RESUMEN
We report an apparently atraumatic asymptomatic flap dislocation 4 months after uneventful laser in situ keratomileusis (LASIK) in the right eye of a 43-year-old woman. The patient developed partial dislocation of the LASIK flap during the week after the 4 month examination. The LASIK flap was subsequently lifted to perform an enhancement, and the postenhancement course has been unremarkable. This case illustrates the potential susceptibility of LASIK flaps to dislocation either spontaneously or, more likely, after presumed minor trauma as late as 4 months after the original procedure.
Asunto(s)
Sustancia Propia/patología , Queratomileusis por Láser In Situ/efectos adversos , Colgajos Quirúrgicos , Dehiscencia de la Herida Operatoria/etiología , Adulto , Sustancia Propia/cirugía , Topografía de la Córnea , Femenino , Humanos , Luxaciones Articulares , Miopía/cirugía , Reoperación , Dehiscencia de la Herida Operatoria/cirugía , Agudeza VisualRESUMEN
gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcstraightepsilonRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.
Asunto(s)
Anafilaxia/etiología , Glicoproteínas de Membrana/deficiencia , Receptores Inmunológicos , Anafilaxia/inmunología , Anafilaxia/patología , Animales , Antígenos de Superficie/genética , Antígenos de Superficie/inmunología , Edema/etiología , Edema/inmunología , Edema/patología , Femenino , Masculino , Mastocitos/inmunología , Mastocitos/patología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ovalbúmina/inmunología , Anafilaxis Cutánea Pasiva/genética , Anafilaxis Cutánea Pasiva/inmunologíaRESUMEN
We have identified the integrin alpha(v)beta3 as a ligand for mouse gp49B1, thus identifying a new class of ligand for a member of the family of inhibitory immunoreceptors that bear C2-type immunoglobulin-like domains. The specific interaction was shown by both cell-protein and cell-cell binding assays. In addition, we found that the interaction of alpha(v)beta3 with gp49B1 on bone marrow-derived mouse mast cells inhibited antigen-induced immunoglobulin E-mediated cell activation. Because neither gp49B1 nor alpha(v)beta3 exhibit substantive allelic variation, their newly appreciated interaction may reflect an innate pathway for down-regulating the activity of mast cells.
Asunto(s)
Antígenos de Superficie/metabolismo , Integrinas/metabolismo , Mastocitos/inmunología , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/metabolismo , Receptores de Vitronectina/metabolismo , Animales , Antígenos de Superficie/genética , Unión Competitiva , Células de la Médula Ósea/inmunología , Inmunoglobulina E/inmunología , Integrinas/genética , Ligandos , Glicoproteínas de Membrana/genética , Ratones , Unión Proteica , Receptores Inmunológicos/genética , Proteínas Recombinantes/metabolismo , Vitronectina/metabolismoRESUMEN
PURPOSE: To evaluate quantitatively over time the reduction in bacterial flora on the human conjunctiva after treatment with topical ciprofloxacin 0.3% (Ciloxan) or topical ofloxacin 0.3% (Ocuflox). SETTING: Sinai Hospital of Baltimore, Baltimore, Maryland, USA. METHODS: Three study arms each consisted of 20 culture-positive eyes from patients 55 years or older. Pretreatment cultures were performed in all eyes. Eyes in the ciprofloxacin and ofloxacin arms received 1 antibiotic drop every 5 minutes for 3 doses. The conjunctiva of each treatment eye was recultured 15, 30, 60, and 120 minutes after application of the final antibiotic drop. Eyes in the control arm were recultured at corresponding time points. After 48 hours of incubation, colony counts were performed. Data were transformed into log units, and statistical analysis was performed. When compared to no treatment, instillation of ofloxacin 0.3% did not produce a significant reduction in bacterial colony forming units (CFUs) at 15, 30, or 60 minutes (P =.17). A marginally significant reduction was achieved 120 minutes after administration (P =.051). RESULTS: When compared to no treatment, instillation of ciprofloxacin 0.3% produced a significant reduction in bacterial CFUs at 15 minutes; this effect persisted for at least 2 hours (P <.0001). The reduction in bacterial CFUs by ciprofloxacin was significantly greater than that by ofloxacin at all measurements (P <.0001). CONCLUSIONS: Ciprofloxacin 0.3% markedly reduced bacterial flora on the ocular surface within 15 minutes of instillation, and the effect lasted for at least 2 hours.
