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1.
J Periodontal Res ; 53(5): 750-761, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29687476

RESUMEN

BACKGROUND AND OBJECTIVE: Epithelial cells derived from different regions exhibit marked differences in their differentiation capacity, allowing them to provide a suitable protective barrier. We aimed to clarify the role of peptidylarginine deiminase (PAD) in modifying the key epidermal proteins filaggrin (FLG) and keratin 1 (K1) during stratification of the rat palate and buccal mucosa. MATERIAL AND METHODS: We performed immunofluorescence, immunoblotting, PAD activity assays and 2-dimensional electrophoresis, and developed an organotypic culture model. RESULTS: PAD1 expression was highest in the palate, whereas PAD2, PAD3 and PAD4 expression was highest in the skin, suggesting the tissue-specific expression of PAD isozymes that leads to differences in calcium dependency. Immunoblotting showed that the FLG monomer, as well as its degradation products and precursor (proFLG), were most abundantly expressed in the skin but had low expression in the palate, whereas only faint proFLG expression was detected in the buccal mucosa. FLG and K1 were colocalized with PAD1 and were likely to be citrullinated in the cornified layers of the skin; this colocalization was not detected on the palatal surface, and dot-like presence of proFLG that might be citrullinated and that of PAD1 were found in the granules of the palate. Organotypic models derived from the rat palate revealed that PAD inhibition reduced the breakdown of FLG, increased its association with K1 together with epithelial compaction, and decreased permeability in a dye permeability assay. Conversely, PAD stimulation had the opposite effects. CONCLUSION: Citrullination is likely a protein modification that plays an important role in maintaining the structure and function of oral cornified mucosa in a way that is distinctly different from that of the skin.


Asunto(s)
Citrulinación/fisiología , Mucosa Bucal/enzimología , Desiminasas de la Arginina Proteica/metabolismo , Animales , Animales Recién Nacidos , Western Blotting , Electroforesis en Gel Bidimensional , Proteínas Filagrina , Técnica del Anticuerpo Fluorescente , Proteínas de Filamentos Intermediarios/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa
2.
Sci Rep ; 7(1): 5865, 2017 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-28724895

RESUMEN

We studied the effects of the internal electric field on two-step photocarrier generation in InAs/GaAs quantum dot superlattice (QDSL) intermediate-band solar cells (IBSCs). The external quantum efficiency of QDSL-IBSCs was measured as a function of the internal electric field intensity, and compared with theoretical calculations accounting for interband and intersubband photoexcitations. The extra photocurrent caused by the two-step photoexcitation was maximal for a reversely biased electric field, while the current generated by the interband photoexcitation increased monotonically with increasing electric field intensity. The internal electric field in solar cells separated photogenerated electrons and holes in the superlattice (SL) miniband that played the role of an intermediate band, and the electron lifetime was extended to the microsecond scale, which improved the intersubband transition strength, therefore increasing the two-step photocurrent. There was a trade-off relation between the carrier separation enhancing the two-step photoexcitation and the electric-field-induced carrier escape from QDSLs. These results validate that long-lifetime electrons are key to maximising the two-step photocarrier generation in QDSL-IBSCs.

3.
Epidemiol Infect ; 144(5): 952-61, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26470913

RESUMEN

Shiga-toxin-producing Escherichia coli (STEC) infections usually cause haemolytic uraemic syndrome (HUS) equally in male and female children. This study investigated the localization of globotriaosylceramide (Gb3) in human brain and kidney tissues removed from forensic autopsy cases in Japan. A fatal case was used as a positive control in an outbreak of diarrhoeal disease caused by STEC O157:H7 in a kindergarten in Urawa in 1990. Positive immunodetection of Gb3 was significantly more frequent in female than in male distal and collecting renal tubules. To correlate this finding with a clinical outcome, a retrospective analysis of the predictors of renal failure in the 162 patients of two outbreaks in Japan was performed: one in Tochigi in 2002 and the other in Kagawa Prefecture in 2005. This study concludes renal failure, including HUS, was significantly associated with female sex, and the odds ratio was 4·06 compared to male patients in the two outbreaks. From 2006 to 2009 in Japan, the risk factor of HUS associated with STEC infection was analysed. The number of males and females and the proportion of females who developed HUS were calculated by age and year from 2006 to 2009. In 2006, 2007 and 2009 in adults aged >20 years, adult women were significantly more at risk of developing HUS in Japan.


