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1.
Lupus ; 25(1): 54-60, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26296361

RESUMEN

OBJECTIVE: We have assessed the effectiveness of tacrolimus for minor flares in systemic lupus erythematosus (SLE) patients. METHODS: The medical records of 313 patients were retrospectively reviewed over a period of seven years, from 2006 to 2013. We enrolled patients with minor flare treated with add-on tacrolimus, without glucocorticoid (GC) intensification (tacrolimus group). Minor flare was defined as a ≥ 1-point increase in a total score between 3 and 11 in the SLE Disease Activity Index (SLEDAI). We enrolled as controls patients who were administered increased doses of GC for minor flare (GC group). All patients were followed for one year. The primary outcome measure was the proportion of responders. RESULTS: There were 14 eligible patients in the tacrolimus group and 20 eligible patients in the GC group. The mean SLEDAI at flare tended to be higher in the tacrolimus group than in the GC group (7.5 vs. 6.2, p = 0.085). A mean dose of 1.6 mg tacrolimus/day was administered for flare, while the mean GC dose was 13.7 mg/day in the GC group. The proportion of responders was 86% (12/14) in the tacrolimus group and 75% (15/20) in the GC group (p = 0.67). The mean dose of GC at 12 months was higher in the GC group than in the tacrolimus group (9.7 mg/day vs. 7.1 mg/day, p < 0.05). Only one patient discontinued tacrolimus because of fatigue after three months. CONCLUSION: Adding tacrolimus without increasing the GC dose may provide an effective treatment option for minor flares in patients with SLE.


Asunto(s)
Inmunosupresores/administración & dosificación , Lupus Eritematoso Sistémico/tratamiento farmacológico , Tacrolimus/administración & dosificación , Adulto , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Registros Médicos , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tacrolimus/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
2.
Biol Sport ; 32(1): 15-20, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25729145

RESUMEN

The aim of this study was to investigate the effects of heat exposure in the absence of hyperthermia on power output during repeated cycling sprints. Seven males performed four 10-s cycling sprints interspersed by 30 s of active recovery on a cycle ergometer in hot-dry and thermoneutral environments. Changes in rectal temperature were similar under the two ambient conditions. The mean 2-s power output over the 1st-4th sprints was significantly lower under the hot-dry condition than under the thermoneutral condition. The amplitude of the electromyogram was lower under the hot-dry condition than under the thermoneutral condition during the early phase (0-3 s) of each cycling sprint. No significant difference was observed for blood lactate concentration between the two ambient conditions. Power output at the onset of a cycling sprint during repeated cycling sprints is decreased due to heat exposure in the absence of hyperthermia.

3.
Phys Rev Lett ; 106(5): 056602, 2011 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-21405419

RESUMEN

Studies of the structure, magnetization, and resistivity under pressure on stoichiometric normal spinel Co[V(2)]O(4) single crystals show (i) absence of a structural distortion, (ii) abnormal magnetic critical exponents, and (iii) metallic conductivity induced by pressures at low temperatures. All these results prove that Co[V(2)]O(4) sits on the edge of the itinerant-electron limit. Compared with similar measurements on Fe[V(2)]O(4) and other A[V(2)]O(4) studies, it is shown that a critical V-V separation for a localized-itinerant electronic phase transition exists.

4.
J Periodontal Res ; 45(1): 45-51, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19602119

RESUMEN

BACKGROUND AND OBJECTIVE: Elimination of pathogens is the main aim of periodontal treatment; however, modulation of the host immune response should also be considered. This study aimed to evaluate the effects of mechanical stimulation on periodontal healing in rats. MATERIAL AND METHODS: Before starting the experiment, lipopolysaccharide and proteases were applied once a day, for 4 wk, to both maxillary first molars of 30 rats to induce periodontal disease, and the application was stopped at the end of the 4-wk period. The experiment started immediately following this pretreatment. In the experiment, the left palatal gingiva was stimulated once daily using a powered toothbrush and the right gingiva served as a control (no mechanical stimulation). Pathological changes, and proliferation and cell death in periodontal tissues, were evaluated histometrically and immunohistochemically at baseline (0 wk), and at 1 and 3 wk of stimulation. RESULTS: The control showed a reduction of polymorphonuclear leukocyte infiltration in connective tissue and an increase in the numbers of gingival and periodontal ligament fibroblasts. Mechanical stimulation reduced polymorphonuclear leukocyte infiltration and the area of destroyed collagen in connective tissue, and increased the number of gingival fibroblasts; however, it had no effect on alveolar bone and root resorption or on the number of periodontal ligament fibroblasts. CONCLUSION: Mechanical stimulation accelerated the healing of gingival inflammation by reducing the infiltration of polymorphonuclear leukocytes and enhancing fibroblast proliferation and collagen synthesis.