Asunto(s)
Antiinfecciosos/uso terapéutico , Ciprofloxacina/uso terapéutico , Conjuntiva/efectos de los fármacos , Conjuntivitis Bacteriana/tratamiento farmacológico , Ofloxacino/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus/crecimiento & desarrollo , Alcaligenes/efectos de los fármacos , Alcaligenes/crecimiento & desarrollo , Alcaligenes/aislamiento & purificación , Antiinfecciosos/administración & dosificación , Ciprofloxacina/administración & dosificación , Recuento de Colonia Microbiana , Conjuntiva/microbiología , Conjuntivitis Bacteriana/microbiología , Humanos , Persona de Mediana Edad , Ofloxacino/administración & dosificación , Soluciones Oftálmicas , Estudios Prospectivos , Infecciones Estafilocócicas/microbiología , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/aislamiento & purificación , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/crecimiento & desarrollo , Staphylococcus epidermidis/aislamiento & purificaciónRESUMEN
The class I(A) phosphoinositide 3-kinases (PI3Ks) consist of a 110-kDa catalytic domain and a regulatory subunit encoded by the p85alpha, p85beta, or p55gamma genes. We have determined the effects of disrupting the p85alpha gene on the responses of mast cells stimulated by the cross-linking of Kit and FcepsilonRI, receptors that reflect innate and adaptive responses, respectively. The absence of p85alpha gene products partially inhibited Kit ligand/stem cell factor-induced secretory granule exocytosis, proliferation, and phosphorylation of the serine/threonine kinase Akt. In contrast, p85alpha gene products were not required for FcepsilonRI-initiated exocytosis and phosphorylation of Akt. LY294002, which inhibits all classes of PI3Ks, strongly suppressed Kit- and FcepsilonRI-induced responses in p85alpha -/- mast cells, revealing the contribution of another PI3K family member(s). In contrast to B lymphocytes, mast cell proliferation was not dependent on Bruton's tyrosine kinase, a downstream effector of PI3K, revealing a distinct pathway of PI3K-dependent proliferation in mast cells. Our findings represent the first example of receptor-specific usage of different PI3K family members in a single cell type. In addition, because Kit- but not FcepsilonRI-initiated signaling is associated with mast cell proliferation, the results provide evidence that distinct biologic functions signaled by these two receptors may reflect differential usage of PI3Ks.
Asunto(s)
Mastocitos/enzimología , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptores de IgE/metabolismo , Animales , Apoptosis , Ciclo Celular , División Celular , Exocitosis , Citometría de Flujo , Interleucina-3/metabolismo , Hígado/embriología , Hígado/enzimología , Mastocitos/patología , Ratones , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Factores de Tiempo , Distribución TisularRESUMEN
PURPOSE: The purpose of this study was to measure improvement in best corrected visual acuity with rigid gas permeable (RGP) contact lenses compared to best corrected spectacle visual acuity for patients with irregular astigmatism. METHODS: We compared best corrected visual acuity obtained with spectacle correction to best corrected visual acuity obtained with rigid gas permeable contact lenses for forty-eight eyes of 29 patients with irregular astigmatism. RESULTS: Patients with 20/20 spectacle visual acuity achieved, on average, no improvement in visual acuity with RGP contact lenses. Patients with 20/25-20/30 spectacle visual acuity achieved a one line average improvement. Patients with 20/40 spectacle visual acuity achieved a two line average improvement. Patients with 20/50-20/200 spectacle visual acuity achieved a four line average improvement and patients with spectacle visual acuity of 20/400, a six line average improvement. CONCLUSIONS: RGP contact lenses can provide a significant improvement in visual acuity compared to spectacle correction for patients with irregular astigmatism.
