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1.
Eur J Cancer ; 103: 17-23, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30196106

RESUMEN

BACKGROUND: Dose-escalation of epertinib (S-222611), a new potent oral EGFR/HER2 inhibitor, has established a recommended daily dose of 800 mg in patients with solid tumours. In this study, we have recruited a larger number of patients to assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour activity. PATIENTS AND METHODS: Patients with solid tumours expressing EGFR or HER2 received a single dose of epertinib at 800 mg on Day 1 to assess PK over 7 days, followed by continuous once-daily dosing from Day 8. RESULTS: We treated 76 patients with breast (n = 27), upper gastrointestinal (GI; n = 30), head and neck (n = 12) or renal cancers (n = 7). Epertinib was well-tolerated with mostly grade I and II adverse events (AEs). The most frequent AE was diarrhoea, which was generally manageable with loperamide. The objective response rate (ORR) in patients with heavily pretreated breast and upper GI cancers was 16.0% (4 PRs) and 8.3% (1CR, 1PR), respectively. All six responding patients had HER2-positive tumours; the ORR for HER2-positive breast and upper GI cancer populations was 19.0% and 20.0%. Partial response in the brain disease of one breast cancer patient lasted 7.5 months. CONCLUSION: Once-daily dosing of epertinib at 800 mg was well-tolerated and demonstrated promising antitumour activity in patients with heavily pretreated HER2-positive breast and upper GI cancer, including those with brain metastases. EUDRACT NUMBER: 2009-017817-31.


Asunto(s)
Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Resultado del Tratamiento
2.
J Neurosci ; 21(23): 9304-14, 2001 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11717364

RESUMEN

The axons of the retinal ganglion cells run on the diencephalotelencephalic boundary on their way to the tectum; however, they do not invade the telencephalon anteriorly. To investigate the mechanisms that prevent the retinal axons from entering the telencephalic territory, the effects of the telencephalic cells were examined on the outgrowth of the retinal axons in vitro; the retinal outgrowth was selectively inhibited by the cellular substrate derived from the telencephalon. The responsible factor for the selective inhibition was, furthermore, found in the telencephalic membranes and the fraction of peripheral membrane molecules from the telencephalon. Because the inhibitory effect was destroyed by chondroitinase ABC but not by heat, this inhibition was attributable to the carbohydrate chains of chondroitin sulfate proteoglycans (CSPGs) adhering to the membranes of the telencephalic cells. To understand the function of the telencephalic CSPGs on the retinal pathfinding in vivo, their carbohydrate chains [chondroitin sulfate glycosaminoglycan (CS-GAG)] were removed from the embryonic brains by intraventricular injection of chondroitinase ABC; the removal of CS-GAG resulted in an anterior enlargement of the optic tract. The results indicate that the telencephalic cells delimit the anterior border of the optic tract with their CSPGs and prevent the retinal axons from aberrantly entering the anterior territory.


Asunto(s)
Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Retina/embriología , Células Ganglionares de la Retina/citología , Telencéfalo/metabolismo , Vías Visuales/embriología , Animales , Axones/efectos de los fármacos , Axones/fisiología , Metabolismo de los Hidratos de Carbono , Carbohidratos/farmacología , Membrana Celular/química , Membrana Celular/metabolismo , Embrión de Pollo , Condroitina ABC Liasa/administración & dosificación , Condroitina ABC Liasa/metabolismo , Proteoglicanos Tipo Condroitín Sulfato/farmacología , Sulfatos de Condroitina/química , Sulfatos de Condroitina/metabolismo , Sulfatos de Condroitina/farmacología , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Cámaras de Difusión de Cultivos , Inyecciones Intraventriculares , Retina/citología , Células Ganglionares de la Retina/efectos de los fármacos , Fracciones Subcelulares/química , Telencéfalo/química , Telencéfalo/citología , Telencéfalo/embriología , Vías Visuales/citología , Vías Visuales/efectos de los fármacos
3.
Eur J Cancer ; 51(2): 137-45, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25434923