Asunto(s)
Brotes de Enfermedades , Infecciones por Escherichia coli/epidemiología , Síndrome Hemolítico-Urémico/epidemiología , Escherichia coli Shiga-Toxigénica/fisiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Encéfalo/microbiología , Niño , Preescolar , Diarrea/epidemiología , Diarrea/microbiología , Infecciones por Escherichia coli/complicaciones , Femenino , Síndrome Hemolítico-Urémico/microbiología , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Riñón/microbiología , Masculino , Persona de Mediana Edad , Insuficiencia Renal/epidemiología , Insuficiencia Renal/microbiología , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Trihexosilceramidas/análisis , Adulto Joven
4.
Eur J Gynaecol Oncol ; 34(1): 90-3, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23590010

RESUMEN

BACKGROUND: A combination therapy with gemcitabine and oxaliplatin (GEMOX) yielded a moderate activity in platinum-resistant ovarian cancers; however, frequent severe toxicities, such as thrombocytopenia and neurotoxicity, were observed. A certain modification of schedule might therefore facilitate the clinical application of the regimen. The authors report two cases that achieved complete response to a weekly administration of bevacizumab and GEMOX. MATERIALS AND METHODS: Two patients with platinum-resistant recurrent ovarian cancers received a weekly regimen of GEMOX with bevacizumab: 2 mg/kg of bevacizumab, 300 mg/m2 of gemcitabine, and 30 mg/m2 of oxaliplatin, three weeks on and one week off, Q4 weeks. Complete remission was observed after three to four courses of therapy. Hematologic and non-hematologic toxicities more than grade 2 were not observed during chemotherapy. The patients are now without tumor progression more than 12 months after initiation of therapy. CONCLUSION: Weekly administration of bevacizumab and GEMOX had potential activity in recurrent and refractory ovarian carcinomas. These findings warrant necessity of further trial in such clinical settings.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Gemcitabina
5.
Oncogene ; 32(7): 894-902, 2013 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-22450745

RESUMEN

The small GTPase Ral is known to be highly activated in several human cancers, such as bladder, colon and pancreas cancers. It is reported that activated Ral is involved in cell proliferation, migration and metastasis of bladder cancer. This protein is activated by Ral guanine nucleotide exchange factors (RalGEFs) and inactivated by Ral GTPase-activating proteins (RalGAPs), the latter of which consist of heterodimers containing a catalytic α1 or α2 subunit and a common ß subunit. In Ras-driven cancers, such as pancreas and colon cancers, constitutively active Ras mutant activates Ral through interaction with RalGEFs, which contain the Ras association domain. However, little is known with regard to the mechanism that governs aberrant activation of Ral in bladder cancer, in which Ras mutations are relatively infrequent. Here, we show that Ral was highly activated in invasive bladder cancer cells due to reduced expression of RalGAPα2, the dominant catalytic subunit in bladder, rather than increased expression of RalGEFs. Exogenous expression of wild-type RalGAPα2 in KU7 bladder cancer cells with invasive phenotype, but not mutant RalGAPα2-N1742K lacking RalGAP activity, resulted in attenuated cell migration in vitro and lung metastasis in vivo. Furthermore, genetic ablation of Ralgapa2 promoted tumor invasion in a chemically-induced murine bladder cancer model. Importantly, immunohistochemical analysis of human bladder cancer specimens revealed that lower expression of RalGAPα2 was associated with advanced clinical stage and poor survival of patients. Collectively, these results are highly indicative that attenuated expression of RalGAPα2 leads to disease progression of bladder cancer through enhancement of Ral activity.


Asunto(s)
Carcinoma/genética , Carcinoma/patología , Proteínas Activadoras de GTPasa/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Femenino , Proteínas Activadoras de GTPasa/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Eur J Gynaecol Oncol ; 33(3): 269-73, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22873097

