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1.
Mater Today Bio ; 8: 100078, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33083780

RESUMEN

Here, we investigated the usefulness of silk fibroin nanofibers obtained via mechanical grinding of degummed silkworm silk fibers as an additive in bioinks for extrusion three-dimensional (3D) bioprinting of cell-laden constructs. The nanofibers could be sterilized by autoclaving, and addition of the nanofibers improved the shear thinning of polymeric aqueous solutions, independent of electric charge and the content of cross-linkable moieties in the polymers. The addition of nanofibers to bioinks resulted in the fabrication of hydrogel constructs with higher fidelity to blueprints. Mammalian cells in the constructs showed >85% viability independent of the presence of nanofibers. The nanofibers did not affect the morphologies of enclosed cells. These results demonstrate the great potential of silk fibroin nanofibers obtained via mechanical grinding of degummed silkworm silk fibers as an additive in bioinks for extrusion 3D bioprinting.

3.
J Heart Lung Transplant ; 20(9): 956-63, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11557190

RESUMEN

BACKGROUND: Current studies provide evidence that a small G protein, RhoAp21, and its target protein, Rho-associated coiled-coil forming protein kinase (ROCK), regulate not only cell shape but also cell migration. However, contribution of Rho/ROCK signaling to graft rejection is unknown. The purpose of this study was to evaluate the inhibitory effect of Y-27632, a highly selective ROCK inhibitor, on rejection of heterotopic cardiac transplantation in mice. METHODS: BALB/c (H-2(d)) hearts were transplanted into C3H/He (H-2(k)) as allografts that were full histoincompatibility combinations. The recipients received several doses of Y-27632, commencing 1 day before cardiac transplantation until rejection. We used immunohistochemical study to detect the expression of myocardial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and we immunoenzymatically measured serum interleukin (IL)-6. Furthermore, we evaluated cardiac allograft vasculopathy treated with either FK506 or Y-27632 at Day 100. RESULTS: The Y-27632-treated (2 mg/kg/day) allografts prolonged the mean survival time (49.6 +/- 10.1 days, n = 12) as compared with the untreated allografts (8.1 +/- 0.4 days, n = 7, p < 0.001). Histologic examinations of the Y-27632-treated allografts at Day 7 showed greatly reduced leukocyte infiltration compared with the untreated allografts. The Y-27632-treated allografts revealed faint expression of myocardial ICAM-1 and VCAM-1 at Day 7. The serum IL-6 levels also decreased in the Y-27632-treated mice. In the long-surviving Y-27632-treated allografts at Day 100, we saw neither active rejection nor apparent thickening of vascular intima. CONCLUSION: Our results suggest that ROCK plays a major role in cardiac rejection in the BALB/c-to-C3H/He mouse model. Inhibition of this Rho/ROCK signaling may be an alternative therapeutic option for managing acute and chronic rejection.


Asunto(s)
Amidas/antagonistas & inhibidores , Inhibidores Enzimáticos/uso terapéutico , Trasplante de Corazón/mortalidad , Piridinas/antagonistas & inhibidores , Trasplante Heterotópico/mortalidad , Animales , Anticuerpos/efectos de los fármacos , Anticuerpos/inmunología , Modelos Animales de Enfermedad , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/mortalidad , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón/inmunología , Trasplante de Corazón/patología , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/inmunología , Interleucina-6/sangre , Leucocitos/efectos de los fármacos , Leucocitos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Modelos Cardiovasculares , Trasplante Heterotópico/patología , Trasplante Homólogo , Molécula 1 de Adhesión Celular Vascular/efectos de los fármacos , Molécula 1 de Adhesión Celular Vascular/inmunología
4.
Eur J Pharmacol ; 406(2): 273-9, 2000 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-11020491

RESUMEN

To evaluate (+)-(R)-trans-4-(l-Aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate (Y-27632), a selective Rho-kinase inhibitor, as a novel bronchodilator in vivo and in vitro, we investigated the effect of Y-27632 on the acetylcholine- or ovalbumin-induced increase in lung resistance (R(L)) in non-sensitized or passively sensitized guinea pigs, and the relaxant effects of salbutamol, Y-27632 and theophylline on acetylcholine- or ovalbumin-induced contraction of isolated trachea. Y-27632 inhalation (1 mM, 2 min) inhibited acetylcholine- or ovalbumin-induced increase in R(L) without changes in mean blood pressure, and the effect persisted for at least 3 h. Salbutamol, Y-27632 and theophylline each completely reversed the acetylcholine- or ovalbumin-induced contraction of isolated trachea with rank order of potency, salbutamol>Y-27632>theophylline. The relaxant effect of Y-27632 was not affected by propranolol. We conclude that, although Y-27632 is not as potent as a beta-adrenoceptor agonist, Y-27632 may become an alternative inhaled bronchodilator, because Y-27632 is more potent than theophylline, and the relaxant effect is independent of beta-adrenoceptors.


