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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.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular , Línea Celular Tumoral , Fibronectinas/genética , Fibronectinas/uso terapéutico , Humanos , Hipoxia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Compuestos de Fenilurea , QuinolinasRESUMEN
The treatment of [Co(d- or l-ebp)]- with CdX2 (X = Br-, I-) gave a cyclic CoIII3CdII3 complex with a 12-membered metalloring, [Cd3X3{Co(d- or l-ebp)}3] (d3- or l3-1X). The use of a 1 : 1 mixture of [Co(d-ebp)]- and [Co(l-ebp)]-, instead of [Co(d- or l-ebp)]-, led to the creation of a cyclic CoIII6CdII6 complex with a 24-membered metalloring, [Cd6X6(H2O)6{Co(d-ebp)}3{Co(l-ebp)}3] (d3l3-2X). Compounds d3l3-2X were also produced when d3-1X and l3-1X were mixed in water in a 1 : 1 ratio, illustrating the conversion of a pair of homochiral metallorings into a double-sized heterochiral metalloring.
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BACKGROUND AND PURPOSE: Mutations in colony-stimulating factor 1 receptor (CSF1R) cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Patients with ALSP can be misdiagnosed as having acute ischemic stroke due to hyperintensity lesions on diffusion-weighted magnetic resonance imaging. Mutant CSF1R proteins identified in ALSP show a complete loss of autophosphorylation of CSF1R. METHODS: We conducted mutation screening of CSF1R in 123 patients with definite acute ischemic cerebrovascular syndrome and positive family history of stroke. The pathogenicity of identified variants was evaluated using functional analyses. The levels of autophosphorylation of CSF1R in response to treatment with ligands of CSF1R were examined in cells transfected with wild-type and mutant CSF1R. RESULTS: We identified eight CSF1R variants, six were known non-pathogenic polymorphisms, whereas the other two were missense variants inducing substitution of amino acid residues (p.Glu573Lys and p.Gly747Arg). Functional assay showed that the levels of autophosphorylation of p.Gly747Arg were similar to those of wild-type when treated with ligands. The autophosphorylation of p.Glu573Lys was detectable, but significantly decreased compared with those of wild-type CSF1R (P < 0.001, two-way anova with Bonferroni). The clinical presentation of the patient with p.Glu573Lys was consistent with cerebral embolism. The patient did not have typical clinical findings of ALSP. However, periventricular white matter abnormalities, unrelated to the recent infarct, were evident on brain magnetic resonance imaging. CONCLUSIONS: In contrast to ALSP-associated missense mutations, CSF1R p.Glu573Lys variant in a patient with acute ischemic cerebrovascular syndrome showed a partial loss of autophosphorylation of CSF1R; its clinical significance warrants further investigation.
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Leucoaraiosis/genética , Leucoencefalopatías/genética , Mutación Missense , Receptores del Factor Estimulante de Colonias/genética , Sustancia Blanca/patología , Anciano , Anciano de 80 o más Años , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Leucoaraiosis/diagnóstico por imagen , Leucoaraiosis/patología , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Receptores del Factor Estimulante de Colonias/metabolismo , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND AND PURPOSE: To establish and validate diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony-stimulating factor 1 receptor (CSF1R) mutation. METHODS: We developed diagnostic criteria for ALSP based on a recent analysis of the clinical characteristics of ALSP. These criteria provide 'probable' and 'possible' designations for patients who do not have a genetic diagnosis. To verify its sensitivity and specificity, we retrospectively applied our criteria to 83 ALSP cases who had CSF1R mutations (24 of these were analyzed at our institutions and the others were identified from the literature), 53 cases who had CSF1R mutation-negative leukoencephalopathies and 32 cases who had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with NOTCH3 mutations. RESULTS: Among the CSF1R mutation-positive cases, 50 cases (60%) were diagnosed as 'probable' and 32 (39%) were diagnosed as 'possible,' leading to a sensitivity of 99% if calculated as a ratio of the combined number of cases who fulfilled 'probable' or 'possible' to the total number of cases. With regard to specificity, 22 cases (42%) with mutation-negative leukoencephalopathies and 28 (88%) with CADASIL were correctly excluded using these criteria. CONCLUSIONS: These diagnostic criteria are very sensitive for diagnosing ALSP with sufficient specificity for differentiation from CADASIL and moderate specificity for other leukoencephalopathies. Our results suggest that these criteria are useful for the clinical diagnosis of ALSP.
