RESUMEN
Chromosomal sex determination is widely used by vertebrates, however, only two genes have been identified as master sex-determining genes: SRY/Sry in mammals and DMY in the teleost medaka. Transfer of both genes into genetically female (XX) individuals can induce male development. However, transgenic strains have not been established in both cases because of infertility of the transgenic founders in mammals and low germline transmission rates in medaka. In this study, we used a BAC clone containing DMY in a 117 kb genomic region and two types of fluorescent marker to establish two DMY-transgenic medaka strains. In these strains, exogenous DMY is completely linked to a male phenotype and early gonadal development is not different from that of the wild-type strain. Sex-linkage analysis showed that the exogenous DMY was located on linkage group (LG) 23 in one strain and on LG 5 in the other strain, whereas the sex chromosome in medaka is on LG 1. Real-time PCR analysis indicated that these strains have multiple copies of DMY and higher DMY expression levels than the wild-type strain. These results showed that LGs 23 and 5 function as sex chromosomes in the two strains, respectively. This is not only the first example of the artificial generation of heritable sex chromosomes in vertebrates but also the first evidence showing plasticity of homomorphic sex chromosomes. This plasticity appears to be a characteristic of lower vertebrates and the underlying cause of frequent sex chromosome switching, recently reported in several fish and frog species.
Asunto(s)
Cromosomas Artificiales , Proteínas de Peces/genética , Genes sry/genética , Oryzias/genética , Cromosomas Sexuales/genética , Animales , Animales Modificados Genéticamente , Dosificación de Gen , Oryzias/crecimiento & desarrolloRESUMEN
Esophageal schwannoma is rare and it is difficult preoperatively to confirm a definitive diagnosis, even using current imaging techniques. We present a case of a benign esophageal schwannoma that was surgically excised and confirmed by immunohistochemical staining. Conventional radiological studies, including barium meal, computed tomography and endoscopic examination had shown a solid submucosal tumor of the upper thoracic esophagus but had been unable to confirm the diagnosis. Positron emission tomography was carried out to evaluate the malignant potential and showed a high uptake of 18F-fluorodeoxyglucose (FDG) into the tumor in both the early and delayed phase, suggesting that the tumor was a potentially malignant tumor such as a gastrointestinal stromal tumor. This is the first reported case of esophageal schwannoma that indicated a high FDG uptake. Although consensus has not been reached regarding the precise mechanism of FDG accumulation in schwannomas, we discuss our clinicopathological findings and review other studies of the subject.
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Neoplasias Esofágicas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neurilemoma/diagnóstico por imagen , Neurilemoma/cirugía , Tomografía de Emisión de Positrones/métodos , Anciano , Anastomosis Quirúrgica , Biopsia con Aguja , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagectomía , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Estadificación de Neoplasias , Neurilemoma/patología , Medición de Riesgo , Sensibilidad y Especificidad , Toracotomía , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
AIM: To compare the interocular and intraocular differences of capillary perfusion, and the intraocular regional differences of retinal blood flow in the macular area of healthy volunteers. METHODS: Tissue blood flow in the macula was examined in both eyes of 20 healthy volunteers with the Heidelberg retinal flowmeter. Blood flow measurements were made in a 10 degrees x 2.5 degrees area superior and inferior to the macula. The mean blood flow (MBF) was calculated by an automatic full field perfusion image analyser program. The MBF in the right and left eyes and in the superior and inferior macular areas of the same eye were compared. RESULTS: The ratios of the MBF in the right eye to the left eye in the macular areas were 1.00, and 1.03, respectively. The ratio of the MBF in the superior macular area to the inferior area was 1.01 for the right eyes and 1.04 for the left eyes. CONCLUSIONS: Because no significant differences were found in the MBF between the two eyes and between the superior and inferior macular areas in the same eye, interocular (for example, affected eye versus fellow eye) and intraocular (superior versus inferior macular areas) comparisons of MBF can be made to determine if changes in retinal perfusion have occurred.