Asunto(s)
Astigmatismo/terapia , Lentes de Contacto , Astigmatismo/etiología , Córnea/metabolismo , Enfermedades de la Córnea/complicaciones , Humanos , Oxígeno/metabolismo , Permeabilidad , Resultado del Tratamiento , Agudeza VisualAsunto(s)
Antiinfecciosos/uso terapéutico , Ciprofloxacina/uso terapéutico , Úlcera de la Córnea/microbiología , Corynebacterium/efectos de los fármacos , Infecciones Bacterianas del Ojo/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Antiinfecciosos/farmacología , Ciprofloxacina/farmacología , Úlcera de la Córnea/tratamiento farmacológico , Corynebacterium/aislamiento & purificación , Farmacorresistencia Microbiana , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/aislamiento & purificaciónRESUMEN
SLP-76 is an adapter protein expressed in T cells and myeloid cells that is a substrate for ZAP-70 and Syk. SLP-76-deficient mice exhibit a profound block in T-cell development. We found that although SLP-76 is expressed in mouse mast cells, SLP-76(-/-) mice have normal numbers of mast cells in their skin and bronchi. SLP-76(-/-) mice are resistant to IgE-mediated passive anaphylaxis. SLP-76(-/-) mice sensitized with IgE anti-dinitrophenyl (DNP) and then challenged with DNP-HSA developed only mild and transient tachycardia, failed to increase their plasma histamine level, and all survived the antigen challenge. Bone marrow-derived mast cells (BMMCs) from SLP76(-/-) mice failed to release beta-hexosaminidase and to secrete IL-6 after FcepsilonRI cross-linking. Tyrosine phosphorylation of phospholipase C-gamma1 (but not of Syk) and calcium mobilization in response to IgE cross-linking were reduced in SLP-76-deficient BMMCs. These results suggest that SLP-76 plays an important role in FcepsilonRI-mediated signaling in mast cells.
Asunto(s)
Mastocitos/metabolismo , Fosfoproteínas/deficiencia , Fosfoproteínas/genética , Receptores de IgE/fisiología , Transducción de Señal/genética , Proteínas Adaptadoras Transductoras de Señales , Traslado Adoptivo , Animales , Sitios de Unión/genética , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/fisiología , Degranulación de la Célula/genética , Diferenciación Celular/genética , Células Cultivadas , Citocinas/metabolismo , Inmunoglobulina E/administración & dosificación , Inmunoglobulina E/fisiología , Mastocitos/fisiología , Ratones , Ratones Endogámicos , Ratones Noqueados , Anafilaxis Cutánea Pasiva , Fosfoproteínas/biosíntesis , Receptores de IgE/genética , Receptores de IgE/inmunologíaRESUMEN
We describe a technique for implanting ciliary sulcus posterior chamber intraocular lenses (PCIOLs). This technique uses radial keratotomy (RK) markers to facilitate PCIOL centration, 2-point scleral suture fixation for each haptic to prevent PCIOL tilt, and partial thickness sclerotomies to prevent suture erosion. Postoperative results of 20 eyes with PCIOLs sutured to the ciliary sulcus were reviewed. Suture placement was determined using a Mendez degree gauge with Bores axis marker (Katena USA, Denville, NJ). Two-point scleral suture fixation without a scleral flap was used for each haptic. Average follow-up was 17.1 months. Postoperative best corrected visual acuity was 20/40 or better in 95% of eyes. Average best-corrected post-operative visual acuity was 20/29. One patient with a previous retinal disease lost 3 lines of visual acuity. This technique results in excellent postoperative visual acuity without PCIOL decentration, tilt, or suture erosion.
Asunto(s)
Implantación de Lentes Intraoculares/métodos , Esclerótica/cirugía , Técnicas de Sutura , Afaquia Poscatarata/cirugía , Estudios de Seguimiento , Humanos , Resultado del Tratamiento , Agudeza VisualRESUMEN
Cross-linking of FcepsilonRI on mast cells elicits positive signal transduction cascades that lead to the release of a variety of proinflammatory mediators. Mouse mast cells also express gp49B1 on their surface, an immunoglobulin superfamily member that bears two immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic domain and inhibits FcepsilonRI-induced release of secretory granule mediators and the cysteinyl leukotriene, LTC4. gp49B1 belongs to a growing family of inhibitory receptors expressed in mouse and man. Thus, FcepsilonRI-induced mast cell activation is counterregulated by several receptors belonging to the same superfamily as FcepsilonRI itself.