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Axones/patología , Leucoencefalopatías/diagnóstico , Leucoencefalopatías/genética , Neuroglía/patología , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Esferoides Celulares/patología , Adolescente , Adulto , Anciano , CADASIL/diagnóstico , CADASIL/genética , CADASIL/patología , Trastornos del Conocimiento/etiología , Diagnóstico Diferencial , Femenino , Humanos , Leucoencefalopatías/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Receptor Notch3/genética , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated. METHODS: Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data. RESULTS: In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18-78 years), the mean age at death was 53 years (range 23-84 years) and the mean disease duration was 6.8 years (range 1-29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158-11.177). There was an age-dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion-restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy-nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype-genotype correlations. CONCLUSIONS: The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.
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Leucoencefalopatías/genética , Leucoencefalopatías/patología , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Axones/patología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Femenino , Heterocigoto , Humanos , Leucoencefalopatías/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/etiología , Trastornos del Movimiento/fisiopatología , Mutación/genética , Neuroglía/patología , Penetrancia , Tractos Piramidales/diagnóstico por imagen , Tractos Piramidales/patología , Caracteres Sexuales , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adulto JovenRESUMEN
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurodegenerative disease resulting from mutations in the colony stimulating factor 1 receptor gene. Accurate diagnosis can be difficult because the associated clinical and MR imaging findings are nonspecific. We present 9 cases with intracranial calcifications distributed in 2 brain regions: the frontal white matter adjacent to the anterior horns of the lateral ventricles and the parietal subcortical white matter. Thin-section (1-mm) CT scans are particularly helpful in detection due to the small size of the calcifications. These calcifications had a symmetric "stepping stone appearance" in the frontal pericallosal regions, which was clearly visible on reconstructed sagittal CT images. Intrafamilial variability was seen in 2 of the families, and calcifications were seen at birth in a single individual. These characteristic calcification patterns may assist in making a correct diagnosis and may contribute to understanding of the pathogenesis of leukoencephalopathy.
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Calcinosis/diagnóstico por imagen , Leucoencefalopatías/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Axones , Calcinosis/patología , Femenino , Humanos , Leucoencefalopatías/patología , Masculino , NeuroglíaRESUMEN
Treatment of various gem-difluorocyclopropenes with 1.2 equiv. of n-Bu3SnH in the presence of 20 mol% of Et3B at 80 °C for 4 h led to the quantitative formation of the hydrostannylated products in a highly regio- and trans-selective manner. Additionally, the prepared trans-gem-difluorocyclopropylstannanes were treated with 1.5 equiv. of MeLi in THF at -78 °C for 5 min, followed by quenching the reaction with various agents, such as H2O, alcohols, carboxylic acids, and tosylamide, to give the corresponding ß-fluoroallylic alcohols, ethers, esters, and amides respectively with exclusive Z selectivity in acceptable yields.
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In sharp contrast to previous studies on FeRh bulk, thin films, and nanoparticles, we report the persistence of ferromagnetic order down to 3 K for size-selected 3.3 nm diameter nanocrystals embedded into an amorphous carbon matrix. The annealed nanoparticles have a B2 structure with alternating atomic Fe and Rh layers. X-ray magnetic dichroism and superconducting quantum interference device measurements demonstrate ferromagnetic alignment of the Fe and Rh magnetic moments of 3 and 1µ(B), respectively. The ferromagnetic order is ascribed to the finite-size induced structural relaxation observed in extended x-ray absorption spectroscopy.
