Osaka University Medical School Research Articles

FIBRONECTIN AS A POTENT INHIBITOR OF CALCIUM OXALATE UROLITHIASIS

Fibronectin (230 kD.) is a multifunctional alpha2-glycoprotein distributed throughout the extracellular matrix and body fluids. Many investigators have demonstrated that fibronectin, because of its cell adhesive action, is related to biological processes such as morphogenesis, wound healing and metastasis. Recent studies have shown that a variety of molecules, including fibronectin, inhibit endocytosis of calcium oxalate crystals in vitro. We investigated other roles of fibronectin in calcium oxalate stone formation. Immunoblotting of the crystal surface binding substance obtained from pooled healthy male urine samples was used to analyze whether fibronectin was adsorbed onto the surface of calcium oxalate crystals. To clarify the relationship between fibronectin and calcium oxalate crystals, we performed 6 experiments. Experiment 1 was immunohistochemical examination of fibronectin expression in stone forming rat model kidneys, and experiment 2 examined the fibronectin content of stone forming rat kidney models with the enzyme-linked immunosorbent assay. Experiment 3 was designed to determine fibronectin content of Madin-Darby canine kidney (MDCK) cells stimulated by addition of calcium oxalate crystals and experiment 4 identified the inhibitory effect of fibronectin on calcium oxalate crystal growth by the seed crystal method. For experiment 5 we used an aggregometer system to clarify the inhibitory effect of fibronectin on calcium oxalate crystal aggregation and experiment 6 examined the inhibitory effect of fibronectin on the adhesion of calcium oxalate crystals to MDCK cells. In the crystal surface binding substance immunoreactive bands at 230 kD., which correspond to the molecular weight of fibronectin, were detected by Western blot analysis. In stone forming rat kidneys strong expression of fibronectin was found on the renal tubules to which the crystals were attached. The fibronectin content of these kidneys was significantly greater than that of kidneys without calcium oxalate crystals. The fibronectin content of MDCK cells tended to increase in proportion to the concentration of calcium oxalate crystals added to the culture medium. The growth inhibition assay showed that the inhibitory effect of fibronectin on calcium oxalate crystal growth was small in relation to the quantity of fibronectin excreted. However, fibronectin had inhibitory effects on calcium oxalate crystal aggregation and adhesion of the crystals to MDCK cells. Fibronectin secretion can be stimulated by calcium oxalate crystals, and this protein, which is excreted from the tubular cells, may inhibit calcium oxalate crystal aggregation and attachment to cells.

A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration.

The neuronal ceroid lipofuscinoses (NCLs) constitute a group of neurodegenerative storage diseases characterized by progressive psychomotor retardation, blindness and premature death. Pathologically, there is accumulation of autofluorescent material in lysosome-derived organelles in a variety of cell types, but neurons in the central nervous system appear to be selectively affected and undergo progressive death. In this report we show that a novel form of NCL, congenital ovine NCL, is caused by a deficiency in the lysosomal aspartyl proteinase cathepsin D. A single nucleotide mutation in the cathepsin D gene results in conversion of an active site aspartate to asparagine, leading to production of an enzymatically inactive but stable protein. This results in severe cerebrocortical atrophy and early death, providing strong evidence for an important role of cathepsin D in neuronal development and/or homeostasis.

MECHANISMS IN OBESITY HYPERTENSION IN ACUTE-ONSET AND CHRONIC-ONSET OBESE HYPERTENSIVES

Department of Geriatric Medicine, Osaka University Medical School, Suita City, Osaka, Japan (Masuo) (Mikami) (Ogihara) 1Sepulveda VA Medical Center, Sepulveda, California, USA