Asunto(s)
Enfermedades Periodontales/fisiopatología , Cepillado Dental/instrumentación , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/fisiopatología , Proceso Alveolar/patología , Proceso Alveolar/fisiopatología , Animales , Proteínas Bacterianas/efectos adversos , Muerte Celular/fisiología , Proliferación Celular , Colágeno , Tejido Conectivo/patología , Tejido Conectivo/fisiopatología , Modelos Animales de Enfermedad , Inserción Epitelial/patología , Inserción Epitelial/fisiopatología , Escherichia coli , Fibroblastos/patología , Encía/patología , Encía/fisiopatología , Gingivitis/patología , Gingivitis/fisiopatología , Lipopolisacáridos/efectos adversos , Masculino , Infiltración Neutrófila/fisiología , Neutrófilos/patología , Péptido Hidrolasas/efectos adversos , Enfermedades Periodontales/patología , Ligamento Periodontal/patología , Ligamento Periodontal/fisiopatología , Estimulación Física , Ratas , Ratas Wistar , Resorción Radicular/patología , Resorción Radicular/fisiopatología , Streptomyces griseus , Factores de Tiempo , Cicatrización de Heridas/fisiología
5.
J Oral Rehabil ; 36(8): 584-91, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19548957

RESUMEN

The purpose of this study was to examine the relationship of dietary preference to bite force and occlusal contact area in Japanese elementary school children. A total of 348 children, aged 7-12 years, from two public elementary schools located in Okayama Prefecture, Japan, participated in the study. Clinical examination included decayed, missing and filled teeth (dmft and DMFT), and total numbers of deciduous and permanent teeth. Bite force and occlusal contact area were measured using a pressure-detecting sheet. Dietary preference was assessed using a questionnaire in which the answers were given in like/dislike form. Mann-Whitney U-test and multiple logistic regression analysis were applied to analyse the data. In multiple logistic regression analysis after adjustment for age, gender and total number of teeth present, children who liked cabbage and celery showed significantly higher bite force (P = 0.05 and P < 0.01, respectively) than those who disliked these. Children who liked cabbage and celery also showed higher occlusal contact area (P < 0.05 and P < 0.01, respectively) than those who disliked these. The Japanese elementary school children who liked hard foods such as cabbage and celery showed higher bite force and higher occlusal contact area than those who disliked these foods. A positive attitude towards harder food items might contribute to healthy development of the masticatory apparatus.


Asunto(s)
Pueblo Asiatico , Fuerza de la Mordida , Preferencias Alimentarias/fisiología , Masticación/fisiología , Niño , Oclusión Dental , Femenino , Humanos , Japón , Masculino , Reproducibilidad de los Resultados , Estadísticas no Paramétricas
6.
Oncogene ; 25(44): 5994-6002, 2006 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-16652150

RESUMEN

Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of high-grade gliomas in a more objective manner than standard pathology. RNAs from 29 malignant gliomas were analysed using Agilent microarrays. We identified 21 genes whose expression was most strongly and consistently related to patient survival based on univariate proportional hazards models. In six out of 10 genes, changes in gene expression were validated by quantitative real-time PCR. After adjusting for clinical covariates based on a multivariate analysis, we finally obtained a statistical significance level for DDR1 (discoidin domain receptor family, member 1), DYRK3 (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 3) and KSP37 (Ksp37 protein). In independent samples, it was confirmed that DDR1 protein expression was also correlated to the prognosis of glioma patients detected by immunohistochemical staining. Furthermore, we analysed the efficacy of the short interfering RNA (siRNA)-mediated inhibition of DDR1 mRNA synthesis in glioma cell lines. Cell proliferation and invasion were significantly suppressed by siRNA against DDR1. Thus, DDR1 can be a novel molecular target of therapy as well as an important predictive marker for survival in patients with glioma. Our method was effective at classifying high-grade gliomas objectively, and provided a more accurate predictor of prognosis than histological grading.