RESUMEN

BACKGROUND: S-222611 is a reversible inhibitor of EGFR, HER2 and HER4 with preclinical activity in models expressing these proteins. We have performed a Phase 1 study to determine safety, maximum tolerated dose (MTD), pharmacokinetic profile (PK) and efficacy in patients with solid tumours expressing EGFR or HER2. PATIENTS AND METHODS: Subjects had advanced tumours not suitable for standard treatment, expressing EGFR or HER2, and/or with amplified HER2. Daily oral doses of S-222611 were escalated from 100mg to 1600 mg. Full plasma concentration profiles for drug and metabolites were obtained. RESULTS: 33 patients received S-222611. It was well tolerated, and the most common toxicities, almost all mild (grade 1 or 2), were diarrhoea, fatigue, rash and nausea. Only two dose-limiting toxicities occurred (diarrhoea and rash), which resolved on interruption. MTD was not reached. Plasma exposure increased with dose up to 800 mg, exceeding levels eliciting pre-clinical responses. The plasma terminal half-life was more than 24h, supporting once daily dosing. Responses were seen over a wide range of doses in oesophageal, breast and renal tumours, including a complete clinical response in a patient with HER2-positive breast carcinoma previously treated with lapatinib and trastuzumab. Four patients have remained on treatment for more than 12 months. Downregulation of pHER3 was seen in paired tumour biopsies from a responding patient. CONCLUSIONS: Continuous daily oral S-222611 is well tolerated, modulates oncogenic signalling, and has significant antitumour activity. The recommended Phase 2 dose, based on PK and efficacy, is 800 mg/day.


Asunto(s)
Receptores ErbB/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Quinazolinas/uso terapéutico , Receptor ErbB-2/antagonistas & inhibidores , Administración Oral , Adulto , Anciano , Área Bajo la Curva , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Exantema/inducido químicamente , Fatiga/inducido químicamente , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Neoplasias/metabolismo , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/efectos adversos , Quinazolinas/farmacocinética , Resultado del Tratamiento , Adulto Joven
4.
FEBS Lett ; 455(1-2): 135-9, 1999 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-10428487

RESUMEN

We investigated the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and the role of PPARgamma in cell growth in human gastric cancer cells. Reverse transcription-polymerase chain reaction, Northern blot and Western blot analyses showed that a human gastric cancer cell line, MKN45, expressed PPARgamma mRNA and protein. Luciferase assay in MKN45 cells showed that troglitazone, a selective ligand for PPARgamma, transactivated the transcription of a peroxisome proliferator response element-driven promoter. Troglitazone or pioglitazone, selective ligands for PPARgamma, inhibited the growth of MKN45 cells in a dose-dependent manner. Co-incubation of MKN45 cells with troglitazone induced DNA ladder formation. These results suggest that human gastric cancer cells express PPARgamma and that activation of PPARgamma inhibits cell growth and induces apoptosis in gastric cancer cells.


Asunto(s)
Apoptosis , División Celular , Receptores Citoplasmáticos y Nucleares/metabolismo , Neoplasias Gástricas/patología , Factores de Transcripción/metabolismo , Acil-CoA Oxidasa , Secuencia de Bases , Cartilla de ADN , Humanos , Luciferasas/genética , Oxidorreductasas/genética , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/genética
5.
FEBS Lett ; 447(1): 76-80, 1999 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-10218586

RESUMEN

We identified a novel member of the Ikaros gene family, which has critical roles in the development of lymphoid lineages. This gene, which we named Eos, was expressed predominantly in the developing central and peripheral nervous system. Eos protein could interact with itself and Ikaros protein through its C-terminal portion in the yeast two hybrid assay. These findings suggested that Eos may have important roles in neural development similarly to the Ikaros family in the development of hemolymphoid tissue.


Asunto(s)
Proteínas Portadoras/genética , Proteínas de Unión al ADN , Familia de Multigenes , Proteínas del Tejido Nervioso/genética , Dedos de Zinc/genética , Secuencia de Aminoácidos , Animales , Astrocitos/citología , Proteínas Portadoras/aislamiento & purificación , Sistema Nervioso Central/química , Factor de Transcripción Ikaros , Hibridación in Situ , Ratones , Ratones Endogámicos ICR , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/aislamiento & purificación , Sistema Nervioso Periférico/química , Unión Proteica , ARN Mensajero/aislamiento & purificación , Homología de Secuencia de Aminoácido , Distribución Tisular , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
6.
Am J Med Genet ; 41(1): 32-4, 1991 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-1951460

RESUMEN

We describe a 20-week-gestation male fetus with partial dup(5p) and proximal dup(13q), 47,XY,t(5;13)(p15;q21), + der(13)t(5;13)(p15;q21) mat. This finding is attributable to second meiotic nondisjunction of the rearranged chromosome in a maternal balanced reciprocal translocation. To the best of our knowledge, there have been only 3 previous reports of a similar error in the segregation of the rearranged chromosomes. For the first time evidence has been given that this unusual segregation is due to maternal second meiotic nondisjunction, using QFQ banding heteromorphisms. Second meiotic malsegregation should be taken into account in the consideration of reproductive problems in carriers of balanced translocations.


