210 results on '"S, Hashida"'
Search Results
2. Augmented Expression of Atrial Myosin Light Chain 1 in Ventricular Aneurysms of Human: Enzyme Immunoassay for Atrial Myosin Light Chain 1
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S. Hashida, Kouji Fujimoto, Eishichi Miyamoto, Hirofumi Yasue, Eiji Ishikawa, and Koichi Nakao
- Subjects
Adult ,Male ,medicine.medical_specialty ,Myosin light-chain kinase ,medicine.drug_class ,Heart Ventricles ,Myocardial Infarction ,Biophysics ,Gene Expression ,Left Ventricles ,Myosins ,Biology ,Right ventricles ,Monoclonal antibody ,Biochemistry ,Immunoenzyme Techniques ,Reference Values ,Internal medicine ,Myosin ,medicine ,Humans ,Heart Atria ,Myocardial infarction ,Heart Aneurysm ,Molecular Biology ,Aged ,chemistry.chemical_classification ,Analysis of Variance ,medicine.diagnostic_test ,Myocardium ,Antibodies, Monoclonal ,Cell Biology ,medicine.disease ,Molecular biology ,Endocrinology ,Enzyme ,chemistry ,Immunoassay ,cardiovascular system ,Female - Abstract
We established an enzyme immunoassay (EIA) for atrial myosin light chain 1 (ALC1) using monoclonal antibodies KA1 and KB1, which were specific for ALC1 and for both ALC1 and ventricular myosin light chain 1, respectively. The serum ALC1 levels of healthy subjects were 0.28 +/- 0.14 ng/ml (mean +/- SD). The tissue ALC1 levels of normal adult human atria were much higher than those of ventricles (p < 0.01, 2,120 +/- 1,200 in right atria, 2,180 +/- 1,450 in left atria vs. 36.0 +/- 20.2 in right ventricles, 37.7 +/- 15.3 in left ventricles, ng/mg of proteins). The tissue ALC1 levels of ventricular aneurysms were significantly higher than those of normal ventricles (p < 0.01, 206.7 +/- 101.8). These results indicate that ALC1 is augmented in aneurysms and that the EIA provides a useful tool to investigate the roles of ALC1.
- Published
- 1995
- Full Text
- View/download PDF
3. Reliable Web-Based CSCW Systems Using Information Fusion of Various Multiple Biological Sensors
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Yoshitaka Sakurai, S. Hashida, H. Ihara, and Setsuo Tsuruta
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Cooperative learning ,Collaborative software ,Multimedia ,business.industry ,Computer science ,Interface (computing) ,computer.software_genre ,Sensor fusion ,Human–computer interaction ,Computer-supported cooperative work ,Web application ,Augmented reality ,business ,Cyberspace ,computer - Abstract
In Web-based CSCW (Computer-Supported Cooperative Work) often including cooperative learning, remote members communicate their intentions in cyberspace, using textual sentences, pictures and voice. However, often, communication between members cannot be correctly done and interface errors occur. Different from face-to-face communication, partners' situations including their interest, concentration, boredom, and tiredness cannot be easily transmitted. Oversight and mishearing of remote partners is often overlooked. Besides, it is further difficult to understand their real intentions sufficiently. To overcome these problems, ?Augmented Cyberspace? for dependable Web-based CSCW Systems, is proposed, which is also applicable to system such as e-learning. This assesses situations of remote users through fusing information of multiple biological sensors and the related general contexts. By transmitting and using information of such users? situations, the system augments the cyberspace through stressing or providing warnings in conventional media such as text, image, and voice.Experimental results showed the necessity and feasibility for information fusion of multiple sensors.
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- 2008
- Full Text
- View/download PDF
4. Diagnosis of HIV-1 infection with whole saliva by detection of antibody IgG to HIV-1 with ultrasensitive enzyme immunoassay using recombinant reverse transcriptase as antigen
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S, Ishikawa, S, Hashida, K, Hashinaka, K, Hirota, A, Saitoh, A, Takamizawa, H, Shinagawa, S, Oka, K, Shimada, and E, Ishikawa
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Adult ,Male ,Adolescent ,HIV Infections ,HIV Antibodies ,Middle Aged ,Sensitivity and Specificity ,Immunoenzyme Techniques ,Immunoglobulin G ,HIV-1 ,Humans ,Female ,Child ,Saliva - Abstract
Whole-saliva samples were collected from 45 asymptomatic carriers, 18 patients with AIDS-related complex (ARC) or AIDS, and 76 medical students by simple spitting with no stimulation and tested by an ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for anti-HIV-1 IgG using recombinant reverse transcriptase as antigen and beta-D-galactosidase as label. With as little as 1 microliter of whole saliva, the lowest signals among the 45 asymptomatic carriers, 8 patients with ARC, and 10 patients with AIDS were 38-, 78-, and 3-fold, respectively, higher than the highest signal among the medical students. When the volume of whole saliva for test was increased up to 100 microliters, no significant effect was observed on signals for seropositive cases and signals for the medical students increased only very slightly. Therefore, whole-saliva samples containing extremely low levels of anti-HIV-1 IgG, even 2,000-fold lower than the lowest level among the 45 asymptomatic carriers tested, were considered to be discriminated from those of seronegative individuals. Thus, the sensitivity and specificity were expected to be both 100% with whole saliva even for a larger number of samples, although the number of samples tested was limited.
- Published
- 1995
5. Noncompetitive enzyme immunoassay (hetero-two-site enzyme immunoassay) for gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) and measurement of immunoreactive gamma 2-MSH in plasma of healthy subjects
- Author
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Y, Yogi, S, Hashida, R, Ekman, T, Setoguchi, and E, Ishikawa
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Adult ,Male ,Immunochemistry ,Molecular Sequence Data ,Biotin ,Binding, Competitive ,Sensitivity and Specificity ,Immunoenzyme Techniques ,Molecular Weight ,Evaluation Studies as Topic ,Reference Values ,Humans ,Amino Acid Sequence ,Melanocyte-Stimulating Hormones - Abstract
A noncompetitive enzyme immunoassay (hetero-two-site enzyme immunoassay) for gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) was developed. gamma 2-MSH (1-12) was biotinylated, trapped onto an anti-gamma 2-MSH (1-12) IgG-coated polystyrene bead, eluted at pH 1 after washing to eliminate other biotinylated substances, and measured using two streptavidin-coated polystyrene beads and affinity-purified anti-gamma 2-MSH (1-12) Fab'-peroxidase conjugate. The detection limit of gamma 2-MSH (1-12) was 10-30 amol (16-48 fg)/assay and 130-400 fmol (210-630 pg)/L of plasma. There was little or only slight cross reaction with alpha-MSH, beta-MSH, and gamma 1-MSH. By this immunoassay, the concentration and molecular size of immunoreactive gamma 2-MSH in plasma of healthy subjects were examined, and the results were compared with those by competitive enzyme immunoassay. Immunoreactive gamma 2-MSH measured by competitive enzyme immunoassay was a mixture of substances with high molecular weights (100-500 kDa), and its concentration was calculated to be 50-60 pmol/L using gamma 2-MSH (1-12) as standard. Immunoreactive gamma 2-MSH detected by the noncompetitive enzyme immunoassay after removal of high molecular weight substances was not homogeneous and smaller than gamma 2-MSH (1-12), and its concentration was approximately 1 pmol/L. The exact nature of these immunoreactive gamma 2-MSHs remains to be elucidated. gamma 2-MSH (1-12) added to plasma was degraded rapidly, and the concentration of gamma 2-MSH (1-12) was very low, if any, in plasma of healthy subjects.
- Published
- 1995
6. Ultrasensitive enzyme immunoassay
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S, Hashida, K, Hashinaka, and E, Ishikawa
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Immunoenzyme Techniques ,Animals ,Humans ,Proteins ,Reproducibility of Results ,Antigen-Antibody Complex ,Blood Proteins ,Antigens ,Peptides ,Haptens ,Sensitivity and Specificity ,Antibodies - Abstract
Ultrasensitive enzyme immunoassay methods are reviewed not only for antigens but also for antibodies and haptens with emphasis on factors which limit the sensitivity. Ultrasensitive immunoassays can be developed by noncompetitive solid phase assay systems rather than competitive ones for antigens and antibodies. However, no noncompetitive immunoassays have been available for hapten molecules which cannot be bound simultaneously by two different antibody molecules. This has been overcome by developing methods to derivatize haptens with amino groups so that the derivatized haptens may be measured by two-site noncompetitive assays. For ultrasensitive noncompetitive solid phase immunoassays, the nonspecific binding of labeled reactants (background noise) should be minimized. This has been achieved by developing methods to transfer the complex of analytes and labeled reactants from solid phase to solid phase with minimal dissociation of the complex. Thus, the sensitivity for antigens, haptens and antibodies has been markedly improved and some applications have been made.