Asunto(s)
Perfilación de la Expresión Génica , Glioma/genética , Glioma/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , ADN Complementario , Femenino , Glioma/diagnóstico , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia , Factores de Tiempo
7.
Neuroscience ; 310: 731-41, 2015 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-26455951

RESUMEN

Homeostasis of magnesium ion (Mg(2+)) plays key roles in healthy neuronal functions, and deficiency of Mg(2+) is involved in various neuronal diseases. In neurons, we have reported that excitotoxicity induced by excitatory neurotransmitter glutamate increases intracellular Mg(2+) concentration ([Mg(2+)]i). However, it has not been revealed whether neuronal activity under physiological condition modulates [Mg(2+)]i. The aim of this study is to explore the direct relationship between neural activity and [Mg(2+)]i dynamics. In rat primary-dissociated hippocampal neurons, the [Mg(2+)]i and [Ca(2+)]i dynamics were simultaneously visualized with a highly selective fluorescent Mg(2+) probe, KMG-104, and a fluorescent Ca(2+) probe, Fura Red, respectively. [Mg(2+)]i increase concomitant with neural activity by direct current stimulation was observed in neurons plated on an indium-tin oxide (ITO) glass electrode, which enables fluorescent imaging during neural stimulation. The neural activity-dependent [Mg(2+)]i increase was also detected in neurons whose excitability was enhanced by the treatment of a voltage-gated K(+) channel blocker, tetraethylammonium (TEA) at the timings of spontaneous Ca(2+) increase. Furthermore, the [Mg(2+)]i increase was abolished in Mg(2+)-free extracellular medium, indicating [Mg(2+)]i increase is due to Mg(2+) influx induced by neural activity. The direct neuronal depolarization by veratridine, a Na(+) channel opener, induced [Mg(2+)]i increase, and this [Mg(2+)]i increase was suppressed by the pretreatment of a non-specific Mg(2+) channel inhibitor, 2-aminoethoxydiphenyl borate (2-APB). Overall, activity-dependent [Mg(2+)]i increase results from Mg(2+) influx through 2-APB-sensitive channels in rat hippocampal neurons.


Asunto(s)
Calcio/metabolismo , Hipocampo/fisiología , Magnesio/metabolismo , Potenciales de la Membrana , Neuronas/fisiología , Animales , Células Cultivadas , Estimulación Eléctrica , Hipocampo/metabolismo , Neuronas/metabolismo , Ratas , Ratas Wistar
8.
Cancer Gene Ther ; 8(10): 796-802, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11687903

RESUMEN

Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.


Asunto(s)
Neoplasias Encefálicas/terapia , Colágeno/genética , Endotelio Vascular/metabolismo , Terapia Genética/métodos , Melanoma Experimental/terapia , Neovascularización Patológica/terapia , Fragmentos de Péptidos/genética , Virus de los Bosques Semliki/fisiología , Animales , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/virología , Células Cultivadas , Colágeno/sangre , Endostatinas , Endotelio Vascular/virología , Femenino , Expresión Génica , Técnicas de Transferencia de Gen , Vectores Genéticos/administración & dosificación , Humanos , Melanoma Experimental/irrigación sanguínea , Melanoma Experimental/virología , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Fragmentos de Péptidos/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia
9.
J Neuroimmunol ; 48(1): 45-51, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8227307

RESUMEN

We have previously identified the suppression of lymphocyte blastogenesis and the acceleration of growth of subcutaneous tumors by bilateral anterior hypothalamic lesions in rats. The present study was performed to clarify the changes in lymphocyte subsets and natural killer (NK) activity after making the lesions. The influence on immunological memory was also studied. The CD4/CD8 ratio of peripheral blood lymphocytes and spleen cells, T cell receptor alpha beta-positive cells of the thymocytes and NK activity of the spleen cells decreased significantly. Major histocompatibility complex (MHC) antigen expression on RBL-1 cells injected intraperitoneally into pre-immunized rats was also suppressed. These results suggest that the anterior hypothalamus has some influences on the control of the cellular immunological functions at the peripheral level, on the maturation of T cells at the level of thymus and on the antigen recognition by T cell receptors and MHC antigens.