Asunto(s)
Antígenos de Superficie/inmunología , Inmunoglobulinas/inmunología , Mastocitos/inmunología , Glicoproteínas de Membrana/inmunología , Receptores de IgE/inmunología , Animales , Genes de Inmunoglobulinas , Humanos , Inmunoglobulinas/genética , Ratones , Receptores Inmunológicos/genética , Receptores Inmunológicos/inmunologíaRESUMEN
We define by molecular, pharmacologic, and physiologic approaches the proximal mechanism by which the immunoglobulin superfamily member gp49B1 inhibits mast cell activation mediated by the high affinity Fc receptor for IgE (FcepsilonRI). In rat basophilic leukemia-2H3 cells expressing transfected mouse gp49B1, mutation of tyrosine to phenylalanine in either of the two immunoreceptor tyrosine-based inhibitory motifs of the gp49B1 cytoplasmic domain partially suppressed gp49B1-mediated inhibition of exocytosis, whereas mutation of both abolished inhibitory capacity. Sodium pervanadate elicited tyrosine phosphorylation of native gp49B1 and association of the tyrosine phosphatases src homology 2 domain-containing phosphatase-1 (SHP-1) and SHP-2 in mouse bone marrow-derived mast cells (mBMMCs). SHP-1 associated transiently with gp49B1 within 1 min after coligation of gp49B1 with cross-linked FcepsilonRI in mBMMCs. SHP-1-deficient mBMMCs exhibited a partial loss of gp49B1-mediated inhibition of FcepsilonRI-induced exocytosis at concentrations of IgE providing optimal exocytosis, revealing a central, but not exclusive, SHP-1 requirement in the counter-regulatory pathway. Coligation of gp49B1 with cross-linked FcepsilonRI on mBMMCs inhibited early release of calcium from intracellular stores and subsequent influx of extracellular calcium, consistent with SHP-1 participation. Because exocytosis is complete within 2 min in mBMMCs, our studies establish a role for SHP-1 in the initial counter-regulatory cellular responses whereby gp49B1 immunoreceptor tyrosine-based inhibition motifs rapidly transmit inhibition of FcepsilonRI-mediated exocytosis.
Asunto(s)
Antígenos de Superficie/fisiología , Calcio/metabolismo , Inmunoglobulina E/fisiología , Mastocitos/inmunología , Glicoproteínas de Membrana/fisiología , Proteínas Tirosina Fosfatasas/metabolismo , Receptores de IgE/antagonistas & inhibidores , Receptores Inmunológicos , Tirosina/antagonistas & inhibidores , Secuencia de Aminoácidos , Animales , Antígenos de Superficie/genética , Sitios de Unión , Células de la Médula Ósea/inmunología , Células Cultivadas , Exocitosis , Péptidos y Proteínas de Señalización Intracelular , Glicoproteínas de Membrana/genética , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Proteína Fosfatasa 1 , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Proteína Tirosina Fosfatasa no Receptora Tipo 6 , Proteínas Tirosina Fosfatasas/química , Receptores de IgE/química , Proteínas Tirosina Fosfatasas con Dominio SH2 , Homología de Secuencia de Aminoácido , Dominios Homologos srcRESUMEN
Members of the gp49-related family of mouse and human immunoglobulin (Ig) superfamily receptors have significant amino acid sequence homology in their C2-type, Ig-like domains and include the killer cell Ig-like receptors (KIRs) for major histocompatibility complex class I molecules. We now report the cloning, complete sequence, and organization of the mouse gp49A gene that encodes the only member of this newly-appreciated family without either of two mutually exclusive functional motifs, namely, immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or a charged transmembrane amino acid for heterodimerization with activation molecules. The gp49A and gp49B genes are 94% identical over 5.6 kilobases, the 5' flanking regions are 94% identical over 1900 nucleotides, and the 3' flanking regions are 97% identical for 121 nucleotides and then diverge completely; the gp49B gene encodes gp49B1 bearing two ITIMs. As measured by flow cytometry with specific antibody, gp49A is expressed on immature bone-marrow-derived mast cells, mature serosal mast cells, and several mouse mast cell lines. The substantial sequence identity of the introns of the gp49A and gp49B genes is comparable to that of the exons, establishing the gene pair as the most homologous of the gp49-related family and suggesting that the gp49A and gp49B genes arose by duplication with relatively little subsequent mutation. The findings also represent the first demonstration that gp49A is expressed on mast cells in tandem with inhibitory gp49B1, and establish that the gp49A gene is not a pseudogene, but rather encodes a protein product with characteristics different from the other family members.