Gene Therapy for Cardiovascular Disease Using Hepatocyte Growth Factor

Annals of the New York Academy of SciencesVolume 902, Issue 1 p. 369-376 Gene Therapy for Cardiovascular Disease Using Hepatocyte Growth Factor RYUICHI MORISHITA, Corresponding Author RYUICHI MORISHITA Department of Geriatric Medicine, Osaka University Medical School, Suita 565, Japan Division of Gene Therapy Science, Osaka University Medical School, Suita 565, Japan Address for correspondence: Ryuichi Morishita, M.D., Ph.D., Associate Professor, Division of Gene Therapy Science, Osaka University Medical School, Suita 565, Japan. Voice: 81–6–6879-3902; fax: 81–6–6879-3909. morishit@geriat.med.osaka-u.ac.jpSearch for more papers by this authorMOTOKUNI AOKI, MOTOKUNI AOKI Department of Geriatric Medicine, Osaka University Medical School, Suita 565, JapanSearch for more papers by this authorSHIGEFUMI NAKAMURA, SHIGEFUMI NAKAMURA Department of Geriatric Medicine, Osaka University Medical School, Suita 565, JapanSearch for more papers by this authorJITSUO HIGAKI, JITSUO HIGAKI Department of Geriatric Medicine, Osaka University Medical School, Suita 565, JapanSearch for more papers by this authorYASUFUMI KANEDA, YASUFUMI KANEDA Division of Gene Therapy Science, Osaka University Medical School, Suita 565, JapanSearch for more papers by this authorTOSHIO OGIHARA, TOSHIO OGIHARA Department of Geriatric Medicine, Osaka University Medical School, Suita 565, JapanSearch for more papers by this author RYUICHI MORISHITA, Corresponding Author RYUICHI MORISHITA Department of Geriatric Medicine, Osaka University Medical School, Suita 565, Japan Division of Gene Therapy Science, Osaka University Medical School, Suita 565, Japan Address for correspondence: Ryuichi Morishita, M.D., Ph.D., Associate Professor, Division of Gene Therapy Science, Osaka University Medical School, Suita 565, Japan. Voice: 81–6–6879-3902; fax: 81–6–6879-3909. morishit@geriat.med.osaka-u.ac.jpSearch for more papers by this authorMOTOKUNI AOKI, MOTOKUNI AOKI Department of Geriatric Medicine, Osaka University Medical School, Suita 565, JapanSearch for more papers by this authorSHIGEFUMI NAKAMURA, SHIGEFUMI NAKAMURA Department of Geriatric Medicine, Osaka University Medical School, Suita 565, JapanSearch for more papers by this authorJITSUO HIGAKI, JITSUO HIGAKI Department of Geriatric Medicine, Osaka University Medical School, Suita 565, JapanSearch for more papers by this authorYASUFUMI KANEDA, YASUFUMI KANEDA Division of Gene Therapy Science, Osaka University Medical School, Suita 565, JapanSearch for more papers by this authorTOSHIO OGIHARA, TOSHIO OGIHARA Department of Geriatric Medicine, Osaka University Medical School, Suita 565, JapanSearch for more papers by this author First published: 25 January 2006 https://doi.org/10.1111/j.1749-6632.2000.tb06340.xCitations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume902, Issue1ATHEROSCLEROSIS V THE FIFTH SARATOGA INTERNATIONAL CONFERENCEMay 2000Pages 369-376 RelatedInformation

Essential Role of Neural Wiskott-Aldrich Syndrome Protein in Neurite Extension in PC12 Cells and Rat Hippocampal Primary Culture Cells

Neural Wiskott-Aldrich syndrome protein (N-WASP) is an actin-regulating protein that induces filopodium formation downstream of Cdc42. It has been shown that filopodia actively extend from the growth cone, a guidance apparatus located at the tip of neurites, suggesting their role in neurite extension. Here we examined the possible involvement of N-WASP in the neurite extension process. Since verprolin, cofilin homology and acidic region (VCA) of N-WASP is known to be required for the activation of Arp2/3 complex that induces actin polymerization, we prepared a mutant (Deltacof) lacking four amino acid residues in the cofilin homology region. The corresponding residues in WASP had been reported to be mutated in some Wiskott-Aldrich syndrome patients. Expression of Deltacof N-WASP suppressed neurite extension of PC12 cells. In support of this, the VCA region of Deltacof cannot activate Arp2/3 complex enough compared with wild-type VCA. Furthermore, H208D mutant, which has been shown unable to bind to Cdc42, also works as a dominant negative mutant in neurite extension assay. Interestingly, the expression of H208D-Deltacof double mutant has no significant dominant negative effect. Finally, the expression of the Deltacof mutant also severely inhibited the neurite extension of primary neurons from rat hippocampus. Thus, N-WASP is thought to be a general regulator of the actin cytoskeleton indispensable for neurite extension, which is probably caused through Cdc42 signaling and Arp2/3 complex-induced actin polymerization.

