RESUMEN
We describe an approach for exploring microscopic properties of granular media that couples x-ray microtomography and distinct-element-method (DEM) simulations through image analysis. We illustrate it via the study of the intriguing phenomenon of instant arching in an hourglass (in our case a cylinder filled with a polydisperse mixture of glass beads that has a small circular shutter in the bottom). X-ray tomography provides three-dimensional snapshots of the microscopic conditions of the system both prior to opening the shutter, and thereafter, once jamming is completed. The process time in between is bridged using DEM simulation, which settles to positions in remarkably good agreement with the x-ray images. Specifically designed image analysis procedures accurately extract the geometrical information, i.e., the positions and sizes of the beads, from the raw x-ray tomographs, and compress the data representation from initially 5 gigabytes to a few tens of kilobytes per tomograph. The scope of the approach is explored through a sensitivity analysis to input data perturbations in both bead sizes and positions. We establish that accuracy of size--much more than position--estimates is critical, thus explaining the difficulty in considering a mixture of beads of different sizes. We further point to limits in the replication ability of granular flows away from equilibrium; i.e., the difficulty of numerically reproducing chaotic motion.
RESUMEN
Recombinant human Fab antibodies were generated with different reactivities against the hepatitis B virus surface (HBs) antigen. To isolate the antibodies, a method was used that combined transformation of human B cells by Epstein-Barr virus (EBV) infection with a primer-vector system developed for isolating DNA fragments of human Ig Fab portions. With this method, monoclonal and oligoclonal cell lines producing anti-HBs antibodies were established and three anti-HBs Fab antibodies were isolated from two of these cell lines. From analysis of affinity characteristics, immunohistochemical activity, and cytolysis activity, these three Fab antibodies were classified into three different groups. The first group had high affinity for HBs, the second had the ability to kill HBV-infected cells, and the third was applicable to immunohistochemical staining with HBV-infected cells. The combined effect of these antibodies was also investigated by complement-dependent cytotoxicity assay.
Asunto(s)
Anticuerpos Antivirales/biosíntesis , Antígenos de Superficie de la Hepatitis B/inmunología , Fragmentos Fab de Inmunoglobulinas/biosíntesis , Anticuerpos Monoclonales/genética , Afinidad de Anticuerpos , Especificidad de Anticuerpos , Línea Celular Transformada , Humanos , Fragmentos Fab de Inmunoglobulinas/genética , Proteínas Recombinantes de Fusión/análisis , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genéticaRESUMEN
Using the gene trap method and the selection of embryonic stem cells in vitro, we have identified several novel genes involved in mouse development. The detailed analysis of one of these, named midnolin (midbrain nucleolar protein), is reported here. Expression of the midnolin gene is developmentally regulated: it is strongly expressed at the mesencephalon (midbrain) of the embryo in day 12.5 (E12.5) mice. The midnolin encodes a protein of 508 amino acids (aa), which contains a Ubiquitin-like domain. The intracellular distribution of the midnolin was studied by using midnolin-green fluorescent protein (GFP) fusion proteins. Midnolin was found to be localized in the nucleus and nucleolus, but not in the cytoplasm. The nucleolar localization signal was determined to be a 28aa peptide (440-QQKRLRRKARRDARGPYHWTPSRKAGRS-467) located at the C-terminal region of the midnolin. Our results suggest that midnolin is involved in regulation of genes related to neurogenesis in the nucleolus.
Asunto(s)
Mesencéfalo/metabolismo , Proteínas Nucleares/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Células CHO , Línea Celular , Clonación Molecular , Cricetinae , ADN/química , ADN/genética , ADN Complementario/química , ADN Complementario/genética , Embrión de Mamíferos/metabolismo , Femenino , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Proteínas Fluorescentes Verdes , Hibridación in Situ , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Masculino , Mesencéfalo/embriología , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Datos de Secuencia Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Análisis de Secuencia de ADN , Eliminación de Secuencia , Homología de Secuencia de Aminoácido , Distribución TisularRESUMEN
We report on a 9-year-old boy with radio-ulnar synostosis, short stature, microcephaly, scoliosis, and mental retardation. We propose that he has a new syndrome.