RESUMEN

The normal serum CA125 half-life and distribution of the normal serum nadir CA125 value in patients with epithelial ovarian carcinoma (EOC) have not been determined yet. Among patients with EOC, 41 patients met the inclusion criteria of the present study: the patients that underwent complete cytoreductive surgery and six cycles of platinum-containing chemotherapy, and who had no recurrent disease more than five years. Serum CA125 half-life (T1/2) during primary surgery and primary chemotherapy was calculated and serum nadir CA125 level was evaluated by logarithmic-transformed serum CA125. Median value of nadir CA125 was 7 U/ml (range 3-20 U/ml), and the mean ln (serum nadir CA125) was 1.96 +/- 0.45. Mean T1/2 was 10.4 days in all patients, and T1/2 value was associated with the preoperative serum levels of CA125. Predicted slope of CA125 regression curve was also influenced by the preoperative CA125 value. The present study provides fundamental information with regard to normal half-life time and normal nadir of CA125 in EOC patients.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno Ca-125/sangre , Neoplasias Glandulares y Epiteliales/sangre , Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/sangre , Neoplasias Ováricas/terapia , Adulto , Anciano , Análisis de Varianza , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Carboplatino/administración & dosificación , Carcinoma Epitelial de Ovario , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Semivida , Humanos , Irinotecán , Modelos Lineales , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Valores de Referencia , Inducción de Remisión , Taxoides/administración & dosificación
8.
Nutr Metab Cardiovasc Dis ; 21(9): 672-8, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20399087

RESUMEN

BACKGROUND AND AIM: Oxidative stress may play an important role in the development of atherosclerosis. Some angiotensin II type 1 (AT(1)) receptor antagonists have the capacity of reducing oxidative stress in addition to the hemodynamic actions. Accordingly, we assessed the hypothesis that olmesartan, a novel AT(1) receptor antagonist, reduced the severity of atherosclerosis in apolipoprotein (apo) E-deficient mice associated with reducing oxidative stress. METHODS AND RESULTS: Atherosclerosis was induced in apo E-deficient mice fed a high fat diet. Mice were intraperitoneally treated with an injection of olmesartan (1mg/kg/day) daily over 8 weeks, and were compared with the untreated controls. Blood pressure was not changed significantly by the olmesartan treatment. Fatty streak plaque developed in apo E-deficient mice, and was suppressed in mice that received olmesartan. In addition, olmesartan reduced not only superoxide production but the overload of oxidative stress in aortic walls. There were no significant differences in serum lipid levels between olmesartan-treated and -untreated groups. In vitro study showed that both olmesartan and its active metabolite RNH-6270, an enantiomer of olmesartan, suppressed interferon-γ, macrophage inflammatory protein-2, and thioredoxin (a marker of oxidative stress) concentrations in cultured cells. CONCLUSION: Olmesartan may suppress atherosclerosis via reducing not only superoxide production but also the overload of oxidative stress in this animal model.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Apolipoproteínas E/deficiencia , Aterosclerosis/tratamiento farmacológico , Imidazoles/farmacología , Superóxidos/metabolismo , Tetrazoles/farmacología , Animales , Aorta/efectos de los fármacos , Biomarcadores/sangre , Células Cultivadas , Quimiocina CXCL2/antagonistas & inhibidores , Quimiocina CXCL2/sangre , Interferón gamma/antagonistas & inhibidores , Interferón gamma/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Tiorredoxinas/antagonistas & inhibidores , Tiorredoxinas/sangre
10.
Br J Ophthalmol ; 93(8): 1020-6, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19429593

RESUMEN

AIM: To address the cellular components and the contractile mechanisms of the idiopathic epiretinal membrane (ERM). METHODS: Ten surgically removed ERMs were fixed in 4% paraformaldehyde and analysed by whole-mount immunohistochemistry with anti-glial fibrillar acidic protein (GFAP) and alpha smooth-muscle actin (alphaSMA) antibodies. Type I collagen gel contraction assay, an established wound-healing assay in vitro, was performed using cultured bovine hyalocytes or normal human astrocytes (NHA) to evaluate the contractile property of the cells in the presence of tissue growth factor (TGF)-beta2. The expression of alphaSMA was also analysed by western blot analysis to examine myofibroblastic transdifferentiation of the cells. Vitreous-induced collagen gel contraction was also evaluated. RESULTS: All membranes were composed of alphaSMA immunopositive cells in contracted foci and GFAP immunopositive cells in the periphery. No apparent double positive cells were observed in any membranes examined. Cultured hyalocytes showed overexpression of alphaSMA and hypercontraction of collagen gels in response to TGF-beta2, while glial cells showed marginal change. The vitreous from ERM patients also caused overexpression of alphaSMA and hypercontraction of the gels embedding hyalocytes, which were almost completely inhibited in the presence of anti-TGF-beta2 neutralising antibody. CONCLUSIONS: Hyalocytes might be one of the critical components of ERM mediating its contractile property through the effect of TGF-beta2 in the vitreous fluid.


