RESUMEN
The transcription factor-like nuclear regulator (TFNR) is a novel human gene that maps on 5q13, distal to the duplicated region that includes SMN1, the spinal muscular atrophy (SMA) determining gene. The location of TFNR allowed us to design an evolutionary model of the SMA region. The 9.5-kb TFNR transcript is highly expressed in cerebellum and weakly in all other tissues tested. TFNR encodes a protein of 2254 amino acids (aa) and contains nine repeats of a novel 55-aa motif, of yet unknown function. The coding region is organized in 32 exons. Alternative splicing of exon 15 results in a truncated protein of 796 aa. TFNR comprises a series of polypeptides that range from 55 to 250 kDa. Immunocytological studies showed that the TFNR protein is present exclusively in the nucleus, where it is concentrated in several nuclear structures. Amino acids 155-474 show significant homology to TFC5, a subunit of the yeast transcription factor TFIIIB, suggesting that TFNR is a putative transcription factor. Based on its proximity to SMN1 and its expression pattern, TFNR may be a candidate gene for atypical forms of SMA with cerebral atrophy and axonal neuropathy that have been shown to carry large deletions in the SMA region.
Asunto(s)
Cromosomas Humanos Par 5 , Proteínas Fúngicas/genética , Proteínas Nucleares/genética , Proteínas de Saccharomyces cerevisiae , Empalme Alternativo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Secuencia de Bases , ADN Complementario , Exones , Duplicación de Gen , Humanos , Hibridación Fluorescente in Situ , Intrones , Datos de Secuencia Molecular , Proteínas Nucleares/química , Oxidorreductasas , Mapeo Físico de Cromosoma , ARN Mensajero/genética , Homología de Secuencia de Aminoácido , Factor de Transcripción TFIIIBRESUMEN
Human chromosome 5q11.2-q13.3 and its ortholog on mouse chromosome 13 contain candidate genes for an inherited human neurodegenerative disorder called spinal muscular atrophy (SMA) and for an inherited mouse susceptibility to infection with Legionella pneumophila (Lgn1). These homologous genomic regions also have unusual repetitive organizations that create practical difficulties in mapping and raise interesting issues about the evolutionary origin of the repeats. In an attempt to analyze this region in detail, and as a way to identify additional candidate genes for these diseases, we have determined the sequence of 179 kb of the mouse Lgn1/SMA interval. We have analyzed this sequence using BLAST searches and various exon prediction programs to identify potential genes. Since these methods can generate false-positive exon declarations, our alignments of the mouse sequence with available human orthologous sequence allowed us to discriminate rapidly among this collection of potential coding regions by indicating which regions were well conserved and were more likely to represent actual coding sequence. As a result of our analysis, we accurately mapped two additional genes in the SMA interval that can be tested for involvement in the pathogenesis of SMA. While no new Lgn1 candidates emerged, we have identified new genetic markers that exclude Smn as an Lgn1 candidate. In addition to providing important resources for studying SMA and Lgn1, our data provide further evidence of the value of sequencing the mouse genome as a means to help with the annotation of the human genomic sequence and vice versa.
Asunto(s)
Cromosomas Humanos Par 5/genética , Enfermedad de los Legionarios/genética , Atrofia Muscular Espinal/genética , Proteínas del Tejido Nervioso/genética , Animales , Secuencia de Bases , Mapeo Cromosómico , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , ADN/genética , Cartilla de ADN/genética , Exones , Marcadores Genéticos , Humanos , Ratones , Datos de Secuencia Molecular , Proteína Inhibidora de la Apoptosis Neuronal , Polimorfismo Genético , Proteínas de Unión al ARN , Proteínas del Complejo SMN , Homología de Secuencia de Ácido Nucleico , Especificidad de la EspecieRESUMEN
Recently, the human orthologue to the cell cycle checkpoint genes rad17 (Schizosaccharomyces pombe) and RAD24 (Saccharomyces cerevisiae), called HRAD17, has been isolated and localized to chromosome 4. Independently, we have isolated the HRAD17 transcript and mapped it to chromosome 5q13 between the CCNB1 and BTF2p44cen genes. Furthermore, we have identified the complete exon-intron structure of HRAD17. The gene is organized into 14 exons, the translation initiation site lies within exon 2, and the stop codon within exon 14. Two further HRAD17 pseudogenes, HRAD17P1 and HRAD17P2, were identified on chromosomes 7p21 and 13q14.3, respectively, encompassing exons 3-14 and bearing 84% and 93% homology, respectively. Additionally, we have isolated the coding region of the mouse orthologue, Mrad17, and mapped it on chromosome 13 between Ccnb1 and Btf2p44, the same two genes between which it maps in human. The predicted Mrad17 polypeptide encompasses 687 amino acids and shows 89% similarity to HRAD17. Both genes are most highly expressed in testis compared to all other tissues, as shown by Northern blot hybridization. Histological studies, based on in situ hybridization with radioactively labeled antisense HRAD17 riboprobes, showed a strong expression within the germinal epithelium of the seminiferous tubuli in normal testis whereas in testicular tumors (seminomas) only weak, diffuse signals were seen. In light of the known function of the yeast orthologue at meiotic and mitotic checkpoints, as well as the strong expression in testis and weak expression in seminomas, we suggest a putative involvement of HRAD 17 in testicular tumorigenesis.
