RESUMEN
Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development. In addition, we found distinct alterations of hematopoiesis-regulating factors such as Kit-ligand and Jagged1 accompanied by a significantly diminished ability to support CD34+ hematopoietic stem and progenitor cells in long-term culture-initiating cells (LTC-ICs) assays. This deficient osteogenic differentiation and insufficient stromal support was reversible and correlated with disease status as indicated by Osteocalcin serum levels and LTC-IC frequencies returning to normal values at remission. In line with this, cultivation of healthy MSC in conditioned medium from four AML cell lines resulted in decreased proliferation and osteogenic differentiation. Taken together, AML-derived MSC are molecularly and functionally altered and contribute to hematopoietic insufficiency. Inverse correlation with disease status and adoption of an AML-like phenotype after exposure to leukemic conditions suggests an instructive role of leukemic cells on bone marrow microenvironment.
Asunto(s)
Regulación Leucémica de la Expresión Génica , Leucemia Mieloide Aguda/genética , Células Madre Mesenquimatosas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/genética , Antígenos CD34/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Estudios de Casos y Controles , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Femenino , Hematopoyesis/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteína Jagged-1 , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/patología , Persona de Mediana Edad , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogénesis/efectos de los fármacos , Fenotipo , Proteínas Serrate-Jagged , Transducción de Señal , Factor de Células Madre/genética , Factor de Células Madre/metabolismoRESUMEN
We report on a family with co-occurrence of affective disorder and Hailey-Hailey disease in two brothers and the mother. The putative chromosomal locus of Hailey-Hailey disease, which is a rare dominantly inherited dermatosis, may be a promising candidate region for genetic studies in affective disorder.
Asunto(s)
Trastorno Bipolar/genética , Pénfigo Familiar Benigno/genética , Trastorno Bipolar/psicología , Deleción Cromosómica , Mapeo Cromosómico , Humanos , Masculino , Persona de Mediana Edad , Pénfigo Familiar Benigno/psicología , Fenotipo , Aberraciones Cromosómicas Sexuales/genética , Cromosoma YRESUMEN
Advances of therapeutic strategies in the management of critically ill patients have resulted in an increased life expectancy and more frequent presentations to ophthalmic surgeons. Six patients with postoperative endophthalmitis after elective intraocular surgery suffering from Sharp-syndrome, metastasizing antrum carcinoma, granulomatous vasculitis and immunosuppressive therapy, agranulocytosis, silico-tuberculosis and chronic lymphatic leukemia revealed traditionally pathogenic agents (Proteus mirabilis, P. aeruginosa, enterococci, coagulase-negative Staph). Two patients had to be enucleated, one turned blind and three had a visual acuity 5/100 to 20/60. In our hands prognosis for successful therapy in immunodeficient patients seems worse than in otherwise healthy persons. Painstaking evaluation of history, medical work-up, conjunctival swabs and application of bactericidal topical antibiotics preoperatively and perioperatively are particularly important in these patients.
Asunto(s)
Endoftalmitis/diagnóstico , Oftalmopatías/cirugía , Infecciones Oportunistas/diagnóstico , Infección de la Herida Quirúrgica/diagnóstico , Anciano , Anciano de 80 o más Años , Antibacterianos , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Conjuntiva/microbiología , Quimioterapia Combinada/administración & dosificación , Endoftalmitis/microbiología , Endoftalmitis/cirugía , Enucleación del Ojo , Femenino , Estudios de Seguimiento , Humanos , Lentes Intraoculares , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/cirugía , Reoperación , Desprendimiento de Retina/cirugía , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/cirugía , VitrectomíaRESUMEN
Expression patterns of cytokeratins (CKs), actin, lactoferrin (Lf), lysozyme (Ly), vimentin, and S-100 protein were immunohistochemically examined in paraffin sections from eight normal major and accessory lacrimal glands (LGs). Luminal duct cells and a number of secretory cells stained with the antibodies (ABs) KL1 and Pkk1 (CK 7, 8, 17, 18), while basal duct and myoepithelial cells reacted with the AB 34 beta E12 (CK 5). Myoepithelial cells expressing CK 5 and actin were restricted to acini and intralobular ducts, and their number was greater in major LGs than accessory ones. Lf and Ly were found in 50%-75% of acini and intralobular ducts. Vimentin was absent in parenchyma of LGs. S-100 protein reaction was observed in a number of acinar and luminal duct cells of major LGs whereas epithelia of accessory LGs remained negative. Distribution patterns of CKs, Lf, and Ly in major and accessory LGs are identical. The difference with respect to the number of myoepithelial cells as well as S-100 protein reactivity between major and accessory LGs reactivity appeared to be relevant to the differences in their secretory mechanisms and local environment.