Asunto(s)
Discapacidad Intelectual/genética , Microcefalia/genética , Radio (Anatomía)/anomalías , Escoliosis/genética , Sinostosis/genética , Cúbito/anomalías , Niño , Dermatoglifia , Trastornos del Crecimiento/genética , Humanos , Discapacidad Intelectual/complicaciones , Masculino , Microcefalia/complicaciones , Radiografía , Radio (Anatomía)/diagnóstico por imagen , Escoliosis/complicaciones , Síndrome , Sinostosis/complicaciones , Cúbito/diagnóstico por imagenRESUMEN
A new autosomal dominant syndrome resembling craniofrontonasal syndrome was identified by Teebi [1987: Am J Med Genet 28:581-591]. We report on an additional case of Teebi hypertelorism syndrome. A 6-year-old girl presented with brachycephaly, peculiar facial appearance resembling mild frontonasal "dysplasia", small hands and feet with interdigital webbing. In addition, she had previously undescribed manifestations including ventricular septal defect, lipoma of the occipital area, and hypoplastic left hemisphere of the cerebellum. These seem to expand the phenotype of Teebi hypertelorism syndrome. The proposita's father had mild manifestations of the condition including flat occiput, widow's peak, small ears, bulbous nose, brachydactyly with interdigital webbing, and mild shawl scrotum.
Asunto(s)
Anomalías Múltiples/genética , Hipertelorismo/genética , Niño , Familia , Femenino , Humanos , Fenotipo , SíndromeRESUMEN
We review clinical information on 141 individuals with Dubowitz syndrome, 105 reported since 1965, and 36 previously unreported. We define the Dubowitz syndrome phenotype on the basis of clinical descriptions. The facial appearance is characteristic and present in most patients with Dubowitz syndrome. The phenotypic spectrum is quite variable and ranges from normal growth and head circumference with mild psychomotor retardation and lack of eczema to a condition of severe growth retardation, mental retardation, microcephaly, and eczema. Overall, the condition may involve the cutaneous, ocular, dental, digestive, musculoskeletal, urogenital, cardiovascular, neurological, hematological, and immune systems. Characteristic behavior patterns which have not been cited previously are present in our cases; most patients are hyperactive, shy, hate crowds, and like music, rhythm, and vibrations from music speakers, tape recorders, or transmitted through floors. Dubowitz syndrome is an autosomal recessive disorder with possibly increased frequency of parental consanguinity. Heterogeneity cannot be excluded at this time.
Asunto(s)
Anomalías Múltiples , Retardo del Crecimiento Fetal , Discapacidad Intelectual , Adolescente , Adulto , Peso al Nacer , Niño , Preescolar , Eccema , Femenino , Crecimiento , Trastornos del Crecimiento , Humanos , Lactante , Masculino , Microcefalia , Embarazo , Complicaciones del Embarazo/epidemiología , Estudios Retrospectivos , Caracteres Sexuales , SíndromeRESUMEN
We report on an 8-year-old Japanese boy with Setleis syndrome. The patient had a very characteristic "coarse" facial appearance, bitemporal "forceps marks," skin aplasia, sparse hair, and skin hypo- and hyperpigmentation. He also had previously undescribed manifestations, including an aberrant hair pattern of the forehead, linear skin lesions on the forehead, short palpebral fissures, a small skin tag on the right cheek, cone-shaped teeth, and pectus carinatum. Dermatoglyphic studies documented aberrant distal palmar creases (simian crease variant), 8 arches, and reduced total finger ridge count. When serial photographs were reviewed, his facial characteristics became more obvious with increasing age.
Asunto(s)
Cara/anomalías , Niño , Dermatoglifia , Estudios de Seguimiento , Cabello , Humanos , Masculino , SíndromeRESUMEN
We describe a total of 18 individuals, in 3 families, with a median nodule of the upper lip. In family 1, the proposita, an 8-month-old infant girl, was otherwise phenotypically normal except for a median nodule of the upper lip. The proposita's elder brother and mother, both phenotypically normal, also had the similar nodule of the upper lip. On the mother's side, the proposita's greatgrandmother, greatgrandaunt, grandfather, greataunt, two aunts, and one female cousin all had a median nodule of the upper lip. In family 2, the proposita, proposita's mother and maternal grandfather had a median nodule of the upper lip. In family 3, the proposita, proposita's father, paternal grandfather, paternal uncle, and cousin had a median nodule of the upper lip. Analysis of 3 families indicates that the condition is an autosomal dominant trait.
Asunto(s)
Labio/anomalías , Adulto , Niño , Preescolar , Femenino , Genes Dominantes , Humanos , Lactante , Masculino , LinajeRESUMEN
We report on a newborn girl with duplication of 18q12.2-->18qter and deficiency of 18p11.2-->18pter which resulted from meiotic recombination of the maternal pericentric inversion, inv(18)(p11.2q12.2). Her clinical manifestations were compatible with those of partial trisomy 18q syndrome. We review the previously reported 9 cases in 8 families of rec(18) resulting from recombination of a parental pericentric inversion.