Asunto(s)
Cromosomas Humanos Par 13 , Cromosomas Humanos Par 5 , Meiosis/genética , No Disyunción Genética , Translocación Genética/genética , Anomalías Múltiples , Femenino , Heterocigoto , Humanos , Recién Nacido , Masculino , Trisomía
7.
Brain Dev ; 16(1): 27-31, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-8059925

RESUMEN

Prenatal diagnoses of peroxisomal disorders, including peroxisome-deficient Zellweger syndrome, isolated deficiency of peroxisomal beta-oxidation enzyme and rhizomelic type chondrodysplasia punctata were investigated by means of the lignoceric acid oxidation assay, indirect immunofluorescence staining and pulse-chase experiments, using cultured amniocytes. Assessment of peroxisomal beta-oxidation activity by means of [1-14C]lignoceric acid oxidation is essential for the diagnosis of a single enzyme deficiency of peroxisomal beta-oxidation with detectable enzyme protein. For the diagnosis of Zellweger syndrome, the absence of peroxisomes was readily determined by immunofluorescence staining of only a few amniocytes. Evidence for abnormal processing of 3-ketoacyl-CoA thiolase leads to the diagnosis of rhizomelic chondrodysplasia punctata. All the fetuses were considered to be normal and the neonates were normal. Use of these methods requires only a small number of amniocytes and will facilitate the prenatal diagnosis of peroxisomal disorders.


Asunto(s)
Líquido Amniótico/metabolismo , Errores Innatos del Metabolismo/diagnóstico , Microcuerpos/metabolismo , Diagnóstico Prenatal , Acetil-CoA C-Aciltransferasa/metabolismo , Adulto , Líquido Amniótico/citología , Preescolar , Condrodisplasia Punctata/diagnóstico , Ácidos Grasos/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Immunoblotting , Inmunohistoquímica , Errores Innatos del Metabolismo/metabolismo , Errores Innatos del Metabolismo/patología , Oxidación-Reducción , Embarazo , Síndrome de Zellweger/diagnóstico
8.
Eur J Obstet Gynecol Reprod Biol ; 89(2): 213-5, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10725587

RESUMEN

Microangiopathic thrombosis, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), seem to occur with certain stresses, including pregnancy. This report documents the clinical outcome with or without plasma therapy and dismal outcomes of two cases with postpartum microangiopathic thrombosis. One carried a pregnancy to successful cesarean delivery and suffered from postpartum TTP/HUS followed by plasma therapy-assisted recovery. Another developed postpartum TTP/HUS and was complicated with subarachnoid hemorrhage. Submission to plasma therapy should always be considered in a woman with postpartum microangiopathic thrombosis.


Asunto(s)
Transfusión Sanguínea , Síndrome Hemolítico-Urémico/terapia , Intercambio Plasmático , Trastornos Puerperales/terapia , Púrpura Trombocitopénica Trombótica/terapia , Trombosis/terapia , Adulto , Femenino , Humanos , Embarazo
9.
Ann Otol Rhinol Laryngol ; 104(10 Pt 1): 793-7, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7574257

RESUMEN

An immunohistochemical study of transforming growth factor-alpha (TGF-alpha) distribution was carried out to clarify the mechanism responsible for accelerated epidermal cell proliferation after perforation of the rabbit tympanic membrane. In the normal tympanic membrane, TGF-alpha expression was not observed, whereas after perforation, over the whole tympanic membrane including the margin of the perforation, TGF-alpha-positive cells appeared and were scattered in the epidermal cell layer. After healing of the perforation, a marked decrease of TGF-alpha-positive cells in the tympanic membrane was observed. This finding suggests that TGF-alpha induces proliferation of epidermal cells after the perforation stimulus.


