RESUMEN
Distinguishing autosomal-dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease-causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients.
Asunto(s)
Quistes/etiología , Quistes/patología , Riñón/patología , Hígado/patología , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/genética , Canales Catiónicos TRPP/genética , Anciano , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Pruebas de Función Renal , Pruebas de Función Hepática , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/epidemiología , Prevalencia , Tomografía Computarizada por Rayos XRESUMEN
Estrogen receptors from rat uterus and human breast carcinoma were analyzed by diethylaminoethyl-cellulose chromatography. Cytosols which had been incubated for short periods of time demonstrated a single discrete elution peak, indicating a single ionic form, while cytosols incubated for longer periods of time generated a second ionic form of receptor. Addition of cations to cytosols also promoted the rapid appearance of this second ionic form of receptor. Either leupeptin, a protease inhibitor, or sodium molybdate prevented the appearance of this second ionic form of estrogen receptor. The estrogen receptor from rat uterine cytosol incubated without leupeptin or molybdate had a smaller apparent molecular weight than did estrogen receptor from cytosols incubated with leupeptin or molybdate. Altogether, these experiments suggested that a cation-dependent protease present in the cytosols from both tissues was degrading the estrogen receptor to a second smaller species during extended incubation times.
Asunto(s)
Neoplasias de la Mama/metabolismo , Receptores de Estrógenos/metabolismo , Útero/metabolismo , Animales , Cromatografía DEAE-Celulosa , Citosol/metabolismo , Femenino , Humanos , Leupeptinas/farmacología , Sustancias Macromoleculares , Peso Molecular , Conformación Proteica , Ratas , Sales (Química)RESUMEN
Two young homosexual men with acquired immunodeficiency syndrome (AIDS) presented with five-lobe pneumonia and maculopapular rash, respectively, and were found to have disseminated histoplasmosis by examination of peripheral blood smears. Bone marrow smears from one patient revealed more numerous Histoplasma capsulatum organisms than peripheral blood smears did. Electron microscopy of peripheral-blood buffy coat demonstrated histoplasma organisms in monocytes and neutrophils as well as tubuloreticular structures in small lymphocytes. A search for Histoplasma capsulatum in peripheral blood smears from patients with AIDS is warranted, especially in endemic midwestern states.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Histoplasmosis/patología , Síndrome de Inmunodeficiencia Adquirida/patología , Adulto , Médula Ósea/microbiología , Histoplasma/aislamiento & purificación , Histoplasmosis/etiología , Humanos , Masculino , Microscopía Electrónica , Monocitos/microbiología , Neutrófilos/microbiologíaRESUMEN
Sera from normal persons and patients with IgA, IgD, IgG, and IgM monoclonal gammopathies were electrophoresed in polyacrylamide gels containing sodium dodecyl sulfate. The gels were stained with Coomassie blue or were used for immunodiffusion. By this method IgG multiple myeloma and IgM Waldenström's macroglobulinemia sera were readily distinguished by electrophoresis alone, whereas IgA and IgD myeloma sera were distinguished by further immunodiffusion against anti-alpha-chain antibody and anti-delta-chain antibody.
Asunto(s)
Inmunoglobulinas/metabolismo , Mieloma Múltiple/sangre , Macroglobulinemia de Waldenström/sangre , Electroforesis en Gel de Poliacrilamida , Humanos , Inmunodifusión , Inmunoglobulina A/metabolismo , Inmunoglobulina D/metabolismo , Inmunoglobulina G/metabolismo , Inmunoglobulina M/metabolismo , Dodecil Sulfato de SodioRESUMEN
Brain tumors are highly resistant to therapy. Their diffuse infiltrative nature and the relative inaccessibility of brain tissue to blood and lymph are barriers to surgical and cytotoxic treatments alike. The purpose of this study was to produce immune cells specifically reactive with an anaplastic rat glioma (RT2) and determine whether those cells could affect tumor progression in the brain. RT2-specific cytotoxic cells were prepared by priming rats in vivo with RT2 tumor cells and Corynebacterium parvum and stimulating the primed lymphocytes in vitro with irradiated RT2 tumor cells and interleukin-2 (IL-2). Cultured cells exhibited a high level of cytotoxicity against RT2, but not C6 (an allogeneic glioma), 3M2N (a syngeneic mammary tumor), or CSE (a syngeneic fibrosarcoma) tumor cells. To generate a model for therapy, rats were injected intracerebrally with RT2, generating progressing brain tumors, which killed untreated rats in approximately 2 weeks. To test the therapeutic potential of the effector cells, tumor-bearing rats were treated by intravenous injection of lymphocytes on Day 5 of tumor growth. Treated rats also received a 5-day course of systemic IL-2 beginning on Day 5. Treatment with IL-2 alone, RT2-primed spleen cells, or RT2-primed spleen cells stimulated in vitro with C6 did not affect rat survival. However, tumor-bearing rats treated with RT2-stimulated lymphocytes exhibited increased survival or were cured. Systemic IL-2 was an essential adjunct, because survival was not affected by treatment with effector cells alone. Therapy initiated on Day 8 of tumor progression lacked effect on survival.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Neoplasias Encefálicas/terapia , Glioma/terapia , Inmunoterapia , Linfocitos T Citotóxicos/trasplante , Animales , Neoplasias Encefálicas/mortalidad , Glioma/mortalidad , Masculino , Ratas , Ratas Endogámicas F344 , Análisis de Supervivencia , Factores de TiempoRESUMEN
A single injection of 1.5 mg aflatoxin B1 per kg body weight produced approx. 70% disaggregation of rat liver polysomes into monosomes within 18 h. Isolated monosomes dissociated into 40 S subunits during centrifugation in linear sucrose gradients containing 0.3 M KCI. The 4 S to 5 S molar RNA ratio of the monosomes was calculated to be 0.6, indicating 0.6 tRNA and/or aminoacyl tRNA molecule per ribosome; no peptidyl tRNA was present. These results suggest that a single injection of affatoxin B1 produces monosomes which resemble runoff ribosomes.
