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1.
J Virol ; 74(5): 2426-9, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10666274

RESUMEN

Data from naturally infected deer mice (Peromyscus maniculatus) were used to investigate vertical transmission of Sin Nombre virus (SNV) and SNV-specific antibody. The antibody prevalence in juvenile mice (14 g or less) was inversely proportional to the mass of the animal, with juvenile deer mice weighing less than 11 g most likely to be antibody positive (26.9%) and juvenile mice weighing between 13 and 14 g least likely to be antibody positive (12.9%). Although a significant sex bias in seropositivity was detected in adult deer mice, no significant sex bias in seropositivity was detected in juvenile animals. Ten juvenile deer mice were identified that had initially tested positive for SNV-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA) but had subsequently tested negative when recaptured as adults. SNV RNA was detected by reverse transcriptase PCR (RT-PCR) in the blood of ELISA-positive adult deer mice but not in the blood of ELISA-positive juveniles. One of the juvenile mice initially tested negative for SNV RNA but later tested positive when recaptured as an ELISA-positive adult. The RT-PCR results for that individual correlated with the disappearance and then reappearance of SNV-specific IgG, indicating that the presence of SNV RNA at later time points was due to infection with SNV via horizontal transmission. SNV-specific antibody present in both ELISA-positive juvenile and adult mice was capable of neutralizing SNV. Additionally, our data indicate that SNV is not transmitted vertically.


Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Hantavirus/veterinaria , Orthohantavirus/inmunología , Peromyscus , Enfermedades de los Roedores/inmunología , Factores de Edad , Animales , California/epidemiología , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Orthohantavirus/aislamiento & purificación , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Nevada/epidemiología , Prevalencia , ARN Viral/sangre , Enfermedades de los Roedores/sangre , Enfermedades de los Roedores/epidemiología , Roedores , Estudios Seroepidemiológicos , Factores Sexuales
2.
J Virol ; 72(9): 6997-7004, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9696791

RESUMEN

Human cytomegalovirus (HCMV) lytic-phase DNA replication initiates at the cis-acting origin of replication, oriLyt. oriLyt is a structurally complex region containing repeat elements and transcription factor binding sites. We identified two site-specific alkali-labile regions within oriLyt which flank an alkali-resistant DNA segment. These alkali-sensitive regions were the result of the degradation of two RNA species embedded within oriLyt and covalently linked to viral DNA. The virus-associated RNA, vRNA, was identified by DNase I treatment of HCMV DNA obtained from sucrose gradient purified virus. This heterogeneous population of vRNA was end labeled and used as a hybridization probe to map the exact location of vRNAs within oriLyt. vRNA-1 is localized between restriction endonuclease sites XhoI at nucleotide (nt) 93799 and SacI at nt 94631 and is approximately 500 bases long. The second vRNA, vRNA-2, lies within a region which exhibits a heterogeneous restriction pattern located between the SphI (nt 92636) and BamHI (nt 93513) and is approximately 300 bases long. This region was previously shown to be required for oriLyt replication (D. G. Anders, M. A. Kacica, G. S. Pari, and S. M. Punturieri, J. Virol. 66:3373-3384, 1992). RNase H analysis determined that vRNA-2 forms a persistent RNA-DNA hybrid structure in the context of the viral genome and in an oriLyt-containing plasmid used in the transient-replication assay.


Asunto(s)
Citomegalovirus/genética , ADN Viral , ARN Viral , Recombinación Genética , Origen de Réplica , Sitios de Unión , Línea Celular , Mapeo Cromosómico , Humanos , Conformación de Ácido Nucleico , Mapeo Restrictivo , Hidróxido de Sodio
3.
Alcohol Alcohol ; 29(6): 729-44, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7695792

RESUMEN

The prevalence of TaqI A alleles of the D2 dopamine receptor (DRD2) gene was examined in two subgroups of medically ill nonalcoholics (more prevalent and less prevalent substance users, MPSU and LPSU, respectively) and in two subgroups of medically ill alcoholics (more severe and less severe alcoholics, MSA and LSA, respectively). The prevalence of the A1 allele in the 80 nonalcoholic and 73 alcoholic patients was 30.0% and 52.1%, respectively (P = 0.009). In the four subgroups of these patients, the prevalence of this allele was: LPSU = 18.2%, MPSU = 34.5%, LSA = 44.4% and MSA = 58.3%. Linear trend analysis showed that as the use of substances and severity of alcoholism increase, so does A1 prevalence (P = 0.001). Specific, subgroup comparisons showed A1 prevalence in MSA to be about 3-fold (P = 0.007) and 1.5-fold (P = 0.04) higher than in LPSU and MPSU subgroups, respectively. Similarly, in a combined analysis of independent studies, A1 prevalence in MSA was higher when compared to LSA (P < 5 x 10(-3), MPSU (P < 10(-4) and LPSU (P < 10(-8) subgroups. There was virtually no difference in the prevalence of the A1 allele between LSA and MPSU subgroups. None of the specific medical or neuropsychiatric complications of alcoholism was associated with the A1 allele. In conclusion, the severity of alcohol dependence in alcoholics and of substance use behaviors in controls are important variables in DRD2 allelic association. The present report and converging lines of evidence suggest that the DRD2 locus could represent a prominent gene risk factor for susceptibility to severe alcoholism. However, other genes and environmental factors, when combined, still play the larger role.