- Published
- 1995
7. Immunohistochemical study of chymopapain injected into the rabbit intervertebral disc using anti-chymopapain antibody
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M, Toda, N, Tajima, E, Ishikawa, and S, Hashida
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Microscopy, Electron ,Animals ,Chymopapain ,Proteoglycans ,Collagen ,Rabbits ,Intervertebral Disc ,Immunohistochemistry ,Antibodies ,Injections - Abstract
This study was undertaken to investigate the morphological action of chymopapain (CP) in intervertebral discs. Of 20 mature Japanese white rabbits, 19 lumbar intervertebral discs were used for electron microscopic examination, and 36 discs, for immunohistochemical examination. Discs from 3 hours to 8 weeks after injection were observed by light and electron microscopy using anti-CP rabbit antibody labeled with horseradish peroxidase. Using Kagami's DMF-dehydration, two types of fine fibers were observed in the extracellular matrix of normal nucleus pulposus, in addition to collagen fiber. After injection of CP, the thinner fibers disappeared, while the thicker fibers remained. The injected CP spread from the nucleus pulposus to the annulus fibrosus within several hours and remained as long as 4 weeks. By immunoelectron microscopy, positive granules were divided into Type 1 (lacking relationship to collagen fibers) and Type 2 (adhering to or surrounding collagen fibers). The thinner fibers appear to be proteoglycan monomer and are the target for CP.
- Published
- 1993
8. Detection of one attomole of [Arg8]-vasopressin by novel noncompetitive enzyme immunoassay (hetero-two-site complex transfer enzyme immunoassay)
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S, Hashida, K, Tanaka, N, Yamamoto, T, Uno, K, Yamaguchi, and E, Ishikawa
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Arginine Vasopressin ,Immunoenzyme Techniques ,Immunoglobulin G ,Microchemistry ,Molecular Sequence Data ,Animals ,Indicators and Reagents ,Amino Acid Sequence ,Antigen-Antibody Complex ,Rabbits ,Cross Reactions - Abstract
One attomole of [Arg8]-vasopressin (AVP) was detected by a novel noncompetitive enzyme immunoassay (hetero-two-site complex transfer enzyme immunoassay). AVP was indirectly biotinylated using N-hydroxysuccinimidobiotin and trapped onto an anti-AVP IgG-coated polystyrene ball. After washing, biotinylated AVP was eluted from the polystyrene ball with HCl and was reacted with 2,4-dinitrophenyl-fluorescein disulfide-bovine serum albumin-rabbit anti-AVP IgG conjugate. The complex formed was trapped on [anti-2,4-dinitrophenyl group] IgG-coated polystyrene balls and, after washing, reacted with avidin-beta-D-galactosidase conjugate. The polystyrene balls were washed, and the complex of the three components was eluted with 2,4-dinitrophenyl-L-lysine and transferred to anti-fluorescein IgG-coated polystyrene balls. After washing, the complex was released from the polystyrene balls by reduction with 2-mercaptoethylamine and transferred to [anti-rabbit IgG] IgG-coated polystyrene balls. beta-D-Galactosidase activity bound to the last polystyrene balls was assayed by fluorometry. The detection limit of AVP was 1.1 fg (1 amol)/tube. Interference by proteins in biological fluids was eliminated by separation of peptides from proteins using a molecular sieve. The principle of the present method may be applicable to the measurement of haptens, including peptides, that can be derivatized so as to be bound simultaneously by both anti-hapten antibody and avidin molecules.
- Published
- 1991
9. Complete root resorption of an upper central incisor due to ectopic eruption of canine in a deaf-mute child
- Author
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I, Morisaki, S, Hashida, J, Mihara, M, Takagaki, and S, Sobue
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Incisor ,Male ,Cuspid ,Tooth Eruption, Ectopic ,Adolescent ,Tooth Movement Techniques ,Dental Care for Disabled ,Maxilla ,Root Resorption ,Humans ,Deafness - Abstract
Unilateral complete root resorption of the permanent central incisor was experienced in a boy with deaf and dumb. Transposition of tooth germ or abnormally directed eruption of the canine caused not only an entire root but a part of enamel resorption. The patient was diagnosed clinically and radiographically as an ectopic eruption of the right maxillary upper canine and then treatments were provided to improve esthetic and functional conditions in terms of eruption guidance. It should be emphasized that the early diagnosis and the subsequent eruption guidance is essential in the patient with these kinds of eruption disorder of the mixed dentition.
- Published
- 1990
10. Clinical application of enzyme immunoassay in the analysis of citrullinemia
- Author
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Hitoshi Ichiki, Takeyori Saheki, E. Ishikawa, T. Yamashita, Keiko Kobayashi, S. Hashida, and Yasushi Imamura
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Adult ,medicine.medical_specialty ,Clinical Biochemistry ,Argininosuccinate synthase ,Argininosuccinate Synthase ,Biochemistry ,Immunoenzyme Techniques ,Ligases ,chemistry.chemical_compound ,Internal medicine ,medicine ,Citrulline ,Humans ,Amino Acid Metabolism, Inborn Errors ,chemistry.chemical_classification ,Radial immunodiffusion ,biology ,medicine.diagnostic_test ,Citrullinemia ,Biochemistry (medical) ,Infant, Newborn ,General Medicine ,medicine.disease ,Enzyme ,Endocrinology ,Liver ,chemistry ,Immunoassay ,biology.protein ,Specific activity ,Peroxidase - Abstract
We have developed a sensitive enzyme immunoassay (EIA) for the quantification of argininosuccinate synthetase (ASS) in the range of 0.05-1 ng/tube using a Fab'-peroxidase conjugate prepared with maleimide compound devised by Ishikawa et al. Amounts of hepatic ASS in control subjects were determined by this method with the purified enzyme as a standard and their specific activities were calculated to be 1.3-1.4 mumol product/min (U)/mg of ASS, which was quite similar to that of the purified enzyme. Amounts of ASS in the liver of patients with three types of citrullinemia, type I, II and III according to our arbitrary classification, were determined by the EIA method. The following results were obtained: hepatic ASS from a patient diagnosed as type I citrullinemia because of its abnormally large Km values for citrulline and aspartate was calculated to have a specific activity of 0.18 U/mg of ASS, indicating that the enzyme is a variant; specific activities of ASS in the hepatic extract of type II citrullinemic patients were 1.2-1.3 U/mg of ASS, confirming the finding obtained by single radial immunodiffusion method that the decrease of the activity in type II is caused by a decrease in the total amount of ASS protein; a very small amount of immune cross-reactive material was detected in the liver of a patient diagnosed as type III citrullinemia based on findings of undetectable ASS activity in the liver and cultured skin fibroblast.
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- 1987
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11. CLINICAL USEFULNESS OF A HIGHLY SENSITIVE ENZYME-IMMUNOASSAY OF TSH
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Tomohiko Mori, Katsuji Ikekubo, H. Ogawa, S. Inoue, S. Bito, S. Hashida, E. Ishikawa, and Hiroo Imura
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Adult ,Male ,Thyroiditis ,endocrine system ,medicine.medical_specialty ,Adolescent ,endocrine system diseases ,Pituitary Diseases ,Endocrinology, Diabetes and Metabolism ,Graves' disease ,Thyrotropin ,Immunoenzyme Techniques ,Endocrinology ,TRH stimulation test ,Hypothyroidism ,Reference Values ,Internal medicine ,medicine ,Central hypothyroidism ,Humans ,medicine.diagnostic_test ,business.industry ,Thyroid ,Radioimmunoassay ,Middle Aged ,medicine.disease ,Thyroid Diseases ,Graves Disease ,medicine.anatomical_structure ,Immunoassay ,Female ,business ,Hypothalamic Diseases ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
Using a recently developed sensitive enzyme immunoassay (EIA) for TSH, serum TSH levels in normal subjects and patients with various thyroid disorders were measured. The minimum detectable concentration was less than 0.005 mU/l. An excellent correlation was observed between TSH values measured by EIA and by sensitive radioimmunoassay (r = 0.932). In 26 normal subjects, serum TSH ranged from 0.30 to 2.65 mU/l (geometric mean 0.97 mU/l). In 27 untreated hyperthyroid Graves' patients, serum TSH was detected in all but one, ranging from 0.005 to 0.19 mU/l (geometric mean 0.040). These values were proved to be specific for human TSH by absorption, recovery, cross-reactivity and dilution studies; non-specific serum effects were also ruled out. In 10 patients with destructive thyroiditis, similar TSH values (0.005-0.20 mU/l, mean 0.032) were observed. However, no significant correlations between TSH and circulating thyroid hormone levels were observed in these thyrotoxic conditions. Furthermore, 9 untreated Graves' patients did not respond to a single i.v. injection of TRH. In 13 hypothyroid patients with hypothalamo-pituitary disorders, 10 had basal TSH levels of less than 0.4 mU/l, and TRH tests in five gave peak TSH values of more than 0.8 mU/l, which were associated with significant increases in serum T3. In three patients with Sheehan's syndrome, elevated basal TSH levels were observed. Two of them responded to TRH, but these TSH elevations were not associated with T3 increases. In conclusion, this sensitive EIA could measure TSH levels in most patients with thyrotoxicosis and central hypothyroidism. However, the true significance of these measured values needs to be elucidated by future studies.
