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1.
Pharmazie ; 76(12): 594-601, 2021 12 05.
Article de Anglais | MEDLINE | ID: mdl-34986955

RÉSUMÉ

Resistance to lenvatinib mesylate (LEN), a systemic chemotherapy that can be administered orally, has been a major issue for treatment of hepatocellular carcinoma (HCC). Although HCC is the tumor that most exhibits intratumoral hypoxia, which has been shown to be involved in the development of treatment resistance, there are no reports of LEN resistance in HCC treatment under hypoxia. The purpose of our study was to elucidate the mechanism of treatment resistance to LEN under hypoxia using HCC cell lines. We confirmed LEN resistance under hypoxic conditions in HCC cell lines. There was a significant increase in the IC50 value of PLC/PRF/5 cells from 13.0±0.8 µM in normoxia to 21.3±1.1 µM in hypoxia, but in HepG2 cells, the increase was not significant. To elucidate the LEN resistance mechanism of PLC/PRF/5 cells under hypoxia, we performed microarray analysis and extracted genes that are thought to be related to this mechanism. Furthermore, in-silico analysis confirmed significant changes in the extracellular matrix, and among them, FN1 encoding fibronectin was determined as the hub of the gene cluster. The expression of fibronectin in PLC/PRF/5 cells examined with immunofluorescence staining was significantly elevated in and outside of cells under hypoxia, and tended to decrease when cells were exposed to LEN under normoxia. Furthermore, the fibronectin concentration in the culture solution of PLC/PRF/5 cells examined by ELISA was 2.3 times higher under hypoxia than under normoxia under LEN(-) conditions, and 1.6 times higher under hypoxia than under normoxia under LEN(+) conditions. It is assumed that in PLC/PRF/5 cells, fibronectin is probably suppressed as an indirect effect of LEN under normoxia, but transcription factors such as HIF-1α are induced under hypoxia, thus enhancing the production of fibronectin and attenuating the effect of LEN, resulting in drug resistance. This behavior of fibronectin with LEN exposure under hypoxia is probably specific to PLC/PRF/5 cells. Further studies should verify the combined effective inhibition of fibronectin and the MAPK pathway as a promising therapeutic strategy to enhance the value of LEN in HCC treatment.


Sujet(s)
Carcinome hépatocellulaire , Tumeurs du foie , Carcinome hépatocellulaire/traitement médicamenteux , Carcinome hépatocellulaire/génétique , Carcinome hépatocellulaire/métabolisme , Lignée cellulaire , Lignée cellulaire tumorale , Fibronectines/génétique , Fibronectines/usage thérapeutique , Humains , Hypoxie , Tumeurs du foie/traitement médicamenteux , Tumeurs du foie/génétique , Tumeurs du foie/métabolisme , Phénylurées , Quinoléines
2.
Sci Rep ; 10(1): 4074, 2020 03 05.
Article de Anglais | MEDLINE | ID: mdl-32139763

RÉSUMÉ

Environmental radioactive contamination caused by the Fukushima Dai-ichi Nuclear Power Plant accident has aroused great concern regarding a possible increase in the incidence of childhood thyroid cancer. The ultrasound examinations were conducted immediately after the accident as part of the Fukushima Health Management Survey (FHMS), which is divided into the preliminary baseline survey (PBLS) and the full-scale survey (FSS). Some of their outcomes are reported regularly and made available to the public. We have detailed measurements of the air-dose rates and radioactive elements in soil in many places all over the Fukushima prefecture. To study the dose-response relationship, we begin with the assumption that the external and internal doses are correlated with the air-dose rate and the amount of 131I in soil, respectively. We then investigate the relationship between these estimated doses and the PBLS and FSS thyroid cancer cases. Our analysis shows that the dose-response curve with the FSS data clearly differs from that with the PBLS data. Finally, we consider the potential mitigating effects of evacuation from highly contaminated areas in both external and internal exposure scenarios.