Asunto(s)
Hipotálamo Anterior/fisiología , Linfocitos T/inmunología , Animales , Relación CD4-CD8 , Citometría de Flujo , Antígenos de Histocompatibilidad Clase II/análisis , Memoria Inmunológica , Células Asesinas Naturales/inmunología , Masculino , Ratas , Ratas Endogámicas F344 , Receptores de Antígenos de Linfocitos T alfa-beta/análisis
10.
DNA Cell Biol ; 20(7): 383-90, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11506702

RESUMEN

The ost protooncogene encodes a guanine nucleotide exchange factor for the Rho family of small GTPases, RhoA and Cdc42. The N-terminal domain of Ost (Ost-N) appears to negatively regulate the oncogenic activity of the protein, as deletion of this domain drastically increases its transforming activity in NIH 3T3 cells. Using a yeast two-hybrid system, we identified five genes encoding proteins that can interact with Ost-N. One of them, designated OSTIP2 (Ost interacting protein 2), encoded a previously uncharacterized protein. The OSTIP2 product is highly expressed in skeletal muscle as a 1.2-kb transcript. Full-length OSTIP2 cDNA contained an ORF of 193 amino acids. Transcription-coupled translation of OSTIP2 cDNA in reticulocyte lysates revealed a protein product of 20 kDa, which corresponded to the predicted size of the protein. Bacterially expressed glutathione S-transferase (GST)-Ostip2 fusion protein efficiently associated in vitro with baculovirus-expressed Ost. Interestingly, expression of Ostip2 in NIH 3T3 cells efficiently induced foci of morphologically transformed cells. Moreover, inoculation of athymic (nude) mice with OSTIP2 transfectants strongly induced tumor formation. These results suggest that Ostip2 is a novel oncoprotein that can interact with the Rho exchange factor Ost.


Asunto(s)
Transformación Celular Neoplásica , Factores de Intercambio de Guanina Nucleótido/metabolismo , Proteínas Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Células 3T3 , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , ADN Complementario , Células HeLa , Humanos , Ratones , Ratones Desnudos , Datos de Secuencia Molecular , Proteínas Oncogénicas/metabolismo , Saccharomyces cerevisiae , Técnicas del Sistema de Dos Híbridos , Proteína de Unión al GTP rhoA/metabolismo
11.
Eur J Pharmacol ; 274(1-3): 1-6, 1995 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-7768260

RESUMEN

The mode of binding of [3H]BQ-123 (cyclo(-D-Trp-D-Asp-[prolyl-3,4 (n)-[3H]]Pro-D-Val-Leu)), an endothelin receptor antagonist radioligand, was evaluated in the human neuroblastoma cell line SK-N-MC at 37 degrees C. Scatchard analysis indicated the presence of a single class of [3H]BQ-123 binding sites with a high affinity of 3.2 nM. [3H]BQ-123 binding achieved steady state within 7 min and dissociated with a half-time of 1.4 min, while [125I] endothelin-1 binding barely reached a steady state even after 6 h and showed little dissociation. [3H]BQ-123 binding was sensitive to endothelin-1 and endothelin-2 (Ki values = 0.058 and 0.10 nM, respectively) and the endothelin ETA receptor-selective antagonist BQ-123 (Ki = 3.3 nM), while showing low affinity for endothelin-3 (Ki = 50 nM), the endothelin ETB receptor-selective agonist BQ-3020 (Ki = 970 nM) and other bioactive peptides. Thus, [3H]BQ-123 is a specific and reversible radioligand for endothelin ETA receptors. The rapid reversibility of [3H]BQ-123 binding should provide a tool for estimating the equilibrium inhibition constants (Ki values) of various compounds for endothelin ETA receptors.