Asunto(s)
Proteínas de Ciclo Celular/genética , Seminoma/genética , Seminoma/metabolismo , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Testículo/metabolismo , Animales , Secuencia de Bases , Northern Blotting , Southern Blotting , Mapeo Cromosómico , Cromosomas Humanos Par 5 , ADN Complementario/análisis , Proteínas de Unión al ADN , Exones , Biblioteca de Genes , Humanos , Hibridación in Situ , Hibridación Fluorescente in Situ , Péptidos y Proteínas de Señalización Intracelular , Intrones , Masculino , Ratones , Modelos Genéticos , Datos de Secuencia Molecular , Proteínas Nucleares , Seudogenes , Proteínas de Saccharomyces cerevisiae , Proteínas de Schizosaccharomyces pombe , Testículo/anatomía & histología , Distribución TisularRESUMEN
The evolution of state injury control programs, like the evolution of public health itself, involves many jurisdictions and disciplines outside the health domain and requires the cooperation and coordination of many sectors. Perhaps most important is that it requires involvement by the states to assure success. In California, the federal investment of less than $2 million in capacity building spread over five years has produced more than $8 million in injury control programming in the subsequent four years.
Asunto(s)
Servicios de Salud Comunitaria/organización & administración , Planes Estatales de Salud/organización & administración , Heridas y Lesiones/prevención & control , California/epidemiología , Implementación de Plan de Salud , Planificación en Salud/organización & administración , Humanos , Prevalencia , Planes Estatales de Salud/economía , Estados Unidos , Heridas y Lesiones/epidemiologíaRESUMEN
OBJECTIVE: To describe the trends in firearm fatalities in California between 1987 and 1991 and the 153 firearm injuries in girls and women treated at the King/Drew Medical Center, Los Angeles, Calif, from September 1, 1991, to December 31, 1992. DESIGN: Retrospective study. SETTING: The study was conducted at the King/Drew Medical Center, a university-based county hospital, one of the major trauma centers in Los Angeles. PATIENTS: At the King/Drew Medical Center, 32 patients (21%) required at least one major procedure. Of the 16 patients who died, 14 (88%) died in the emergency department of wounds to the head (six patients), chest (five patients), and abdomen (three patients). The odds ratio of dying if injured in the head, face, or neck was 2.23, and in the abdomen, 1.0. Surgeons rarely probe for the underlying cause of injury. MAIN OUTCOME: The outcome has been a 2.28-fold increase in deaths in girls and women aged 10 to 19 years. RESULTS: Much of the violence against girls and women is perpetrated by those known to them. CONCLUSION: Firearms are the most frequently used weapon in female homicides. Firearm fatalities in women represent a significant problem among all ethnic groups. Trauma centers must take the lead in the collection of meaningful data to implement effective gender- and ethnic-specific violence prevention strategies.
Asunto(s)
Heridas por Arma de Fuego , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Homicidio/estadística & datos numéricos , Humanos , Lactante , Los Angeles/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Salud Urbana , Heridas por Arma de Fuego/mortalidad , Heridas por Arma de Fuego/patologíaRESUMEN
Risk assessments for carcinogens are being developed through an accelerated process in California as a part of the state's implementation of Proposition 65, the Safe Drinking Water and Toxic Enforcement Act. Estimates of carcinogenic potency made by the California Department of Health Services (CDHS) are generally similar to estimates made by the U.S. Environmental Protection Agency (EPA). The largest differences are due to EPA's use of the maximum likelihood estimate instead of CDHS' use of the upper 95% confidence bounds on potencies derived from human data and to procedures used to correct for studies of short duration or with early mortality. Numerical limits derived from these potency estimates constitute "no significant risk" levels, which govern exemption from Proposition 65's discharge prohibition and warning requirements. Under Proposition 65 regulations, lifetime cancer risks less than 10(-5) are not significant and cumulative intake is not considered. Following these regulations, numerical limits for a number of Proposition 65 carcinogens that are applicable to the control of toxic discharges are less stringent than limits under existing federal water pollution control laws. Thus, existing federal limits will become the Proposition 65 levels for discharge. Chemicals currently not covered by federal and state controls will eventually be subject to discharge limitations under Proposition 65. "No significant risk" levels (expressed in terms of daily intake of carcinogens) also trigger warning requirements under Proposition 65 that are more extensive than existing state or federal requirements. A variety of chemical exposures from multiple sources are identified that exceed Proposition 65's "no significant risk" levels.