Sujet(s)
Pollution de l'environnement/effets indésirables , Accident nucléaire de Fukushima , Enquêtes de santé , Radio-isotopes de l'iode/effets indésirables , Tumeurs radio-induites/épidémiologie , Contrôle des radiations , Tumeurs de la thyroïde/épidémiologie , Enfant , Humains , Japon/épidémiologie , Tumeurs radio-induites/étiologie , Dose de rayonnement , Tumeurs de la thyroïde/étiologie
4.
J Thromb Haemost ; 16(5): 960-972, 2018 05.
Article de Anglais | MEDLINE | ID: mdl-29488681

RÉSUMÉ

Essentials We generated recombinant rhodocytin that could aggregate platelets via CLEC-2. Recombinant wild-type rhodocytin formed heterooctamer with four α- and ß-subunits. Asp 4 in α-subunit of rhodocytin was required for binding to CLEC-2. Inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis. SUMMARY: Background Rhodocytin, a disulfide-linked heterodimeric C-type lectin from Calloselasma rhodostoma consisting of α-subunits and ß-subunits, induces platelet aggregation through C-type lectin-like receptor 2 (CLEC-2). CLEC-2 is a physiological binding partner of podoplanin (PDPN), which is expressed on some tumor cell types, and is involved in tumor cell-induced platelet aggregation and tumor metastasis. Thus, modified rhodocytin may be a possible source of anti-CLEC-2 drugs for both antiplatelet and antimetastasis therapy. However, its molecular function has not been well characterized, because of the lack of recombinant rhodocytin that induces platelet aggregation. Objective To produce recombinant rhodocytin, in order to verify its function with mutagenesis, and to develop an anti-CLEC-2 drug based on the findings. Methods We used Chinese hamster ovary cells to express recombinant rhodocytin (wild-type [WT] and mutant), which was analyzed for induction/inhibition of platelet aggregation with light transmission aggregometry, the formation of multimers with blue native PAGE, and binding to CLEC-2 with flow cytometry. Finally, we investigated whether mutant rhodocytin could suppress PDPN-induced metastasis in an experimental lung metastasis mouse model. Results Functional WT] rhodocytin (αWTßWT) was obtained by coexpression of both subunits. Asp4 in α-subunits of rhodocytin was required for CLEC-2 binding. αWTßWT formed a heterooctamer similarly to native rhodocytin. Moreover, an inhibitory mutant of rhodocytin (αWTßK53A/R56A), forming a heterotetramer, bound to CLEC-2 without inducing platelet aggregation, and blocked CLEC-2-PDPN interaction-dependent platelet aggregation and experimental lung metastasis. Conclusion These findings provide molecular characterization information on rhodocytin, and suggest that mutant rhodocytin could be used as a therapeutic agent to target CLEC-2.


Sujet(s)
Antinéoplasiques/pharmacologie , Mouvement cellulaire/effets des médicaments et des substances chimiques , Lectines de type C/antagonistes et inhibiteurs , Tumeurs du poumon/prévention et contrôle , Glycoprotéines membranaires/antagonistes et inhibiteurs , Antiagrégants plaquettaires/pharmacologie , Agrégation plaquettaire/effets des médicaments et des substances chimiques , Protéines recombinantes/pharmacologie , Venins de vipère/pharmacologie , Animaux , Cellules CHO , Cricetulus , Femelle , Cellules HEK293 , Humains , Lectines de type C/composition chimique , Lectines de type C/génétique , Lectines de type C/métabolisme , Tumeurs du poumon/métabolisme , Tumeurs du poumon/secondaire , Glycoprotéines membranaires/métabolisme , Souris de lignée BALB C , Souris nude , Mutation , Multimérisation de protéines , Transduction du signal/effets des médicaments et des substances chimiques , Relation structure-activité , Venins de vipère/composition chimique , Venins de vipère/génétique , Venins de vipère/métabolisme
5.
Spinal Cord ; 56(1): 57-62, 2018 01.
Article de Anglais | MEDLINE | ID: mdl-28895579

RÉSUMÉ

STUDY DESIGN: Experimental animal study. OBJECTIVES: Although a population of gastrin-releasing peptide (GRP) neurons in the lumbar spinal cord has an important role in erection and ejaculation in rats, little information exists on this GRP system in primates. To identify the male-specific GRP system in the primate spinal cord, we studied the lumbosacral cord in macaque monkeys as a non-human primate model. SETTING: University laboratory in Japan. METHODS: To determine the gene sequence of GRP precursors, the rhesus macaque monkey genomic sequence data were searched, followed by phylogenetic analysis. Subsequently, immunocytochemical analysis for GRP was performed in the monkey spinal cord. RESULTS: We have used bioinformatics to identify the ortholog gene for GRP precursor in macaque monkeys. Phylogenetic analysis suggested that primate prepro-GRP is separated from that of other mammalian species and clustered to an independent branch as primates. Immunocytochemistry for GRP further demonstrated that male-dominant sexual dimorphism was found in the spinal GRP system in monkeys as in rodents. CONCLUSION: We have demonstrated in macaque monkeys that the GRP system in the lower spinal cord shows male-specific dimorphism and may have an important role in penile functions not only in rodents but also in primates. SPONSORSHIP: Tissues of Nihonzaru (Japanese macaque monkeys) were provided in part by National Institutes of Natural Sciences (NINS) through the National Bio-Resource Project (NBRP) of the MEXT, Japan. This work was supported in part by KAKENHI from the Japan Society for the Promotion of Science (JSPS) (to KT; 15KK0343, 15J40220 and HS; 15K15202, 15KK0257, 15H05724).