Asunto(s)
Membrana Epirretinal/patología , Cuerpo Vítreo/ultraestructura , Actinas/metabolismo , Anciano , Animales , Astrocitos/ultraestructura , Bovinos , Células Cultivadas , Colágeno/metabolismo , Membrana Epirretinal/etiología , Membrana Epirretinal/metabolismo , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Factor de Crecimiento Transformador beta2/farmacología , Factor de Crecimiento Transformador beta2/fisiología , Cuerpo Vítreo/efectos de los fármacos
11.
Clin Nephrol ; 70(6): 558-60, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19049718

RESUMEN

Induction of continuous ambulatory peritoneal dialysis (CAPD) as treatment of end-stage renal disease is difficult for patients requiring nephrectomy with traditional surgery, and usually hemodialysis is selected for these patients. In a 61-year-old woman with end-stage renal failure a left renal tumor was diagnosed by abdominal ultrasonography, enhanced computed tomography and magnetic resonance imaging. Following an urology consultation, we decided to perform left kidney nephrectomy. We estimated that she had to undergo dialysis permanently after nephrectomy. She desired to be treated by CAPD, however, we decided after allowing for a postoperative period for complete healing of the peritoneum to avoid complications. This is why during the interim period between surgery and induction of CAPD she underwent hemodialysis (HD) in a local outpatient HD center and in our hospital. We selected a retroperitoneoscopic approach for nephrectomy. Pathology evaluation revealed a renal cell carcinoma. 4 months after nephrectomy, CAPD catheter implantation was performed by using laparoscopy and CAPD was started. At the present time, the patient is doing well on CAPD. To our knowledge, there are no clear indications regarding initiation of peritoneal dialysis after nephrectomy. The retroperitoneoscopic approach for nephrectomy allows for initiation of peritoneal dialysis after nephrectomy within a relative short postoperative period.


Asunto(s)
Fallo Renal Crónico/terapia , Neoplasias Renales/cirugía , Laparoscopía/métodos , Nefrectomía/métodos , Diálisis Peritoneal Ambulatoria Continua/métodos , Cuidados Posoperatorios/métodos , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Neoplasias Renales/complicaciones , Neoplasias Renales/diagnóstico , Persona de Mediana Edad , Espacio Retroperitoneal , Tomografía Computarizada por Rayos X
12.
Br J Ophthalmol ; 92(11): 1540-4, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18952656

RESUMEN

AIM: Tumour necrosis factor-alpha (TNF-alpha) is one of the major inflammatory cytokines involved in the pathogenesis of various vitreoretinal diseases. The authors investigated the effect of hypoxia, TNF-alpha and dexamethasone on vascular endothelial growth factor (VEGF) expression by cultured hyalocytes. METHODS: Hyalocytes were isolated from bovine vitreous. Hypoxic and TNF-alpha-dependent effects on cultured hyalocytes were investigated using several assays to determine VEGF protein expression, hypoxia-inducible factor (HIF)-1alpha protein levels, HIF-1alpha-DNA-binding ability and VEGF mRNA stability. The effects of dexamethasone on VEGF expression and its intracellular signalling under hypoxic or TNF-alpha stimulated conditions were also examined. RESULTS: Hypoxic conditions and TNF-alpha stimulation induce VEGF expression in hyalocytes. These stimuli also stabilise HIF-1alpha protein and increase its DNA-binding ability. Dexamethasone significantly inhibits both HIF-1alpha protein levels and HIF-1alpha-DNA-binding activity, and also decreases the hypoxic- and TNF-alpha -dependent induction of VEGF expression in hyalocyte. However, dexamethasone has no significant effect on the stability of VEGF mRNA. CONCLUSIONS: Hyalocytes may be involved in various vitreoretinal diseases by increasing HIF-1alpha protein stability and HIF-1alpha-DNA binding, and thus increasing VEGF production under pathological conditions. Dexamethasone seems to be capable of inhibiting hypoxic and TNF-alpha dependent VEGF production, presumably via its inhibitory effects on HIF-1alpha protein levels and its DNA-binding activity.