Asunto(s)
Amidas/farmacología , Broncodilatadores/farmacología , Inhibidores Enzimáticos/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Piridinas/farmacología , Acetilcolina/farmacología , Administración por Inhalación , Animales , Presión Sanguínea/efectos de los fármacos , Cobayas , Péptidos y Proteínas de Señalización Intracelular , Pulmón/efectos de los fármacos , Masculino , Contracción Muscular/efectos de los fármacos , Quinasas Asociadas a rho
5.
J Dermatol ; 27(12): 774-7, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11211793

RESUMEN

This paper reports two recent cases of tick bite due to Amblyomma testudinarium. The first case was an 86-year-old farmer infested with a fully engorged adult tick attached on his inguinal region. The second case was a 57-year-old male infested with an extraordinarily large number of larval ticks (> 100 larvae). The ticks were identified as A. testudinarium based on morphological characteristics. To our knowledge, the latter case is the eleventh case of larval tick bites among all tick species and the fourth case with larval A. testudinarium in Japan.


Asunto(s)
Mordeduras y Picaduras , Enfermedades Linfáticas/etiología , Infestaciones por Garrapatas/complicaciones , Infestaciones por Garrapatas/diagnóstico , Garrapatas , Anciano , Anciano de 80 o más Años , Animales , Humanos , Japón , Enfermedades Linfáticas/diagnóstico , Masculino , Persona de Mediana Edad
6.
Br J Pharmacol ; 128(4): 925-33, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10556927

RESUMEN

1 G protein-mediated Ca2+ sensitization of airway smooth muscle contraction was investigated with respect to the relative importance of Rho-associated coiled coil forming protein kinase (ROCK) and protein kinase C (PKC). We examined the effects of Y-27632, a ROCK inhibitor, and GF 109203X, a PKC inhibitor, on guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-induced contraction in alpha-toxin- or beta-escin-permeabilized rabbit trachea. 2 Although pre-treatment with Y-27632 dose-dependently inhibited GTPgammaS (10 microM)-induced Ca2+ sensitization of alpha-toxin-permeabilized trachea, a Y-27632-insensitive component (approximately 16% of the maximum contraction) was retained during the early phase of the GTPgammaS response in the presence of Y-27632 (100 microM). 3 GF 109203X (5 microM) abolished 1 microM 4beta-phorbol 12, 13-dibutyrate (PDBu)-induced, but only partially inhibited the GTPgammaS-induced Ca2+ sensitization. A combination of Y-27632 (100 microM) and GF 109203X (5 microM) totally abolished the GTPgammaS response. 4 GTPgammaS caused only a small contraction in the absence of Ca2+. Wortmannin (30 microM), a myosin light chain kinase (MLCK) inhibitor, completely inhibited Ca2+-induced contraction. ATP-triggered contraction of the strip which had been treated with calyculin A (1 microM), a phosphatase inhibitor, in rigor solutions was markedly slowed by worthmannin (30 microM), but not by Y-27632 (100 microM), in the presence of GTPgammaS and Ca2+. 5 GTPgammaS, but not PDBu, contracted the beta-escin-permeabilized trachea in the absence of Ca2+, but the presence of Ca2+-independent MLCK. 6 We conclude that ROCK plays a primary role in G-protein-mediated Ca2+ sensitization, which requires MLCK activity, with minor contribution of PKC to the early phase of contraction, and PDBu utilizes conventional PKC(s) in airway smooth muscle.