Sujet(s)
Dysfonctionnement érectile/étiologie , Peptide libérant la gastrine/génétique , Érection du pénis/physiologie , Caractères sexuels , Traumatismes de la moelle épinière/complications , Animaux , Évolution biologique , Modèles animaux de maladie humaine , Femelle , Peptide libérant la gastrine/métabolisme , Humains , Macaca , Mâle , Nitric oxide synthase type I/métabolisme , Moelle spinale/métabolisme , Moelle spinale/anatomopathologie
7.
Lymphology ; 50(2): 95-108, 2017.
Article de Anglais | MEDLINE | ID: mdl-30234246

RÉSUMÉ

The architecture of craniocervical lymphatic vessels in rodents has been examined previously. In the present study, we evaluated the distribution of collecting lymphatic vessels in the palate of Suncus, which is known to retain the prototype of placental mammals and is more similar to humans in terms of jaw bone morphology when compared with rodents. Three-dimensional reconstructed images of the Suncus palatum revealed that the collecting lymphatic vessels were connected to each other via smaller branches, and ran in an antero-posterior direction in the periosteum. The vessels entered the pair of posterior palatine foramina located near the fourth premolar or the first molar bilaterally, coursed through the posterior palatine canals, and reached the pterygopalatine fossa positioned posteriorly in the palate. The collecting lymphatic vessels changed directions from medial to superior to lateral while wrapping around arteries during their course, perhaps to enable the smooth transition from the palate to the deep cervical node. Inefficient lymphatic flow in humans is attributed to the superior location of the pterygopalatine fossa in the palate when compared with its location in the Suncus.

8.
J Thromb Haemost ; 15(3): 513-525, 2017 03.
Article de Anglais | MEDLINE | ID: mdl-28028907

RÉSUMÉ

Essentials The role of C-type lectin-like receptor-2 (CLEC-2) in cancer progression is unclear. CLEC-2-depleted mouse model is generated by using a rat anti-mouse CLEC-2 monoclonal antibody. CLEC-2 depletion inhibits hematogenous tumor metastasis of podoplanin-expressing B16F10 cells. CLEC-2 depletion prolongs cancer survival by suppressing thrombosis and inflammation. SUMMARY: Background C-type lectin-like receptor 2 (CLEC-2) is a platelet activation receptor of sialoglycoprotein podoplanin, which is expressed on the surface of certain types of tumor cells. CLEC-2-podoplanin interactions facilitate hematogenous tumor metastasis. However, direct evidence of the role of CLEC-2 in hematogenous metastasis and cancer progression is lacking. Objective and methods We generated immunological CLEC-2-depleted mice by using anti-mouse CLEC-2 monoclonal antibody 2A2B10 and investigated whether CLEC-2 promoted hematogenous tumor metastasis and tumor growth and exacerbated the prognosis of mice bearing podoplanin-expressing B16F10 melanoma cells. Results Our results showed that hematogenous metastasis was significantly inhibited in CLEC-2-depleted mice. B16F10 cells co-cultured with wild-type platelets, but not with CLEC-2-deficient platelets, showed increased proliferation. However, B16F10 cell proliferation was not inhibited in CLEC-2-depleted mice. Histological analysis showed that thrombus formation in tumor vessels was significantly inhibited and functional vessel density was significantly increased in CLEC-2-depleted mice. These data suggest that CLEC-2 deficiency may inhibit thrombus formation in tumor vessels and increase the density of functional vessels, thus improving oxygen and nutrient supply to tumors, indirectly promoting tumor proliferation. Furthermore, the overall survival of CLEC-2-depleted mice was significantly prolonged, which may be due to the suppression of thrombus formation in the lungs and subsequent inhibition of systemic inflammation and cachexia. Conclusions These data provide a rationale for the targeted inhibition of CLEC-2 as a new strategy for preventing hematogenous tumor metastasis and for inhibiting cancer-related thromboembolism.