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The atomic structure of CoPt and FePt nanoparticles (with a diameter between 2 and 5 nm) has been studied by transmission electron microscopy. The particles have been produced by a laser vaporization cluster source and annealed under vacuum in order to promote chemical ordering. For both alloys, we observe a coexistence of crystalline and multiply twinned particles with decahedral or icosahedral shapes. In addition to particles corresponding to a single L1(0) ordered domain, we put into evidence that even small particles can display several L1(0) domains. In particular, the chemical order can be preserved across twin boundaries which can give rise to spectacular chemically ordered decahedral particles made of five L1(0) domains. The stability of such structures, which had been recently predicted from theoretical simulations, is thus unambiguously experimentally confirmed.
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The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling; features shared with human placentation. Recognition of these similarities spurred the establishment of in vitro and in vivo research methods using the rat as an animal model to address mechanistic questions regarding development of the hemochorial placenta. The purpose of this review is to provide the requisite background to help move the rat to the forefront in placentation research.
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Intercambio Materno-Fetal , Placentación , Útero/irrigación sanguínea , Animales , Femenino , Humanos , Células Asesinas Naturales/inmunología , Placenta/citología , Placenta/inmunología , Embarazo , Ratas , Especificidad de la Especie , Arteria Uterina/anatomía & histología , Útero/inmunologíaRESUMEN
Ephrin B1 and its cognate receptor, Eph receptor B2, key regulators of embryogenesis, are expressed in human atherosclerotic plaque and inhibit adult human monocyte chemotaxis. Few data exist, however, regarding the gene expression profiles of the ephrin (EFN) and Eph receptor (EPH) family of genes in atherosclerosis-related human cells. Gene expression profiles were determined of all 21 members of this gene family in atherosclerosis-related cells by reverse transcription-polymerase chain reaction analysis. The following 17 members were detected in adult human peripheral blood monocytes: EFNA1 and EFNA3 - EFNA5 (coding for ephrins A1 and A3 - A5); EPHA1, EPHA2, EPHA4 - EPHA6 and EPHA8 (coding for Eph receptors A1, A2, A4 - A6 and A8); EFNB1 and EFNB2 (coding for ephrins B1 and B2); and EPHB1 - EPHB4 and EPHB6 (coding for Eph receptors B1 - B4 and B6). THP-1 monocytic cells, Jurkat T cells and adult arterial endothelial cells also expressed multiple EFN and EPH genes. These results indicate that a wide variety of ephrins and Eph receptors might affect monocyte chemotaxis, contributing to the development of atherosclerosis. Their pathological significance requires further study.
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Efrinas/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Familia de Multigenes/genética , Placa Aterosclerótica/genética , Placa Aterosclerótica/patología , Receptores de la Familia Eph/genética , Adulto , Células Endoteliales/metabolismo , Efrinas/metabolismo , Humanos , Células Jurkat , Monocitos/metabolismo , Receptores de la Familia Eph/metabolismo , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) leads to less re-stenosis than PCI using a bare metal stent (BMS), however there is still controversy whether use of a DES for severe coronary disease leads to an acceptable outcome in patients with diabetes mellitus (DM). In this study 8159 lesions were treated in 6739 patients (mean age 68.9 years) with coronary artery disease. Use of a DES significantly decreased the re-stenosis rate compared with BMS in both DM (9.6% versus 21.3%) and non-DM (9.5% versus 17.1%) patients. The re-stenosis rate was significantly higher in DM than in non-DM patients in the BMS group but not in the DES group. There was no statistically significant difference in event-free survival after stenting of patients with left main coronary artery (LMCA) disease between the BMS and DES groups. It was concluded that, compared with BMS, DES reduced re-stenosis in patients with DM, however, we advise careful treatment after using DES for severe coronary disease, including LMCA lesions, in patients with DM.