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Procesamiento de Imagen Asistido por Computador , Flujometría por Láser-Doppler , Mácula Lútea/irrigación sanguínea , Adolescente , Adulto , Capilares , Femenino , Humanos , Masculino , Perfusión , Flujo Sanguíneo Regional , Reproducibilidad de los Resultados , Vasos Retinianos/fisiologíaRESUMEN
AIMS: To report the efficacy of corneal electrolysis for the treatment of recurrent corneal opacities at the subepithelial region or at the host-graft interface of the stroma in granular corneal dystrophy (GCD). METHODS: In patients with recurrences of opacities at the host-graft interface of the stroma after lamellar keratoplasty, the deep aspect of the graft was partially separated from host tissue to expose the deposits. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In patients with diffuse subepithelial opacities following penetrating keratoplasty, electrolysis was applied directly to the corneal surface. RESULTS: Deposits in the subepithelial region or at the host-graft interface of the stroma disappeared following treatment, and vision recovered. However, GCD recurred 2-3 years after the treatment. CONCLUSIONS: Corneal electrolysis is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty for GCD.
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Distrofias Hereditarias de la Córnea/cirugía , Opacidad de la Córnea/terapia , Trasplante de Córnea , Electrólisis/métodos , Anciano , Distrofias Hereditarias de la Córnea/patología , Opacidad de la Córnea/etiología , Opacidad de la Córnea/patología , Electrólisis/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
We investigated the efficacy and safety of autologous serum eye drops for the treatment of severe dry eye after allogeneic haematopoietic stem cell transplantation (SCT). A total of 14 patients (four males and 10 females; median age, 31.0 years) with severe dry eye associated with chronic graft-versus-host disease (cGVHD) were enrolled in this study. All patients were refractory to treatment with conventional artificial tears. Autologous serum eye drops, a solution made of 20% autologous serum in sterile saline, were applied 10 times per eye per day. The patients were evaluated every 4 weeks according to visual acuity, corneal sensitivity, vital staining of the ocular surface, tear dynamics, and subjective assessments of symptoms (complaints scores). The median follow-up period was 19.4 months (range: 4-41 months). After 4 weeks of treatment, significant improvement was observed in both complaint scores (from 33.7+/-12.3 to 23.6+/-10.6 points; P<0.01) and fluorescein scores (from 5.8+/-2.0 to 2.4+/-0.9 points; P<0.005). Significant improvements were observed also in rose-bengal staining and tear break-up time. In seven of the 14 patients, the responses were maintained for 6-41 months (median:19.4+/-8.3 months), while six of the other seven patients required treatment with punctal plugs in addition to autologous serum eye drops. One of these other seven patients developed eczema around the eyelids, after which the treatment was discontinued. No serious adverse events were observed. We conclude that autologous serum eye drops are safe and effective for treating severe dry eye associated with cGVHD and that more efficient control of dry eye may be achieved by the combined use of autologous serum eye drops with punctal plugs.
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Proteínas Sanguíneas/administración & dosificación , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/etiología , Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adulto , Proteínas Sanguíneas/efectos adversos , Enfermedad Crónica , Femenino , Humanos , Masculino , Síndromes Mielodisplásicos/terapia , Soluciones Oftálmicas/administración & dosificación , Soluciones Oftálmicas/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
AIM: To investigate the phenotypes associated with cytochrome P4501B1 gene (CYP1B1) mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: 66 Japanese patients with PCG were screened for sequence mutations in the CYP1B1 gene using single strand conformation polymorphism analysis followed by automated DNA sequencing. 11 cases had a CYP1B1 mutation in both alleles (the mutation group) and 21 cases did not have a CYP1B1 mutation (the "no mutation" group). The clinical features, such as age of onset, sex, intraocular pressure, and Descemet's membrane rupture, of the two groups were compared. RESULTS: The clinical symptoms and signs did not differ for the two groups. The mean age at onset was 1.7 months in the mutation group and 3.1 months in the no mutation group, and the male:female ratio was 6:5 in the mutation group and 19:2 in the no mutation group. Both of these differences were statistically significant. CONCLUSIONS: In clinically diagnosed cases of PCG, a subgroup shows a CYP1B1 gene mutation. Age at onset was earlier in PCG patients with CYP1B1 mutations than in patients without mutations. Women were more prevalent among patients with mutations than those without mutations.