Asunto(s)
Factor de Crecimiento Transformador alfa/biosíntesis , Perforación de la Membrana Timpánica/metabolismo , Membrana Timpánica/metabolismo , Animales , Anticuerpos Monoclonales , División Celular , Inmunohistoquímica , Conejos , Factores de Tiempo , Factor de Crecimiento Transformador alfa/inmunología , Membrana Timpánica/citología , Membrana Timpánica/inmunología , Perforación de la Membrana Timpánica/inmunología , Cicatrización de Heridas
10.
Int J Gynaecol Obstet ; 43(1): 57-60, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7904956

RESUMEN

Antepartum intracranial hemorrhage, which can cause fetal death prior to the onset of labor, is a rare event. This report documents the clinical findings and magnetic resonance imaging (MRI) of an uncommon case of antenatal acute subdural hematoma. MRI was extremely accurate in delineating the possible extent and location of the lesion. This is the first report to demonstrate MRI of subdural hemorrhage resulting in fetal death in utero.


Asunto(s)
Muerte Fetal/etiología , Enfermedades Fetales/diagnóstico , Hematoma Subdural/diagnóstico , Inicio del Trabajo de Parto , Diagnóstico Prenatal , Enfermedad Aguda , Adulto , Femenino , Hematoma Subdural/complicaciones , Humanos , Imagen por Resonancia Magnética , Embarazo
11.
Int J Gynaecol Obstet ; 44(3): 273-7, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7909767

RESUMEN

This report documents the acute toxicity of anti-leukemic chemotherapy on the fetus in utero by umbilical blood sampling. A patient with acute myelocytic leukemia diagnosed at the 23rd week of gestation received combination chemotherapy, and carried the pregnancy to successful delivery at the 34th week. During the course of pregnancy, the fetal condition was evaluated by serial real time sonograms and umbilical blood sampling through cordocentesis. Fetal hematopoiesis was preserved against maternal chemotherapeutic agents, and no developmental abnormalities were observed. This is the first attempt to evaluate the acute effects of chemotherapeutic agents on the fetus in utero by real time umbilical cord sampling.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sangre Fetal/citología , Retardo del Crecimiento Fetal/inducido químicamente , Feto/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Citarabina/análogos & derivados , Daunorrubicina/administración & dosificación , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Humanos , Recién Nacido , Mercaptopurina/administración & dosificación , Prednisolona/administración & dosificación , Embarazo , Ultrasonografía Prenatal
12.
Acta Otolaryngol ; 85(5-6): 342-8, 1978.
Artículo en Inglés | MEDLINE | ID: mdl-665207

RESUMEN

The extra internal hair cell (EIHC) of the human cochlea was observed by means of a scanning electron microscope. The EIHC was found not infrequently in all turns of the human cochlea. It was located medial to the IHC row. The inner pillar cells showed an abnormal structure. The anatomical relationships between the displaced IHC and EIHC, and the inner pillar cell were classified into five types. The origin of these anomalies is discussed form an embryological viewpoint.


Asunto(s)
Células Ciliadas Auditivas/ultraestructura , Mecanorreceptores/ultraestructura , Anciano , Humanos , Microscopía Electrónica de Rastreo , Órgano Espiral/ultraestructura
13.
Auris Nasus Larynx ; 12 Suppl 1: S108-10, 1985.
Artículo en Inglés | MEDLINE | ID: mdl-3835879

RESUMEN

Middle ear pressure in patients with middle ear effusion were measured using a microtransducer which developed in our laboratory. Middle ear pressure showed not only negative but also positive pressure in these patients. The findings are discussed briefly.


Asunto(s)
Oído Medio/fisiología , Otitis Media con Derrame/fisiopatología , Transductores de Presión , Transductores , Niño , Oído Medio/fisiopatología , Femenino , Humanos , Masculino , Métodos , Presión
14.
Auris Nasus Larynx ; 27(4): 359-62, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10996497

RESUMEN

This paper reports an unusual case in which acute lymphocytic leukemia presented acute profound sensorineural hearing loss as the initial manifestation of the disease. The patient is a 55-year-old woman who complained of left hearing loss of sudden onset. Pure tone audiometry revealed profound sensorineural hearing loss of the left ear at mid and low frequencies. The patient was tentatively diagnosed as idiopathic sudden deafness and admitted for the treatment, but her laboratory data indicated that she was at an advanced stage of leukemia. The patient's hearing loss did not improve subjectively until she deceased 1 year after the admission. The mechanism producing acute hearing loss in leukemic patients is reviewed and discussed, and the importance of differentiating possible underlying diseases before we diagnose idiopathic sudden deafness is stressed.