Asunto(s)
Antagonistas de los Receptores de Endotelina , Endotelinas/metabolismo , Péptidos Cíclicos/metabolismo , Secuencia de Aminoácidos , Azepinas/metabolismo , Unión Competitiva , Endotelinas/antagonistas & inhibidores , Humanos , Indoles/metabolismo , Marcaje Isotópico , Datos de Secuencia Molecular , Neuroblastoma/metabolismo , Neuroblastoma/patología , Oligopéptidos/metabolismo , Ensayo de Unión Radioligante , Receptor de Endotelina A , Receptores de Endotelina/metabolismo , Relación Estructura-Actividad , Tritio , Células Tumorales Cultivadas
12.
J Neurosurg ; 94(3): 474-81, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11235953

RESUMEN

OBJECT: The aim of this study was to further investigate dendritic cell (DC)-based immunotherapy for malignant glioma to improve its therapeutic efficacy. METHODS: Dendritic cells were isolated from the bone marrow and pulsed with phosphate-buffered saline, tumor RNA, tumor lysate, Semliki Forest virus (SFV)-LacZ, SFV-mediated B16 complementary (c)DNA, or SFV-mediated 203 glioma cDNA, respectively, to treat mice bearing tumors of the 203 glioma cell line. The results indicated that pre-immunization with DCs pulsed with the same type of cDNA as in the tumor by a self-replicating RNA vector (that is, SFV) protected mice from tumor challenge, and that therapeutic immunization prolonged the survival of mice with established tumors. The SFV induced apoptosis in DCs and their death facilitated the uptake of apoptotic cells by other DCs, thus providing a potential mechanism for enhanced immunogenicity. CONCLUSIONS: Therapy with DCs that have been pulsed with SFV-mediated tumor cDNA may be an excellent procedure for the development of new cancer vaccines.


Asunto(s)
Neoplasias Encefálicas/terapia , Células Dendríticas/inmunología , Terapia Genética/métodos , Vectores Genéticos , Glioma/terapia , Inmunoterapia/métodos , Virus de los Bosques Semliki , Animales , Apoptosis/genética , Apoptosis/inmunología , Células de la Médula Ósea/citología , Neoplasias Encefálicas/mortalidad , Linfocitos T CD8-positivos/inmunología , ADN Complementario , Células Dendríticas/citología , Glioma/mortalidad , Inmunización , Melanoma , Ratones , Ratones Endogámicos C57BL , Tasa de Supervivencia , Transfección , Células Tumorales Cultivadas
13.
IEEE Trans Med Imaging ; 7(3): 193-7, 1988.
Artículo en Inglés | MEDLINE | ID: mdl-18230468

RESUMEN

A 3D display equipped with a linearly moving mirror reflecting a series of 2D cross sections pictures has been devised. The pictures were displayed by a CRT in perfect synchronization with the back-and-forth movements of the mirror. The 80x80x80 mm(3) 3D space contained 128x128 pixels; with each pixel having 256 grades of intensity, enough to produce a satisfactory 3D image of an ultrasonic echogram of hepatic vessels. The images can be observed from different angles by changing the observer's position or by prompt rotation of the image through a console. Mechanical problems inherent in using moving parts have been solved.

14.
Int J Mol Med ; 1(1): 213-21, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9852222

RESUMEN

The coordinated expression of four different CCAAT/enhancer binding proteins (C/EBPs), C/EBPalpha, C/EBPbeta, C/EBPdelta, and C/EBPepsilon constitutes a critical component of the myeloid differentiation program. C/EBPs are modular proteins, consisting of an activation domain, DNA binding domain and leucine zipper dimerization region. Recent studies including the analysis of mice deficient in several C/EBP proteins emphasize the effects of these molecules in hematopoiesis. C/EBPalpha is a master regulator of myeloid progenitors, C/EBPbeta plays an important role in macrophage and B-cell development, C/EBPgamma is involved in B-cell development, and C/EBPdelta is upregulated during myelopoiesis. Furthermore, C/EBPepsilon is a regulator of terminal differentiation of eosinophils and functional maturation of neutrophils. The formation of alternative combinations of tissue-specific and cell-stage specific C/EBP dimers may allow differential regulation of target genes in hematopoietic cells and commitment to distinctive hematopoietic lineages.


