NATALINO HAJIME YOSHINARI

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Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina

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  • conferenceObject
    Increased decorin and type V collagen in SSc pulmonary fibrosis
    (2012) TEODORO, W.; VELOSA, A. P.; MARCELINO, A.; MARTIN, P.; CARRASCO, S.; GOLDENSTEIN-SCHAINBERG, C.; PARRA, E.; YOSHINARI, N.; CAPELOZZI, V.
    Objective: To evaluate COL V and decorin expression in pulmonary tissue and to characterize biochemical profile of COLV from lung fibroblasts culture from SSc patients. Method: We evaluated COL V and decorin expression and tridimensional reconstruction (3D) of 6 patients with SSc without pulmonary hypertension that underwent surgical lung biopsy and as control was obtained lung fragments from 6 normal individuals who died from trauma. COL V amount in lung sections was evaluated with immunofluorescence. To biochemical characterization of COL V from lung fibroblasts culture was used quantitative immunoblot. Results: It was found that the structure of COLV fibers was distorted and strongly thickened in lung tissue from SSc patients compared with thin fibers pattern in the healthy controls. Decorin was distributed around COL V fibrils in the bronchovascular interstitium and vascular walls. Histomorphometric analysis of SSc lung demonstrated increased expression of both COL V and decorin when compared to the control (p<0.01). The semiquantitative imunoblot detected an increased high molecular weight COLV fraction in patients when compared to the control. Conclusion: The over expression and unusual organization of COLV fibers with biochemical changes associated to increased decorin indicates that matrix signalization pathway is involved in COLV fibrillogenesis process in SSc pulmonary fibrosis.
  • conferenceObject
    COLLAGEN TYPE V FACILITATE THE DIFFERENTIATION OF RABBIT ADIPOSE TISSUE-DERIVED STEM CELLS INTO A CHONDROCYTE-LIKE PHENOTYPE ""IN VITRO""
    (2012) CRUZ, Isabele B.; GOLDENSTEIN-SCHAINBERG, C.; FULLER, R.; VELOSA, A. P.; CARRASCO, S.; CAPELOZZI, V.; YOSHINARI, N. H.; TEODORO, W. R.
  • conferenceObject
    CORRELATION BETWEEN SHORTER DISEASE DURATION IN SYSTEMIC SCLEROSIS (SSC) AND ANTI-COLLAGEN TYPE V
    (2014) UGOLINI, M.; MANTOVANI, E.; DINIS, V.; BONOLDI, V.; RIBEIRO, A.; YOSHINARI, N.; ANDRADE, D.
  • article 73 Citação(ões) na Scopus
    Survival, Causes of Death, and Prognostic Factors in Systemic Sclerosis: Analysis of 947 Brazilian Patients
    (2012) SAMPAIO-BARROS, Percival D.; BORTOLUZZO, Adriana B.; MARANGONI, Roberta G.; ROCHA, Luiza F.; RIO, Ana Paula T. Del; SAMARA, Adil M.; YOSHINARI, Natalino H.; MARQUES-NETO, Joao Francisco