Asunto(s)
Aflatoxinas/farmacología , Polirribosomas/efectos de los fármacos , Animales , Centrifugación por Gradiente de Densidad , Electroforesis en Gel de Poliacrilamida , Hígado/análisis , Hígado/efectos de los fármacos , Hígado/ultraestructura , Masculino , Métodos , ARN de Transferencia/análisis , Ratas , Ratas Endogámicas F344 , Ribosomas/análisis , Ribosomas/efectos de los fármacosAsunto(s)
Citoplasma/efectos de los fármacos , Ácidos Grasos Insaturados/farmacología , Ácidos Grasos/farmacología , Hígado/ultraestructura , Alquilación , Animales , Ciclopropanos/análogos & derivados , Ciclopropanos/farmacología , Grasas de la Dieta , Retículo Endoplásmico/efectos de los fármacos , Glucosa-6-Fosfatasa/metabolismo , Hígado/enzimología , Hígado/metabolismo , Microsomas Hepáticos/análisis , Fenacetina/metabolismo , Espectrofotometría Infrarroja , TruchaAsunto(s)
Agregación Celular/efectos de los fármacos , Hígado/efectos de los fármacos , Biosíntesis de Proteínas , Ribosomas/efectos de los fármacos , Taninos/farmacología , Aminoácidos/metabolismo , Animales , Ácidos y Sales Biliares/farmacología , Isótopos de Carbono , Núcleo Celular/efectos de los fármacos , Citoplasma/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Leucina/metabolismo , Hígado/citología , Masculino , Microscopía Electrónica , Mitocondrias Hepáticas/efectos de los fármacos , Ratas , Factores de TiempoAsunto(s)
Alcaloides/farmacología , Hígado/citología , Pirroles/farmacología , Ribosomas/efectos de los fármacos , Animales , Isótopos de Carbono , Centrifugación por Gradiente de Densidad , Cicloheximida/farmacología , Leucina/metabolismo , Masculino , Ácido Orótico/metabolismo , Biosíntesis de Proteínas , Ratas , Factores de TiempoAsunto(s)
Hígado/citología , Alcaloides de Pirrolicidina/farmacología , Ribosomas/efectos de los fármacos , Animales , Bovinos , Centrifugación por Gradiente de Densidad , Electroforesis en Gel de Poliacrilamida , Femenino , Técnicas In Vitro , Ratones , Páncreas/enzimología , Potasio/farmacología , ARN/aislamiento & purificación , ARN Mensajero/aislamiento & purificación , Ribonucleasas/metabolismo , SacarosaAsunto(s)
Tetracloruro de Carbono/farmacología , Hígado/ultraestructura , Polirribosomas/efectos de los fármacos , Ribosomas/efectos de los fármacos , Animales , Centrifugación por Gradiente de Densidad , Electroforesis en Gel de Poliacrilamida , Masculino , Ratones , ARN de Transferencia/análisis , Ribosomas/análisis , Inanición , SacarosaAsunto(s)
Antibióticos Antineoplásicos/farmacología , Hígado/ultraestructura , Polirribosomas/efectos de los fármacos , Esparsomicina/farmacología , Animales , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Polirribosomas/análisis , Biosíntesis de Proteínas , ARN de Transferencia/análisis , Factores de TiempoAsunto(s)
Cardiomiopatías/inducido químicamente , Cortisona/efectos adversos , Mineralocorticoides/efectos adversos , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/patología , Fosfatos/efectos adversos , Animales , Diafragma/efectos de los fármacos , Técnicas In Vitro , Microscopía Electrónica , Músculos/efectos de los fármacos , Conejos , RatasAsunto(s)
Electroforesis de las Proteínas Sanguíneas , Proteínas Sanguíneas/aislamiento & purificación , Acrilamidas , Animales , Catalasa/aislamiento & purificación , Bovinos , Centrifugación por Gradiente de Densidad , Detergentes , Electroforesis , Humanos , Inmunoglobulinas/aislamiento & purificación , Hígado/enzimología , Sustancias Macromoleculares , Peso Molecular , Albúmina Sérica Bovina/análisis , Ácidos SulfúricosRESUMEN
A case of idiopathic dilated cardiomyopathy was studied histologically and by quantitative determination of tissue lipid concentration in order to document increased lipid accumulation. Four chambers of the heart were dilated with left ventricular dominance. Microscopically, there was a mixture of primarily fragmented myocytes with sarcoplasmic degeneration and minorly hypertrophic myocytes. There were numerous areas of moth-eaten appearance of myocardium in all of the sections, which corresponded to fatty degeneration, composed of numerous small lipid droplets between decreasing contractile elements. Ultrastructurally, there were widened Z-bands in degenerated myocardium, corresponding to light microscopically enlarged contraction bands. The extent of moth-eaten appearance was more extensive in the left than in the right ventricle, which was also verified by a three-fold increase of triglyceride concentration in the left ventricle compared with age-matched control hearts. The moth-eaten appearance was also observed in the auricles and atria with less immunohistochemical staining intensity for atrial natriuretic polypeptide, demonstrating that this fatty change involves all parts of the myocardium.