Asunto(s)
Hipoxia de la Célula/efectos de los fármacos , Glucocorticoides/farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cuerpo Vítreo/citología , Animales , Bovinos , Hipoxia de la Célula/fisiología , ADN/metabolismo , Dexametasona/farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , ARN Mensajero/metabolismo , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/fisiología
14.
Eur J Vasc Endovasc Surg ; 35(4): 462-5, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18429349

RESUMEN

Purpose. To assess the efficacy of the Inoue stent-graft placement for thoracoabdominal aortic aneurysm (TAAA).Methods. Patients with TAAA underwent Inoue stent-graft placement with single branched stent-graft in 4 patients,straight graft in 3 patients and double branched stent-graft in 1 patient. Half the patients required additional open surgical revascularizations of involved visceral arteries (Hybrid procedures).Results. Stent-grafts were deployed successfully in all patients. One patient with Hybrid procedure developed major complications,required haemodialysis and died in hospital. In another patient the post-operative CT scan demonstrated a type I endoleak, but this had resolved by 3 months.Conclusion. Inoue stent-grafting for TAAA with or without adjunctive open surgical revascularization is feasible.


Asunto(s)
Angioplastia/métodos , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Stents , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vísceras/irrigación sanguínea
15.
Int J Gynecol Cancer ; 18(5): 937-42, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18081792

RESUMEN

Clear cell carcinoma (CCC) of the ovary has been recognized to show resistance to anticancer agents in the first-line chemotherapy. Our aim was to evaluate the effect of second-line chemotherapy in a retrospective study. A total of 75 patients diagnosed with CCC and treated between 1992 and 2002 in collaborating hospitals were reviewed. Criteria for the patients' enrollment were 1) diagnosis of pure-type CCC at the initial operation, 2) treatment after one systemic postoperative chemotherapy, 3) measurable recurrent or refractory tumor, 4) at least two cycles of second-line chemotherapy and assessable for the response, and 5) adequate clinical information. Regimens of first-line chemotherapy were conventional platinum-based therapy in 33 cases, paclitaxel plus platinum in 24 cases, irinotecan plus platinum in 9 cases, and irinotecan plus mitomycin C in 7 cases. Treatment-free periods were more than 6 months in 24 cases (group A) and less than 6 months in 51 cases (group B). In group A, response was observed in two cases (8%): one with conventional platinum therapy and another with irinotecan plus platinum. In group B, three cases (6%) responded: two with platinum plus etoposide and one case with irinotecan plus platinum. Median overall survival was 16 months in group A and 7 months in group B (P = 0.04). These findings suggest recurrent or resistant CCC is extremely chemoresistant, and there is only small benefit of long treatment-free period in CCC patients. Another strategy including molecular-targeting therapy is warranted for the treatment of recurrent or refractory CCC.


Asunto(s)
Adenocarcinoma de Células Claras/tratamiento farmacológico , Adenocarcinoma de Células Claras/patología , Antineoplásicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Adenocarcinoma de Células Claras/epidemiología , Adulto , Anciano , Femenino , Humanos , Japón/epidemiología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Ováricas/epidemiología , Estudios Retrospectivos , Terapia Recuperativa , Tasa de Supervivencia , Factores de Tiempo
16.
Kidney Int ; 73(2): 181-91, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17943079

RESUMEN

Once developed, end-stage renal disease cannot be reversed by any current therapy. Bone morphogenetic protein-7 (BMP-7), however, is a possible treatment for reversing end-stage renal disease. Previously, we showed that the BMP antagonist uterine sensitization-associated gene-1 (USAG-1, also known as ectodin and sclerostin domain-containing 1) negatively regulates the renoprotective action of BMP-7. Here, we show that the ratio between USAG-1 and BMP-7 expression increased dramatically in the later stage of kidney development, with USAG-1 expression overlapping BMP-7 only in differentiated distal tubules. Examination of USAG-1 expression in developing kidney indicated that a mosaic of proximal and distal tubule marker-positive cells reside side by side in the immature nephron. This suggests that each cell controls its own fate for becoming a proximal or distal tubule cell. In kidney injury models, the ratio of USAG-1 to BMP-7 expression decreased with kidney damage but increased after subsequent kidney regeneration. Our study suggests that USAG-1 expression in a kidney biopsy could be useful in predicting outcome.