- Published
- 1987
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12. More useful maleimide compounds for the conjugation of Fab' to horseradish peroxidase through thiol groups in the hinge
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S, Hashida, M, Imagawa, S, Inoue, K H, Ruan, and E, Ishikawa
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Maleimides ,Immunoglobulin Fab Fragments ,Peroxidases ,Protein Conformation ,Humans ,Sulfhydryl Compounds ,Horseradish Peroxidase - Abstract
Nine different maleimide compounds were evaluated for the conjugation of Fab' to horseradish peroxidase through thiol groups in the hinge. The compounds evaluated were succinimidyl maleimidoacetate (I), succinimidyl 4-maleimidobutyrate (II), succinimidyl 6-maleimidohexanoate (III), succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (IV), succinimidyl m-maleimidobenzoate (V), succinimidyl 4-(p-maleimidophenyl)butyrate (VI), sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (VII), sulfosuccinimidyl m-maleimidobenzoate (VIII), and sulfosuccinimidyl 4-(p-maleimidophenyl)butyrate (IX). Maleimide groups of I-IV and VII were fairly stable at pH 7.0 at 30 degrees C, while those of the other compounds were significantly decomposed. I-III and VII-IX were sufficiently soluble in the reaction mixture for the introduction of maleimide groups, while the others were more or less precipitated during the reaction. II and III were the most effective in the introduction of maleimide groups and gave the highest recovery of peroxidase in the conjugate, which reached 80%. From these results, II and III were judged to be the most useful, and IV and VII were judged to be fairly useful.
- Published
- 1984
13. Rat liver thiol proteinases: cathepsin B, cathepsin H and cathepsin L
- Author
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N, Katunuma, T, Towatari, E, Kominami, S, Hashida, K, Takio, and K, Titani
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Cathepsin H ,Cathepsin L ,Cathepsins ,Cathepsin B ,Rats ,Substrate Specificity ,Cysteine Endopeptidases ,Epitopes ,Liver ,Leucine ,Endopeptidases ,Animals ,Amino Acid Sequence ,Lysosomes - Abstract
Data on following points of lysosomal thiol proteinases (cathepsins B, H and L) from rat liver are described in this paper: Partial amino acid sequence of cathepsin B, substrate specificity of cathepsin L, immunological studies of cathepsin B and H and effectiveness of E-64, specific thiol proteinase inhibitor in vivo.
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- 1981
14. [A case of primary sclerosing cholangitis with interesting cholangiopancreatography]
- Author
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Y, Shintani, M, Hirata, M, Sasaki, K, Kosuga, S, Hashida, M, Hashimoto, T, Miyahara, T, Yokota, H, Inoue, and T, Banba
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Cholangiopancreatography, Endoscopic Retrograde ,Sclerosis ,Cholangitis ,Humans ,Female ,Bile Ducts ,Aged - Published
- 1988
15. Characterization of a monoclonal antibody to hog thyroid peroxidase and its use for immunohistochemical localization of the peroxidase in the thyroid gland
- Author
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H, Nakagawa, T, Kotani, S, Ohtaki, J, Kawano, E, Aikawa, M, Imagawa, S, Hashida, and E, Ishikawa
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Immunoenzyme Techniques ,Immunoglobulin Fab Fragments ,Peroxidases ,Histocytochemistry ,Swine ,Immunoglobulin G ,Microsomes ,Chromatography, Gel ,Thyroid Gland ,Animals ,Antibodies, Monoclonal ,Electrophoresis, Polyacrylamide Gel ,Iodide Peroxidase - Abstract
A monoclonal antibody (30.1.2) to hog thyroid peroxidase was produced, purified, and characterized. The IgG of 30.1.2 formed an immune complex with the peroxidase in a 1:2 or 1:1 molar ratio depending on the IgG to antigen ratio in the incubation mixture. Immune complex formation did not inhibit the peroxidase activity, which was actually activated 2-fold in the 1:1 complex. Studies of the binding of the conjugate of the IgG or its Fab' with horseradish peroxidase to untreated and acetone-treated thyroid microsomes showed that the IgG conjugate could bind to only a very small portion of the total binding sites (thyroid peroxidase) present in untreated microsomes even after prolonged incubation. The binding of the Fab' conjugate to untreated microsomes, on the other hand, increased as the incubation time was increased, reaching 40% of the total sites after 20 h of incubation. These findings indicated that thyroid peroxidase is localized on the inner surface of the microsomal membranes and that the Fab' conjugate, but not the IgG conjugate, can slowly penetrate through the membrane barrier to reach the peroxidase. Immunohistochemical experiments using the Fab' conjugate as a probe revealed that most thyroid peroxidase in the thyroid gland is located in the endoplasmic reticulum and perinuclear cisternae of the follicular cell, although a small amount could occasionally be detected in the apical membrane including microvilli. In contrast to previous reports, no thyroid peroxidase could be found in other cellular structures such as Golgi apparatus and apical vesicles by the immunohistochemical technique employed.
- Published
- 1985
16. [Gimbernat's hernia (hernia through the lacunar ligament)--a case report (author's transl)]
- Author
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H, Noda, A, Kohno, J, Osawa, S, Nomi, S, Hashida, S, Arii, M, Shinoda, and J, Murakami
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Male ,Ligaments ,Humans ,Middle Aged ,Hernia, Femoral - Published
- 1977
17. [Clinical and experimental investigations on the pathogenesis of gastric mucosal injury in pancreatic insufficiency. (1). Observations in patients with pancreatic disease]
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S, Hashida
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Adult ,Gastric Acid ,Male ,Peptic Ulcer ,Humans ,Pancreatic Diseases ,Female ,Middle Aged ,Aged - Published
- 1986
18. Inhibitions of cathepsin B and cathepsin L by E-64 in vivo. II. Incorporation of [3H]E-64 into rat liver lysosomes in vivo
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S, Hashida, E, Kominami, and N, Katunuma
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Male ,Time Factors ,Cathepsin L ,Rats, Inbred Strains ,In Vitro Techniques ,Cathepsins ,Cathepsin B ,Rats ,Cysteine Endopeptidases ,Liver ,Leucine ,Endopeptidases ,Animals ,Lysosomes ,Protein Binding ,Subcellular Fractions - Abstract
E-64 is a specific thiol proteinase inhibitor which inhibits lysosomal cathepsins B and L in vitro and in vivo [Hashida, S., Towatari, T., Kominami, E.,Katunuma, N. (1980) J. Biochem. 88, 1805-1811]. This work showed and that E-64 administered in vivo penetrates into lysosomes of the liver, possibly by permeation rather than by endocytosis. When [3H]E-64 was injected into rats i.p., high radioactivity was observed in the serum after a short time and it decreased rapidly. Incorporation of [3H]E-64 into the cytosol fraction of liver also began to decrease 1 h after the injection. Radioactivity in the mitochondrial-lysosomal fraction increased to a maximum after 6 h and then gradually decreased until 72 h. Dose-dependent incorporation of [3H]E-64 into the serum and liver cytosol was observed at all doses tested, but that into the lysosomal fraction increased linearly with doses of only up to 0.l5 mg/100 body weight of E-64. E-64 in the serum and liver cytosol was mostly present in the free form, whereas that in the lysosomal fraction was mostly protein-bound. The time course and dose-response of lysosomal cathepsin B activity to E-64 were closely related to the radioactivity in the protein-bound fraction of the lysosomes. These results suggest that E-64 was transported to the liver cytosol in the free form in the blood and permeated into the lysosomes, where it bound to, and inactivated, E-64 sensitive proteinases.