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Angioplastia Coronaria con Balón , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/terapia , Complicaciones de la Diabetes/patología , Stents , Anciano , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Reestenosis Coronaria/complicaciones , Reestenosis Coronaria/terapia , Stents Liberadores de Fármacos/efectos adversos , Femenino , Hospitalización , Humanos , Estimación de Kaplan-Meier , Masculino , Stents/efectos adversos , Resultado del TratamientoRESUMEN
Interspecies somatic cell nucleus transfer (iSCNT) could be a useful bioassay system for assessing the ability of mammalian somatic cells to develop into embryos. To examine this possibility, we performed canine iSCNT using porcine oocytes, allowed to mature in vitro, as recipients. Canine fibroblasts from the tail tips and dewclaws of a female poodle (Fp) and a male poodle (Mp) were used as donors. We demonstrated that the use of porcine oocytes induced blastocyst formation in the iSCNT embryos cultured in porcine zygote medium-3. In Fp and Mp, the rate of blastocyst formation from cleaved embryos (Fp: 6.3% vs. 22.4%; and Mp: 26.1% vs. 52.4%) and the number of cells at the blastocyst stage (Fp: 30.7 vs. 60.0; and Mp: 27.2 vs. 40.1) were higher in the embryos derived from dewclaw cells than in those derived from tail-tip cells (P<0.05). The use of donor cells of any type in later passages decreased the rate of blastocyst formation. Treatment with trichostatin-A did not improve the rate of blastocyst formation from cleaved dewclaw cell-derived embryos but did so in the embryos derived from the tail-tip cells of Fp. Only blastocysts derived from dewclaw cells of Mp developed outgrowths. However, outgrowth formation was retrieved in the embryos derived from dewclaw cells of Fp by aggregation at the 4-cell stage. We inferred that iSCNT performed using porcine oocytes as recipients could represent a novel bioassay system for evaluating the developmental competence of canine somatic cells.
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Bioensayo/métodos , Embrión de Mamíferos , Técnicas de Transferencia Nuclear , Oocitos/citología , Porcinos/genética , Animales , Perros , Técnicas de Cultivo de Embriones , Embrión de Mamíferos/efectos de los fármacos , Desarrollo Embrionario , Femenino , Fibroblastos , Ácidos Hidroxámicos/farmacología , Masculino , Oocitos/fisiologíaRESUMEN
Invasion of trophoblast cells into the uterine spiral arteries and the uterine wall is characteristic of hemochorial placentation. In the rat, trophoblast cells penetrate through the uterine decidua and well into the metrial gland. In this report, we examined the fate of these invasive trophoblast cells following parturition. Invasive trophoblast endocrine cells were retained in the postpartum mesometrial uterus in the rat. The demise of invasive trophoblast cells was followed by the appearance of differentiated smooth muscle cells surrounding blood vessels previously lined by invasive trophoblast cells and an infiltration of macrophages. Regulation of intrauterine trophoblast cell fate was investigated following premature removal of the fetus or removal of the fetus and chorioallantoic placenta. The presence of the fetus affected the distribution of invasive trophoblast cells within the uterus but did not negatively impact their survival. Premature removal of all chorioallantoic placentas and associated fetuses from a uterus resulted in extensive removal of intrauterine trophoblast cells. In summary, the postpartum demise of intrauterine invasive trophoblast cells is a dynamic developmental event regulated in part by the removal of trophic signals emanating from the chorioallantoic placenta.
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Placentación/genética , Periodo Posparto/fisiología , Trofoblastos/fisiología , Útero/citología , Animales , Gonadotropina Coriónica/fisiología , Femenino , Embarazo , RatasRESUMEN
OBJECTIVES: The aim of this study was to investigate left ventricular (LV) function reserve in hypertrophic cardiomyopathy (HCM) patients with and without cardiac troponin gene mutations before transition to the dilated phase. METHODS: LV ejection fraction (EF) was continuously evaluated in 52 patients with non-obstructive HCM during supine ergometer exercise using radionuclide ventricular function monitoring with a cadmium telluride detector (VEST). On the basis of genetic analysis, patients were divided into two groups: 10 with cardiac troponin gene mutations (group A) and 42 without these gene mutations (group B). RESULTS: Exercise duration, peak exercise load, and heart rate during exercise did not differ between the two groups. The differences from baseline to peak exercise ofthe LV end-diastolic volume