Asunto(s)
Proteínas Morfogenéticas Óseas/análisis , Túbulos Renales/química , Túbulos Renales/embriología , Factor de Crecimiento Transformador beta/análisis , Proteínas Adaptadoras Transductoras de Señales , Animales , Proteína Morfogenética Ósea 7 , Proteínas Morfogenéticas Óseas/genética , Diferenciación Celular , Cisplatino/toxicidad , Femenino , Túbulos Renales/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Nefronas/química , Pronóstico , Regeneración , Factor de Crecimiento Transformador beta/genética
18.
Atheroscler Suppl ; 8(2): 19-24, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17588827

RESUMEN

Presented is a report of a panel discussion held as part of the ISA 2006 Sankyo Forum titled "A Trilogy of Primary Prevention Statin Trials--The Impact of These Landmark Studies on Clinical Practice," Rome, Italy, June 2006. The themes of the panel discussion were the design features of three trials, WOSCOPS, AFCAPS/TexCAPS, and Japan's MEGA Study; comparison of their primary endpoints; and the implications of their results. Among the topics discussed by the panel of experts from Japan, USA, and UK were observations on the benefits associated with pravastatin at low dose as demonstrated in the MEGA Study as well as that study's implications for women, who represented the majority of subjects. Several suggestions were put forth to explain how the low dose used in MEGA elicited similar LDL-C reductions to those observed in WOSCOPS and AFCAPS/TexCAPS at higher doses including the body size hypothesis, genetic variation, and statin-diet interaction. It was felt that in Japan, the current guidelines are adequate; there seemed no merit in radically reducing LDL-C levels since in the Japanese population the risk is generally low. Japanese physicians tend to use small doses of statin and believe that these are effective in lowering cholesterol sufficiently with few side effects and encourage good compliance.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Colesterol/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Femenino , Humanos , Hipercolesterolemia/complicaciones , Masculino , Selección de Paciente , Guías de Práctica Clínica como Asunto , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
19.
Science ; 315(5817): 1388-91, 2007 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-17255474

RESUMEN

We observed Shubnikov-de Haas oscillation and the quantum Hall effect in a high-mobility two-dimensional electron gas in polar ZnO/Mg(x)Zn(1-x)O heterostructures grown by laser molecular beam epitaxy. The electron density could be controlled in a range of 0.7 x 10(12) to 3.7 x 10(12) per square centimeter by tuning the magnesium content in the barriers and the growth polarity. From the temperature dependence of the oscillation amplitude, the effective mass of the two-dimensional electrons was derived as 0.32 +/- 0.03 times the free electron mass. Demonstration of the quantum Hall effect in an oxide heterostructure presents the possibility of combining quantum Hall physics with the versatile functionality of metal oxides in complex heterostructures.

20.
Clin Exp Allergy ; 36(10): 1294-302, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17014439

RESUMEN

BACKGROUND: Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) are thought to contribute to the airway inflammation and airway hyper-responsiveness (AHR) of allergic asthma. Some differences from allergic asthma have been noted, including airway neutrophilia, and the involvement of ICAM-1 in toluene diisocyanate (TDI) asthma is currently unclear. OBJECTIVE: We utilized mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in airway inflammation and AHR in TDI-induced asthma. METHODS: Male C57BL/6J mice (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed 24 h after challenge by TDI or solvent. The production of antigen-specific IgG and IgE by TDI sensitized and non-sensitized mice was determined. RESULTS: TDI challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein-2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable. CONCLUSION: These results suggest that ICAM-1 plays an essential role in airway inflammation and AHR in TDI-induced asthma.


Asunto(s)
Asma/inducido químicamente , Molécula 1 de Adhesión Intercelular/fisiología , Enfermedades Profesionales/etiología , 2,4-Diisocianato de Tolueno/efectos adversos , Animales , Asma/inmunología , Asma/metabolismo , Hiperreactividad Bronquial , Pruebas de Provocación Bronquial , Líquido del Lavado Bronquioalveolar/inmunología , Broncoconstrictores , Quimiocina CXCL2 , Quimiocinas/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Inmunohistoquímica/métodos , Molécula 1 de Adhesión Intercelular/análisis , Molécula 1 de Adhesión Intercelular/genética , Interferón gamma/inmunología , Interleucina-4/inmunología , Interleucina-5/inmunología , Pulmón/química , Pulmón/inmunología , Pulmón/metabolismo , Masculino , Cloruro de Metacolina , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Animales , Enfermedades Profesionales/inmunología , Enfermedades Profesionales/metabolismo , Factores de Tiempo , Factor de Necrosis Tumoral alfa/inmunología
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