- Published
- 1982
19. [Pancreatic hemodynamics in conscious dogs. 3. Pancreatic blood flow under gastric and intestinal stimulation]
- Author
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T, Kawano, K, Inoue, K, Shima, S, Hashida, K, Ogasawara, T, Suzuki, and T, Tobe
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Dogs ,Duodenum ,Regional Blood Flow ,Stomach ,Animals ,Pancreas - Published
- 1983
20. [Carcinoid of the esophagus]
- Author
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M, Hirata, M, Nakanishi, M, Sasaki, K, Fuse, T, Hishizawa, K, Kosuga, S, Hashida, M, Hashimoto, M, Yamamoto, and T, Yokota
- Subjects
Adult ,Male ,Esophageal Neoplasms ,Humans ,Carcinoid Tumor - Published
- 1989
21. [Pancreatic blood flow in conscious dogs. II. Effects of sham-feeding and aggressory state on pancreatic blood flow]
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T, Kawano, K, Inoue, K, Shima, S, Hashida, T, Suzuki, and T, Tobe
- Subjects
Aggression ,Eating ,Dogs ,Regional Blood Flow ,Animals ,Humans ,Pancreas - Published
- 1983
22. [Clinical and experimental evaluation of the pathogenesis of gastric mucosal injury in pancreatic insufficiency. (2). Changes in the gastric mucosal blood flow in dogs]
- Author
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S, Hashida
- Subjects
Peptic Ulcer ,Dogs ,Gastric Mucosa ,Animals ,Pancreatic Diseases - Published
- 1986
23. Comparative study of plasminogen activators in cancers and normal mucosae of human urinary bladder
- Author
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Y, Hasui, J, Suzumiya, K, Marutsuka, A, Sumiyoshi, S, Hashida, and E, Ishikawa
- Subjects
Immunoenzyme Techniques ,Plasminogen Activators ,Mucous Membrane ,Urinary Bladder Neoplasms ,Reference Values ,Tissue Plasminogen Activator ,Urinary Bladder ,Biomarkers, Tumor ,Humans ,Middle Aged ,Urokinase-Type Plasminogen Activator ,Aged ,Neoplasm Staging - Abstract
We have developed a highly sensitive sandwich enzyme immunoassay for determination of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) antigen levels in extracts of human tissues. We determined antigen levels of PAs in extracts of 31 primary cancers and 15 normal mucosal tissues of the urinary bladder using this method. U-PA antigen levels in extracts of bladder cancers were significantly higher than those in normal tissues (p less than 0.005). U-PA antigen levels significantly increased as histological grading of malignancy advanced. There was no correlation between t-PA antigen level and malignancy. These results indicate that an increase of u-PA antigen level may be a parameter of malignant transformation and may play an important role in invasiveness of cancer.
- Published
- 1989
24. [Clinical and statistical survey of the children at the Pedodontic Clinic of the Osaka University Dental Hospital]
- Author
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S, Hashida, J, Mihara, K, Hashida, N, Sumi, M, Rakugi, T, Ooshima, and S, Sobue
- Subjects
Male ,Adolescent ,Cleft Lip ,Infant ,Dental Caries ,Bottle Feeding ,Cleft Palate ,Tooth Diseases ,Child, Preschool ,Dietary Carbohydrates ,Humans ,Female ,Child ,Malocclusion - Published
- 1985
25. Inhibitions by E-64 derivatives of rat liver cathepsin B and cathepsin L in vitro and in vivo
- Author
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S, Hashida, T, Towatari, E, Kominami, and N, Katunuma
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Agmatine ,Cathepsin L ,Stereoisomerism ,Cathepsins ,Guanidines ,Cathepsin B ,Rats ,Cysteine Endopeptidases ,Kinetics ,Structure-Activity Relationship ,Liver ,Leucine ,Endopeptidases ,Animals ,Protease Inhibitors ,Sulfhydryl Compounds ,Lysosomes - Abstract
The mechanism of inhibition of cathepsin B [EC 3.4.22.1] and cathepsin L [EC 3.4.22.-] by E-64 was investigated. Kinetic studies indicated that E-64 was an irreversible inhibitor of these enzymes. [3H]E-64 is incorporated into cathepsin B in a one/one molar ratio in parallel with inactivation of the enzyme. Titration of one of the 10 SH groups of native cathepsin B with 2,2'-dithiodipyridine resulted in complete loss of enzyme activity. Decrease of titratable SH groups and activity of cathepsin B was proportional to the concentration of E-64 added, indicating that E-64 binds to an equimolar amount of active SH residues of cathepsin B. The effects of E-64 and its derivatives on lysosomal cathepsin B and cathepsin L in rat liver were studied in vitro and in vivo. The D form of E-64 inhibited the cathepsin both in vitro and in vivo, although its inhibitory effects were less than those of E-64-(L). E-64-b(RR), in which the terminal agmatine of E-64 is replaced by leucine, was as active as E-64-(L) in vitro, but was completely inactive in vivo. Among the E-64 derivatives tested, E-64-c(SS), in which the terminal agmatine of E-64 is replaced by isoarylamide, showed strong inhibitory activity in vivo, like E-64-(L).
- Published
- 1980
26. [Pancreatic blood flow in conscious dogs. (I) Measurement of basal flow and its changes during food intake]
- Author
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T, Kawano, K, Inoue, K, Shima, S, Hashida, T, Suzuki, and T, Tobe
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Eating ,Blood Volume ,Dogs ,Regional Blood Flow ,Animals ,Pancreas - Published
- 1983
27. Lymphangioleiomyomatosis: Rapidly Progressive Retroperitoneal Cystic Tumor Mimicking Malignancy.
- Author
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Hamada N, Hashida S, Okawa S, and Suwaki T
- Published
- 2024
- Full Text
- View/download PDF
28. Oncologic Outcomes of Patients with Early-Stage Cervical Cancer after Minimally Invasive Radical Hysterectomy and Sentinel Lymph Node Biopsy.
- Author
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Tanaka T, Nishie R, Murakami H, Tsuchihashi H, Toji A, Ueda S, Morita N, Hashida S, Terada S, Maruoka H, Taniguchi K, Komura K, and Ohmichi M
- Abstract
Background : The sentinel lymph node is the first node that cancer cells reach when migrating from the primary site. However, oncological outcomes after sentinel lymph node biopsy (SNB) have not been reported for cervical cancer. In this study, oncological outcomes were compared between patients receiving SNB and pelvic lymphadenectomy (PLD) for early-stage cervical cancer. Methods : One hundred and four patients with clinical stage 1A2, 1B1, and 2A1 cervical cancer were included in this study. All patients underwent laparoscopic or robot-assisted radical hysterectomy with SNB or PLD. Fifty-two patients with tumors ≤2 cm underwent SNB. Disease-free survival (DFS) and overall survival (OS) were compared between the groups. Results : The median (interquartile range) tumor size was 12 (7-20) mm in the SNB group and 20 (13-25) mm in the PLD group. Lymph node metastasis occurred in one patient in the SNB group and in nine patients in the PLD group. The median follow-up periods were 42 (24-60) and 82 (19-101) months in the SNB group and PLD group, respectively. The 3-year DFS rates were 100% in SNB and 91.5% in PLD. The 3-year OS was 100% in both groups. Conclusions : SNB was sufficient in cervical cancer patients with tumors ≤2 cm, suggesting that PLD might not be necessary for these patients.
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- 2024
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29. Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience.
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Nishie R, Tanaka T, Hirosuna K, Miyamoto S, Murakami H, Tsuchihashi H, Toji A, Ueda S, Morita N, Hashida S, Daimon A, Terada S, Maruoka H, Konishi H, Kogata Y, Taniguchi K, Komura K, and Ohmichi M
- Abstract
Background : The application of personalized cancer treatment based on genetic information and surgical samples has begun in the field of cancer medicine. However, a biopsy may be painful for patients with advanced diseases that do not qualify for surgical resection. Patient-derived xenografts (PDXs) are cancer models in which patient samples are transplanted into immunodeficient mice. PDXs are expected to be useful for personalized medicine. The aim of this study was to establish a PDX from body fluid (PDX-BF), such as peritoneal and pleural effusion samples, to provide personalized medicine without surgery. Methods : PDXs-BF were created from patients with ovarian cancer who had positive cytology findings based on peritoneal and pleural effusion samples. PDXs were also prepared from each primary tumor. The pathological findings based on immunohistochemistry were compared between the primary tumor, PDX, and PDX-BF. Further, genomic profiles and gene expression were evaluated using DNA and RNA sequencing to compare primary tumors, PDXs, and PDX-BF. Results : Among the 15 patients, PDX-BF was established for 8 patients (5 high-grade serous carcinoma, 1 carcinosarcoma, 1 low-grade serous carcinoma, and 1 clear cell carcinoma); the success rate was 53%. Histologically, PDXs-BF have features similar to those of primary tumors and PDXs. In particular, PDXs-BF had similar gene mutations and expression patterns to primary tumors and PDXs. Conclusions : PDX-BF reproduced primary tumors in terms of pathological features and genomic profiles, including gene mutation and expression. Thus, PDX-BF may be a potential alternative to surgical resection for patients with advanced disease.