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Hidrocarburo de Aril Hidroxilasas/genética , Glaucoma/congénito , Edad de Inicio , Secuencia de Bases , Citocromo P-450 CYP1B1 , Femenino , Glaucoma/genética , Humanos , Lactante , Recién Nacido , Masculino , Mutación/genética , Fenotipo , Polimorfismo Conformacional Retorcido-Simple , Estudios Retrospectivos , Factores Sexuales , Gemelos Monocigóticos/genéticaRESUMEN
AIMS: To evaluate corneal electrolysis as a treatment for recurrent diffuse corneal opacities at the host-graft interface of the stroma or at the subepithelial region in two types of granular corneal dystrophy (GCD). METHODS: Recurrence developed at the host-graft interface of the stroma after lamellar keratoplasty in a patient with Avellino corneal dystrophy (ACD). At surgery, the deep aspect of the graft in this patient was partially separated from host tissue to expose the deposits, with one third of the host-graft junction left intact. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In two patients with homozygous ACD and one patient with the superficial variant of GCD, diffuse subepithelial opacities developed following penetrating keratoplasty. Electrolysis was applied directly to the corneal surface. RESULTS: Deposits at the host-graft interface of the stroma and in the subepithelial region disappeared following treatment, and vision recovered in all patients. CONCLUSIONS: This method is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty.
Asunto(s)
Distrofias Hereditarias de la Córnea/cirugía , Opacidad de la Córnea/terapia , Trasplante de Córnea/métodos , Electrólisis/métodos , Complicaciones Posoperatorias/terapia , Anciano , Distrofias Hereditarias de la Córnea/fisiopatología , Opacidad de la Córnea/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/fisiopatología , Recurrencia , Resultado del Tratamiento , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND: Mutations of the transforming growth factor beta-induced (TGFBI) gene whose product is called keratoepithelin (KE) have been identified in 4 major autosomal dominantly inherited corneal dystrophies. The purpose of this study was to identify the mutations in Japanese patients with these dystrophies, and to investigate the nature of corneal deposits. METHOD: Mutations of the TGFBI gene were screened by polymerase chain reaction (PCR) followed by direct sequencing of the PCR products in Japanese patients clinically diagnosed as having granular corneal dystrophy, Avellino corneal dystrophy, lattice corneal dystrophy, and Reis-Bücklers' dystrophy. Corneal specimens obtained from corneal transplants were analyzed by histochemistry (Masson trichrome and Congo red stains), immunohistochemistry, and western blotting using anti KE antibody. I reviewed papers about TGFBI gene mutations previously published. RESULTS: The genotype/phenotype relationship of corneal dystrophies associated with mutations of the TGFBI gene is markedly evident. Avellino corneal dystrophy associated with the R 124 H mutation was the most common form of corneal stromal dystrophy in Japan. In Japan this dystrophy has been called granular corneal dystrophy up to now. Thiel-Behnke dystrophy (R 555 Q) has been also misdiagnosed as Reis-Bücklers' dystrophy. The original Reis-Bücklers' dystrophy is associated with R 124 L, which is compatible with superficial granular corneal dystrophy. Corneal deposits were associated with TGFBI products whose sizes were specific for their mutations. CONCLUSIONS: Mutations of the gene resulted in different types of KE aggregation accompanied with characteristic changes of processing and metabolism. The classification of these diseases according to genetic pathogenesis may be more appropriate than the use of clinical or histological findings.
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Distrofias Hereditarias de la Córnea/genética , Mutación/genética , Factor de Crecimiento Transformador beta/genética , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/patología , Humanos , Inmunohistoquímica , Factor de Crecimiento Transformador beta1RESUMEN
PURPOSE: To learn the clinical value of DNA diagnosis for Leber's hereditary optic neuropathy (LHON), we reviewed the results of DNA diagnosis performed at Keio University Hospital. METHODS AND PATIENTS: Included were 224 patients, 87 patients at Keio University Hospital and 137 patients from other clinics, with bilateral optic neuropathy who were suspected of having LHON. With informed consent, the 3460, 9804, 11,778, 13,730, and 14,484 mutations of mitochondria DNA (mt-DNA) were examined form 1990 to 1998. Percentage of male patients, age at onset of the disease, and percentage of familial history were compared between patients with and without the mutations. The clinical diagnosis at the time of DNA analysis were examined in patients without the mutation. RESULTS: Seventy two(32%) of the 224 patients had one of the five mtDNA mutations, 63(88%) patients had the 11,778 mutation, 6(8%) had the 14,484 mutation, and 3(4%) had the 3460 mutation. In 72 patients with one of the LHON mutations, 89% of the patients were male, the average age of the disease onset was 24.3 years, and 42% of the patients had a familial history of the disease. Eighty (53%) of 152 patients who did not have one of the 5 mutations were diagnosed as having bilateral optic atrophy with unknown causes. CONCLUSION: Although DNA diagnosis of LHON is a useful clinical test, we must know the clinical characteristics of the disease, before taking advantage of this analysis.