Human G-protein β3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure

The activity of a sodium-proton exchanger is enhanced in the patients with essential hypertension and regulated via G-protein, which is a signal transducer between receptors and intracellular effectors. A recent study has revealed that a novel variant (C825T) in exon 10 of the gene encoding the β3 subunit of heterotrimetric G proteins ( GNB3) is a genetic factor predisposing to hypertension in Caucasians. We examined the association between GNB3/C825T and blood pressure, lipids, electrolytes, and other parameters in a Japanese population. Subjects (n = 352) were selected from the Ohasama Study, the population of which is regarded as from a rural community in Japan. To obtain precise clinical measurements, 24-h ambulatory blood pressure monitoring (ABPM), brain magnetic resonance imaging (MRI), and carotid ultrasonography (CUS) were conducted in this population. In addition, we recruited 762 subjects from outpatients at the Osaka University Medical School to carry out the association study between hypertension and GNB3. The GNB3 genotype distribution did not differ significantly between normotensives and hypertensives in either of the two studies. The T825 allele of GNB3 was not associated with the presence of hypertension, blood pressure level, the number of brain lacunae or carotid wall thickness. However, the serum potassium and total cholesterol levels were significantly higher in subjects with the T allele ( P < .005). The T825 allele of GNB3 is associated with increased serum potassium and total cholesterol levels but not with blood pressure in a Japanese population.

Experience of Clinical Practice During the Student Era at Osaka University Medical School

Experience of Clinical Practice During the Student Era at Osaka University Medical School

Cholesteatoma otitis media with intact ossicular chain

Thirty-one cases of cholesteatoma with intact ossicular chain were reviewed to examine the extension of cholesteatoma, operation procedures, pre- and postoperative hearing levels, and postoperative condition of the ear drum. They were operated on at Departments of Hyogo College of Medicine and Osaka University Medical School from 1989–1996, which were 20.4% of all of the primary cholesteatoma cases ( n=152). Twelve cases located at attic were operated by atticotomy or canal wall up and scutumplasty, 17 cases located at attic/antrum were operated by canal wall down and reconstruction, and two cases located around stapes were operated through the ear canal. Preoperative hearing level was mild (34.2±18.4 dB) and postoperative one was slightly improved (28.7±11.2 dB). In ossicular reconstruction, modified Wullstein type III method showed better hearing gain than Wullstein type I method. Postoperative attic retraction and/or pocket occurred in 15 cases (48.4%), but no recurrent cholesteatoma was found during the present follow-up period. These findings suggested that cholesteatoma with intact ossicular chain showed good postoperative hearing results, but postoperative retraction of the ear drum should be followed up for a long time.

Dynamic measurement of intrinsic PEEP does not represent the lowest intrinsic PEEP.

Dynamic intrinsic PEEP (PEEPi-dyn) is the airway pressure required to overcome expiratory flow and is considered to represent the lowest regional PEEPi. However, there are few data to validate this assumption. We investigated if PEEPi-dyn represents the lowest PEEPi. The animal laboratory at the Osaka University Medical School. We compared static PEEPi (PEEPi-stat) and PEEPi-dyn in healthy animals. Five adult white rabbits (2.77+/-0.05 kg) were anesthetized, tracheostomized, and intubated with several different sizes of endotracheal tubes (ETT) (2.0, 2.5, 3.0, 3.5, or 4.0 mm i.d.). The animals were paralyzed and ventilated (Siemens Servo 900C). Baseline ventilator settings were at a rate of 50/min, inspiratory:expiratory (I:E) ratio of 2:1 or 4:1, and minute ventilation was manipulated to create 3 or 5 cm H2O PEEPi-stat. PEEPi-stat was measured using the expiratory hold button of the ventilator. PEEPi-dyn showed large variations. In all ventilator settings, PEEPi-dyn was higher than PEEPi-stat (p<0.001). The larger the ETT, the higher the PEEPi-dyn at an I:E ratio of 2:1 (p<0.05). The higher the minute ventilation, the greater the difference between PEEPi-stat and PEEPi-dyn. The tidal volume and the difference showed a significant correlation (r2 = 0.514, p<0.001). The value of PEEPi-dyn was dependent on ventilatory settings, and PEEPi-dyn does not necessarily represent the lowest regional PEEPi within the lungs.