Sujet(s)
Lectines de type C/métabolisme , Tumeurs/anatomopathologie , Activation plaquettaire , Agrégation plaquettaire , Thrombose/génétique , Animaux , Anticorps monoclonaux/composition chimique , Plaquettes/métabolisme , Plaquettes/anatomopathologie , Prolifération cellulaire , Évolution de la maladie , Protéines à fluorescence verte/composition chimique , Hémoglobines/composition chimique , Mélanome expérimental , Souris , Souris knockout , Métastase tumorale , Pronostic , Rats
9.
Curr Med Mycol ; 2(2): 45-50, 2016 Jun.
Article de Anglais | MEDLINE | ID: mdl-28681020

RÉSUMÉ

BACKGROUND AND PURPOSE: Superficial mycotic infections have been only poorly described in koalas and there are no reliable mycologically confirmed data regarding clinical isolation of dermatophytes in this animal. We report an 11-year-old female koala, kept in a zoo in Tokyo, Japan, and presenting with hyperkeratotic lesions and scaly plaques on forepaw claws and pads reminiscent of fungal infection. CASE REPORT: Direct microscopy of the scrapings was indicative of a dermatophyte infection. By culture and subsequent repeated subculturing of clinical specimens on Sabouraud dextrose agar, Mycobiotic agar, and potato dextrose agar, two distinct strains with different colony morphotypes (designed as types I and II) were identified. Macroscopic and microscopic characteristics of the strains were suggestive of three different species, i.e. Microsporum canis, M. gypseum, and M. fulvum. However, partial sequencing of internal transcribed spacer (ITS) region of rDNA, translation elongation factor-1α (Tef-1α), and beta-tubulin (BT2) genes confirmed the identity of both isolates as M. gypseum. The animal was treated with a continuous terbinafine regimen (250 mg/kg) once daily for 12 weeks. CONCLUSION: To the best of our knowledge, the present report is the first confirmed case of dermatophytosis in a koala. The genetics underlying a variety of phenotypic traits in most classical dermatophyte species are unknown, and further studies are needed to understand this phenomenon.

10.
Radiat Prot Dosimetry ; 159(1-4): 38-45, 2014 Jun.
Article de Anglais | MEDLINE | ID: mdl-24870362

RÉSUMÉ

The incidences of chromosome aberrations were analysed in splenic lymphocytes from mice that were continuously exposed to (137)Cs gamma rays within the low-dose-rate (LDR) range to evaluate the dose-response and dose-rate effects. Chromosome aberrations were detected by fluorescence in situ hybridisation method, and these were found to increase in frequency up to 8000 mGy at 20 mGy for 22 h d(-1) and to 700 mGy at 1 mGy for 22 h d(-1). Translocations increased in a linear quadratic manner with age in non-exposed mice. The dose-response relationship for the frequency of translocations at each dose rate (20 and 1 mGy for 22 h d(-1)) was obtained using age-adjusted multiple linear regression analysis. Values of the linear term, shown as the slope, decreased as the dose rate was reduced from 20 to 1 mGy for 22 h d(-1), indicating a positive dose-rate effect in the LDR range. These results will be useful for estimating the risk of LDR radiation exposure and radiation protection.


Sujet(s)
Aberrations des chromosomes/effets des radiations , Lymphocytes/effets des radiations , Facteurs âges , Animaux , Relation dose-effet des rayonnements , Femelle , Rayons gamma , Hybridation fluorescente in situ , Souris , Souris de lignée C3H
11.
Dentomaxillofac Radiol ; 43(6): 20140127, 2014.
Article de Anglais | MEDLINE | ID: mdl-24850145

RÉSUMÉ

Although necrotizing sialometaplasia (NS) of the parotid gland is rare and occasionally presents as a lesion that mimics a malignant tumour, imaging findings in cases of NS have been rarely reported. We describe here a case of NS in which there was an increasing lesion manifesting overnight on the parotid gland in an 83-year-old male. We also investigated the use of pre-operative imaging based on previous reports and discuss the importance of these images in helping to guard against overzealous treatment. It is critically important to closely examine whether there are aspects of NS, such as the present case, in pre-operative MRI findings that can be useful in proper diagnosis and treatment.