decreased similarly in the twogroups. In contrast, the difference of the LV end-systolicvolume in group A increased significantly compared withgroup B (17.7% (SD 12.7%) vs 3.4% (SD 13.2%);p=0.0031). Consequently, the difference of LVEF ingroup A decreased significantly in contrast with group B(-14.1% (SD 11.1%) vs -1.2% (SD 11.7%); p=0.0025).Additionally, the changes in LVEF and stroke volumedecreased significantly more in group A than in group B(-22.2% (SD 18.6%) vs -1.1% (SD 17.8%); p=0.0017and -12.9% (SD 21.7%) vs 12.3% (SD 24.4%);p=0.0042, respectively). CONCLUSIONS: These results suggest that HCM patientswith cardiac troponin gene mutations may displayexercise-induced LV systolic dysfunction more frequentlythan HCM patients without this abnormality
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Cardiomiopatía Hipertrófica/genética , Ejercicio Físico/fisiología , Mutación/genética , Troponina I/genética , Disfunción Ventricular Izquierda/genética , Adulto , Anciano , Cardiomiopatía Hipertrófica/fisiopatología , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sístole/fisiología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Metaflumizone, (EZ)-2'-[2-(4-cyanophenyl)-1-(alpha,alpha,alpha-trifluoro-m-tolyl)ethylidene]-4-(trifluoromethoxy) carbanilohydrazide, was discovered by Nihon Nohyaku in the early 1990s and belongs to the new class of semicarbazone insecticides. It is now being globally co-developed as the animal health product, ProMeris((R)), in cooperation with Fort Dodge Animal Health and as an agricultural and consumer insecticide in cooperation with BASF. Metaflumizone was developed in a synthesis program initiated from a pyrazoline insecticide lead. In this paper, we describe the development, discovery and structure activity relationships for metaflumizone and related compounds.
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Insecticidas/química , Semicarbazonas/química , Spodoptera , Animales , Larva , Dosificación Letal MedianaRESUMEN
AIMS: To determine the effect of 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado), an adenosine A2A receptor agonist, on retinal ischaemia/reperfusion damage in rats. METHODS: Retinal ischaemia/reperfusion damage was induced by elevating the intraocular pressure of one eye to 130 mm Hg for 60 minutes and returning it to normal. 7 days later, retinal ischaemia/reperfusion damage was histologically quantified by measuring the thickness of retinal layers. Intraocular pressure was measured by pressure transducer. RESULTS: Retinal ischaemia/reperfusion caused cell loss in the ganglion cell layer and thinning of the inner plexiform and nuclear layer. Both ocular topical and intravenous administration of 2-CN-Ado caused a reduction of retinal ischaemia/reperfusion damage. A selective A2A receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine (CSC), but not a selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a selective A2B receptor antagonist, alloxazine, reduced the protective effect of 2-CN-Ado. While ocular topical administration of 2-CN-Ado caused a sustained reduction of intraocular pressure, intravenous administration of 2-CN-Ado showed a transient ocular hypotensive effect. CONCLUSIONS: These results suggest that 2-CN-Ado attenuates retinal ischaemia/reperfusion damage, and at least some of this protective effect of 2-CN-Ado might be mediated via activation of the adenosine A2A receptor.
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Agonistas del Receptor de Adenosina A2 , Adenosina/análogos & derivados , Precondicionamiento Isquémico , Daño por Reperfusión/prevención & control , Vasos Retinianos/patología , Adenosina/química , Adenosina/farmacología , Adenosina/uso terapéutico , Administración Tópica , Animales , Antihipertensivos/farmacología , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Presión Intraocular/efectos de los fármacos , Masculino , Fenetilaminas/farmacología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Vasos Retinianos/metabolismoRESUMEN
The angiopoietin (Ang) family of proteins are central to the regulation of angiogenesis. The purposes of this study were to determine cDNA sequences of canine Ang-1 and Ang-2 and investigate their expressions in normal tissues and spontaneous tumours. The cDNA sequences of canine Ang-1 and Ang-2 were 1,494 and 1,488 bp, and the deduced amino acid sequences were 497 and 495 residues, respectively. The cDNA sequences of canine Ang-1 and Ang-2 showed high homology with those of the other mammalian species. Canine Ang-1 and Ang-2 mRNA were detectable in all 22 normal tissues and spontaneous tumours. Higher mRNA expression level of canine Ang-2 was demonstrated in mammary simple carcinomas, haemangiosarcoma and hepatocellular carcinoma in comparison with normal tissues.