    Objective. To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). Methods. From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. Results. One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS <20). Conclusion. Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc. (First Release Aug 15 2012; J Rheumatol 2012;39:1971-8; doi:10.3899/jrheum.111582)
  • article 74 Citação(ões) na Scopus
    Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis
    (2019) SOBANSKI, Vincent; GIOVANNELLI, Jonathan; ALLANORE, Yannick; RIEMEKASTEN, Gabriela; AIRO, Paolo; VETTORI, Serena; COZZI, Franco; DISTLER, Oliver; MATUCCI-CERINIC, Marco; DENTON, Christopher; LAUNAY, David; HACHULLA, Eric; CERINIC, Marco Matucci; GUIDUCCI, Serena; WALKER, Ulrich; KYBURZ, Diego; LAPADULA, Giovanni; IANNONE, Florenzo; DISTLER, Oliver; MAURER, Britta; JORDAN, Suzana; BECVAR, Radim; SIERAKOWSKY, Stanislaw; BIELECKA, Otylia Kowal; CUTOLO, Maurizio; SULLI, Alberto; VALENTINI, Gabriele; CUOMO, Giovanna; VETTORI, Serena; SIEGERT, Elise; REDNIC, Simona; NICOARA, Ileana; KAHAN, Andre; ALLANORE, Yannick; VLACHOYIANNOPOULOS, Panayiotis; MONTECUCCO, Carlo; CAPORALI, Roberto; STORK, Jiri; INANC, Murat; CARREIRA, Patricia E.; NOVAK, Srdan; CZIRJAK, Laszlo; VARJU, Cecilia; CHIZZOLINI, Carlo; KUCHARZ, Eugene J.; KOTULSKA, Anna; KOPEC-MEDREK, Magdalena; WIDUCHOWSKA, Malgorzata; COZZI, Franco; ROZMAN, Blaz; MALLIA, Carmel; COLEIRO, Bernard; GABRIELLI, Armando; FARGE, Dominique; WU, Chen; MARJANOVIC, Zora; FAIVRE, Helene; HIJ, Darin; DHAMADI, Roza; AIRO, Paolo; HESSELSTRAND, Roger; WOLLHEIM, Frank; WUTTGE, Dirk M.; ANDREASSON, Kristofer; MARTINOVIC, Duska; BALBIR-GURMAN, Alexandra; BRAUN-MOSCOVICI, Yolanda; TROTTA, Francesco; MONACO, Andrea Lo; HUNZELMANN, Nicolas; PELLERITO, Raffaele; BAMBARA, Lisa Maria; CARAMASCHI, Paola; MOROVIC-VERGLES, Jadranka; BLACK, Carol; DENTON, Christopher; DAMJANOV, Nemanja; HENES, Joerg; SANTAMARIA, Vera Ortiz; HEITMANN, Stefan; KRASOWSKA, Dorota; SEIDEL, Matthias; HASLER, Paul; BURKHARDT, Harald; HIMSEL, Andrea; BAJOCCHI, Gianluigi; NUOVA, Arcispedale Santa Maria; SALVADOR, Maria Joao; SILVA, Jose Antonio Pereira Da; STAMENKOVIC, Bojana; STANKOVIC, Aleksandra; SELMI, Carlo Francesco; SANTIS, Maria De; MARASINI, Bianca; TIKLY, Mohammed; ANANIEVA, Lidia P.; DENISOV, Lev N.; MUELLER-LADNER, Ulf; FRERIX, Marc; TARNER, Ingo; SCORZA, Raffaella; PUPPO, Francesco; ENGELHART, Merete; STRAUSS, Gitte; NIELSEN, Henrik; DAMGAARD, Kirsten; SZUCS, Gabriella; SZAMOSI, Szilvia; MENDOZA, Antonio Zea; PUENTE, Carlos de la; GIRALDO, Walter Alberto Sifuentes; MIDTVEDT, Oyvind; REISETER, Silje; GAREN, Torhild; HACHULLA, Eric; LAUNAY, David; VALESINI, Guido; RICCIERI, Valeria; IONESCU, Ruxandra Maria; OPRIS, Daniela; GROSEANU, Laura; WIGLEY, Fredrick M.; CORNATEANU, Roxana Sfrent; IONITESCU, Razvan; GHERGHE, Ana Maria; SOARE, Alina; GORGA, Marilena; BOJINCA, Mihai; MIHAI, Carina; MILICESCU, Mihaela; SUNDERKOETTER, Cord; KUHN, Annegret; SANDORFI, Nora; SCHETT, Georg; DISTLER, Joerg