Sujet(s)
Imagerie diagnostique/méthodes , Maladies de la glande parotide/diagnostic , Sialométaplasie nécrosante/diagnostic , Sujet âgé , Biopsie/méthodes , Diagnostic différentiel , Radio-isotopes du gallium , Humains , Imagerie par résonance magnétique/méthodes , Mâle , Maladies de la glande parotide/imagerie diagnostique , Tumeurs de la parotide/diagnostic , Radiopharmaceutiques , Sialométaplasie nécrosante/imagerie diagnostique , Tomodensitométrie/méthodes , Échographie
12.
Transplant Proc ; 46(3): 689-91, 2014 Apr.
Article de Anglais | MEDLINE | ID: mdl-24767325

RÉSUMÉ

BACKGROUND: In living-donor liver transplantation (LDLT), the recipient's portal vein is short. Furthermore, portal vein thrombosis and stenosis can be lethal complications. We had begun the systemic administration of gabexate mesilate, a strong serine protease inhibitor, which has cytoprotective effects of endothelial cells. It is often effective on disseminated intravascular coagulation. The purpose of this study was to examine the effects of gabexate mesilate and to reveal risk factors for portal vein stenosis in LDLT. METHODS: From 1991 to 2012, we performed 153 LDLTs. For the present cohort study, patients were divided into 2 groups. In group I, we treated with gabexate mesilate mildly (0-20 mg/kg/d; n = 29). In group II, we treated with gabexate mesilate at full dose (40 mg/kg/d; n = 124). We investigated the survival rates of both groups and performed univariate and multivariate analyses to identify the independent risk factors for portal vein stenosis. RESULTS: The survival rate of group II was significantly better than that of group I (P < .05). On univariate analysis, the risk factors identified to be associated with a P value of <.20 were old age (P = .0385), heavy body weight (P = .1840), tall height (P = .1122), small lumen diameter of portal vein (P = .1379), high volume of blood loss (P = .0589), small amount of gabexate mesilate infusion (P = .0103), and large graft weight (P = .1326). On multiple logistic regression analysis we identified old age (P = .0073) and small amount of gabexate mesilate infusion (P = .0339) to be the independent risk factors for portal vein stenosis. CONCLUSIONS: On multivariate analysis, we found that gabexate mesilate infusion contributed to the reduction of portal vein stenosis.


Sujet(s)
Sténose pathologique/étiologie , Transplantation hépatique , Donneur vivant , Veine porte/anatomopathologie , Adulte , Enfant , Études de cohortes , Femelle , Humains , Mâle , Facteurs de risque , Jeune adulte
13.
J Clin Pediatr Dent ; 37(4): 411-3, 2013.
Article de Anglais | MEDLINE | ID: mdl-24046992

RÉSUMÉ

The dental management of an 8-year-old girl with osteopathia striata with cranial sclerosis (OS-CS) is described. The girl presented with various oral abnormalities. The aim of this case report was to describe in detail the dental findings in a patient with OC-CS and the precautions to be taken when planning treatment. In the present case, many dental anomalies, such as delayed eruption of the permanent teeth, obliteration of the dental pulp, short roots, fused roots and taurodontism, were detected. In patients with OS-CS, routine dental care from an early stage is recommended to manage this anomaly properly.


Sujet(s)
Soins dentaires pour malades chroniques , Calcification pulpaire/étiologie , Ostéosclérose/complications , Malformations dentaires/étiologie , Enfant , Fente palatine/étiologie , Femelle , Dents fusionnées/étiologie , Humains , Mégalencéphalie/étiologie , Éruption dentaire , Racine dentaire/malformations
14.
Transplant Proc ; 45(5): 2066-8, 2013 Jun.
Article de Anglais | MEDLINE | ID: mdl-23769110

RÉSUMÉ

BACKGROUND: On March 11, 2011, our hospital was severely damaged by the Great East Japan Earthquake. We report the rare case of a 5-month-old patient with hepatic artery thrombosis (HAT) after living donor liver transplantation (LDLT), who survived the earthquake that occurred 3 days after the reoperation; we were able to save this patient without abilities to perform blood tests or computed tomography (CT) for 4 days. METHODS: This female infant with biliary atresia underwent LDLT 5 months after birth and developed peritonitis owing to perforation of the small intestine 7 days later. Her blood pressure decreased and she developed HAT. We performed emergency reconstruction of the hepatic artery and repair of the small intestine, and 3 days after surgery, the Great East Japan Earthquake occurred. RESULTS: We could not perform blood tests or CT scans because the water supply was damaged. Gas supply lines were also damaged and sterilization was not possible; surgical tools were limited. However, emergency power was available, so we performed ultrasonography every 6 hours and predicted liver function from intrahepatic blood flow and monitored for Glisson's capsule edema. The blood examination system recovered 14 days after LDLT, and we confirmed improvement of liver function. The patient was extubated 37 days after LDLT and discharged on postoperative day 67. CONCLUSIONS: Portable ultrasonography was useful in evaluating intrahepatic blood flow and Glisson's capsule edema. Furthermore, it was effective during a disaster because it required no water or gas.