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- 2024
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30. Two cases of strangulated bowel obstruction due to exposed vessel and nerve after laparoscopic and robot-assisted lateral lymph node dissection (LLND) for rectal cancer.
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Fujiwara R, Yano M, Matsumoto M, Higashihara T, Tsudaka S, Hashida S, Ichihara S, and Otani H
- Abstract
Background: The majority of small bowel obstructions (SBO) are caused by adhesion due to abdominal surgery. Internal hernias, a very rare cause of SBO, can arise from exposed blood vessels and nerves during pelvic lymphadenectomy (PL). In this report, we present two cases of SBO following laparoscopic and robot-assisted lateral lymph node dissection (LLND) for rectal cancer, one case each, of which obstructions were attributed to the exposure of blood vessels and nerves during the procedures., Case Presentation: Case 1: A 68-year-old man underwent laparoscopic perineal rectal amputation and LLND for rectal cancer. Four years and three months after surgery, he visited to the emergency room with a chief complaint of left groin pain. Computed tomography (CT) revealed a closed-loop in the left pelvic cavity. We performed an open surgery to find that the small intestine was fitted into the gap between the left obturator nerve and the left pelvic wall, which was exposed by LLND. The intestine was not resected because coloration and peristalsis of the intestine improved after the hernia was released. The obturator nerve was preserved. Case 2: A 57-year-old man underwent a robot-assisted rectal amputation with LLND for rectal cancer. Eight months after surgery, he presented to the emergency room with a complaint of abdominal pain. CT revealed a closed-loop in the right pelvic cavity, and he underwent a laparoscopic surgery with a diagnosis of strangulated SBO. The small intestine was strangulated by an internal hernia caused by the right umbilical arterial cord, which was exposed by LLND. The incarcerated small intestine was released from the gap between the umbilical arterial cord and the pelvic wall. No bowel resection was performed. The umbilical arterial cord causing the internal hernia was resected., Conclusion: Although strangulated SBO due to an exposed intestinal cord after PL has been a rare condition to date, it is crucial for surgeons to keep this condition in mind., (© 2024. The Author(s).)
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- 2024
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31. Gastrointestinal: Unusual cause of recurrent bradycardia and syncopal symptoms.
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Matsuura H, Hashida S, and Kishida M
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- Humans, Gastrointestinal Tract, Electrocardiography adverse effects, Bradycardia etiology, Bradycardia complications, Syncope etiology, Syncope diagnosis
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- 2024
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32. Consistency between Primary Uterine Corpus Malignancies and Their Corresponding Patient-Derived Xenograft Models.
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Ueda S, Tanaka T, Hirosuna K, Miyamoto S, Murakami H, Nishie R, Tsuchihashi H, Toji A, Morita N, Hashida S, Daimon A, Terada S, Maruoka H, Kogata Y, Taniguchi K, Komura K, and Ohmichi M
- Subjects
- Female, Humans, Animals, Mice, Heterografts, Disease Models, Animal, Mutation, RNA, Xenograft Model Antitumor Assays, Uterine Neoplasms genetics
- Abstract
Patient-derived xenograft (PDX) models retain the characteristics of tumors and are useful tools for personalized therapy and translational research. In this study, we aimed to establish PDX models for uterine corpus malignancies (UC-PDX) and analyze their similarities. Tissue fragments obtained from 92 patients with uterine corpus malignancies were transplanted subcutaneously into immunodeficient mice. Histological and immunohistochemical analyses were performed to compare tumors of patients with PDX tumors. DNA and RNA sequencing were performed to validate the genetic profile. Furthermore, the RNA in extracellular vesicles (EVs) extracted from primary and PDX tumors was analyzed. Among the 92 cases, 52 UC-PDX models were established, with a success rate of 56.5%. The success rate depended on tumor histology and staging. The pathological and immunohistochemical features of primary and PDX tumors were similar. DNA sequencing revealed similarities in gene mutations between the primary and PDX tumors. RNA sequencing showed similarities in gene expressions between primary and PDX tumors. Furthermore, the RNA profiles of the EVs obtained from primary and PDX tumors were similar. As UC-PDX retained the pathological and immunohistochemical features and gene profiles of primary tumors, they may provide a platform for developing personalized medicine and translational research.
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- 2024
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33. Triple repeated fetal congenital heart disease linked to PLD1 mutation: a case report.
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Masuda Y, Nagayasu Y, Murakami H, Nishie R, Morita N, Hashida S, Daimon A, Nunode M, Maruoka H, Yoo M, Sano T, Odanaka Y, Fujiwara S, Fujita D, Okamoto N, and Ohmichi M
- Subjects
- Adult, Fetus, Pulmonary Atresia, Mutation, Pregnancy, Humans, Fetal Death etiology, Ultrasonography, Prenatal methods, Female, Heart Defects, Congenital diagnosis, Heart Defects, Congenital genetics, Fetal Diseases
- Abstract
Background: Congenital heart disease occurs in approximately 1 in 100 cases. Although sibling occurrence is high (3-9%), the causative genes for this disease are still being elucidated. PLD1 (Phospholipase D1) is a recently discovered gene; however, few case reports have been published on it. In this report, we describe a case of triplicate fetal congenital heart disease that was diagnosed as a PDL1 mutation. Our objective is to explore the clinical manifestations of PLD1 mutations in this particular case., Case Presentation: A 32-year-old Japanese woman (gravida, para 0) was introduced since fetus four chamber view was not clear and was diagnosed with ductus arteriosus-dependent left ventricular single ventricle and pulmonary atresia at 21 weeks and 1 day of gestation during her first pregnancy. Artificial abortion using Gemeprost was performed at 21 weeks and 5 days of gestation. The second pregnancy was diagnosed as pulmonary atresia with intact ventricular septum with cardiomegaly, a cardiothoracic area ratio of more than 35%, and a circulatory shunt at 13 weeks and 3 days of gestation. Subsequently, intrauterine fetal death was confirmed at 14 weeks and 3 days of gestation. Regarding the third pregnancy, fetal ultrasonography at 11 weeks and 5 days of gestation showed mild fetal hydrops and moderate tricuspid valve regurgitation. At 16 weeks and 5 days of gestation, the fetus was suspected to have a left ventricular-type single ventricle, trace right ventricle, pulmonary atresia with intact ventricular septum, or cardiomyopathy. Cardiac function gradually declined at 26 weeks of gestation, and intrauterine fetal death was confirmed at 27 weeks and 5 days of gestation. The fourth pregnancy resulted in a normal heart with good progression and no abnormal baby. We submitted the first and second fetuses' umbilical cord, third fetus' placenta, and the fourth fetus' blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth., Conclusions: This report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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34. Lymphatic Complications Following Sentinel Node Biopsy or Pelvic Lymphadenectomy for Endometrial Cancer.
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Terada S, Tanaka T, Murakami H, Tsuchihashi H, Toji A, Daimon A, Miyamoto S, Nishie R, Ueda S, Hashida S, Morita N, Maruoka H, Konishi H, Kogata Y, Taniguchi K, Komura K, and Ohmichi M
- Abstract
Sentinel node biopsy (SNB) is performed worldwide in patients with endometrial cancer (EC). The aim of this study was to evaluate and compare the occurrence rate of lymphatic complications between SNB and pelvic lymphadenectomy (LND) for EC. The medical records of women who underwent SNB or pelvic LND for EC between September 2012 and April 2022 were assessed. A total of 388 patients were enrolled in the current study. Among them, 201 patients underwent SNB and 187 patients underwent pelvic LND. The occurrence rates of lower-extremity lymphedema (LEL) and pelvic lymphocele (PL) were compared between the patients who underwent SNB and those who underwent pelvic LND. The SNB group had a significantly lower occurrence rate of lower-extremity LEL than the pelvic LND group (2.0% vs. 21.3%, p < 0.01). There were no patients who had PL in the SNB group; however, 4 (2.1%) patients in the pelvic LND group had PL. The occurrence rates of lower-extremity LEL and PL were significantly lower in patients who underwent SNB than those who underwent pelvic LND. SNB for EC has a lower risk of lymphatic complications compared to systemic LND.