Asunto(s)
Antígenos de Superficie/biosíntesis , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/genética , Secuencia de Aminoácidos , Animales , Antígenos de Superficie/inmunología , Antígenos de Superficie/metabolismo , Secuencia de Bases , Médula Ósea/metabolismo , Línea Celular , Células Cultivadas , Secuencia Conservada , ADN Complementario/metabolismo , Exones , Citometría de Flujo , Humanos , Inmunoglobulinas/genética , Intrones , Masculino , Mastocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Modelos Genéticos , TransfecciónRESUMEN
PURPOSE: To compare the traditional method of culturing bacterial keratitis (platinum spatula) with the use of a commercially available Mini-tip Culturette (Becton-Dickinson, Cockeysville, MD, U.S.A.). METHODS: An experimental model of bacterial keratitis was created in rabbit corneas by intrastromal injection of bacteria. Cultures were taken of rabbit corneas with both the Mini-tip Culturette and the platinum spatula. Culture results were compared with corneal colony counts. Humans with community-acquired presumed bacterial keratitis were cultured with both the Mini-tip Culturette and the platinum spatula. The sensitivity and specificity of the Mini-tip Culturette method was determined and compared with the platinum-spatula technique. RESULTS: Rabbit keratitis model: 100% of corneas had established infections by colony count. Each ulcer was culture positive with platinum spatula, moist Mini-tip Culturette, and dry Mini-tip Culturette. Human keratitis: Seven patients had culture-negative keratitis with both the Mini-tip Culturette and the platinum spatula. Five patients were culture positive with both the Mini-tip Culturette and the platinum spatula. One of the positive cultures had growth of multiple organisms by using the platinum spatula but not with the Mini-tip Culturette. The sensitivity of the Mini-tip Culturette was 83.3%. The specificity of the Mini-tip Culturette was 100%. Detected organisms included group A beta-hemolytic Streptococcus, S. aureus, coagulase-negative Staphylococcus, Serratia marcescens, and Pseudomonas aeruginosa. CONCLUSION: The Mini-tip Culturette is a highly specific and moderately sensitive method for culturing bacterial keratitis.
Asunto(s)
Bacterias/aislamiento & purificación , Técnicas Bacteriológicas/instrumentación , Córnea/microbiología , Úlcera de la Córnea/microbiología , Infecciones Bacterianas del Ojo/microbiología , Animales , Recuento de Colonia Microbiana , Úlcera de la Córnea/diagnóstico , Modelos Animales de Enfermedad , Infecciones Bacterianas del Ojo/diagnóstico , Humanos , Platino (Metal) , Conejos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To ascertain the importance of routine cultures and gram stains in the management of ulcerative keratitis. METHODS: We retrospectively reviewed 119 consecutive corneal ulcers seen at Sinai Hospital of Baltimore. Cultures were obtained of the corneal ulcer and of the lids and conjunctivae of both eyes. Gram stains were performed by the hospital microbiology department on corneal scrapings from each ulcer. RESULTS: Positive corneal cultures were obtained from 56 eyes (47.1%). Initial antibiotic therapy was changed based on culture results in 14.3% of culture-positive eyes that demonstrated a worsening clinical course. Gram stains were negative in all cases. The sensitivity and specificity of the lid and conjunctival cultures were determined. CONCLUSIONS: Corneal cultures are important in the management of ulcerative keratitis. Lid and conjunctival cultures have low sensitivity and specificity.
