF-I gene is useful to detect a kind of particular osteoporosis.

Absorptiometry, Photon↗

Temperature- and capsaicin-sensitive nerve fibers in brown adipose tissue attenuate thermogenesis in the rat.

We examined the function of putative sensory fibers that are contained in intercostal nerves and innervate interscapular brown adipose tissue (IBAT) in urethane-anesthetized rats. Warming the IBAT to 40-44 degrees C with two small heaters placed bilaterally on the skin above it attenuated the subsequent noradrenaline-induced thermogenesis (NIT) of the IBAT. In this range of warming, higher IBAT temperatures resulted in more attenuation. Denervation of IBAT blocked the effect of thermal stimulation on the NIT. Thus, activation of nerve fibers in IBAT that are sensitive to warmth or to the nociceptive effects of heat probably attenuated the NIT. Since the putative sensory fibers in the IBAT contain calcitonin gene-related peptide (CGRP) and substance P, which are thought to act in peripheral tissues, we tested the effects of injection of these neuropeptides into the IBAT. Administration of 5.2 nmol CGRP but not substance P or vehicle saline mimicked the effect of thermal stimulation of IBAT. As the neuropeptide-containing primary sensory neurons are characterized by their sensitivity to capsaicin, we also tested its effects (1 mg/kg, s.c.) and found that it also attenuated the NIT. Denervation of the IBAT or pretreatment with capsazepine, a capsaicin receptor antagonist, blocked the effect of capsaicin. We propose that temperature- and capsaicin-sensitive nerve fibers release CGRP to attenuate the NIT of brown adipocytes.

Adipose Tissue, Brown↗

A new approach to dynamic graciloplasty.

The reestablishment of anal function by transposition of the gracilis muscle, combined with the implantation of electrodes and a neuromuscular stimulator (dynamic graciloplasty), has recently been developed. With this method, the transposed muscle maintains contraction by electrical stimulation to maintain neoanal pressure without fatigue. It is necessary to convert the fatigue-prone gracilis muscle to fatigue-resistant muscle by long-term electrical stimulation (conditioning). In most patients receiving dynamic graciloplasty, the conditioning is accomplished after the transposition. However, conditioning before graciloplasty should reduce the risk of ischemia in the transposed muscle after the graciloplasty and improve the outcome. This new sequence of procedures is described, in combination with J-pouch construction, in a patient who required abdominoperineal excision of the rectum for lower rectal cancer. The graciloplasty was performed after conditioning of the gracilis muscle in situ; the conditioning did not cause the patient discomfort and resulted in good anal function.

Adenocarcinoma↗

Effects of a 7-day infusion of glucose on insulin secretion in vivo and in vitro in ventromedial hypothalamic-lesioned obese rats.

Excessive stimulation of insulin secretion may be one cause of the beta-cell dysfunction induced by hyperglycemia. We investigated a possible link between the prior endogenous hypersecretion of insulin and this dysfunction by performing a 7-day glucose infusion (50% wt/vol, 1.2 ml/h) on ventromedial hypothalamic VMH-lesioned hyperinsulinemic rats. Intravenous glucose tolerance tests (i.v.GTT 1.0 g/kg) revealed that a 3-day glucose infusion enhanced the insulin responses in both the sham- and VMH-lesioned rats compared with saline infusions. A similar 7-day glucose infusion enhanced the insulin response to glucose in sham-lesioned rats but not in VMH-lesioned rats. Batch-incubation of islets isolated from sham-lesioned rats showed an enhanced insulin response to glucose after 7 days of glucose treatment compared with the saline infusions. Conversely, the glucose infusion in VMH-lesioned rats markedly suppressed the in vitro insulin response. In sham- and VMH-lesioned rats, similar islet insulin contents were produced by saline and glucose treatments. Electron microscopy revealed that glucose infusions impaired the granule-releasing function of the beta-cells in VMH-lesioned rats, while insulin synthesis was accelerated in either group. These findings support the notion that excessive secretion is partly responsible for the beta-cell dysfunction induced by hyperglycemia without signs of exhaustion.

Animals↗

Isolation and radiation hybrid mapping of dinucleotide repeat polymorphism at the human estrogen receptor beta locus.

A gene for a second type of human estrogen receptor, the estrogen receptor beta (ESR beta), was recently identified. We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human estrogen receptor beta gene. High heterozygosity (0.93) makes this polymorphism a useful marker in the genetic study of disorders affecting female endocrine systems; calcium metabolism; and breast, uterine, and ovarian cancers.

Alleles↗

Reconstruction of the aortic arch in invasive thymoma under retrograde cerebral perfusion.

Extensive en-bloc resection of the aortic arch and anterior wall of the main pulmonary artery was performed in a 46-year-old man with invasive thymoma. The aortic arch was replaced with a Hemashield vascular graft under hypothermic circulatory arrest with retrograde cerebral perfusion. Patch plasty with Xenomedica was performed for the anterior wall of the main pulmonary artery under cardiopulmonary bypass. The patient was treated with postoperative radiotherapy and has remained asymptomatic for 15 months after the operation. An extensive operation is considered necessary to improve the prognosis of invasive thymoma.

Aorta, Thoracic↗

EGG phosphatidylcholine combined with vitamin B12 improved memory impairment following lesioning of nucleus basalis in rats.

We investigated the effects of egg phosphatidylcholine (PC) combined with vitamin B12 on memory in the Morris water maze task, and on choline and acetylcholine (ACh) concentrations in the brain of rats. Animals with nucleus basalis Magnocellularis (NBM) lesion received intragastric administration of egg PC or vitamin B12, or both for 18 days. Memory acquisition and retention were remarkably impaired in NBM lesioned rats compared with in sham-operated control. NBM lesioned group had lower choline and ACh concentrations than control group in the frontal cortex. High dose of egg PC alone significantly increased choline concentration, but did not change ACh concentration in the frontal cortex. High dose of vitamin B12 alone did not change choline and ACh concentrations in the brain. Either egg PC or vitamin B12 did not improve memory acquisition and retention. However, low dose of egg PC combined with vitamin B12 significantly increased ACh concentration and improved memory acquisition and retention in the NBM lesioned rats. We concluded that egg PC combined with vitamin B12 improved the memory impairment of NBM lesioned rats through the action on the cholinergic neurons.

Acetylcholine↗