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Angiopoyetina 1/biosíntesis , Angiopoyetina 2/biosíntesis , Enfermedades de los Perros/genética , Neoplasias/veterinaria , Secuencia de Aminoácidos , Angiopoyetina 1/genética , Angiopoyetina 2/genética , Animales , Secuencia de Bases , Enfermedades de los Perros/metabolismo , Perros , Expresión Génica , Datos de Secuencia Molecular , Neoplasias/genética , Neoplasias/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/veterinaria , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Alineación de Secuencia , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
OBJECTIVES: In the molecular era, two types of phenotypic differences are recognized between electrocardiography (ECG) and echocardiography in hypertrophic cardiomyopathy (HCM); ECG abnormalities in carriers without left ventricular hypertrophy (LVH), and normal ECG patterns in carriers with LVH. The goal of this study was to evaluate the diagnostic value of ECG for detecting carriers without LVH, and also to assess normal ECG patterns in carriers with LVH from the genetic standpoint of HCM. SETTING: A matched case-control study in a university hospital and general hospitals in Japan. PATIENTS AND DESIGN: ECG and echocardiographic findings were analysed in 173 genotyped subjects (107 genetically affected, 66 unaffected) from families with disease-causing mutations in four genes. RESULTS: ECG abnormalities were found in 18 (54.5%) of 33 nonhypertrophic carriers, but only nine (13.6%) of 66 noncarriers (P < 0.001). For detecting nonhypertrophic carriers, ST-T abnormalities showed the highest accuracy amongst the three major ECG criteria. In contrast, normal ECG patterns were found in eight (10.8%) of 74 carriers with LVH. The sensitivity of ECG for detecting carriers with LVH in families with the cardiac myosin-binding protein C, cardiac troponin T and cardiac troponin I gene mutations was 83%, 88% and 94% respectively. CONCLUSION: These findings suggest that ECG may have favourable diagnostic value even for detecting nonhypertrophic carriers. Furthermore, diagnostic value of ECG may differ according to the genes involved. Our data may contribute to interpretation of phenotypic differences between ECG and echocardiography from the viewpoint of molecular genetics of HCM.
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Cardiomiopatía Hipertrófica Familiar/diagnóstico , Ecocardiografía , Electrocardiografía , Adulto , Anciano , Cardiomiopatía Hipertrófica Familiar/genética , Proteínas Portadoras/genética , Distribución de Chi-Cuadrado , Femenino , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Mutación , Penetrancia , Sensibilidad y Especificidad , Troponina I/genética , Troponina T/genéticaRESUMEN
BACKGROUND: Dye-enhanced laser ablation (DLA) using a low-power diode laser for indocyanine green (ICG)-stained tissue has proven its effectiveness in dye-enhanced laser photocoagulation of retinal vessels or endoscopic surgical mucosectomy. We have applied DLA in hepatectomy and described its histological distinction in comparison with the cavitron ultrasonic surgical aspirator (CUSA). METHODS: A diode laser (UDL-60 Laser unit, Olympus, Tokyo, Japan) with 810 +/- 20 nm wavelength was employed for this study. The ICG dye (Diagnogreen, Daiichi Pharmaceutical, Tokyo, Japan) with a peak absorption wavelength at 800-810 nm was injected topically into the resection plane of the liver. The liver tissue was divided by touching the tip of the diode laser. Three different concentrations of ICG solution such as 2.0, 1.0 and 0.5 mg/ml were tested in the preliminary animal experiment. The use of a low-power diode laser at 10 W with an ICG concentration of 0.5 mg/ml was the appropriate combination for liver resection. In the clinical series, 27 hepatectomies were performed by DLA, and 10 with CUSA. RESULTS: DLA demonstrated smooth cutting and good hemostasis in liver resection. Among the hepatectomy cases given DLA, no postoperative hemorrhage or bile leakage was noted. The postoperative hospital stay was significantly shorter in the DLA than the CUSA group. The cut surface of the liver was sealed microscopically with a layer of protein coagulum. CONCLUSIONS: A layer of protein sealant on the cut surface of the liver contributes to the short postoperative hospital stay when using DLA.