Asunto(s)
Calcio/metabolismo , Proteínas de Unión al GTP/fisiología , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/fisiología , Tráquea/metabolismo , Amidas/farmacología , Animales , Inhibidores Enzimáticos/farmacología , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Indoles/farmacología , Péptidos y Proteínas de Señalización Intracelular , Maleimidas/farmacología , Fosfatasa de Miosina de Cadena Ligera , Forbol 12,13-Dibutirato/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Piridinas/farmacología , Conejos , Tráquea/efectos de los fármacos , Tráquea/enzimología , Quinasas Asociadas a rho
7.
J Asthma ; 36(7): 619-26, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10524546

RESUMEN

Intracellular levels of cAMP were found to regulate T cell activity. We examined whether beta2-agonists altered cytokine production and cyclic adenosine monophosphate (cAMP) accumulation in concanavalin A (ConA)-activated peripheral T cells from asthmatic patients. Procaterol and isoproterenol weakly decreased the ConA-elicited interleukin (IL)-4 and IL-5 secretion; however, the inhibitory effect of procaterol on the ConA-induced IL-2 secretion was inferior to that of isoproterenol in normal controls and was little in asthmatics. The intracellular accumulation of cAMP by procaterol was not altered compared with that by isoproterenol. Results suggest that there is a qualitative difference between procaterol- and isoproterenol-induced cAMP accumulation in T cells.


Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Asma/metabolismo , Interleucinas/biosíntesis , Linfocitos T/metabolismo , Células Cultivadas , Concanavalina A/farmacología , AMP Cíclico/metabolismo , Humanos , Interleucina-2/biosíntesis , Interleucina-4/biosíntesis , Interleucina-5/biosíntesis , Isoproterenol/farmacología , Activación de Linfocitos , Procaterol/farmacología
8.
Am J Respir Cell Mol Biol ; 20(6): 1190-200, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10340938

RESUMEN

The mechanism of Ca2+ sensitization of contraction has not been elucidated in airway smooth muscle (SM). To determine the role of a small G protein, rhoA p21, and its target protein, rho-associated coiled coil-forming protein kinase (ROCK), in receptor-coupled Ca2+ sensitization of airway SM, we studied the effect of (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexane carboxamide dihydrochloride, monohydrate (Y-27632), a ROCK inhibitor, on isometric contractions in rabbit tracheal and human bronchial SM. Y-27632 completely reversed 1 microM carbachol (CCh)-induced contraction of intact trachea with a concentration producing half-maximum inhibition of effect (IC50) of 1.29 +/- 0.2 microM (n = 5). Although 4beta-phorbol 12,13-dibutyrate (1 microM)-induced Ca2+ sensitization was relatively resistant to Y-27632 in alpha-toxin-permeabilized trachea, CCh (100 microM) plus guanosine triphosphate (GTP) (3 microM)- and guanosine 5'-O-(3'-thiotriphosphate) (10 microM)-induced contractions were relaxed completely by Y-27632 with IC50 of 1.44 +/- 0.3 (n = 6) and 1.15 +/- 0.3 microM (n = 6). Endothelin-1 (1 microM) plus GTP (3 microM)- developed force was also reversed by Y-27632 with IC50 of 4. 10 +/- 1.1 microM (n = 6) in the alpha-toxin-permeabilized bronchus. Both the rabbit and human SM expressed rhoA p21, ROCK I, and its isoform ROCK II. Collectively, rho/ROCK-mediated Ca2+ sensitization plays a central role in the sustained phase of airway SM contraction, and selective inhibition of this pathway may become a new strategy to resolve airflow limitation in asthma.


Asunto(s)
Amidas/farmacología , Bronquios/metabolismo , Calcio/antagonistas & inhibidores , Músculo Liso/metabolismo , Piridinas/farmacología , Tráquea/metabolismo , 1-Metil-3-Isobutilxantina/farmacología , Animales , Carbacol/farmacología , Colinérgicos/farmacología , Detergentes/farmacología , Relación Dosis-Respuesta a Droga , Endotelina-1/farmacología , Proteínas de Unión al GTP/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/farmacología , Humanos , Péptidos y Proteínas de Señalización Intracelular , Toxinas Marinas , Contracción Muscular , Quinasa de Cadena Ligera de Miosina/metabolismo , Octoxinol/farmacología , Oxazoles/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Conejos , Transducción de Señal , Fosfolipasas de Tipo C/farmacología , Quinasas Asociadas a rho
9.
Exp Hematol ; 27(3): 512-9, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10089914