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- 2023
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35. Molecular composition of adiponectin in urine is a useful biomarker for detecting early stage of diabetic kidney disease.
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Kawano T, Aiba M, Ishizu M, Mori H, Matsuhisa M, Hashida S, Colpitts T, and Watanabe T
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- Humans, Adiponectin urine, Sensitivity and Specificity, Sand, Biomarkers urine, Diabetic Nephropathies diagnosis, Diabetes Mellitus
- Abstract
We previously developed two immune complex transfer enzyme immunoassays (ICT-EIA) to measure total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) in urine and have verified their usefulness as biomarkers for diabetic kidney disease. In this study, we developed T-AN and H-AN assays using the sandwich EIA (Sand-EIA). The reactivities of Sand-EIAs were compared with ICT-EIAs by measuring size exclusion chromatography (SEC) fractions of urine and adiponectin standard. As a result, ICT-EIAs showed higher macromolecular specificity. We then analyzed the molecular profile of adiponectin in the urine of 5 patients with different eGFR stages by measuring SEC fractions of urine. The results showed that smaller adiponectin correlated relatively well with eGFR stage. Finally, because SEC is time-consuming, we investigated that the ratio of T-ANs by Sand-EIA and ICT-EIA could be a good indicator of the monomer adiponectin. The ratio was evaluated using 77 urine samples from patients with diabetes and showed a significant decrease at an earlier stage compared with other biomarkers. In conclusion, we demonstrated a new index to estimate monomer adiponectin in urine by using Sand-EIA and ICT-EIA, and urinary monomer adiponectin can be a good early indicator of deterioration of renal function in diabetic patients. J. Med. Invest. 70 : 464-470, August, 2023.
- Published
- 2023
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36. Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma.
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Maruoka H, Tanaka T, Murakami H, Tsuchihashi H, Toji A, Nunode M, Daimon A, Miyamoto S, Nishie R, Ueda S, Hashida S, Terada S, Konishi H, Kogata Y, Taniguchi K, Komura K, and Ohmichi M
- Subjects
- Female, Humans, Biomarkers, Ovary, Adenocarcinoma, Clear Cell diagnosis, Adenocarcinoma, Clear Cell genetics, Extracellular Vesicles genetics, MicroRNAs genetics, Ovarian Neoplasms diagnosis, Ovarian Neoplasms genetics
- Abstract
Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC.
- Published
- 2022
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37. Robot-assisted modified radical hysterectomy with removal of lymphatic vessel using indocyanine green: A new method.
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Tanaka T, Nishie R, Ueda S, Hashida S, Miyamoto S, Terada S, Kogata Y, Taniguchi K, Komura K, and Ohmichi M
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- Female, Humans, Indocyanine Green, Sentinel Lymph Node Biopsy methods, Coloring Agents, Hysterectomy methods, Robotics, Endometrial Neoplasms surgery, Lymphatic Vessels pathology
- Abstract
Background: The sentinel lymph node (SLN) procedures using indocyanine green (ICG) have recently been performed worldwide. The aim of this study was to emphasise the safety of robot-assisted modified radical hysterectomy (RAMRH) with removal of the lymphatic vessels (RLV) using ICG in endometrial cancer according to a single surgeon's experience., Methods: Robot-assisted modified radical hysterectomy with RLV using ICG was performed in patients with endometrial cancer. We compared 34 cases of RAMRH with RLV, with 54 patients without RLV., Results: The median (interquartile range) time for the procedure did not differ between the RAMRH with and without RLV groups (88 [80-114] vs. 88 [79-104] min, p = 0.7). The success rate of RLV was 100% when SLNs were detected., Conclusion: Robot-assisted modified radical hysterectomy with RLV using ICG can completely dissect tissue from the uterus, including lymphatic vessels. This procedure using a robotic system with ICG, is simple and does not require additional time., (© 2022 John Wiley & Sons Ltd.)
- Published
- 2022
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38. A case of infective endocarditis mimicking a large mesenteric abscess.
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Yokota K, Sakamoto A, Takatsu F, and Hashida S
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- Abscess diagnosis, Humans, Abdominal Abscess complications, Abdominal Abscess diagnosis, Endocarditis complications, Endocarditis diagnosis, Endocarditis, Bacterial complications, Endocarditis, Bacterial diagnosis, Staphylococcal Infections complications, Staphylococcal Infections diagnosis
- Abstract
Infective endocarditis (IE) demonstrates a broad array of clinical presentations and complications. However, IE with prominent abdominal findings is uncommon. We encountered a case of IE caused by Staphylococcus aureus that presented a large mesenteric abscess and was initially diagnosed as an intra-abdominal infection. There are few reports of IE with mesenteric abscess formation. Even if an intra-abdominal abscess is the main symptom, the possibility that it is part of a systemic infection should be considered if the causative organism is atypical or if symptoms are present in multiple organs. Physicians should always be aware of the possibility that IE may mimic other diseases, including intra-abdominal infections., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2022
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39. Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization.
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Miyamoto S, Tanaka T, Hirosuna K, Nishie R, Ueda S, Hashida S, Terada S, Konishi H, Kogata Y, Taniguchi K, Komura K, and Ohmichi M
- Abstract
Patient-derived xenograft (PDX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies, and can be developed by the heterotopic or orthotopic grafting of surgically resected tumors into immunodeficient mice. We report the PDX models of cervical cancer and demonstrate the similarities among original and different generations of PDX tumors. Fresh tumor tissues collected from 22 patients with primary cervical cancer were engrafted subcutaneously into NOD.CB17-PrkdcSCID/J mice. Histological and immunohistochemical analyses were performed to compare primary and different generations of PDX tumors. DNA and RNA sequencing were performed to verify the similarity between the genetic profiles of primary and PDX tumors. Total RNA in extracellular vesicles (EVs) released from primary and PDX tumors was also quantified to evaluate gene expression. The total tumor engraftment rate was 50%. Histologically, no major differences were observed between the original and PDX tumors. Most of the gene mutations and expression patterns related to carcinogenesis and infiltration were similar between the primary tumor and xenograft. Most genes associated with carcinogenesis and infiltration showed similar expression levels in the primary tumor and xenograft EVs. Therefore, compared with primary tumors, PDX models could be potentially more useful for translational research.
- Published
- 2022
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40. Endometrial Cancer Patient-Derived Xenograft Models: A Systematic Review.
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Tanaka T, Nishie R, Ueda S, Miyamoto S, Hashida S, Konishi H, Terada S, Kogata Y, Sasaki H, Tsunetoh S, Taniguchi K, Komura K, and Ohmichi M
- Abstract
Background: Because patient-derived xenograft (PDX) models resemble the original tumors, they can be used as platforms to find target agents for precision medicine and to study characteristics of tumor biology such as clonal evolution and microenvironment interactions. The aim of this review was to identify articles on endometrial cancer PDXs (EC-PDXs) and verify the methodology and outcomes., Methods: We used PubMed to research and identify articles on EC-PDX. The data were analyzed descriptively., Results: Post literature review, eight studies were selected for the systematic review. Eighty-five EC-PDXs were established from 173 patients with EC, with a total success rate of 49.1%. A 1-10 mm
3 fragment was usually implanted. Fresh-fragment implantation had higher success rates than using overnight-stored or frozen fragments. Primary tumors were successfully established with subcutaneous implantation, but metastasis rarely occurred; orthotopic implantation via minced tumor cell injection was better for metastatic models. The success rate did not correspond to immunodeficiency grades, and PDXs using nude mice reduced costs. The tumor growth period ranged from 2 weeks to 13 months. Similar characteristics were observed between primary tumors and PDXs, including pathological findings, gene mutations, and gene expression., Conclusion: EC-PDXs are promising tools for translational research because they closely resemble the features of tumors in patients and retain molecular and histological features of the disease.- Published
- 2022
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41. Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer.