Asunto(s)
Anomalías Múltiples/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 18 , Adulto , Inversión Cromosómica , Femenino , Humanos , Recién Nacido , Cariotipificación , Madres , SíndromeRESUMEN
We report on sibs and their mother, all with del(18p). The propositus, an 11-month-old, had developmental delay, round face, hypertelorism, large ears, broad nasal bridge, upturned nostrils, micrognathia, a high palate, redundant skin around the neck, micropenis, and cryptorchidism. The elder sister, a two and 7/12-year-old, had round face, hypertelorism, broad nasal bridge, narrow and high palate, redundant skin around the neck, short fingers, and hypoplastic genitalia. Their mother had microcephaly, hypertelorism, prominent columella, broad nasal bridge, wide mouth, high palate, malaligned teeth, and clinodactyly of the fifth fingers. Serial photographs of the mother showed that the characteristic round face in infancy changed to long face with age. The present report suggests that the mother with del(18p) may be fertile, and proper genetic counseling and long follow-up is necessary for the patient with del(18p) syndrome.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 18/genética , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Adolescente , Adulto , Niño , Bandeo Cromosómico , Discapacidades del Desarrollo/patología , Salud de la Familia , Femenino , Humanos , Hipertelorismo/patología , Lactante , Cariotipificación , SíndromeRESUMEN
We report on a total of 4 individuals in 2 families with Kabuki make-up syndrome. In family 1, the proposita, a 2 4/12-year-old girl and her mother had typical Kabuki make-up syndrome. The proposita also had early breast development. In family 2, the proposita, a 6-month-old girl and her mother had typical Kabuki make-up syndrome. The proposita died at age 6 months. Analysis of 2 families indicates that the condition is an autosomal dominant inheritance with variable expressivity.
Asunto(s)
Anomalías Múltiples/genética , Genes Dominantes , Anomalías Múltiples/fisiopatología , Adulto , Preescolar , Femenino , Humanos , Lactante , Japón , SíndromeRESUMEN
A girl with a 46,X,t(X;21) (q13.3;p11.1) karyotype presented with skin redundancy, especially in the neck, prominent occiput and micrognathia, and later developed hypotonia, hypopigmentation, sparse scalp hair, and profound mental retardation characteristic of Menkes disease. Her serum copper (14 microg/dl) and ceruloplasmin (9 mg/dl) levels were extremely low. Fluorescent in situ hybridization analysis with a 100-kb P1-derived artificial chromosome probe containing the Menkes disease gene demonstrated three twin-signals, one on the normal X chromosome and one each on derivative chromosomes X and 21, indicating that the Xq13.3 breakpoint was located within the gene. Replication pattern analysis showed that the normal X chromosome was late replicating, whereas the derivative X chromosome was selectively early replicating. These results indicated that Menkes disease in our patient resulted from a de novo translocation that disrupts the disease gene.
Asunto(s)
Proteínas de Transporte de Catión , Cromosomas Humanos Par 21/genética , Síndrome del Pelo Ensortijado/genética , Síndrome del Pelo Ensortijado/patología , Proteínas Recombinantes de Fusión , Translocación Genética/genética , Cromosoma X/genética , Adenosina Trifosfatasas/genética , Proteínas Portadoras/genética , ATPasas Transportadoras de Cobre , Replicación del ADN/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , CariotipificaciónRESUMEN
Chromosomes were studied in 9 individuals with pigmentary dysplasias of the skin and other abnormalities. Of the 9 individuals, 5 were chromosomal mosaics in both blood lymphocytes and skin fibroblasts (46,XY/47,XY, + 13;46,XX/47,XX, + 14;46,XY/47,XY, + 18;46,XX/47,XX, + 18;46, XX/47,XX, + mar), while the other 4 individuals were chromosomally normal in both tissues studied. The pigmentary dysplasias involved hypo- or hyperpigmented patches/flecks or lines/whorls. The latter ran along Blachko lines on the back, abdomen and the limbs. These patterns varied not only between individuals but also between different regions of an individual. The possibility of chimerism was studied but ruled out (1/32 to 1/256) in 7 individuals, using chromosomal heteromorphisms in the patients and their parents as markers.
Asunto(s)
Mosaicismo , Trastornos de la Pigmentación/genética , Adolescente , Adulto , Células Cultivadas , Preescolar , Femenino , Fibroblastos/patología , Humanos , Lactante , Cariotipificación , Linfocitos/patología , Masculino , Trastornos de la Pigmentación/patología , Piel/patologíaRESUMEN
Of 10 patients with typical Sotos sequence, 5 had various congenital heart defects. They included 2 patients with secundum atrial septal defect, and one patient each with patent ductus arteriosus with mitral valve regurgitation, tricuspid atresia plus pulmonary atresia, and ventricular septal defect. Increases of head circumference and weight gain were less accelerated in the patients with congenital heart defects than in those without heart defects, while growth in length was comparable between the 2 groups. In view of these findings, it is suggested that the rate of congenital heart defects in patients with Sotos sequence is much higher than that reported in the literature.