RESUMEN

Recent studies show that apoptosis is important for the resolution of chronic inflammation. Using a human myeloblastic leukemia cell line, EoL-1, we investigated the effect of interferon-gamma (IFN-gamma), which differentiates EoL-1 into monocyte/macrophage-like cells on Fas antigen (Fas)- and tumor necrosis factor-alpha (TNF alpha)-induced apoptosis. Both TNF and anti-Fas monoclonal antibody (CH-11) induced apoptosis of EoL-1 cells. Pretreatment with IFN-gamma for 72 hours enhanced the CH-11-induced apoptosis with up-regulation of Fas. However, the treatment markedly inhibited the TNF-induced apoptosis. In flow cytometric analysis, EoL-1 expressed two types of tumor necrosis factor receptors (TNFR1 and TNFR2), and the expression of TNFR2 but not of TNFR1 was up-regulated significantly after the IFN-gamma treatment. The TNF-induced apoptosis was mimicked by a TNFR1 stimulating antibody (htr-9), and was reversed by a TNFR1 blocking antibody (H398). Although the TNFR1-mediated cytotoxic signal was not affected by IFN-gamma pretreatment, blocking TNFR2 by a specific antagonistic antibody (utr-1) canceled the inhibitory effect of IFN-gamma. In conclusion, TNF-induced apoptosis was mediated preferentially by TNFR1, and the anti-apoptotic effect of IFN-gamma was result from up-regulated TNFR2 in EoL-1 cell line. This cell line is a useful model to provide new insights into crosstalk among Fas/FasL-, TNF-, and IFN-gamma-mediated signaling.


Asunto(s)
Antígenos CD/fisiología , Apoptosis/efectos de los fármacos , Interferón gamma/farmacología , Receptores del Factor de Necrosis Tumoral/fisiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Anticuerpos Monoclonales/farmacología , Antígenos CD/biosíntesis , Antígenos CD/efectos de los fármacos , Antígenos CD/genética , Antígenos CD/inmunología , Apoptosis/fisiología , Diferenciación Celular/efectos de los fármacos , Humanos , Leucemia Mieloide Aguda/patología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/fisiología , Receptores del Factor de Necrosis Tumoral/biosíntesis , Receptores del Factor de Necrosis Tumoral/efectos de los fármacos , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/inmunología , Receptores Tipo I de Factores de Necrosis Tumoral , Receptores Tipo II del Factor de Necrosis Tumoral , Proteínas Recombinantes , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia Arriba , Receptor fas/inmunología , Receptor fas/fisiología
10.
J Physiol ; 511 ( Pt 3): 915-33, 1998 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-9714870

RESUMEN

1. To examine the contributions of the putative Ca2+ releasers, inositol 1,4,5-trisphosphate (InsP3), cyclic ADP ribose (cADPR), and nicotinate adenine dinucleotide phosphate (NAADP), to carbachol (CCh)-induced contraction in airway smooth muscle, we measured force development of permeabilized rabbit tracheal smooth muscle, human bronchial smooth muscle and guinea-pig ileum longitudinal smooth muscle. 2. In the presence of 50 microM GTP, CCh and InsP3 contracted alpha-toxin-permeabilized tracheal smooth muscle dose dependently; the EC50 values for CCh and InsP3 were 1.84 microM and 363 microM, and the maximum responses (normalized to the 30 mM caffeine response) to 100 microM CCh and to 800 microM InsP3 were 206 +/- 13.4 % (mean +/- S.E.M.) and 84.4 +/- 5.3 %, respectively. 3. However, cADPR (10-300 microM), beta-NAD+ (2.5 mM), FK506 (30 microM) and NAADP (100 microM) neither contracted the strip by themselves nor affected the subsequent CCh (1 microM) response. alpha-Toxin-permeabilized bronchial smooth muscle and ileum smooth muscle also responded to caffeine, InsP3 and CCh but not to cADPR. 4. Both 100 microM 8-amino-cADPR, a selective cADPR antagonist, and 100 microM thionicotinamide-NADP, a selective NAADP antagonist, failed to inhibit the CCh response, although procaine abolished the caffeine, InsP3 and CCh responses in the permeabilized tracheal smooth muscle. 5. Although inhibition of the caffeine response by 30 microM ryanodine was nearly complete, approximately 30 % of the InsP3 (300 microM) plus GTP (50 microM) response was retained, and the resultant response disappeared after the caffeine response was evoked in the presence of ryanodine. 6. Heparin (300 microg ml-1) blocked InsP3 (300 microM) and CCh (3 microM) responses in beta-escin-permeabilized tracheal smooth muscle, while Ruthenium Red (100 microM) partially inhibited the CCh response. 7. Collectively, InsP3 but not cADPR or NAADP plays a key role in CCh-initiated contraction, and InsP3 utilizes a single compartment of the caffeine/ryanodine-sensitive stored Ca2+ in airway smooth muscle.