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Tanaka T, Ueda S, Miyamoto S, Hashida S, Terada S, Konishi H, Kogata Y, Taniguchi K, Komura K, and Ohmichi M
- Subjects
- Female, Humans, Hysterectomy methods, Neoplasm Staging, Prognosis, Retrospective Studies, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms surgery
- Abstract
Minimally invasive surgery (MIS) is performed to treat cervical cancer patients; however, a recent study showed that MIS was associated with higher recurrence and death rate compared with abdominal radical hysterectomy (ARH). In the current study, the prognosis of patients with early-stage cervical cancer who underwent MIS with vaginal closure or ARH was evaluated. One hundred and eighty-two patients underwent radical hysterectomy for cervical cancer with stage of IA2, IB1, and IIA1. MIS was performed by laparoscopy or a robot using the vaginal closure method. Disease-free survival (DFS) and overall survival (OS) were evaluated between the groups. Among the patients, 67 underwent MIS and 115 underwent ARH. The recurrence rate was 4.5% in MIS patients and 3.5% in ARH patients with a median follow-up (interquartile range) of 36 (18-60) and 78 (48-102) months, respectively. DFS and OS were not different between the groups (3y-DFS, 95.3% vs. 96.1%, p = 0.6; 3y-OS, 100% vs. 100%, p = 0.06). In early-stage cervical cancer patients, MIS with vaginal closure did not increase the risk for recurrence or death. Surgical techniques and procedures to avoid spillage of tumor cells could be important for a better prognosis.
- Published
- 2022
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42. Insulin receptor cleavage induced by estrogen impairs insulin signaling.
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Yuasa T, Takata Y, Aki N, Kunimi K, Satoh M, Nii M, Izumi Y, Otoda T, Hashida S, Osawa H, and Aihara KI
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- Estrogens, Female, Humans, Insulin, Pregnancy, Receptor, Insulin metabolism, Diabetes, Gestational, Insulin Resistance
- Abstract
Introduction: Soluble insulin receptor (sIR), which is the ectodomain of insulin receptor (IR), is present in human plasma. Plasma sIR levels are positively correlated with blood glucose levels and negatively correlated with insulin sensitivity. An in vitro model of IR cleavage shows that extracellular calpain 2 directly cleaves IR, which generates sIR, and sequential cleavage of the IRβ subunit by γ-secretase impairs insulin signaling in a glucose concentration-dependent manner. Nevertheless, sIR levels vary among subjects with normal glucose levels., Research Design and Methods: We examined sIR levels of pregnant women throughout gestation. Using an in vitro model, we also investigated the molecular mechanisms of IR cleavage induced by estradiol., Results: In pregnant women, sIR levels were positively correlated with estrogen levels and significantly increased at late pregnancy independent of glucose levels. Using an in vitro model, estrogen elicited IR cleavage and impaired cellular insulin signaling. Estradiol-induced IR cleavage was inhibited by targeting of calpain 2 and γ-secretase. Estrogen exerted these biological effects via G protein-coupled estrogen receptor, and its selective ligand upregulated calpain 2 expression and promoted exosome secretion, which significantly increased extracellular calpain 2. Simultaneous stimulation of estrogen and high glucose levels had a synergic effect on IR cleavage. Metformin prevented calpain 2 release in exosomes and restored insulin signaling impaired by estrogen., Conclusions: Estradiol-induced IR cleavage causes cellular insulin resistance, and its molecular mechanisms are shared with those by high glucose levels. sIR levels at late pregnancy are significantly elevated along with estrogen levels. Therefore, estradiol-induced IR cleavage is preserved in pregnant women and could be part of the etiology of insulin resistance in gestational diabetes mellitus and overt diabetes during pregnancy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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43. Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review.
- Author
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Tanaka T, Nishie R, Ueda S, Miyamoto S, Hashida S, Konishi H, Terada S, Kogata Y, Sasaki H, Tsunetoh S, Taniguchi K, Komura K, and Ohmichi M
- Subjects
- Animals, Female, Humans, Mice, Inbred NOD, Mice, Nude, Mice, SCID, Mice, Uterine Cervical Neoplasms pathology, Xenograft Model Antitumor Assays methods
- Abstract
Background: Patient-derived xenograft (PDX) models have been a focus of attention because they closely resemble the tumor features of patients and retain the molecular and histological features of diseases. They are promising tools for translational research. In the current systematic review, we identify publications on PDX models of cervical cancer (CC-PDX) with descriptions of main methodological characteristics and outcomes to identify the most suitable method for CC-PDX., Methods: We searched on PubMed to identify articles reporting CC-PDX. Briefly, the main inclusion criterion for papers was description of PDX created with fragments obtained from human cervical cancer specimens, and the exclusion criterion was the creation of xenograft with established cell lines., Results: After the search process, 10 studies were found and included in the systematic review. Among 98 donor patients, 61 CC-PDX were established, and the overall success rate was 62.2%. The success rate in each article ranged from 0% to 75% and was higher when using severe immunodeficient mice such as severe combined immunodeficient (SCID), nonobese diabetic (NOD) SCID, and NOD SCID gamma (NSG) mice than nude mice. Subrenal capsule implantation led to a higher engraftment rate than orthotopic and subcutaneous implantation. Fragments with a size of 1-3 mm
3 were suitable for CC-PDX. No relationship was found between the engraftment rate and characteristics of the tumor and donor patient, including histology, staging, and metastasis. The latency period varied from 10 days to 12 months. Most studies showed a strong similarity in pathological and immunohistochemical features between the original tumor and the PDX model., Conclusion: Severe immunodeficient mice and subrenal capsule implantation led to a higher engraftment rate; however, orthotopic and subcutaneous implantation were alternatives. When using nude mice, subrenal implantation may be better. Fragments with a size of 1-3 mm3 were suitable for CC-PDX. Few reports have been published about CC-PDX; the results were not confirmed because of the small sample size.- Published
- 2021
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44. Efficacy and Safety of Ramucirumab/nab-paclitaxel for Previously Treated Advanced Gastric Cancer in Community Hospitals.
- Author
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Hashida S, Tanaka N, Takahashi Y, Onoda Y, Colvin HS, Ohashi R, and Okamoto K
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Treatment Outcome, Ramucirumab, Adenocarcinoma drug therapy, Albumin-Bound Paclitaxel therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents therapeutic use, Hospitals, Community, Stomach Neoplasms drug therapy
- Abstract
As the nanoparticle albumin-bound paclitaxel (nab-PTX) is free of ethanol and premedication, the duration of administration is shorter and patients can drive themselves to and from the hospital. In the 2018 Japanese gastric cancer treatment guidelines, ramucirumab (RAM) plus weekly nab-PTX is conditionally recommended for previously treated patients with advanced gastric cancer. Here, we retrospectively analysed the efficacy and safety of RAM+nab-PTX for such patients in community hospitals. From January 2018 to December 2019, 43 patients with metastatic and recurrent gastric cancer received RAM+nab-PTX treatment. Six patients (13.9%) were older than 80 years and 9 patients (20.9%) showed ECOG-PS 2. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs) were reviewed retrospectively. Median PFS was 114 days (95% confidence interval [CI]: 84-190) and median OS was 297 days (95% CI: 180-398). ORR and DCR were 32.4% and 72.2%, respectively. The incidence rates of ≥grade 3 neutropenia and febrile neutropenia were 53.5% and 2.3%, respectively. No treatment-related deaths occurred. RAM plus nab-PTX combination therapy demonstrated manageable toxicity even patients who were elderly or had an ECOG-PS 2. This treatment is useful in community hospital settings., Competing Interests: No potential conflict of interest relevant to this article was reported.
- Published
- 2021
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45. Urinary adiponectin excretion is an early predictive marker of the decline of the renal function in patients with diabetes mellitus.
- Author
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Ishizu M, Mori H, Ohishi M, Kuroda A, Akehi Y, Yoshida S, Aihara KI, Aiba M, Kawano T, Hashida S, and Matsuhisa M
- Subjects
- Adiponectin, Albumins, Biomarkers, Diabetes Mellitus, Type 2 complications, Disease Progression, Glomerular Filtration Rate, Humans, Kidney physiology, Prospective Studies, Diabetic Nephropathies diagnosis
- Abstract
Aims: Since diabetes-associated kidney complication changes from diabetic nephropathy to diabetic kidney disease (DKD), more suitable biomarkers than urinary albumin are required. It has been hypothesized that urinary adiponectin (u-ADPN) is associated with the progression of DKD. We therefore evaluated the effectiveness of u-ADPN in predicting the decline of the renal function in patients with diabetes prior to end-stage renal disease., Methods: An ultrasensitive immune complex transfer enzyme immunoassay (ICT-EIA) was used to measure total and high molecular weight (HMW) adiponectin separately. We evaluated the relationships between the creatinine-adjusted urinary total-ADPN and HMW-ADPN, albumin (UACR) and liver-type fatty acid binding protein (L-FABP) at baseline and the 2-year change of the estimated glomerular filtration rate (ΔeGFR)., Results: This 2-year prospective observational study included 201 patients with diabetes. These patients were divided into three groups according to their ΔeGFR: ≤-10 mL/min/1.73m
2 , >-10 and ≤0 mL/min/1.73m2 , and >0 mL/min/1.73m2 . Jonckheere-Terpstra test showed that lower ΔeGFR was associated with higher u-HMW-ADPN (p = 0.045). In logistic regression analysis, u-HMW-ADPN was associated with ΔeGFR after adjusted age, sex, and basal eGFR., Conclusion: Urinary HMW-ADPN could predict a declining renal function in patients with diabetes., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
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46. Development of fully automated and ultrasensitive assays for urinary adiponectin and their application as novel biomarkers for diabetic kidney disease.