Asunto(s)
Gigantismo/complicaciones , Cardiopatías Congénitas/complicaciones , Antropometría , Preescolar , Femenino , Gigantismo/genética , Cabeza/anomalías , Humanos , Lactante , Cariotipificación , MasculinoRESUMEN
We report on a female baby with Fryns syndrome who died soon after birth. The patient had short limbs, coarse face, hypoplastic lungs, diaphragmatic hernia, and acral hypoplasia. Literature review disclosed varying degrees of skeletal manifestations in Fryns syndrome; short limbs may be a component of Fryns syndrome.
Asunto(s)
Anomalías Múltiples , Huesos/anomalías , Anomalías Múltiples/genética , Adulto , Cara/anomalías , Femenino , Hernia Diafragmática/genética , Humanos , Recién Nacido , Deformidades Congénitas de las Extremidades , Pulmón/anomalías , SíndromeRESUMEN
We report on a 2-year-old boy with Juberg-Marsidi syndrome. He has mental retardation, short stature, micropenis, cryptorchidism, and minor facial abnormalities. His Leydig cells responded to the administration of human chorionic gonadotropin and there were positive responses of LH and FSH to the administration of LH-RH. He showed normal weight gain and head circumference which have not been described previously. The association of Juberg-Marsidi syndrome with HbH disease was ruled out in the propositus.
Asunto(s)
Anomalías Múltiples/genética , Sordera/genética , Enanismo/genética , Hipogonadismo/genética , Discapacidad Intelectual/genética , Pene/anomalías , Cromosoma X , Preescolar , Gonadotropina Coriónica/uso terapéutico , Criptorquidismo/genética , Hormona Folículo Estimulante/uso terapéutico , Humanos , Hipogonadismo/tratamiento farmacológico , Hormona Luteinizante/uso terapéutico , Masculino , SíndromeRESUMEN
We report on 2 sibs with desquamative interstitial pneumonia. The female died at age 1 7/12 years despite use of prednisolone and methylprednisolone, while the male, now age 3 years. is alive with oxygen support. The occurrence of desquamative interstitial pneumonia in sibs born to normal parents suggests that in some cases the disease is an autosomal-recessive trait.
Asunto(s)
Enfermedades Pulmonares Intersticiales/genética , Femenino , Humanos , Lactante , Enfermedades Pulmonares Intersticiales/patología , Masculino , Núcleo FamiliarRESUMEN
We report on a 30-year-old woman with premature aging, immunodeficiency, and other abnormalities. She had many manifestations of the Mulvihill-Smith syndrome, a disorder that has been described in 4 sporadic individuals, ranging in age from 4 to 17 years. The common manifestations include short stature, microcephaly, a senile face with an underdeveloped lower half, diminished facial subcutaneous fat, multiple pigmented nevi, sensorineural hearing loss, and a low IgG level. Our patient also had severe mental retardation, brachydactyly, severe T cell dysfunction, and suffered from severe verruca vulgaris and a chronic, active Epstein-Barr virus infection. The fact that her parents were first cousins suggests autosomal recessive inheritance of her disorder. Two alternative possibilities were considered: the disorder in the patient represents the Mulvihill-Smith syndrome with immune deficiency as a sign of its advanced stage, or a hitherto undescribed syndrome.
Asunto(s)
Síndromes de Inmunodeficiencia/genética , Síndrome de Werner/genética , Adulto , Sordera/genética , Femenino , Genes Recesivos , Trastornos del Crecimiento/genética , Humanos , Discapacidad Intelectual/genética , Microcefalia/genética , SíndromeRESUMEN
We report on 10 Japanese individuals from 3 families affected with Aarskog syndrome. Pulmonary stenosis and ventricular septal defect with spontaneous closure were detected respectively, in 2 of them as an uncommon finding. A review documented 169 non-Japanese cases (2 with congenital heart defects), while of 30 Japanese individuals reported till now, 4 (including ours) had cardiac anomalies. We propose that this combination is not coincidental and that in all cases of Aarskog syndrome a cardiac evaluation is indicated.
Asunto(s)
Anomalías Múltiples , Enanismo , Cara/anomalías , Genitales Masculinos/anomalías , Cardiopatías Congénitas , Niño , Preescolar , Deformidades Congénitas de la Mano , Humanos , Masculino , Síndrome , Cromosoma XRESUMEN
We report on a family in which three individuals, a male and two females were affected with nonsyndromal diffuse cystic dysplasia of the kidneys. The parents had no renal abnormality. The occurrence of diffuse cystic dysplasia in three sibs born to normal parents suggests autosomal recessive inheritance.