Asunto(s)
ADN Mitocondrial/genética , Mutación , Atrofia Óptica Hereditaria de Leber/diagnóstico , Adulto , Femenino , Humanos , Masculino , Atrofia Óptica Hereditaria de Leber/genéticaRESUMEN
PURPOSE: To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. RESULTS: Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. CONCLUSIONS: The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population.
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Hidrocarburo de Aril Hidroxilasas , Sistema Enzimático del Citocromo P-450/genética , Glaucoma/congénito , Mutación Missense , Secuencia de Aminoácidos , Animales , Preescolar , Citocromo P-450 CYP1B1 , Glaucoma/etnología , Haplotipos , Humanos , Lactante , Japón/epidemiología , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Polimorfismo Conformacional Retorcido-Simple , Ratas , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
PURPOSE: We present favorable results with amniotic membrane transplantation in a patient who developed fat adherence syndrome after retinal surgery. DESIGN: Interventional case report. METHODS: A 37-year-old man had diplopia resulting from hypotropia of the left eye after retinal detachment surgery. Removal of a previously implanted silicon sponge had little effect because of fibrous adhesion between the inferior rectus muscle and adjacent periorbital fat. We performed amniotic membrane transplantation combined with conventional extraocular muscle surgery. RESULTS: Postoperatively, supraduction of the left eye became almost full. The field of binocular vision was extended markedly by treatment, both in the primary position and with downward gaze. These improvements remained stable over 1 year of follow-up. CONCLUSION: Amniotic membrane transplantation appears to be effective for preventing regrowth of restrictive scar tissue in the fat adherence syndrome.
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Tejido Adiposo/cirugía , Amnios/trasplante , Músculos Oculomotores/cirugía , Enfermedades Orbitales/cirugía , Complicaciones Posoperatorias/cirugía , Desprendimiento de Retina/cirugía , Tejido Adiposo/patología , Adulto , Diplopía/etiología , Diplopía/cirugía , Humanos , Masculino , Trastornos de la Motilidad Ocular/etiología , Trastornos de la Motilidad Ocular/cirugía , Enfermedades Orbitales/etiología , Complicaciones Posoperatorias/patología , Síndrome , Adherencias Tisulares/cirugía , Visión BinocularRESUMEN
PURPOSE: To determine whether visual field defects can be detected by the multifocal VEP technique. METHODS: Multifocal VEPs were elicited by a pseudorandom binary m-sequence stimulus (VERIS II). The stimulus was a dartboard-like pattern of 61 sectors, and the luminance of each sector alternated between white and black. The stimulus area subtended approximately 25 degrees. Each recording was divided into 8 equal segments, and the total recording time was about 4 min. Multifocal VEPs were recorded from 25 normal subjects and six patients with visual field loss. The responses summed within 4 quadrants were used in the analysis and were compared with the visual fields obtained by perimetry. RESULTS: In six perimetrically-documented visual field defects, the responses summed over each quadrant of the field were reduced in the corresponding affected quadrants. In addition, recovery of the visual field loss following treatment was accompanied by a recovery of the responses. CONCLUSIONS: Multifocal VEPs summed within four quadrants can be used for an objective evaluation of the visual fields. The testing can be obtained in 4 min with no pain or discomfort to the patient.
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Potenciales Evocados Visuales , Hemianopsia/diagnóstico , Campos Visuales , Adulto , Anciano , Encefalopatías/complicaciones , Femenino , Hemianopsia/etiología , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Neuritis Óptica/complicacionesRESUMEN
PURPOSE: We present two cases of severe dry eye in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (SCT) who were successfully treated by the systemic administration of FK506 and corticosteroids. METHODS AND RESULTS: A 29-year-old man with chronic myelogenous leukemia underwent SCT. Oral and lung CGVHD developed on approximately day 130, and dry eye associated with CGVHD was diagnosed on day 168. The patient began receiving cyclosporin A (150 mg/d) for the treatment of oral and lung CGVHD. Treatment with prednisolone (1 mg/kg/d) began on approximately day 300. Oral and lung GVHD improved slightly, but worsened again although systemic administration of cyclosporin A and prednisolone were continued. Cyclosporin A was discontinued, and systemic administration of FK506 was started on day 376. Forty-four days later, marked improvement in the ocular surface and other organs was observed. However, the dry eye worsened while tapering FK506, with no flare of other affected organs. A 43-year-old woman with myelodysplastic syndrome underwent SCT. She received FK506 for prophylaxis of CGVHD. She had mild dry eye before SCT. Oral and intestinal CGVHD developed, and the dry eye worsened significantly on approximately day 150 while tapering FK506. Treatment with prednisolone (1 mg/kg/d) began, and the dose of FK506 was increased. By day 240, the symptoms of dry eye and the findings of the ocular surface markedly improved, and CGVHD in other organs was completely resolved. However, the improvement in the dry eye was lost when FK506 was tapered for the second time. CONCLUSION: Systemic administration of FK506 with corticosteroids is an effective treatment of severe dry eye in patients with CGVHD, but long-term administration may be required to achieve a lasting response. These cases also suggest that further investigation into the use of topical FK506 and prednisolone as a maintenance therapy should be pursued.