Asunto(s)
Pérdida Auditiva Sensorineural/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Enfermedad Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Audiometría de Tonos Puros , Diagnóstico Diferencial , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tomografía Computarizada por Rayos X
15.
J Laryngol Otol ; 94(12): 1345-52, 1980 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7441047

RESUMEN

A Scheibe-type dysgenesis of the inner ear was found in the temporal bones of an 85-year-old deaf-mute woman. Both temporal bones showed similar histopathological findings, which were confined mainly to the cochlea and saccule. The stria vascularis was atrophic and contained cysts with eosinophilic content throughout the cochlea. The scala media had disappeared owing to marked collapse of Reissner's membrane. The saccule showed collapse. Many eosinophilic spherical masses were observed in the area of the macula sacculi and attached to the saccular wall.


Asunto(s)
Oído Interno/anomalías , Anciano , Cóclea/patología , Sordera/etiología , Sordera/patología , Femenino , Humanos , Sáculo y Utrículo/patología , Hueso Temporal/patología
16.
Jpn J Antibiot ; 38(5): 1368-88, 1985 May.
Artículo en Japonés | MEDLINE | ID: mdl-3900457

RESUMEN

In order to compare the clinical efficacy and safety of TMS-19-Q.GC tablet (TMS) with josamycin tablet (JM) in acute tonsillitis, the double blind trial was carried out with the daily dosage of 200 mg X 3 in TMS and 400 mg X 3 in JM. Number of cases evaluated for clinical efficacy were 154 cases (73 treated with TMS and 81 treated with JM). The effective rating of TMS and JM were 89.0% and 88.9% judged by doctors in charge, and 82.2% and 85.2% judged by committee respectively. Bacteriological effects were satisfactory to yield the eradication rates of 93.8% in TMS and 94.7% in JM. Number of cases evaluated for safety were 199 cases (101 treated with TMS and 98 treated with JM). The incidence of side effect was 4.0% (4/101) in TMS and 5.1% (5/98) in JM and most of them were mild gastro-intestinal disorders. Number of cases evaluated for utility were 156 cases (74 treated with TMS and 82 treated with JM). The usefulness rates were 85.1% in TMS and 86.6% in JM. There was no significant difference between TMS and JM, in clinical effect, bacteriological effect, safety and utility. From these results, daily 600 mg dosage of TMS was as useful as daily 1,200 mg dosage of JM in the treatment for acute tonsillitis.


Asunto(s)
Leucomicinas/uso terapéutico , Miocamicina/análogos & derivados , Tonsilitis/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Ensayos Clínicos como Asunto , Método Doble Ciego , Femenino , Humanos , Leucomicinas/administración & dosificación , Masculino , Persona de Mediana Edad , Comprimidos , Tonsilitis/microbiología
17.
Rinsho Byori ; 42(3): 218-22, 1994 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-7512167

RESUMEN

CD36 is a glycoprotein that is expressed on platelets, monocytes, and endothelial cells. To analyze the mechanism of CD36 deficiency on the platelet membrane, we have examined the expression of mRNA by RT-PCR and the Sau96I site on PCR products. In cases 3, 5, and 6, we have detected the normal size, but few products by agarose gel electrophoresis and in all cases, several restriction enzyme patterns with Sau96I digestion have been observed. These findings suggest that transcriptional control may affect the expression of the CD36 molecule on the platelet membrane and a different mechanism may be present for the transcription of the CD36 mRNA in megakaryocytes from monocytes.


Asunto(s)
Ingeniería Genética , Patología Clínica/métodos , Antígenos CD/genética , Plaquetas/inmunología , Antígenos CD36 , Humanos , Glicoproteínas de Membrana Plaquetaria/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/sangre
18.
Nihon Jibiinkoka Gakkai Kaiho ; 97(2): 233-9, 1994 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-8169728

RESUMEN

We investigated the clinical features of 64 cases of sudden deafness in patients more than 60 years of age. Forty-eight cases (75%) had profound deafness, 13 moderate and three mild deafness. The audiograms of 25 cases showed a flat pattern, 13 a gradually descending curve, and 13 total deafness. In 60 cases, the unaffected ear also had hearing impairment of variable severity. Fifty-one of these 60 cases demonstrated a physiological hearing threshold shift termed presbycusis in the unaffected ear. Hearing impairment in 35 cases (55%) was cured or improved by medical treatment including steroids. But in the majority of cases, the hearing threshold level of the affected ear did not improve above that of the unaffected ear when the unaffected ear had a hearing impairment. In particular, hearing impairment in five cases with total deafness in the unaffected ear did not improve. The elderly often had various systemic complications, including nine cases of diabetes and seven of hypertension. We treated patients with diabetes using steroids under the consultation of diabetic specialists. As a result, there was no case of complications induced by steroids. We consider the effect of treatment of sudden deafness in the elderly to be best judged in various degrees of hearing impairment in the unaffected ear.