Asunto(s)
Alcoholismo/genética , Alelos , ADN Polimerasa Dirigida por ADN/genética , Hepatopatías Alcohólicas/genética , Receptores de Dopamina D2/genética , Adulto , Anciano , Femenino , Genotipo , Humanos , Drogas Ilícitas , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/genética , Polimerasa Taq
4.
Int J Eat Disord ; 15(3): 205-17, 1994 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8199600

RESUMEN

The prevalence of Taql A D2 dopamine receptor (DRD2) alleles was determined in 73 obese women and men. In this sample with a mean body mass index of 35.1, the A1 (minor) allele of the DRD2 gene was present in 45.2% of these nonalcohol, nondrug abusing subjects. The DRD2 A1 allele was not associated with a number of cardiovascular risk factors examined, including blood lipids (cholesterol, high-density lipoprotein [HDL]- and low-density lipoprotein [LDL]-cholesterol, and triglycerides). However, phenotypic factors characterized by the presence of parental history and postpuberty onset of obesity as well as carbohydrate preference were associated with obese subjects carrying the A1 allele. The cumulative number of these three factors was positively and significantly (p < .0002) related to A1 allelic prevalence. The data showing an association of the minor allele of the DRD2 gene with phenotypic characteristics suggest that this gene, located on q22-q23 region of chromosome 11, confers susceptibility to a subtype of this disorder.


Asunto(s)
Obesidad/genética , Receptores de Dopamina D2/genética , Adolescente , Adulto , Factores de Edad , Anciano , Alelos , Índice de Masa Corporal , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Cromosomas Humanos Par 11 , Femenino , Preferencias Alimentarias/fisiología , Preferencias Alimentarias/psicología , Humanos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/psicología , Fenotipo , Reacción en Cadena de la Polimerasa , Factores de Riesgo
5.
Am J Med Genet ; 46(6): 689-93, 1993 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-8362911

RESUMEN

Familial Mediterranean fever (FMF) is an autosomal recessively inherited inflammatory disorder characterized by recurrent short episodes of fever, peritonitis, arthritis, and pleuritis. Recently, linkage was demonstrated between FMF and the VNTR probes 3'HVR and 5'HVR of the alpha-globin complex at 16p13.3 (theta = 0.06-0.10, Lodmax = 9.76-14.47) and the insertion/deletion polymorphism detected by the probe CMM65 of D16S84 (theta = 0.04, Lodmax = 9.17). We have now mapped the FMF gene between the two flanking markers D16S283/D16S291 (theta = 0.038) and D16S80 (theta = 0.159). The proximity of the microsatellite markers in D16S283 and D16S291 to the FMF gene allows preclinical diagnosis in most pedigrees with affected individuals.


Asunto(s)
Cromosomas Humanos Par 16 , Fiebre Mediterránea Familiar/genética , ADN Satélite , Ligamiento Genético , Marcadores Genéticos , Humanos , Recombinación Genética
6.
Nat Genet ; 4(3): 289-94, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7689389

RESUMEN

Maternally transmitted non-syndromic deafness was described recently both in pedigrees with susceptibility to aminoglycoside ototoxicity and in a large Arab-Israeli pedigree. Because of the known action of aminoglycosides on bacterial ribosomes, we analysed the sequence of the mitochondrial rRNA genes of three unrelated patients with familial aminoglycoside-induced deafness. We also sequenced the complete mitochondrial genome of the Arab-Israeli pedigree. All four families shared a nucleotide 1555 A to G substitution in the 12S rRNA gene, a site implicated in aminoglycoside activity. Our study offers the first description of a mitochondrial rRNA mutation leading to disease, the first cases of non-syndromic deafness caused by a mitochondrial DNA mutation and the first molecular genetic study of antibiotic-induced ototoxicity.


Asunto(s)
Sordera/genética , ARN Ribosómico/genética , ARN/genética , Aminoglicósidos , Antibacterianos/efectos adversos , Secuencia de Bases , Sordera/inducido químicamente , Etnicidad , Femenino , Humanos , Israel , Masculino , Datos de Secuencia Molecular , Linaje , Mutación Puntual , ARN Mitocondrial
7.
Pediatr Res ; 31(6): 557-60, 1992 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1635816

RESUMEN

Mitochondrial DNA deletions have been described in the Kearns-Sayre syndrome (KSS) and the Pearson's marrow-pancreas syndrome. In some cases, the same 4,977-bp deletion has been identified in these two very different diseases. Therefore, it is not currently possible to predict the clinical phenotype from the size or location of the deletion. Instead, differential tissue distribution of the deletion has been implicated as one possible determinant of phenotype. In particular, in KSS the deletions have not been detected by Southern blotting in the blood, whereas in Pearson's syndrome they are easily detectable. We describe here an 11-y-old boy with clinically characteristic KSS and a 7.4-kb mitochondrial DNA deletion between nucleotides 7,194 and 14,595. Southern blotting reveals that 75% of the mitochondrial DNA molecules from his peripheral blood have this deletion. This case blurs further the molecular distinction between the KSS and Pearson's marrow-pancreas syndrome, questioning whether tissue distribution is a sufficient explanation for the very different phenotypes of these disorders.


Asunto(s)
Deleción Cromosómica , ADN Mitocondrial/genética , Síndrome de Kearns-Sayre/genética , Anemia Sideroblástica/genética , Secuencia de Bases , Niño , Mapeo Cromosómico , Humanos , Masculino , Datos de Secuencia Molecular , Enfermedades Pancreáticas/genética , Fenotipo , Síndrome
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