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Síndromes de Ojo Seco/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Prednisolona/administración & dosificación , Tacrolimus/administración & dosificación , Adulto , Enfermedad Crónica , Quimioterapia Combinada , Síndromes de Ojo Seco/etiología , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Síndromes Mielodisplásicos/terapiaRESUMEN
PURPOSE: To evaluate visual field loss using multifocal ERG(m-ERG), multifocal VEP(m-VEP), and Heidelberg Retina Flowmeter(HRF) in a patient with branch retinal artery occlusion(BRAO) and brain infarction. CASE: A 38-year-old man noticed inferior-nasal visual field loss in the left eye, and was referred to Keio University Hospital. He suffered from paralysis in the left leg due to brain infarction at the age of 24. However, he had not noticed visual field loss due to the brain infarction. His left fundus showed retinal edema in the area of a superior-temporal retinal artery occulusion. He was diagnosed as having BRAO. The Goldmann and Humphry perimetric examinations revealed homonymous quadrantanopia in the upper left field as well as inferior visual field defect in the left eye. RESULTS: Both m-ERG and m-VEP, especially second-kernel responses, were reduced in the affected retinal area of BRAO. But only m-VEP was affected in the corresponding area of homonymous quadrantanopia in the upper left field. The retinal flow in the area with BRAO evaluated by HRF was decreased in some areas and not in others, suggesting that retinal function was not necessarily consistent with retinal circulation. CONCLUSIONS: m-ERG and m-VEP are useful To differentiate retinal lesions from brain lesions in visual field loss.
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Infarto Cerebral/complicaciones , Oclusión de la Arteria Retiniana/fisiopatología , Campos Visuales , Adulto , Infarto Cerebral/fisiopatología , Electrorretinografía , Potenciales Evocados Visuales , Humanos , MasculinoRESUMEN
PURPOSE: To examine the physiologic condition of the middle retinal layer of patients with X-linked juvenile retinoschisis (xlRS) by studying the on- and off-responses of the photopic electroretinograms (ERGs). METHODS: Eleven unrelated Japanese men (mean age; 24.9 +/- 7.6 years) who were clinically diagnosed with xlRS and molecularly confirmed as having XLRS1 mutations were investigated. For the photopic ERGs, the a-, b- and d-wave amplitudes elicited by long duration stimuli were recorded, and the responses from the xlRS patients were compared to those recorded from normal subjects (n = 14, mean age, 27.5 +/- 4.5 years). We also examined the relationship between the photopic ERG responses and the genotype. RESULTS: No significant difference was found between the a- and d-wave amplitudes in the xlRS patients (34.2 +/- 8.7 microV, 52.5 +/- 10.4 microV, respectively), and those in normal subjects (40.4 +/- 10.3 microV, 44.7 +/- 6.3 microV, respectively). The mean b-wave amplitude in the xlRS patients was significantly smaller (10.5 +/- 7.7 microV) than the mean of normal subjects (46.4 +/- 10.2 microV) (P < 0.0001). No significant correlation was found between the ERG responses and the locus of the mutation. CONCLUSION: The photopic ERG demonstrated considerable impairment of the on-pathway arising from an abnormality of the on-bipolar cells or possibly secondary to Müller cell abnormality in xlRS.