Asunto(s)
Proteínas de Unión al ADN/fisiología , Hematopoyesis , Proteínas Nucleares/fisiología , Factores de Transcripción/fisiología , Transcripción Genética , Animales , Proteínas Potenciadoras de Unión a CCAAT , Regulación de la Expresión Génica , Humanos , Ratones
15.
Curr Eye Res ; 17(11): 1087-96, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9846628

RESUMEN

PURPOSE: There is considerable evidence that vascular endothelial growth factor (VEGF) mediates ocular neovascularization in retinal vascular diseases. We investigated the time-dependent changes in the expression of VEGF and its receptor KDR/ Flk in a transient retinal ischemia-reperfusion injury model. METHODS: Transient retinal ischemia was induced by increasing the intraocular pressure in albino rats eyes for 45 min. In situ hybridization was used to identify the retinal cells synthesizing VEGF mRNA and KDR mRNA at various times following reperfusion. Immunohistochemical analysis was also carried out to detect VEGF immunoreactivity. RESULTS: In the control, non-ischemic retinas, signals for VEGF mRNA and KDR mRNA were observed in the cells of the ganglion cell layer. Immunoreactivity to VEGF was also found in the nerve fiber layer, the ganglion cell layer, and the retinal pigment epithelial (RPE) cell layer. Immediately and 6 h after reperfusion, VEGF and KDR mRNA expression was markedly decreased, but recovered by 24 h to the levels observed in normal retinas. Immunoreactivity for VEGF was also decreased immediately and 6 h after reperfusion, and was detected in the endothelial cells of the retinal vessels after 24 h. Immunoreactivity to VEGF recovered by 48 h after reperfusion. CONCLUSIONS: The hybridization pattern of VEGF and KDR mRNA in the ganglion cell layer strongly suggests that the ganglion cells are the major source of this growth factor. The decrease of VEGF mRNA, KDR/Flk mRNA and VEGF protein levels after ischemia and recovery after reperfusion suggest that transient hypoxia might mediate short-term down-regulation of VEGF and KDR mRNA.


Asunto(s)
Factores de Crecimiento Endotelial/metabolismo , Linfocinas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores de Factores de Crecimiento/metabolismo , Receptores Mitogénicos/metabolismo , Daño por Reperfusión/metabolismo , Enfermedades de la Retina/metabolismo , Vasos Retinianos/metabolismo , Animales , Técnicas para Inmunoenzimas , Hibridación in Situ , Masculino , Fibras Nerviosas/metabolismo , Epitelio Pigmentado Ocular/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Factores de Crecimiento Endotelial Vascular , Daño por Reperfusión/patología , Enfermedades de la Retina/patología , Células Ganglionares de la Retina/metabolismo , Vasos Retinianos/patología , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular
16.
Curr Eye Res ; 18(4): 261-9, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10372985

RESUMEN

PURPOSE: The purpose of this study was to determine whether the inactivated hemagglutinating virus of Japan (HVJ)-liposome method can induce phosphorothioate oligonucleotides effectively into an experimentally-induced choroidal neovascularization of rats. We also examined whether antisense phosphorothioate oligonucleotides against VEGF could be induced into choroidal neovascularization as a therapeutic agent by the HVJ-liposome method. METHODS: The experiments were conducted on a rat model of choroidal neovascularization. FITC-labeled phosphorothioate oligonucleotides were coencapsulated in liposomes. The liposomes were coated with the envelope of inactivated HVJ and injected into the vitreous cavity following photocoagulation of pigmented rat eyes. The eyes were removed following injection, fixed, frozen and cut into thin sections. Induction of oligonucleotides was observed under a laser confocal scanning microscope for fluorescence and the development of choroidal neovascularization was evaluated histopathologically. RESULTS: Phosphorothioate oligonucleotides were effectively induced into ganglion cells and into the cells of the choroidal neovascularization induced by laser photocoagulation. Highly effective induction of oligos was observed 3 to 14 days after intravitreal injection of HVJ-liposomes after which the level decreased. Antisense oligonucleotides against VEGF were induced specifically into cells in the choroidal neovascularization, however neovascularization was still observed. CONCLUSIONS: Phosphorothioate oligonucleotides can be effectively induced into ganglion cells, and specifically into cells in choroidal neovascularization. Although antisense oligonucleotides against VEGF failed to prevent choroidal neovascularization, the HVJ-liposome method provided a highly effective means of inducing antisense oligos for in vivo antisense therapy.