Asunto(s)
Calcio/metabolismo , Inositol 1,4,5-Trifosfato/farmacología , Contracción Muscular/fisiología , Músculo Liso/fisiología , Tráquea/fisiología , Adenosina Difosfato Ribosa/farmacología , Administración Tópica , Anestésicos Locales/farmacología , Animales , Antiinflamatorios/farmacología , Anticoagulantes/farmacología , Bronquios/fisiología , Cafeína/farmacología , Carbacol/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Dimetilsulfóxido/farmacología , Guanosina Trifosfato/farmacología , Cobayas , Heparina/farmacología , Humanos , Íleon/fisiología , Inmunosupresores/farmacología , Contracción Muscular/efectos de los fármacos , NADP/análogos & derivados , NADP/farmacología , Parasimpaticomiméticos/farmacología , Procaína/farmacología , Conejos , Rianodina/farmacología , Especificidad de la Especie , Tacrolimus/farmacología , Fosfolipasas de Tipo C/farmacología
11.
Intern Med ; 37(12): 1064-7, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9932643

RESUMEN

A 29-year-old man developed atopic bronchial asthma in association with eosinophilia and hyperimmunoglobulinemia E (hyper-IgE). A biopsy specimen from an inguinal lymph node showed changes consistent with Kimura's disease. IPD-1151T (suplatast tosilate), an anti-allergy drug, attenuated eosinophilia and hyper-IgE as well as the serum level of eosinophil cationic protein (ECP). The drug, however, did not affect the positivity for specific IgE antibodies against common allergens or the bronchial hyperresponsiveness to acetylcholine. Interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha were measured to be undetectable in serum before or during therapy. However, the expressions of mRNAs for IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha in peripheral blood T-lymphocytes and the expression of IL-5 mRNA in peripheral blood eosinophils were detected before and during therapy, which were unchanged by therapy with IPD-1151T. The present results suggest that different mechanisms other than the predominance of type 2 helper (T(H2))-like T-lymphocytes may underlie Kimura's disease and atopic bronchial asthma regarding the findings of eosinophilia and hyper-IgE, which could be modulated by IPD-1151T.


Asunto(s)
Hiperplasia Angiolinfoide con Eosinofilia/complicaciones , Antialérgicos/uso terapéutico , Arilsulfonatos/uso terapéutico , Asma/complicaciones , Eosinofilia/etiología , Síndrome de Job/etiología , Ribonucleasas , Compuestos de Sulfonio/uso terapéutico , Adulto , Hiperplasia Angiolinfoide con Eosinofilia/patología , Anticuerpos Antiidiotipos/análisis , Asma/tratamiento farmacológico , Asma/patología , Biopsia , Proteínas Sanguíneas/metabolismo , Citocinas/genética , Ensayo de Inmunoadsorción Enzimática , Proteínas en los Gránulos del Eosinófilo , Eosinofilia/tratamiento farmacológico , Eosinofilia/patología , Eosinófilos/metabolismo , Eosinófilos/patología , Estudios de Seguimiento , Humanos , Inmunoglobulina E/inmunología , Síndrome de Job/tratamiento farmacológico , Síndrome de Job/patología , Masculino , Reacción en Cadena de la Polimerasa , ARN Mensajero/biosíntesis , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/patología
12.
Cell Calcium ; 22(1): 21-30, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9232349

RESUMEN

To determine the mechanisms of receptor-dependent Ca2+ sensitization in airway smooth muscle, canine tracheal smooth muscle (CTSM) was permeabilized with alpha-toxin or beta-escin. Although the effects of 5-hydroxytryptamine (100 microM), histamine (100 microM), and the thromboxane A2 analogue U-46619 (100 microM) were negligible, carbachol (100 microM) and endothelin-1 (ET-1, 1 microM) evoked additional contractions of 47.0 +/- 5.90% and 25.0 +/- 5.37% (n = 6) at pCa 6.7 with GTP (3 microM) (normalized to the maximum contraction at pCa 4.5) in alpha-toxin-permeabilized CTSM. GDP-beta-S (1 mM) reversed the carbachol and ET-1 responses completely. GTP-gamma-S (30 microM) and 4 beta-phorbol 12,13-dibutyrate (PDBu, 3 microM) increased the Ca2+ sensitivity (median effective pCa) of contraction by 1.8- and 4.4-fold, respectively (n = 4-11, P < 0.05). The effects of saturating concentrations of GTP-gamma-S and PDBu were additive. A synthetic peptide (T2) corresponding to the actin-binding site of calponin caused a dose-dependent contraction of beta-escin permeabilized CTSM, with the peak effect (25 +/- 4%, n = 4) at 1200 microM, PDBu (3 microM) caused contraction of the T2 peptide-treated CTSM. In conclusion, Ca2+ sensitization of CTSM depends on receptor type and is mediated by G proteins and protein kinase C whose effects are additive, with a partial contribution by calponin.