H. W.; BEYER, Christian; MERONI, Pierluigi; INGEGNOLI, Francesca; MOUTHON, Luc; KEYSER, Filip De; SMITH, Vanessa; CANTATORE, Francesco Paolo; CORRADO, Ada; ULLMAN, Susanne; IVERSEN, Line; MUEHLEN, Carlos Alberto von; BOHN, Jussara Marilu; LONZETTI, Lilian Scussel; POZZI, Maria Rosa; EYERICH, Kilian; HEIN, Ruediger; KNOTT, Elisabeth; WILAND, Piotr; SZMYRKA-KACZMAREK, Magdalena; SOKOLIK, Renata; MORGIEL, Ewa; MADEJ, Marta; HOUSSIAU, Frederic A.; ALEGRE-SANCHO, Juan Jose; KRUMMEL-LORENZ, Brigitte; SAAR, Petra; ARINGER, Martin; GUENTHER, Claudia; WESTHOVENS, Rene; LANGHE, Ellen de; LENAERTS, Jan; ANIC, Branimir; BARESIC, Marko; MAYER, Miroslav; UPRUS, Maria; OTSA, Kati; YAVUZ, Sule; GRANEL, Brigitte; RADOMINSKI, Sebastiao Cezar; MUELLER, Carolina de Souza; AZEVEDO, Valderilio Feijo; JIMENEZ, Sergio; BUSQUETS, Joanna; AGACHI, Svetlana; GROPPA, Liliana; CHIABURU, Lealea; RUSSU, Eugen; POPA, Sergei; ZENONE, Thierry; PILECKYTE, Margarita; STEBBINGS, Simon; HIGHTON, John; MATHIEU, Alessandro; VACCA, Alessandra; SAMPAIO-BARROS, Percival D.; YOSHINARI, Natalino H.; MARANGONI, Roberta G.; MARTIN, Patricia; FUOCCO, Luiza; STAMP, Lisa; CHAPMAN, Peter; O'DONNELL, John; SOLANKI, Kamal; DOUBE, Alan; VEALE, Douglas; O'ROURKE, Marie; LOYO, Esthela; LI, Mengtao; MOHAMED, Walid Ahmed Abdel Atty; ROSATO, Edoardo; AMOROSO, Antonio; GIGANTE, Antonietta; OKSEL, Fahrettin; YARGUCU, Figen; TANASEANU, Cristina-Mihaela; POPESCU, Monica; DUMITRASCU, Alina; TIGLEA, Isabela; FOTI, Rosario; CHIRIEAC, Rodica; ANCUTA, Codrina; FURST, Daniel E.; VILLIGER, Peter; ADLER, Sabine; LAAR, Jacob van; KAYSER, Cristiane; EDUARDO, Andrade Luis C.; FATHI, Nihal; HASSANIEN, Manal; LEFEBVRE, Paloma Garcia de la Pena; RUBIO, Silvia Rodriguez; EXPOSITO, Marta Valero; SIBILIA, Jean; CHATELUS, Emmanuel; GOTTENBERG, Jacques Eric; CHIFFLOT, Helene; LITINSKY, Ira; EMERY, Paul; BUCH, Maya; GALDO, Francesco Del; VENALIS, Algirdas; BUTRIMIENE, Irena; VENALIS, Paulius; RUGIENE, Rita; KARPEC, Diana; SAKETKOO, Lesley Ann; LASKY, Joseph A.; KERZBERG, Eduardo; MONTOYA, Fabiana; COSENTINO, Vanesa; LIMONTA, Massimiliano; BRUCATO, Antonio Luca; LUPI, Elide; ROSNER, Itzhak; ROZENBAUM, Michael; SLOBODIN, Gleb; BOULMAN, Nina; RIMAR, Doron; COUTO, Maura; SPERTINI, Francois; RIBI, Camillo; BUSS, Guillaume; KAHL, Sarah; HSU, Vivien M.; CHEN, Fei; MCCLOSKEY, Deborah; MALVEAUX, Halina; PASQUALI, Jean Louis; MARTIN, Thierry; GORSE, Audrey; GUFFROY, Aurelien; POINDRON, Vincent
    Objective Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. Methods A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty-four clinical and serologic variables were used for clustering. Results Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. Conclusion Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis.