Asunto(s)
Coroides/irrigación sanguínea , Técnicas de Transferencia de Gen , Neovascularización Patológica/patología , Oligonucleótidos Antisentido/administración & dosificación , Tionucleótidos/genética , Animales , Portadores de Fármacos , Factores de Crecimiento Endotelial/genética , Fluoresceína-5-Isotiocianato , Colorantes Fluorescentes , Vectores Genéticos , Liposomas , Linfocinas/genética , Oligonucleótidos Antisentido/farmacología , Ratas , Ratas Endogámicas BN , Respirovirus/genética , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular
17.
Neurosurg Focus ; 9(6): e7, 2000 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-16817690

RESUMEN

OBJECT: The authors investigated immunogene therapy for malignant glioma to determine whether its therapeutic efficacy could be improved. METHODS: Four groups of 203-glioma-bearing mice were treated with injections of phosphate-buffered saline, Semliki Forest virus (SFV)-LacZ, retrovirus vector DFG-interleukin (IL)-12, and SFV-IL12, respectively. The results indicated that therapeutic immunization with SFV-IL12 prolonged the survival of mice with established tumors. Semliki Forest virus induces apoptotic death to glioma cells, which facilitates the uptake of apoptotic cells by dendritic cells, providing a potential mechanism for enhanced immunogenicity. CONCLUSIONS: Immunogene therapy with IL-12 via SFV may be an excellent candidate for the development of new cancer vaccines.


Asunto(s)
Neoplasias Encefálicas/terapia , Terapia Genética/métodos , Glioma/terapia , Inmunoterapia/métodos , Interleucina-12/genética , Virus de los Bosques Semliki/genética , Animales , Apoptosis/inmunología , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Cricetinae , Células Dendríticas/inmunología , Ingeniería Genética/métodos , Glioma/inmunología , Glioma/patología , Riñón/citología , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/genética , Tasa de Supervivencia , Transfección
18.
Dev Biol (Basel) ; 108: 29-39, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12220140

RESUMEN

The first nationwide nucleic acid amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type 1 (HIV-1) of voluntarily donated blood after serological pre-screening and before release of cellular components and plasma for fractionation was implemented by the Japanese Red Cross Blood Transfusion Services. The NAT screening assay using multiplex reagent is time-saving, cost effective, and labour-saving procedure for all blood and blood products including short-shelf life platelets. During the 50-mini-pool NAT screening of serologically negative donations (February 1, 2001-April 30, 2001), we were able to screen out 112 HBV-positive, 25 HCV-positive, and 4 HIV-1 positive units from blood and blood components.


Asunto(s)
Donantes de Sangre , Sangre/virología , VIH-1/aislamiento & purificación , Virus de Hepatitis/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Viremia , Transfusión Sanguínea , ADN Viral , VIH-1/genética , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Virus de Hepatitis/genética , Humanos , Japón , Tamizaje Masivo , ARN Viral/análisis , Cruz Roja
19.
Neurol Med Chir (Tokyo) ; 29(1): 15-9, 1989 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-2472559

RESUMEN

Changes in cerebral blood flow (CBF) were measured and compared in 40 patients with putaminal hemorrhage who underwent either stereotactic hematoma aspiration or conservative treatment. There were no statistically significant differences in mean CBF or hemispheric CBF between the two treatment groups. Although there are claims of the superiority of surgery from the standpoint of integrated cortical function following mild putaminal hemorrhage, the results of this investigation indicate that conservative therapy is adequate in such cases, based on improvement in CBF.


Asunto(s)
Hemorragia Cerebral/fisiopatología , Circulación Cerebrovascular , Putamen , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Ganglios Basales/fisiopatología , Enfermedades de los Ganglios Basales/terapia , Hemorragia Cerebral/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Técnicas Estereotáxicas , Succión/métodos
20.
Neurol Med Chir (Tokyo) ; 34(9): 583-7, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7526247

RESUMEN

The presence of tumor-infiltrating lymphocytes (TILs) and the expression of adhesion molecules were examined in 12 glioma tissues. Most TILs were T lymphocytes, and both cytotoxic/suppressor and helper/inducer. T lymphocyte phenotypes were found. Neural cell adhesion molecule was intensely expressed in 11 gliomas, and intercellular adhesion molecule-1 (ICAM-1) in seven. Many TILs were found only in gliomas expressing ICAM-1, but there was no relationship with clinical course in the patients.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Moléculas de Adhesión Celular Neuronal/metabolismo , Glioma/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Adulto , Anciano , Neoplasias Encefálicas/inmunología , Niño , Femenino , Glioma/inmunología , Humanos , Inmunohistoquímica , Lactante , Masculino , Persona de Mediana Edad
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