Sujet(s)
Tremblements de terre , Artère hépatique/anatomopathologie , Transplantation hépatique/effets indésirables , Donneur vivant , Thrombose/complications , Femelle , Humains , Nourrisson , Japon
15.
J Int Med Res ; 40(4): 1459-66, 2012.
Article de Anglais | MEDLINE | ID: mdl-22971497

RÉSUMÉ

OBJECTIVE: This study aimed to develop a model for predicting the outcome and evaluating the treatment of patients with threatened of preterm labour. METHODS: Clinical data from 236 patients at <32 weeks gestation who were in preterm labour were analysed to develop a discriminant function using multiple logistic regression to identify significant risk factors. The function was validated retrospectively in a further 501 patients and prospectively in 63 patients with premature labour. RESULTS: Factors that increased the risk of preterm birth were premature rupture of the membranes, intrauterine infection, dilatation of the cervix and uterine bleeding. Factors that decreased the risk of preterm birth were hospital admission after 28 weeks of gestation and intravenous administration of ritodrine. The predictive accuracy of the function was 75.4% in the 236 patients analysed, 84.8% in the further 501 retrospectively studied patients and 85.7% in the prospective group. CONCLUSIONS: The discriminant function described was clinically useful for predicting the outcome of threatened preterm labour before initiating treatment and for determining the medical care of patients, including maternal transfer to a high-level perinatal care centre.


Sujet(s)
Modèles biologiques , Travail obstétrical prématuré/prévention et contrôle , Adulte , Analyse discriminante , Femelle , Humains , Modèles logistiques , Travail obstétrical prématuré/traitement médicamenteux , Odds ratio , Grossesse , Études prospectives , Études rétrospectives , Facteurs de risque , Ritodrine/usage thérapeutique , Sensibilité et spécificité , Tocolyse , Tocolytiques/usage thérapeutique , Résultat thérapeutique , Jeune adulte
16.
Transplant Proc ; 43(9): 3292-5, 2011 Nov.
Article de Anglais | MEDLINE | ID: mdl-22099780

RÉSUMÉ

OBJECTIVE: Pancreas transplantation has been associated with the highest surgical complication rate among routinely performed organ transplant procedures. Complications can be caused not only from the pancreas itself but also from the simultaneously transplanted duodenum: gastrointestinal bleeding, duodenal ulcer, pseudoaneurysm, arterioenteric fistula, and severe rejection. Herein we report a patient who underwent simultaneous pancreas-kidney transplantation (SPKT) and experienced a duodenal perforation because of rejection. METHODS: The 60-year-old man with insulin-dependent diabetes underwent SPKT with enteric drainage. At 15 days there after he displayed melena. RESULTS: We suspected it to be caused by rejection and ischemic changes. We slightly increased the doses, of tacrolimus and methylprednisolone. But 17 days after SPKT, the ulcer perforated, requiring a repair operation and increased dose of mycophenolate mofetil. However, the ulcers perforated repeatedly, requiring 4 repair operations. Unfortunately the patient developed pneumonia that mitigated continues repairs or rejection therapies, so we expated the duodenum and pancreas but saved the kidney. The pathologic findings showed the ulcer to have been caused by severe rejection. Despite those episodes, the patient was weaned from hemodialysis. CONCLUSIONS: Perforation of the transplanted duodenum is one of the most difficult complications among SPKT patients. This potentially lethal complication may be caused by mucosal rejection, ischemic changes, and the exocrine output from the pancreatic graft.


Sujet(s)
Ulcère duodénal/diagnostic , Ulcère duodénal/étiologie , Transplantation rénale/effets indésirables , Transplantation pancréatique/effets indésirables , Rejet du greffon , Humains , Mâle , Adulte d'âge moyen , Complications postopératoires , Donneurs de tissus , Résultat thérapeutique
17.
Transplant Proc ; 43(9): 3299-301, 2011 Nov.
Article de Anglais | MEDLINE | ID: mdl-22099782