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Electrorretinografía , Ligamiento Genético , Interneuronas/fisiología , Células Fotorreceptoras Retinianas Conos/fisiopatología , Degeneración Retiniana/fisiopatología , Cromosoma X , Adolescente , Adulto , Proteínas del Ojo/genética , Genotipo , Humanos , Luz , Masculino , Mutación , Degeneración Retiniana/genéticaRESUMEN
We examined a Japanese family with X-linked retinitis pigmentosa (RP) associated with a nonsense mutation, R120X, in the RP2 gene. The 26-year-old proband presented at the age of seven years with a two-year history of night blindness. Visual disability worsened with increasing age. At age 24, visual acuity was 0.08 in both eyes. Testing for refractive error indicated mild myopia. Visual fields showed bilateral-constriction to 10 degrees. He had central macular areolar sclerosis in both eyes. Two maternal uncles had vision of light perception to hand movement in their early forties together with dense bilateral cataracts. The ocular phenotype of this family with R120X was considered severe; reported phenotypes associated with this mutation have not been uniform.
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Codón sin Sentido/genética , Proteínas del Ojo , Ligamiento Genético , Proteínas/genética , Retinitis Pigmentosa/genética , Cromosoma X , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Preescolar , ADN/análisis , Proteínas de Unión al GTP , Humanos , Péptidos y Proteínas de Señalización Intracelular , Japón , Masculino , Proteínas de la Membrana , Datos de Secuencia Molecular , Ceguera Nocturna/genética , Oftalmoscopía , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: We performed electrophysiologic tests on two patients with digitalis toxicity who first had photophobia and xanthopsia and revealed reversible reduced visual acuity and binocular central scotoma. CASES: The patients were a 72-year-old male and a 54-year-old male who had symptoms of digitalis toxicity. FINDINGS: The corrected visual acuity was severely decreased during digitalis toxicity, 0.02 oculus dexter (OD) and 0.1 oculus sinister (OS) in case 1 and 0.04 OD and 0.2 OS in case 2. But visual acuity recovered as the blood levels of digitalis decreased to the normal level and the corrected visual acuity was 0.7 OD and 0.8 OS in case 1 and 0.8 OD and 0.9 OS in case 2. We recorded 30 Hz-flicker electroretinogram (ERG), single flash ERG, photopic ERG, and scotopic ERG when digitalis blood levels were elevated and normal. Decreased amplitudes of 30 Hz-flicker ERG and photopic ERG suggested that photoreceptor function was disturbed at digitalis toxicity and cone dysfunction was more severely disturbed than rod dysfunction. CONCLUSION: 30 Hz-flicker ERG, as well as electrocardiogram and digitalis blood level, is a relatively convenient and useful measure of digitalis toxicity. It is necessary consiler toxicity when severe visual dysfunction is observed in patients with digitalis therapy.
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Digoxina/envenenamiento , Agudeza Visual/efectos de los fármacos , Anciano , Electrorretinografía , Humanos , Masculino , Persona de Mediana Edad , Escotoma/inducido químicamenteRESUMEN
PURPOSE: To elucidate histopathologic features of the lacrimal gland in chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. METHODS: Lacrimal gland specimens from five patients who had dry eye as part of the symptoms of chronic GVHD were examined by immunohistochemistry and transmission electron microscopy. Lacrimal gland specimens from five patients with Sjögren's syndrome (SS) were used as control samples. RESULTS: Lymphocytes, predominantly T cells, were found primarily in the periductal areas of the lacrimal gland from patients with chronic GVHD, whereas B cells were the dominant infiltrating cells in the acinar areas of the lacrimal gland from patients with SS. Notable findings in the lacrimal gland from patients with chronic GVHD were marked fibrosis of the glandular interstitium and an increase in the number of CD34(+) stromal fibroblasts. These findings were more prominent in patients with severe dry eye than in those with mild dry eye. Electron microscopic observations of the lacrimal gland from patients with chronic GVHD revealed that stromal fibroblasts were attached to various inflammatory cells, especially T cells, through primitive or rudimentary contacts. In addition, the presence of a well-developed rough endoplasmic reticulum in the fibroblasts and newly synthesized collagen fibrils in the extracellular matrix indicated an active production of extracellular matrix components. Electron micrographs revealed multilayered and thickened basal laminae of blood vessels, ducts, and lobules in the lacrimal gland of patients with chronic GVHD; however, these observations were infrequently observed in the lacrimal glands of patients with SS. CONCLUSIONS: The results suggest substantial differences in the lacrimal gland histopathology of patients with chronic GVHD and SS. In addition, it is likely that stromal fibroblasts are actively involved in the pathogenic process of chronic GVHD in the lacrimal gland by producing excessive extracellular matrix components.