Asunto(s)
Calcio/metabolismo , Proteínas de Unión al GTP/metabolismo , Músculo Liso/metabolismo , Receptores Muscarínicos/metabolismo , Tráquea/metabolismo , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico , Aluminio/farmacología , Animales , Toxinas Bacterianas/farmacología , Proteínas de Unión al Calcio/metabolismo , Carbacol/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Perros , Endotelina-1/farmacología , Escina/farmacología , Femenino , Flúor/farmacología , Guanosina 5'-O-(3-Tiotrifosfato)/farmacología , Proteínas Hemolisinas/farmacología , Histamina/farmacología , Contracción Isométrica , Masculino , Proteínas de Microfilamentos , Músculo Liso/efectos de los fármacos , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/farmacología , Forbol 12,13-Dibutirato/farmacología , Endoperóxidos de Prostaglandinas Sintéticos/farmacología , Proteína Quinasa C/efectos de los fármacos , Proteína Quinasa C/metabolismo , Receptores Muscarínicos/efectos de los fármacos , Serotonina/farmacología , Tromboxano A2/análogos & derivados , Tromboxano A2/farmacología , Tráquea/anatomía & histología , Calponinas
14.
Intern Med ; 35(3): 231-5, 1996 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8785461

RESUMEN

Bronchiolitis obliterans organizing pneumonia (BOOP) occurred in a 53-year-old woman with well-documented Sjögren's syndrome (SjS) and polymyositis (PM). BOOP has often been reported as a pulmonary manifestation of collagen vascular diseases, mainly rheumatoid arthritis (RA), but the association of BOOP and PM has rarely been documented. A search of the literature showed only 16 case reports of BOOP associated with polymyositis-dermatomyositis (PM-DM). It is interesting that BOOP occurred prior to PM-DM, while it is commonly believed to occur after RA.


Asunto(s)
Neumonía en Organización Criptogénica/complicaciones , Polimiositis/complicaciones , Síndrome de Sjögren/complicaciones , Biopsia , Neumonía en Organización Criptogénica/diagnóstico , Neumonía en Organización Criptogénica/tratamiento farmacológico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Persona de Mediana Edad , Músculo Esquelético/patología , Polimiositis/diagnóstico , Polimiositis/tratamiento farmacológico , Prednisolona/uso terapéutico , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Tomografía Computarizada por Rayos X
15.
Prostate ; 27(6): 304-13, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7501542

RESUMEN

To understand the role of estrogen in the pathogenesis of benign prostatic hyperplasia, expressions of estrogen receptor (ER) mRNA and ER protein by in situ hybridization and by immunohistochemistry, respectively, were investigated in human prostatic tissues. In non-malignant region, ER mRNA and ER protein were found in cytoplasm and nucleus, respectively, of stromal cells, but not in glandular epithelial and basal cells. In benign regions, ER mRNA/ER protein positive cells were found in fibromyoadenomatous and myoadenomatous hyperplasia, but not in adenomatous hyperplasia. A striking feature was periacinar arrangement of ER mRNA/ER protein positive stromal cells in all prostate carcinoma treated with androgen withdrawal. The ER mRNA/ER protein positive cells were immunohistochemically identified as fibroblasts, myoblasts, and smooth muscle cells. These results indicate that stromal cells are the primary target of estrogen in prostate, and that androgen withdrawal upregulates the expression of ER gene.


Asunto(s)
Próstata/química , Próstata/patología , Enfermedades de la Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Receptores de Estrógenos/análisis , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Desmina/análisis , Desmina/metabolismo , Humanos , Inmunohistoquímica , Hibridación in Situ , Queratinas/análisis , Queratinas/metabolismo , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Próstata/ultraestructura , Enfermedades de la Próstata/patología , Hiperplasia Prostática/patología , Neoplasias de la Próstata/química , Neoplasias de la Próstata/patología , ARN Mensajero/análisis , ARN Mensajero/química , ARN Mensajero/genética , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Vimentina/análisis , Vimentina/metabolismo
16.
J Histochem Cytochem ; 43(3): 321-7, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7532657