Methicillin-resistant Staphylococcus aureus infections after scleral buckling procedures for retinal detachments associated with atopic dermatitis

Objective To determine the incidence and the clinical course of methicillin-resistant Staphylococcus aureus as a cause of acute-onset infections in patients with atopic dermatitis after a scleral buckling procedures. Design A retrospective chart review. Participants Two hundred eighty-seven patients (293 eyes) who underwent scleral buckling procedures to treat rhegmatogenous retinal detachments at either Osaka Rosai Hospital or Osaka University Medical School between July 1, 1995, and June 30, 1997, participated. Of these, 32 eyes (10.9%) were associated with atopic dermatitis. Intervention Demographic and clinical data were abstracted from patients’ medical records. Main outcome measures The incidence, clinical features, and management of postoperative infections associated with methicillin-resistant S. aureus were studied. Results Methicillin-resistant S. aureus infection after scleral buckling procedures was identified in 6 (18.8%) of 32 eyes of patients with atopic dermatitis but in only 1 (0.4%) of the other 261 cases without atopic dermatitis ( P < 0.001). The average interval from the scleral buckling procedures to the initial onset of infection was 8.3 ± 9.1 days (range, 2–28 days). Bacterial infection and inflammation were controlled in four eyes by prompt removal of the infected buckle in combination with vancomycin administration. In the other three eyes, however, repeat intravitreous injections of vancomycin or emergent vitrectomies were required because of the development of endophthalmitis. Conclusions Methicillin-resistant S. aureus is an important causative pathogen of scleral buckling infections, particularly in patients with retinal detachment associated with atopic dermatitis. Preoperative evaluation and intraoperative attention to contamination are recommended to prevent methicillin-resistant S. aureus infections in these patients.

Genetic analysis of candidate gene polymorphisms in elderly hypertension

Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (< 60) and elderly (> or = 60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging.

Evaluation of cytotoxicity of ocular drugs and excipients in an immortalized human corneal epithelial cell line: [formula omitted]1, T. Järvinen 2, K. Araki-Sasaki 3, H. Watanabe 4 and A. Urtti 1. Department of 1 Pharmaceutics and 2 Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland, 3 Toyanaka Municipal Hospital, Osaka, Japan, 4 Department of Ophthalmology, Osaka University

Evaluation of cytotoxicity of ocular drugs and excipients in an immortalized human corneal epithelial cell line: [formula omitted]1, T. Järvinen 2, K. Araki-Sasaki 3, H. Watanabe 4 and A. Urtti 1. Department of 1 Pharmaceutics and 2 Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland, 3 Toyanaka Municipal Hospital, Osaka, Japan, 4 Department of Ophthalmology, Osaka University

Glycosaminoglycans in Crystal-Surface Binding Substances and Their Role in Calcium Oxalate Crystal Growth

No AccessJournal of UrologyUrological Survey: Abstracts: Urolithiasis, Endourology and Laparoscopic Surgery1 May 1998Glycosaminoglycans in Crystal-Surface Binding Substances and Their Role in Calcium Oxalate Crystal Growth K. Yoshimura, T. Yoshioka, O. Miyake, M. Honda, S. Yamaguchi, T. Koide, and A. Okuyama K. YoshimuraK. Yoshimura More articles by this author , T. YoshiokaT. Yoshioka More articles by this author , O. MiyakeO. Miyake More articles by this author , M. HondaM. Honda More articles by this author , S. YamaguchiS. Yamaguchi More articles by this author , T. KoideT. Koide More articles by this author , and A. OkuyamaA. Okuyama More articles by this author View All Author Informationhttps://doi.org/10.1097/00005392-199805000-00137AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Glycosaminoglycans in Crystal-Surface Binding Substances and Their Role in Calcium Oxalate Crystal Growth." The Journal of Urology, 159(5), p. 1780 Departments of Urology, Osaka University Medical School, Ikeda Municipal Hospital and Osaka Kosei-nenkin Hospital, Osaka, Japan.© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 159Issue 5May 1998Page: 1780 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information K. Yoshimura More articles by this author T. Yoshioka More articles by this author O. Miyake More articles by this author M. Honda More articles by this author S. Yamaguchi More articles by this author T. Koide More articles by this author A. Okuyama More articles by this author Expand All Advertisement Loading ...

A Japanese approach to establish an electronic patient record system in an intelligent hospital

In order to respond to the growing needs for clinical, educational and academic functions, the Osaka University Medical School and its attached hospital were moved to a new campus in 1993. On this occasion the university hospital has planned to construct an ‘intelligent’ hospital. The new hospital consists of 19 clinics for an average of 2200 outpatients’ visits per day and 1076 beds in 24 nursing units, nine Hospital Service Divisions, Pharmacy Department, Nursing Department and Department of Administration. Two aspects must be emphasised in the ‘intelligent’ hospital. Firstly, as human resources are limited, the hospital is required to introduce new technologies which will save man-power and reallocate the power. Simultaneously, the hospital will provide amenities which will facilitate the human work. Secondly, integration of various types of hospital information will be much more important. In order to support the decision making of the hospital manager and clinical staffs, hospital management data and patient data must be collected and integrated by means of information technologies. One of the final goals in an intelligent hospital is to establish an Electronic Patient Record (EPR) system which replaces conventional paper medical record charts. In this paper, our approach is described and some barriers in terms of security and privacy issues will be discussed.