RÉSUMÉ

INTRODUCTION: Posttransplantation lymphoproliferative disorder (PTLD) remains an uncommon complication of solid organ transplantation, with a high mortality rate reported after conventional therapies. Epstein-Barr virus (EBV) may cause PTLD, but most EBV infections after transplantation are clinically silent reactivations, so the detection of PTLD is often delayed. Recently we experienced the rare case of intrarenal graft PTLD found by macrohematuria in a simultaneous pancreas and kidney transplant recipient. The grafts were saved by treatments with rituximab, cyclophosphamide, hydroxydaunorubicin, and prednisone-based chemotherapy (R-CHOP) after reduction of immunosuppression (IR). METHODS: This 37-year-old man with insulin-dependent diabetes underwent simultaneous pancreas and kidney transplantation (SPK) with enteric drainage. Six months after transplantation, he displayed macrohematuria, which we investigated by blood tests, computer tomography (CT) scan, positron emission tomography (PET)-CT, and magnetic resonance imaging, recognizing a tumor in the transplanted renal graft. An open biopsy showed a CD20-positive PTLD. We started treatments with IR, rituximab (375 mg/m(2), weekly for 2 cycles) and R-CHOP therapy: rituximab (375 mg/m(2)) plus CHOP every 3 weeks for 6 cycles. RESULTS: IR and R-CHOP therapy achieved a complete remission (CR). CR has continued for 14 months at the time of writing. The maximum level of EBV DNA was 259 copies/µg DNA, but 2 months after these therapies, the level had decreased to normal. The patient had no impairment of pancreas and kidney graft functions. CONCLUSIONS: The outcome of intragraft PTLD in the kidney of an SPK recipient suggested that the negative impact of IR on graft function may be compensated by the immunosuppressive effects of rituximab, allowing reduced immunosuppression during chemotherapy.


Sujet(s)
Anticorps monoclonaux d'origine murine/pharmacologie , Hématurie/diagnostic , Immunosuppresseurs/usage thérapeutique , Transplantation rénale/effets indésirables , Transplantation rénale/méthodes , Syndromes lymphoprolifératifs/étiologie , Transplantation pancréatique/méthodes , Adulte , Anticorps monoclonaux d'origine murine/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Cyclophosphamide/usage thérapeutique , Doxorubicine/usage thérapeutique , Infections à virus Epstein-Barr/complications , Humains , Tumeurs du rein/diagnostic , Tumeurs du rein/thérapie , Imagerie par résonance magnétique/méthodes , Mâle , Tomographie par émission de positons/méthodes , Complications postopératoires , Prednisone/usage thérapeutique , Induction de rémission , Rituximab , Tomodensitométrie/méthodes , Vincristine/usage thérapeutique
18.
Diabet Med ; 28(11): 1381-7, 2011 Nov.
Article de Anglais | MEDLINE | ID: mdl-21672009

RÉSUMÉ

AIMS: We previously showed that the C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with myocardial infarction in Japanese individuals by a genome-wide association study. Given that diabetes mellitus is an important risk factor for myocardial infarction, the association of rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to diabetes. The purpose of this study was to examine the relation of rs6929846 of BTN2A1 to Type 2 diabetes mellitus. METHODS: A total of 8650 Japanese individuals from two independent subject panels were examined: Panel A comprised 1141 individuals with Type 2 diabetes and 3161 control subjects and panel B comprised 1664 individuals with Type 2 diabetes and 2684 control subjects. RESULTS: The chi-square test revealed that rs6929846 of BTN2A1 was significantly related to the prevalence of Type 2 diabetes in subject panel A (P = 0.0002) and subject panel B (P=0.006). Multivariable logistic regression analysis with adjustment for age, sex, body mass index and smoking status revealed that rs6929846 was significantly associated with Type 2 diabetes (P = 0.0006; odds ratio 1.25) in all individuals, with the T allele representing a risk factor for this condition. Multiple regression analysis with adjustment for age, sex and body mass index revealed that rs6929846 was significantly (P=0.04) related to blood glycosylated haemoglobin content in control subjects. CONCLUSIONS: BTN2A1 may be a susceptibility gene for Type 2 diabetes in Japanese individuals.


Sujet(s)
Asiatiques/génétique , Diabète de type 2/génétique , Glycoprotéines membranaires/génétique , Infarctus du myocarde/génétique , Polymorphisme de nucléotide simple , Sujet âgé , Indice de masse corporelle , Butyrophilines , Études cas-témoins , Loi du khi-deux , Diabète de type 2/complications , Diabète de type 2/épidémiologie , Femelle , Prédisposition génétique à une maladie , Étude d'association pangénomique , Génotype , Humains , Modèles logistiques , Mâle , Analyse multifactorielle , Infarctus du myocarde/épidémiologie , Infarctus du myocarde/étiologie , Odds ratio , Analyse de régression , Facteurs de risque
19.
Int J Androl ; 34(3): 268-75, 2011 Jun.
Article de Anglais | MEDLINE | ID: mdl-20522123