RESUMEN

Assessments of RNA integrity and its hybridizability are essential for successful implementation of in situ hybridization (ISH) for mRNA or viral RNA, particularly when paraffin-embedded specimens from surgical, biopsy, and autopsy cases are used. In this study, we examined the suitability of ISH of 28S ribosomal RNA (rRNA) for this purpose. Oligo-DNA with nucleotide sequences complementary to a well-conserved segment of 28S rRNA with auxiliary adenine-thymine-thymine (ATT) repeats at the 3' and 5' ends was synthesized. The oligo-DNA was made antigenic by converting the adjacent thymines to T-T dimers by UV irradiation and was used as a probe for ISH of 28S rRNA. The T-T dimers were detected by enzyme immunohistochemistry. When the results of ISH rRNA staining and that of total RNA staining by methyl green/pyronin Y were compared for various types of sections prepared from rat and human tissues, the staining intensities of total RNA did not always match those of ISH rRNA staining. In paraffin sections of formalin-fixed tissues, the degree of proteinase digestion influenced the ISH rRNA staining intensity, whereas it had no effect on the total RNA staining intensity. The intensities of ISH rRNA staining agreed well with those of various types of mRNA staining by ISH in 10 cases of paraffin-embedded pathological specimens. We therefore believe that ISH rRNA staining is a convenient parameter for evaluation of levels of hybridizable RNAs in tissue sections.


Asunto(s)
Colon/patología , Hibridación in Situ/métodos , ARN Mensajero/análisis , ARN Ribosómico 28S/análisis , ARN Viral/análisis , Útero/citología , Animales , Anticuerpos Monoclonales , Autopsia , Secuencia de Bases , Biopsia , Northern Blotting , Colon/citología , Colon/cirugía , Sondas de ADN , Endopeptidasas , Femenino , Técnicas Histológicas , Humanos , Hígado/química , Ratones , Sondas de Oligonucleótidos , ARN/análisis , Ratas , Ratas Wistar , Estándares de Referencia , Secuencias Repetitivas de Ácidos Nucleicos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
17.
Arch Dermatol Res ; 287(3-4): 266-72, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7598531

RESUMEN

We carried out biochemical and immunohistochemical analyses of cathepsins B, H, L and D in human melanocytic tumours using monospecific antibodies against rat cathepsins. In Western blot analysis, anti-rat cathepsin antibodies reacted with the cathepsins from normal human tissues and human malignant melanoma. However, the molecular profiles of the cathepsins from human melanoma were slightly different from those of the rat cathepsins, suggesting a distinct intracellular processing mechanism for cathepsins in human melanoma. Although cathepsins B, H, L and D were expressed in primary and metastatic melanomas and pigmented naevi immunohistochemically, the intensity of staining in metastatic melanomas was stronger than in primary melanomas and pigmented naevi. These findings suggest that anti-rat cathepsin antibodies may be useful in biochemical and/or immunohistochemical analysis of human melanocytic tumours.


Asunto(s)
Catepsinas/metabolismo , Cisteína Endopeptidasas , Endopeptidasas , Melanoma/enzimología , Neoplasias Cutáneas/enzimología , Animales , Catepsina B/metabolismo , Catepsina D/metabolismo , Catepsina H , Catepsina L , Catepsinas/inmunología , Humanos , Inmunohistoquímica , Melanoma/patología , Melanoma/secundario , Nevo Azul/enzimología , Nevo Azul/patología , Nevo Pigmentado/enzimología , Nevo Pigmentado/patología , Procesamiento Proteico-Postraduccional , Ratas , Neoplasias Cutáneas/patología
18.
Arch Dermatol Res ; 287(2): 209-13, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7763093

RESUMEN

We studied the relationship between cathepsin B (CB)-like enzyme activities and cysteine proteinase inhibitor (CPI) activities in lesions of human pigmented naevi (PN), primary melanomas (PM) and metastases/metastatic melanomas (MM). The CB-like enzyme activities in PM and MM were 2.5 and 6.8 times higher than in PN, respectively. The CB-like/CPI ratios in PM and MM were 1.9 and 11.6 times higher than in PN, respectively. CPI had the highest activity in PM and the lowest activity in MM. The disease-free interval of patients with a high CB-like enzyme activity (> or = 80 U/mg protein) and/or a high CB-like/CPI ratio (> or = 7) was shorter than that of patients with a low CB-like enzyme activity (< 80 U/mg protein) and/or a low CB-like/CPI ratio (< 7). Analysis of CB-like enzyme activity and/or the CB-like/CPI ratio may be useful in predicting the prognosis of human malignant melanoma.