Asunto(s)
Biomarcadores , Aparato Lagrimal/metabolismo , Actinas/metabolismo , Anticuerpos Monoclonales , Especificidad de Anticuerpos , Epitelio/metabolismo , Humanos , Técnicas para Inmunoenzimas , Queratinas/metabolismo , Aparato Lagrimal/citología , Lactoferrina/metabolismo , Muramidasa/metabolismo , Proteínas S100/metabolismo , Vimentina/metabolismoRESUMEN
The distribution of cytokeratins (CK), actin, lactoferrin (Lf), lysozyme (Ly), vimentin and S-100 protein was immunohistochemically investigated in paraffin-embedded specimens of five inflammatory and five neoplastic lesions of lacrimal glands (LGs). Atrophic acini in dacryoadenitis reacted with antibodies (ABs) KL1 and Pkk1 (CK 7, 8, 17, 18) in a manner similar to ducts. Apart from myoepithelial cells and some luminal-duct cells, the remaining epithelia in dacryoadenitis were negative with AB 34 beta E12 (CK 5). The number of AB HHF35 (actin)-positive myoepithelial cells was not altered in dacryoadenitis. Epithelia in dacryoadenitis reacted weakly but consistently with Lf while revealing weak and inconsistent staining for Ly. Vimentin was negative in epithelial cells in dacryoadenitis except in one case. S-100 protein was detected only in epithelia of inflammatory major LGs. Epimyoepithelial islands in lymphoepithelial proliferation reacted variably for CKs, Lf, Ly and vimentin and remained negative for actin and S-100. In pleomorphic adenomas, neoplastic cells showing duct-like differentiation (luminal) reacted consistently with CK 7, 8, 17, 18 and S-100 protein and inconsistently with CK 5, Lf and Ly but remained negative for actin and vimentin. Other neoplastic cells (ovoid/peripheral cells) stained consistently for CK 5, vimentin and S-100 protein and focally for CK 7, 8, 17, 18, actin, Lf and Ly. Spindle-form neoplastic cells found in the stroma exhibited vimentin and S-100 protein and, less frequently, actin. Determination of these antigens in pleomorphic LG adenomas may help to evaluate their prognosis.
Asunto(s)
Biomarcadores , Dacriocistitis/metabolismo , Neoplasias del Ojo/metabolismo , Enfermedades del Aparato Lagrimal/metabolismo , Aparato Lagrimal/metabolismo , Actinas/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Lactante , Queratinas/metabolismo , Lactoferrina/metabolismo , Masculino , Persona de Mediana Edad , Muramidasa/metabolismo , Proteínas S100/metabolismo , Vimentina/metabolismoRESUMEN
A 13-year-old boy developed Clostridium perfringens panophthalmitis due to a penetrating scleral injury. The characteristic symptoms were unusually severe periocular pain, lid edema, decreased motility and protrusion of the eye, severe conjunctival chemosis, pus covering the conjunctiva and cornea, green-brown hypopyon, gas bubbles in the anterior chamber, and amaurosis within 60 hours. In view of the patient's ocular status and impaired general condition enucleation was unavoidable. The results of laboratory workups are reported in addition to the clinical and ophthalmologic findings.
Asunto(s)
Lesiones Oculares Penetrantes/complicaciones , Gangrena Gaseosa/patología , Panoftalmitis/patología , Esclerótica/lesiones , Adolescente , Clostridium perfringens/aislamiento & purificación , Enucleación del Ojo , Cuerpos Extraños en el Ojo/complicaciones , Lesiones Oculares Penetrantes/patología , Gangrena Gaseosa/cirugía , Humanos , Masculino , Panoftalmitis/cirugía , Cuerpo Vítreo/lesionesRESUMEN
Two patients with bilateral extensive confluent choroidal lesions, exudative retinal detachments, positive lyme serology and a typical history are documented: A 32-year-old woman presented 14 days after a "flu-like" illness with bilateral acute extensive choroidal lesions and exudative retinal detachments (OD from 5 to 8:30 o'clock, OS from 5 to 8 o'clock, both including the macula) accompanied by a mild lymphocytic meningitis. The laboratory work-up revealed increased serum and CSF titers of antibodies against Borrelia burgdorferi (Lyme immunofluorescent test (IFT) and Lyme-IgM IFT) which declined after a 14-day treatment with doxycycline (200 mg/d), CSF titers non-detectable (serum IgG: from 1:640 to 1:320, serum IgM: from 1:40 to 1:20). A distinct improvement with visual acuity increasing from OD 0.2/OS 0.3 p to OD/OS 0.8 p was observed after seven days of treatment. A 40-year-old man with a 14-day history of tick-bite developed the same, though more severe ocular findings and a lymphocytic meningitis. The serological work-up revealed increased antibody titers against Borrelia burgdorferi (ELISA); the IgM titer was normal. After a 10-day treatment with penicillin, antibody titers against the spirochete decreased slightly and the patient's neurologic and ophthalmologic status improved dramatically. Five weeks after admission visual acuity was OD/OS 0.5 (compared to OD/OS 0.1) and has remained at 0.8 p (OD/OS) since the ninth week after onset. The clinical course of the disease and the decreasing lyme serology strongly suggest an infection with Borrelia burgdorferi. The authors propose thorough laboratory work-ups including tests for Lyme disease in selected patients with diffuse choroidal lesions.