RÉSUMÉ

The aim of this study was to investigate the effect of ischaemic post-conditioning (IPostC) against ischaemia-reperfusion (IR) injury on bilateral testes after unilateral testicular ischaemia in the rat. Eight-week-old male Sprague-Dawley rats were divided into control group; IR group (60 min ischaemia-24 h reperfusion); IPostC1 × 10 group (60 min ischaemia followed by one cycle of 10 sec reperfusion-10 sec ischaemia; then 24 h reperfusion); IPostC3 × 10 group (three cycles of 10 sec reperfusion-10 sec ischaemia; then 24 h reperfusion); IPostC5 × 10 group (five cycles of 10 sec reperfusion-10 sec ischaemia; then 24 h reperfusion) and IPostC3 × 30 group (three cycles of 30 sec reperfusion-30 sec ischaemia; then 24 h reperfusion). In the IR and IPostC groups, the right testicular vessels were clamped using a special vascular clip. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were measured in testicular tissue samples bilaterally. Additionally, bilateral testicular tissue samples were processed for histological evaluation including haematoxylin-eosin, 4-hydroxy-2-nonenal (4-HNE) and TdT-mediated dUTP Nick End Labelling (TUNEL) staining. The levels of MDA and MPO as well as the positive cells per seminiferous tubule in TUNEL and 4-HNE stain in bilateral testes from the IR group were significantly higher compared with the control group. IPostC3 × 30 protocol significantly ameliorated the aforesaid parameters in both testes compared with the IR group. For the first time, we have demonstrated that IPostC protects both testes after unilateral testicular ischaemia-reperfusion. IPostC3 × 30 protocol offered the most effective protection.


Sujet(s)
Postconditionnement ischémique , Lésion d'ischémie-reperfusion , Testicule/traumatismes , Animaux , Infertilité masculine/prévention et contrôle , Mâle , Malonaldéhyde/analyse , Stress oxydatif , Myeloperoxidase/analyse , Rats , Rat Sprague-Dawley , Espèces réactives de l'oxygène , Torsion du cordon spermatique/anatomopathologie , Torsion du cordon spermatique/thérapie , Testicule/vascularisation , Testicule/anatomopathologie
20.
J Dent Res ; 89(10): 1117-22, 2010 Oct.
Article de Anglais | MEDLINE | ID: mdl-20647497

RÉSUMÉ

Synovitis, which is characterized by the infiltration of inflammatory cells, often accompanies progression of temporomandibular joint disorder (TMD) symptoms. Because IL-1ß is elevated in synovial fluids obtained from TMDs, we hypothesized that IL-1ß-responsive genes in synoviocytes may help identify the putative genes associated with synovitis. Using microarray analysis, we found that monocyte chemoattractant protein-1 (MCP-1) mRNA levels were elevated in IL-1ß-stimulated synoviocytes. MCP-1 is a member of the chemokine superfamily. The production of MCP-1 was increased in synoviocytes treated with IL-1ß. When IL-1ß was injected into the cavities of rat TMJs, inflammatory cells and MCP-1-positive cells were detected in the synovial tissues. Furthermore, MCP-1 levels were higher in synovial fluids from individuals with pain compared with those without pain. Inhibitors of MAP-kinases and NF-κB reduced IL-1ß-induced MCP-1 production. These results suggest that MCP-1 stimulated by IL-1ß is one of the factors associated with the inflammatory progression of TMDs.


Sujet(s)
Chimiokine CCL2/analyse , Troubles de l'articulation temporomandibulaire/immunologie , Adolescent , Adulte , Animaux , Anthracènes/pharmacologie , Autoantigènes/analyse , Autoantigènes/effets des médicaments et des substances chimiques , Calcium-Calmodulin-Dependent Protein Kinases/antagonistes et inhibiteurs , Techniques de culture cellulaire , Chimiokine CCL2/effets des médicaments et des substances chimiques , Cytokines/analyse , Cytokines/effets des médicaments et des substances chimiques , Femelle , Flavonoïdes/pharmacologie , Humains , Interleukine-1 bêta/antagonistes et inhibiteurs , Interleukine-1 bêta/pharmacologie , JNK Mitogen-Activated Protein Kinases/antagonistes et inhibiteurs , Luxations/immunologie , Mâle , Analyse sur microréseau , Facteur de transcription NF-kappa B/antagonistes et inhibiteurs , Arthrose/immunologie , ARN messager/analyse , Rats , Rats de lignée LEW , Synovie/composition chimique , Synovie/effets des médicaments et des substances chimiques , Synovie/immunologie , Membrane synoviale/effets des médicaments et des substances chimiques , Membrane synoviale/immunologie , Synovite/immunologie , Disque de l'articulation temporomandibulaire/immunologie , Jeune adulte
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