Asunto(s)
Catepsina B/análisis , Inhibidores de Cisteína Proteinasa/análisis , Melanoma/patología , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Melanoma/clasificación , Melanoma/enzimología , Melanoma/cirugía , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Nevo Pigmentado/enzimología , Nevo Pigmentado/cirugía , Valor Predictivo de las Pruebas , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/cirugía
19.
Cancer Res ; 53(20): 4927-32, 1993 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-8104688

RESUMEN

Immunohistochemical staining with monoclonal antibodies detected ICAM-1 in about 69% of 55 primary melanoma lesions and in about 89% of 28 metastatic lesions. The average number of melanoma cells stained by anti-ICAM-1 monoclonal antibodies was approximately 65% in both primary and metastatic lesions. ICAM-1 expression in primary lesions was significantly associated with their thickness. Furthermore, ICAM-1 expression in primary lesions was associated with a reduction in the disease-free interval and with survival. At variance with the information in the literature, the association with clinical parameters of the disease did not reach the level of statistical significance. This discrepancy is likely to reflect the inclusion in the present study of a small number of primary lesions with a thickness < 1.5 mm. At variance with recently published data, the level of serum ICAM-1 in 75 patients with malignant melanoma was found to be nonsignificantly different from that in 47 age- and sex-matched controls. The level of serum ICAM-1 was significantly increased only in patients with stage III melanoma with lesions and in those with stage IV melanoma. Two novel and clinically relevant findings of the present investigation are (a) the significantly higher serum ICAM-1 level in patients with liver metastases than in those with metastases in other anatomic sites and (b) the progressive increase of ICAM-1 level in serial blood samples from patients with disease progression. The latter findings suggest that monitoring of serum ICAM-1 level may represent a valuable noninvasive indicator system to detect liver metastases and to monitor the clinical course of the disease in patients with malignant melanoma.


Asunto(s)
Moléculas de Adhesión Celular/análisis , Melanoma/sangre , Melanoma/patología , Anticuerpos Monoclonales , Antígenos CD/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Moléculas de Adhesión Celular/biosíntesis , Moléculas de Adhesión Celular/sangre , Dacarbazina/administración & dosificación , Humanos , Técnicas para Inmunoenzimas , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular , Interferón beta/uso terapéutico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Metástasis Linfática , Melanoma/terapia , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/secundario , Vincristina/administración & dosificación
20.
Cancer Res ; 53(14): 3349-54, 1993 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-7686817

RESUMEN

Immunoperoxidase staining of frozen sections from surgically removed melanoma lesions showed that anti-human leukocyte antigen (HLA)-A2, A28 monoclonal antibody (mAb) stained keratinocytes, but did not stain melanoma cells in 21% of the 14 primary and 44% of the 9 metastatic lesions tested. The loss of HLA-A2 and/or A28 allospecificities did not affect the staining patterns with mAb recognizing monomorphic determinants of HLA Class I antigens, in terms of percentage of stained melanoma cells and intensity of staining. This finding is not likely to reflect the sensitivity of the immunoperoxidase technique, since cytofluorographic analysis detected no significant difference in the staining pattern by mAb to monomorphic determinants of HLA Class I antigens between a melanoma cell line and an autologous transfectant that had acquired HLA-A2 antigens following gene transfer. The results of the present study imply that the frequency of abnormalities in HLA Class I antigen expression by melanoma cells is higher than that described in the literature, since selective losses of HLA Class I allospecificities are not detected by staining of melanoma cells with mAb to monomorphic determinants of HLA Class I antigens. The latter reagents have been used in most of the published studies to characterize the expression of HLA Class I antigens in melanoma lesions. Furthermore, the present results provide a mechanism for the unexpected resistance to cytotoxic T-cell-mediated lysis and the unexpected poor clinical course of the disease in some patients despite a high expression of HLA Class I antigens as measured by staining of melanoma cells with mAb to monomorphic determinants.


Asunto(s)
Anticuerpos Monoclonales , Antígenos de Neoplasias/análisis , Epítopos/análisis , Antígeno HLA-A2/análisis , Antígenos de Histocompatibilidad Clase I/análisis , Melanoma/inmunología , Antígenos de Neoplasias/inmunología , Epítopos/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Queratinocitos/inmunología
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