Asunto(s)
Carcinógenos Ambientales/análisis , Contaminación Ambiental/legislación & jurisprudencia , Neoplasias/prevención & control , Riesgo , Contaminación del Agua/legislación & jurisprudencia , Animales , California , Carcinógenos Ambientales/toxicidad , Humanos , Concentración Máxima Admisible , Etiquetado de ProductosRESUMEN
Annual incidence rates for 1975-1985 were derived for Kaposi's sarcoma, non-Hodgkin's lymphomas, and seven other malignancies. Never-married men in the San Francisco Bay area constituted the study population. The pattern of increase in incidence of non-Hodgkin's lymphoma among men aged 25-44 years was similar to that seen for Kaposi's sarcoma; both increased significantly in San Francisco between 1980 and 1985 (p less than 0.001), with an increase among census tracts with high incidence of acquired immunodeficiency syndrome (AIDS) that was greater than the increase seen in other San Francisco census tracts. Among men in tracts with a high incidence of AIDS, non-Hodgkin's lymphoma reached an incidence in 1985 that was five times greater than preepidemic rates. These increased rates support the conclusion of clinical studies that non-Hodgkin's lymphoma is an additional manifestation of AIDS. Similar increases in incidence rates were not observed for other malignancies, suggesting that reports of these malignancies in homosexuals may be isolated incidents. Whether rates of non-Hodgkin's lymphoma will continue to increase and whether rates of other potentially AIDS-associated malignancies will increase in the future may depend on the latency of these malignancies and the survival period of AIDS patients.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , Linfoma no Hodgkin/epidemiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/epidemiología , Homosexualidad , Humanos , Linfoma no Hodgkin/complicaciones , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/epidemiología , San Francisco , Sarcoma de Kaposi/complicaciones , Sarcoma de Kaposi/epidemiologíaRESUMEN
Agricultural workers exposed to chlordimeform (Cdf) used as a pesticide on cotton in Imperial County, California, were monitored during the 1982 application season. Cdf metabolites were found in the urine of 132 workers and were positively correlated with the length of exposure and nature of job activity. Persons mixing and loading and engaged in miscellaneous tasks such as cleaning and maintenance of equipment had the greatest exposure. There was no evidence of urinary tract irritation by microscopic analysis of the urine, nor were significant differences found between preseason and postseason serum chemistry results. Despite the use of protective clothing and closed system transfer devices, Cdf was absorbed by workers as evidenced by urinary metabolite excretion.
Asunto(s)
Enfermedades de los Trabajadores Agrícolas/inducido químicamente , Amidinas/efectos adversos , Clorfenamidina/efectos adversos , Clorfenamidina/orina , Exposición a Riesgos Ambientales , Femenino , Humanos , Inactivación Metabólica , Masculino , RiesgoRESUMEN
To identify risk factors for the occurrence of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual men, we conducted a case-control study in New York City, San Francisco, Los Angeles, and Atlanta. Fifty patients (cases) (39 with Kaposi's sarcoma, 8 with pneumocystis pneumonia, and 3 with both) and 120 matched homosexual male controls (from sexually transmitted disease clinics and private medical practices) participated in the study. The variable most strongly associated with illness was a larger number of male sex partners per year (median, 61 for patients; 27 and 25 for clinic and private practice controls, respectively). Compared with controls, cases were also more likely to have been exposed to feces during sex, have had syphilis and non-B hepatitis, have been treated for enteric parasites, and have used various illicit substances. Certain aspects of a lifestyle shared by a subgroup of the male homosexual population are associated with an increased risk of Kaposi's sarcoma and pneumocystis pneumonia.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/etiología , Neumonía por Pneumocystis/etiología , Sarcoma de Kaposi/etiología , Adolescente , Adulto , Homosexualidad , Humanos , Drogas Ilícitas , Inmunidad Celular , Estilo de Vida , Masculino , Persona de Mediana Edad , Nitratos , Pentanoles , Conducta Sexual , Estados UnidosAsunto(s)
Amianto/análisis , Contaminantes Ambientales/análisis , Adulto , Arizona , Niño , Descontaminación , Exposición a Riesgos Ambientales , Agencias Gubernamentales , Humanos , Minería , RiesgoRESUMEN
A nationwide survey of heavy-metal exposure in children living near primary nonferrous metal smelters demonstrated high urine arsenic levels in children living near a copper smelter in Ajo, Arizona. Airborne smelter emissions and drinking water were the apparent sources of exposure. To determine whether increased arsenic absorption had produced adverse health effects, we conducted an evaluation of 132 Ajo children 5 to 18 years old and compared results with those of 47 children from a comparison town with low arsenic exposure. Environmental testing showed that Ajo's municipal water supply contained arsenic in concentrations of 0.09 mg/l (the EPA standard is 0.05 mg/l); arsenic concentrations in dust averaged 342.2 microgram/g. Urine arsenic levels in Ajo children correlated positively with amount of tap-water consumed (r = .32, p less than. 0002) and with distance of residence from the smelter (r = .20, p less than .02). Tap-water drinkers had significantly higher urine arsenic levels than bottled water drinkers (t = 4.21 p less than .001). Mean urine arsenic levels were significantly higher for children in Ajo (4.75 microgram/100 ml) than for children in the comparison town (1.17 microgram/100 ml). Hair arsenic levels correlated poorly with arsenic exposure. Despite the study population's chronic exposure to elevated environmental levels of arsenic, no clinical or hematologic abnormalities attributable to arsenic were found.