  • article 17 Citação(ões) na Scopus
    Influence of Suture on Peripheral Nerve Regeneration and Collagen Production at the Site of Neurorrhaphy: An Experimental Study
    (2011) MARTINS, Roberto Sergio; TEODORO, Walcy Rosolio; SIMPLICIO, Hougelle; CAPELLOZI, Vera Luiza; SIQUEIRA, Mario Gilberto; YOSHINARI, Natalino Hajime; PLESE, Jose Pindaro Pereira; TEIXEIRA, Manoel Jacobsen
    BACKGROUND: Restoration of nerve continuity and effective maintenance of coaptation are considered fundamental principles of end-to-end peripheral nerve repair. OBJECTIVE: To evaluate the influence of the number of stitches on axonal regeneration and collagen production after neurorrhaphy. METHODS: Thirty male Wistar rats were equally divided into 3 groups and were all operated on with the right sciatic nerve exposed. In 2 groups, the nerve was sectioned and repaired by means of 3 (group B) or 6 (group C) epineurium sutures with 100 monofilament nylon. One group (group A) was used as a control. Each animal from groups B and C underwent electrophysiological evaluation with motor action potential recordings before nerve section and again at an 8-week interval after neurorrhaphy. Nerve biopsy specimens were used for histomorphometric assessment of axonal regeneration and quantification of collagen at the repair site. RESULTS: Animals from group C had significantly lower motor action potential conduction velocities compared with control animals (P = .02), and no significant difference was seen between groups B and C. Parameters obtained from morphometric evaluation were not significantly different between these 2 groups. Type I collagen and III collagen in the epineurium were significantly higher in group C than in either the control group (P = .001 and P = .003) or group B (P = .01 and P = .02). No differences were identified for collagen I and III in the endoneurium. CONCLUSION: Using 6 sutures for nerve repair is associated with worse electrophysiological outcomes and higher amounts of type I and III collagen in the epineurium compared with control. Neurorraphy with 6 stitches is also related to a significant increase in epineurium collagen I and III compared with 3-stitch neurorraphy.
  • conferenceObject
    Fibrogenesis failure of type V collagen observed in pulmonary and cutaneous fibroblast culture reinforce the pathogenic participation of this collagen in the pathway of systemic sclerosis
    (2012) TEODORO, W. R.; MORAIS, J.; MARTIN, P.; VELOSA, A. P. P.; CARRASCO, S.; SOUZA, R. B. C.; KATAYAMA, M. L.; GOLDEINSTEIN-SCHAINBERG, C.; PARRA, E. R.; CAPELOZZI, V. L.; YOSHINARI, N. H.
    Introduction: Unusual type V collagen (COLV) accumulation was demonstrated in systemic sclerosis (SSc) by our group. In this regard, this study analyzed tridimensional reconstruction (3D), biochemical and molecular profile of COLVα1 and COLVα2 chains in pulmonary and cutaneous fibroblasts culture from patients with SSc. Materials and Methods: Pulmonary and cutaneous fibroblasts for culture were obtained from 7 patients with SSc and from six controls respectively. COLV 3D reconstruction was performed by confocal microscopy. COLVα1 and COLVα2 gene expression was performed by RT-PCR and COLV protein expression by immunoblotting. Results: COL V 3D reconstruction showed distorted and strongly thickened fibers with irregular bundles resulting in a dense network in lung and skin fibroblast cultures from SSc patients compared to the thin fibers from fibroblast controls. Collagen quantification showed significant increased COLV fiber expression in SSc cutaneous and pulmonary fibroblasts (P<0.01) compared with the respective controls. In the same way, molecular evaluation demonstrated an increased significance (P=0.05) of COLVα1 and COLVα2 mRNA expression in cutaneous and pulmonary fibroblasts from SSc patients to that of control groups. The immunoblotting analysis demonstrated the increased weight of the molecular COLV chains. Conclusion: COLV overexpression and an unusual organization of these fibers including molecular and biochemical changes, suggest an interference process of the COLV fibrillogenesis in patients with SSc, reinforcing the participation of this collagen in SSc pathogenesis and open new therapeutic perspectives for these patients.
  • article 3 Citação(ões) na Scopus
    First report of mild Brazilian spotted fever associated to arthritis
    (2014) BONOLDI, Virginia Lucia Nazario; MARANGONI, Roberta Gongalves; GAUDITANO, Giancarla; MORAES-FILHO, Jonas; LABRUNA, Marcelo Bahia; YOSHINARI, Natalino Hajime
    We describe the first Brazilian case of mild Rickettsiosis, complicated by knee monoarthritis, in young adult bitten by a tick on his left leg in Camburi zone, located in Sao Sebastiao municipality, southern coastal region of the State of Sao Paulo, in the Atlantic rainforest region, Brazil. The patient developed inoculation eschar at the tick bite site associated with enlarged lymph nodes in the left groin, fever, polyarthralgia, headache and macular rash. Twenty days after tick bite episode, he displayed monoarthritis in his right knee. The diagnosis of mild Rickettsiosis was established by sequential immunological analysis in serum and synovial fluid, using the indirect immunofluorescence (IF) assay for antibodies reactive with Rickettsia parkeri and Rickettsia rickettsii. The mild Rickettsiosis is an emerging zoonosis, that must be investigated by physicians, including rheumatologists, in patients that present macular rash, fever and eventually arthritis, after visiting the southern coastal Atlantic rainforest region in Brazil.