Functional modification of cytochrome C by peroxynitrite and selective inhibitors: Hidehiko Nakagawa, Yukiko Ohshima, Nobuo Ikota, Shigcomi Shimizu †, Yoshihide Tsujimoto †, and Toshihiko Ozawa, National Institute of Radiological Sciences, Chiba and †Biomedical Research Center, Osaka University Medical School, Osaka, Japan

Functional modification of cytochrome C by peroxynitrite and selective inhibitors: Hidehiko Nakagawa, Yukiko Ohshima, Nobuo Ikota, Shigcomi Shimizu †, Yoshihide Tsujimoto †, and Toshihiko Ozawa, National Institute of Radiological Sciences, Chiba and †Biomedical Research Center, Osaka University Medical School, Osaka, Japan

Using a reference point and videokeratography for intraoperative identification of astigmatism axis

Purpose: To estimate the misalignment of the astigmatism axis caused by intraoperative identification of the axis without using reference points.Settings: Osaka University Medical School, Suita, Japan.Methods: This study included 38 eyes of 19 patients with no ocular pathology except refractive error and 32 eyes of 16 patients with cataract. A point was marked on the nasal conjunctiva, on the “intraoperative” horizontal axis as estimated by the examiner using a surgical microscope while the patient lay on the operating table in the supine position. Videokeratography was performed with the patient seated, and the degree of axial misalignment was determined by measuring the angle between the conjunctival mark and the horizontal axis identified on the video image.Results: Mean axial misalignment for all patients was 4.4 degrees ± 2.8 (SD), which could theoretically cause about a 15% loss of surgical effect. The maximal misalignment was 14 degrees, which would correspond to a 48% loss of astigmatic correction.Conclusion: The results of this study suggest that intraoperative identification of the astigmatism axis without using reference points may reduce the surgical effect because of axis misalignment. The use of a reference point and preoperative videokeratography may increase the accuracy of identification of the astigmatism axis.

Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis : Matsuda, Y., Matsumoto, Yamada, A., Ichida, T., Asakura, H., Komoriya, Y., Nishiyama, E., Nakamura, T. Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Osaka 565, Japan Hepatol 1997; 26 (1): 81–89

Dinucleoside phosphorochloridite was synthesized from phosphorus trichloride and three nucleoside analogs, 3′-fluoro-2′,3′-dideoxythymidine (FLT), 2′,3′-dideoxy-5-fluoro-3′-thiacytidine (FTC), and 2′,3′-dideoxy-3′-thiacytidine (3TC), in a multistep synthesis. Polymer-bound N-Boc p-acetoxybenzyl 5′-O-2′-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the β-triphosphotriester derivatives containing three different nucleosides.

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Department of Orthopaedic Surgery; Kansai Rosai Hospital; Amagasaki-City, Japan (Noboru) Department of Orthopaedic Surgery; Osaka University Medical School; Suita, Japan (Yonenobu)

Mitochondrial Encephalopathy and Cytochrome C

Benefits from treatment of mitochondrial encephalomyopathy (MEM) with cytochrome C (6.25 mg) and vitamins Bl (25 mg) and B2 (12.5 mg), in daily injections, are reported from Osaka University Medical School and other centers in Japan.

Transcriptional regulation of albumin gene with various nutritional methods before and after hepatectomy : Takashi Morimoto, Toshimasa Tsujinaka, Atsuhiro Ogawa, Masanori Kishibuchi, Chikara Ebisui, Kazuomi Kan, Junya Fujita, Masahiko Yano, Hitoshi Shiozaki, and Morito Monden From the Second Department of Surgery, Osaka University Medical School, 2-2, Yamada-oka, Suita, Osaka, 565, Japan

Transcriptional regulation of albumin gene with various nutritional methods before and after hepatectomy : Takashi Morimoto, Toshimasa Tsujinaka, Atsuhiro Ogawa, Masanori Kishibuchi, Chikara Ebisui, Kazuomi Kan, Junya Fujita, Masahiko Yano, Hitoshi Shiozaki, and Morito Monden From the Second Department of Surgery, Osaka University Medical School, 2-2, Yamada-oka, Suita, Osaka, 565, Japan