Asunto(s)
Pérdida Auditiva Súbita/fisiopatología , Anciano , Umbral Auditivo , Femenino , Humanos , Masculino , Persona de Mediana Edad
19.
Nihon Jibiinkoka Gakkai Kaiho ; 99(6): 869-74, 1996 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-8753072

RESUMEN

In Japan, the elderly population has progressively increased. It is therefore expected that various social services for the elderly will be demanded. As most of the elderly have hearing impairment due to presbycusis, it is difficult to communicate smoothly with them. To provide the various social services, it is necessary to investigate hearing acuity in the elderly. Accordingly, the Hearing Research Group, which belongs to the Research Project on Aging and Health in the Ministry of Health and Welfare of Japan, investigated the hearing acuity of people 65 years old, or more. One thousand one hundred ninety two subjects were divided into five groups, Group A consisted of 170 males and 216 females between 65 and 69 years old, Group B, 186 males and 158 females between 70 and 74; Group C, 147 males and 140 females between 75 and 79; Group D, 63 males and 61 females between 80 and 84; and Group E, 29 males and 22 females 85 years old or more. We examined the 175 subjects 80 years old or more. Therefore, it is considered that this study could indicate the present condition of hearing acuity of the elderly of Japan. The average hearing levels measured at seven frequencies (125, 250 and 500Hz, and 1, 2, 4, and 8KHz) were 35.0dB in group A, 42.1 in group B, 46.1 in group C, 52.1 in group D, and 55.6 in group E. There were no differences in the average hearing level between males and females in any group. The audiogram pattern indicated a gradually descending curve in most subjects in all groups. The average speech discrimination rate was 75.4% in group A, 70% in group B, 63.8% in group C, 59.7% in group D, and 52.1% in group E. The percentage of subjects showing a short increment sensitivity index of more than 70% was 45.2% in group A, 49.3% in group B, 47.9% in group C, 51.6% in group D, and 59.7% in group D. In conclusion, hearing loss due to aging tended to be more progressive at higher frequencies while hearing acuity of frequencies covering normal speech was preserved. However, the speech discrimination rate decreased relative to changes in the pure tone hearing level. It was considered that the pathology of hearing loss due to aging begins with retrocochlear changes and cochlear factors are added to retrocochlear changes with aging.


Asunto(s)
Anciano/fisiología , Audición/fisiología , Anciano de 80 o más Años , Audiometría del Habla , Femenino , Humanos , Masculino
20.
Hokkaido Igaku Zasshi ; 67(3): 297-307, 1992 May.
Artículo en Japonés | MEDLINE | ID: mdl-1324879

RESUMEN

The expression of HLA class II molecules is mainly regulated transcriptionally and this regulation is thought to play an important role to the control of immune response. In this report, we have studied the effect of adenylate cyclase activator, forskolin, to the expression of HLA class II molecules on the cell surface of an human multiple myeloma cell line, RPMI8226. On the northern blot analysis and FACS analysis, we have revealed that forskolin upregulated the expression of mRNAs of DQB and DRB gene and their products on its surface. On the sequence analysis of upstream of HLA-DQB gene, we have identified not only Y-,X-, W-box, which were thought to regulatory region of truncated gene, but also cAMP responsible element (CRE) like regulatory region, which located upstream of W-box. On the gel retardation assay, when we used DNA probes that were specific for CRE like region and Y-box, we have found newly detectable bands, which appeared by forskolin treatment. These data suggest that forskolin upregulates HLA class II molecules by means of the interaction between CRE and cAMP responsible element binding protein (CREB).


Asunto(s)
Colforsina/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Antígenos de Histocompatibilidad Clase II/genética , AMP Cíclico/metabolismo , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/inmunología , Transcripción Genética , Células Tumorales Cultivadas
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