Asunto(s)
Córnea/microbiología , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/microbiología , Infecciones Bacterianas del Ojo/microbiología , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/microbiología , Antibacterianos/uso terapéutico , Conjuntiva/microbiología , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Párpados/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Mast cells are constitutively present at the portals between self and nonself, and contain a large and diverse complement of proinflammatory mediators. These characteristics suggest that the activation of mast cells must be carefully regulated in vivo. Regulation of pathologic and physiologic mast cell activation has been traditionally associated simply with the presence or absence of an activating signal. We examine here evidence supporting a new paradigm: mast cell homeostasis may result from inhibition of activation mediated by receptors on the surface of mast cells, typified by a member of the gp49 family.
Asunto(s)
Antígenos de Superficie/inmunología , Hipersensibilidad/inmunología , Inflamación/inmunología , Mastocitos/inmunología , Glicoproteínas de Membrana/inmunología , Receptores Inmunológicos/inmunología , Secuencia de Aminoácidos , Animales , Humanos , Datos de Secuencia MolecularRESUMEN
PURPOSE: The purpose of the study is to compare the clinical efficacy and safety of ciprofloxacin ophthalmic solution 0.3% (Ciloxan) with a standard therapy regimen (fortified tobramycin, 1.3%-cefazolin, 5.0%) for treating bacterial corneal ulcers. METHODS: This randomized, parallel group, double-masked, multicenter study was conducted in 324 patients at 28 centers in the United States, Europe, and India. Patients were randomized into 2 treatment groups: 160 to ciprofloxacin and 164 to fortified tobramycin-cefazolin. Positive microbiologic cultures were obtained in 188 (58%) of 324 patients. Of these, 176 patients met protocol criteria and were evaluated for treatment efficacy: 82 in the ciprofloxacin group and 94 in the standard therapy group. The dosing schedule for both treatment groups was 1 to 2 drops of the first study medication (ciprofloxacin or fortified tobramycin) every 30 minutes for 6 hours, then hourly for the remainder of day 1; 1 to 2 drops every hour on days 2 and 3; 1 to 2 drops every 2 hours on days 4 and 5, followed by 1 to 2 drops every 4 hours on days 6 to 14. The second medication (ciprofloxacin or cefazolin) was instilled 5 to 15 minutes after the first drug, following the same dosing frequency. Physician's judgment of clinical success, cure rate, changes in ocular sings, and symptoms and the rate of treatment failures were the primary efficacy criteria. RESULTS: Topical ciprofloxacin monotherapy is equivalent clinically and statistically to the standard therapy regimen of fortified antibiotics. No statistically significant treatment differences were found between ciprofloxacin (91.5%) and standard therapy (86.2%) in terms of overall clinical efficacy (P = 0.34). Similarly, no differences were noted in resolution of the clinical signs and symptoms (P > 0.08) or the time to cure (P = 0.55). The incidence of treatment failures was less in the ciprofloxacin group (8.5%) compared with the standard therapy group (13.8%). Significantly fewer patients treated with ciprofloxacin reported discomfort than did patients treated with the standard therapy regimen (P = 0.01). CONCLUSION: Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.