  • article 39 Citação(ões) na Scopus
    Experimental diabetes modulates collagen remodelling of joints in rats
    (2012) ATAYDE, Sandra A.; YOSHINARI, Natalino H.; NASCIMENTO, Dafne P.; CATANOZI, Sergio; ANDRADE, Priscila C.; VELOSA, Ana Paula P.; PARRA, Edwin R.; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; CAPELOZZI, Vera L.; TEODORO, Walcy R.
    The aim of this study was to evaluate extracellular matrix components in articular cartilage, ligaments and synovia in an experimental model of diabetes. Young Wistar rats were divided into a streptozotocin-induced (STZ; 35 mg/kg) diabetic group (DG; n=15) and a control group (CG; n=15). Weight, blood glucose and plasma anti-carboxymethyllysine were measured 70 days after STZ infusions. Knee joints, patellar ligaments, and lateral and medial collateral ligaments were isolated and stained with hematoxylineosin and Picrosirius. The total collagen content was determined by morphometry. Immunofluorescence was employed to evaluate types I, III, and V collagen in ligaments and synovial tissues and types II and XI collagen in cartilage. Results: Higher blood glucose levels and plasma anti-carboxymethyllysine were observed in DG rats when compared to those in CG rats. The final weight was significantly lower in the DG rats than in the CG rats. Histomorphometric evaluation depicted a small quantity of collagen fibers in ligaments and articular cartilage in DG rats, as well as increased collagen in synovial tissue. There was a decrease in cartilage proteoglycans in DG rats when compared with CG rats. Immunofluorescence staining revealed an increase of collagen III and V in ligaments, collagen XI in cartilage, and collagen I in synovial tissue of DG rats compared with CG rats. Conclusion: The ligaments, cartilage and synovia are highly affected following STZ-induced diabetes in rats, due the remodeling of collagen types in these tissues. This process may promote the degradation of the extracellular matrix, thus compromising joint function. Our data may help to better understand the pathogenesis of joint involvement related to diabetes.
  • article 7 Citação(ões) na Scopus
    The Current State of Knowledge on Baggio-Yoshinari Syndrome (Brazilian Lyme Disease-like Illness): Chronological Presentation of Historical and Scientific Events Observed over the Last 30 Years
    (2022) YOSHINARI, Natalino Hajime; BONOLDI, Virginia Lucia Nazario; BONIN, Serena; FALKINGHAM, Erica; TREVISAN, Giusto
    Baggio-Yoshinari Syndrome (BYS) is an emerging Brazilian tick-borne infectious disease that clinically mimics Lyme Disease (LD) present in the Northern Hemisphere. LD is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex and transmitted by Ixodid ticks of complex Ixodes rticinus. On the contrary, BYS is transmitted by hard Ixodid ticks of the genera Amblyomma, Rhipicephalus and Dermacentor. In 1992, the first cases of BYS were described in patients that developed EM rash, flu-like symptoms and arthritis after tick bite episodes. Since these findings, research in BYS has been developing for more than 30 years and shows that its epidemiological, clinical and laboratorial features are different from LD. Borrelia burgdorferi was never isolated in Brazil. In addition, specific serologic tests have shown little positivity. Furthermore, peripheral blood analysis of patients using electron microscopy exhibited structures resembling spirochete-like microorganisms or the latent forms of spirochetes (L form or cell wall deficient bacteria). For these reasons, Brazilian zoonosis was defined as an exotic and emerging Brazilian infectious disease, transmitted by ticks not belonging to the Ixodes ricinus complex, caused by latent spirochetes belonging to the B. burgdorferi sensu lato complex with atypical morphology. The Brazilian ecosystem, combined with its ticks and reservoir biodiversity, possibly contributed to the origin of this new zoonosis, which emerged as a result of the passage of B. burgdorferi through exotic vectors and reservoirs.