- Author
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Watanabe T, Fujimoto Y, Morimoto A, Nishiyama M, Kawai A, Okada S, Aiba M, Kawano T, Kawahigashi M, Ishizu M, Mori H, Matsuhisa M, Hata A, Funaki M, and Hashida S
- Subjects
- Adiponectin chemistry, Adult, Aged, Automation, Biomarkers chemistry, Biomarkers urine, Female, Humans, Male, Middle Aged, Molecular Weight, Protein Multimerization, Protein Structure, Quaternary, Adiponectin urine, Diabetic Nephropathies urine, Limit of Detection, Urinalysis methods
- Abstract
Glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) are used to diagnose and classify the severity of chronic kidney disease. Total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) assays were developed using the fully automated immunoassay system, HI-1000 and their significance over conventional biomarkers were investigated. The T-AN and H-AN assays had high reproducibility, good linearity, and sufficient sensitivity to detect trace amounts of adiponectin in the urine. Urine samples after gel filtration were analyzed for the presence of different molecular isoforms. Low molecular weight (LMW) forms and monomers were the major components (93%) of adiponectin in the urine from a diabetic patient with normoalbuminuria. Urine from a microalbuminuria patient contained both high molecular weight (HMW) (11%) and middle molecular weight (MMW) (28%) adiponectin, although the LMW level was still high (52%). The amount of HMW (32%) and MMW (42%) were more abundant than that of LMW (24%) in a diabetic patient with macroalbuminuria. T-AN (r = - 0.43) and H-AN (r = - 0.38) levels showed higher correlation with estimated GFR (eGFR) than UAER (r = - 0.23). Urinary levels of both T-AN and H-AN negatively correlated with renal function in diabetic patients and they may serve as new biomarkers for diabetic kidney disease.
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- 2020
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47. A case of pyometra with a colouterine fistula due to rectal cancer presenting as acute abdomen.
- Author
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Kanemura M, Yoshida A, Toji A, Hashida S, Murayama Y, and Iwai E
- Abstract
Pyometra usually develops in elderly women, and it can be caused by various etiologies. We describe a rare case of pyometra with a colouterine fistula due to rectal cancer presenting as acute abdomen. A 67-year-old woman with purulent vaginal discharge and abdominal distension was referred to our hospital for suspected pyometra. Because the vaginal echogram showed pyometra at her initial medical examination, drainage was performed. Her symptoms subsequently disappeared temporarily, but 4 months later, she developed acute abdomen. The computed tomography scan showed a pelvic mass with expansion of the intestine. The patient underwent en bloc resection of the mass. Histopathologic analysis of the tumor showed rectal cancer with invasion of the uterus and ileum, and a colouterine fistula. Although pyometra due to a colouterine fistula is a very rare condition, the incidence of associated malignancy is considerable. Physicians should be aware of this potential presentation of colorectal cancer., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2020.)
- Published
- 2020
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48. Usefulness of Urinary Creatinine/Urea Nitrogen Ratio as Indicator of Body Protein Catabolism in Dogs Fed Low Protein Diets.
- Author
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Yamamoto S, Ohta Y, Hasegawa E, Hashida S, Kaneko Y, Mizutani S, Ong BHE, Naganobu K, and Torisu S
- Abstract
Low protein diets (LPs) constitute a reportedly effective form of nutritional therapy for canine chronic kidney disease and cirrhosis. These diets have long been feared to result in reduced muscle mass due to protein catabolism. This adverse effect, however, remains largely unrecognized in veterinary medicine as there are no easily applicable catabolism indicators. Therefore, we focused on urinary creatinine, a metabolite of protein in the urine, and examined whether its ratio to urinary urea nitrogen (UCrn/UN) can be used to assess protein catabolism. In Experiment 1, we first consecutively fed seven healthy beagles an LP, standard protein (SP), and high protein (HP) diet for 1 week each and then measured the UCrn/UN ratio at 2-h intervals from fasting to 16 h post-prandially. We consequently found that the UCrn/UN ratio was significantly elevated in the LP pre-prandially and at all post-prandial measurement points ( P < 0.01). No significant differences were observed between the SP and HP. Analysis of fasting plasma amino-acid concentrations revealed that the concentration of methionine was significantly lower in the LP than in the other diets ( P < 0.05). Although the effects of this change in amino-acid concentration were unclear, the UCrn/UN ratio was considered having increased due to a deficiency in protein and/or amino acids during LP feeding. In Experiment 2, we continuously fed five healthy beagles an LP for 18 weeks and then measured the UCrn/UN ratio as described above. We also measured changes in body composition with computed tomography. At weeks 10 and 18, the fasting UCrn/UN ratio was significantly higher than it was prior to the start of the LP; however, post-prandially, the UCrn/UN ratio decreased to the point that the significant difference disappeared. Muscle mass decreased at weeks 10 and 18. These results suggest that the fasting UCrn/UN ratio could be used as an indicator of protein catabolism in LP feeding. Our experiments thus indicate that examination of potential increases in the UCrn/UN ratio 1 week after introduction of LP feeding to healthy dogs could enable detection of body protein catabolism in long-term feeding of LP before muscle breakdown occurs., (Copyright © 2019 Yamamoto, Ohta, Hasegawa, Hashida, Kaneko, Mizutani, Ong, Naganobu and Torisu.)
- Published
- 2019
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49. Uterine leiomyoma in a 13-year-old adolescent successfully treated with laparoscopic myomectomy: A case report.
- Author
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Morita N, Tanaka T, Hashida S, Tsunetoh S, Taniguchi K, Komura K, and Ohmichi M
- Subjects
- Adolescent, Female, Humans, Leiomyoma diagnostic imaging, Uterine Neoplasms diagnostic imaging, Laparoscopy methods, Leiomyoma surgery, Uterine Myomectomy methods, Uterine Neoplasms surgery
- Abstract
Rationale: Uterine leiomyoma, which is very common gynecological tumor in the reproductive years, is extremely rare in adolescence. We herein report a case of a uterine leiomyoma treated with laparoscopic surgery in an adolescent., Patient Concerns: A 13-year-old girl with no gravida and her first menses at 11 years of age reported feeling bloated. She had a regular menstrual cycle but felt increased abdominal distension., Diagnosis: Transabdominal ultrasound and magnetic resonance imaging revealed uterine leiomyoma with a diameter of 10 cm., Intervention: Laparoscopic myomectomy was performed., Outcomes: The total weight of the leiomyoma removed was 660 g with pathological diagnosis of uterine leiomyoma. The postoperative course was uneventful. The patient was free of disease at the follow-up consultation 18 months after the treatment., Lessons: Laparoscopic approach is a very useful and minimally invasive surgery for symptomatic leiomyoma in adolescents.
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- 2019
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50. Bulky cardiac metastasis of intracranial solitary fibrous tumor/hemangiopericytoma: Delayed metastasis after cranial tumor resection.
- Author
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Hashida S, Yokota H, Oyama Y, Kawakami M, Murakami S, and Kawakami H
- Abstract
We report a case of bulky cardiac metastasis of intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC). A 72-year-old woman developed a chief complaint of chest pain. Contrast-enhanced computed tomography revealed multiple enhanced masses in the heart, retroperitoneum, and femur. Initially, multiple metastases of cardiac primary angiosarcoma were suspected because the cardiac mass was the largest. However, it was diagnosed as SFT/HPC on the basis of biopsy and immunostaining for the retroperitoneal lesion. She had a history of resected brain tumor surgery for a meningioma 11 years earlier, and pathological reconfirmation revealed this was not a meningioma but rather a SFT/HPC. Thus, we found that the enhanced masses were extracranial metastases of an intracranial primary SFT/HPC. She died approximately 3 years after the onset of chest pain. Autopsy confirmed metastasis in the retroperitoneum, liver, lung, mesentery, skeletal muscle, and bone in addition to the heart. SFT/HPC has been reported to easily recur locally and to show systemic metastasis over the long term. Given that SFT/HPC has been recognized as a subtype of meningioma, the differential diagnosis for patients with a history of intracranial tumors, such as meningioma, should include SFT/HPC.
- Published
- 2019
- Full Text
- View/download PDF
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