Asunto(s)
Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Cefazolina/uso terapéutico , Cefalosporinas/uso terapéutico , Ciprofloxacina/uso terapéutico , Úlcera de la Córnea/tratamiento farmacológico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Tobramicina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Antiinfecciosos/efectos adversos , Bacterias/aislamiento & purificación , Cefazolina/efectos adversos , Cefalosporinas/efectos adversos , Niño , Ciprofloxacina/efectos adversos , Córnea/microbiología , Úlcera de la Córnea/microbiología , Método Doble Ciego , Quimioterapia Combinada , Infecciones Bacterianas del Ojo/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas , Estudios Prospectivos , Tobramicina/efectos adversosRESUMEN
Mouse mast cells express gp49B1, a cell-surface member of the Ig superfamily encoded by the gp49B gene. We now report that by ALIGN comparison of the amino acid sequence of gp49B1 with numerous receptors of the Ig superfamily, a newly recognized family has been established that includes gp49B1, the human myeloid cell Fc receptor for IgA, the bovine myeloid cell Fc receptor for IgG2, and the human killer cell inhibitory receptors expressed on natural killer cells and T lymphocyte subsets. Furthermore, the cytoplasmic domain of gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs that are also present in killer cell inhibitory receptors; these motifs downregulate natural killer cell and T-cell activation signals that lead to cytotoxic activity. As assessed by flow cytometry with transfectants that express either gp49B1 or gp49A, which are 89% identical in the amino acid sequences of their extracellular domains, mAb B23.1 was shown to recognize only gp49B1. Coligation of mAb B23.1 bound to gp49B1 and IgE fixed to the high-affinity Fc receptor for IgE on the surface of mouse bone marrow-derived mast cells inhibited exocytosis in a dose-related manner, as defined by the release of the secretory granule constituent beta-hexosaminidase, as well as the generation of the membrane-derived lipid mediator, leukotriene C4. Thus, gp49B1 is an immunoreceptor tyrosine-based inhibition motif-containing integral cell-surface protein that downregulates the high-affinity Fc receptor for IgE-mediated release of proinflammatory mediators from mast cells. Our findings establish a novel counterregulatory transmembrane pathway by which mast cell activation can be inhibited.
Asunto(s)
Mastocitos/fisiología , Glicoproteínas de Membrana/fisiología , Receptores de IgE/fisiología , Receptores Inmunológicos , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , Antígenos de Superficie/inmunología , Células Cultivadas , Secuencia de Consenso , Masculino , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Péptidos/inmunología , Agregación de Receptores , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Transducción de Señal , Tirosina/fisiología , beta-N-Acetilhexosaminidasas/metabolismoRESUMEN
We demostrate that a specific combination of cytokines elicits high levels of interleukin (IL)-6 gene expression in mast cells and define the cellular mechanisms of the exogenous cytokine action. The addition of c-kit ligand (KL) and IL-10 to IL-3-derived mouse bone marrow mast cells (BMMC) elicited an approximately 2-fold increase in steady-state IL-6 mRNA levels that peaked after 0.5 h and was followed by the release of approximately 0.2 ng of IL-6/10(6) cells by 5-7 h. The addition of IL-1beta to KL + IL-10 elicited a prolonged approximately 12-fold increase in the level of IL-6 mRNA by 3-5 h and an approximately 50-fold increase in the level of IL-6 protein released by 7 h. As determined by nuclear run-on analysis, KL + IL-10 stimulated IL-6 gene transcription within 0.5 h, and the addition of IL-1beta did not increase transcription. Instead, IL-1beta slowed by approximately 8-fold the decay of IL-6 mRNA as compared to its decay in BMMC stimulated with KL + IL-10 alone. The exposure of BMMC to cycloheximide 0.5 h before the addition of the three exogenous cytokines inhibited by approximately 50% the level of IL-6 mRNA generated but did not inhibit the effects of KL + IL-10, indicating that IL-1beta induces the synthesis of a protein that stabilizes IL-6 mRNA. The stabilization of IL-6 mRNA was inhibited by the addition of actinomycin D at 0.5 but not 3 h after BMMC were stimulated with IL-1beta in combination with KL + IL-10, suggesting that once transcribed, the stabilizing protein is long-lived. The addition of cycloheximide to BMMC after stimulation with KL + IL-10 with or without IL-1beta increased the levels of steady-state IL-6 mRNA compared to levels in cells without drug, indicating that in addition to stimulating IL-6 transcription, KL + IL-10 induces a protein factor that destabilizes IL-6 mRNA. Thus, there exists a novel Fcepsilon receptor type I-independent mechanism by which a mast cell can provide substantial amounts of IL-6 protein in response to the synergistic action of KL and IL-10 to induce IL-6 gene transcription, and IL-1beta to stabilize otherwise short-lived IL-6 transcripts.