RESUMEN
Flock House virus (FHV) is a nonenveloped, icosahedral insect virus whose genome consists of two molecules of single-stranded, positive-sense RNA. FHV is a highly tractable system for studies on a variety of basic aspects of RNA virology. In this review, recent studies on the replication of FHV genomic and subgenomic RNA are discussed, including a landmark study on the ultrastructure and molecular organization of FHV replication complexes. In addition, we show how research on FHV B2, a potent suppressor of RNA silencing, resulted in significant insights into antiviral immunity in insects. We also explain how the specific packaging of the bipartite genome of this virus is not only controlled by specific RNA-protein interactions but also by coupling between RNA replication and genome recognition. Finally, applications for FHV as an epitopepresenting system are described with particular reference to its recent use for the development of a novel anthrax antitoxin and vaccine.
Asunto(s)
Tecnología Biomédica , Nodaviridae/fisiología , Animales , Biología , Genoma Viral/genética , Humanos , Nodaviridae/química , ARN Viral/química , ARN Viral/genética , Replicación ViralRESUMEN
South Africa implemented a vaccine against hepatitis B virus (HBV) into the Expanded Programme on Immunisation (EPI) in April 1995. The HBV vaccine is given at 6, 10, and 14 weeks, in parallel with OPV, DTP and Hib vaccines. This study assessed the impact of universal childhood HBV vaccination programme in reducing HBsAg carriage, in the first five years (1995--1999) since its implementation. In parallel, we investigated the current burden of HBV infection in mothers of vaccinees and the adult general population. A total of 598 babies (mean age=23.3 months) who received 3 doses of 1.5 microg/0.5 ml Hepaccine-B (Cheil) were recruited from the Northern Province (one of the nine provinces in South Africa). HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were tested using the IMx or Axsym kits (Abbott Laboratories). PCR assays were performed following established protocols. The overall seroprotection rate (i.e. anti-HBs titre> or =10 mIU/ml) was 86.8% (519/598) in vaccinated babies, while 13.2% had anti-HBs levels<10 mIU/ml. Seroprotection rates and geometric mean titres (GMT) decreased significantly with increasing age, possibly reflecting waning anti-HBs titre over time. Total HBV exposure (positive for either HBsAg, anti-HBs, or anti-HBc) was 31.0% (58/187) in mothers of vaccinees and 40% (72/180) in the adult general population. HBsAg carrier rate was virtually similar in both groups (3.2% in mothers of vaccinees vs. 3.3% in the general population). Against this background, no vaccine failures resulting in HBsAg and HBV DNA positivity were seen in vaccinated babies, including 6 babies born to HBsAg positive carrier mothers (one carrier mother was positive for HBeAg and HBV DNA). However, 0.9% (5/582) babies, aged between 8--11 months, tested positive for anti-HBc, all of whom had anti-HBs titres>10 mIU/ml and were negative for HBV DNA. Anti-HBc positivity was probably maternal in origin, or may represent sub-clinical averted HBV infections. It can be concluded that the HBV vaccine is highly effective within the framework of the South African EPI and already shows a positive impact in the elimination of HBsAg carrier rate in children<5 years.
Asunto(s)
Portador Sano/prevención & control , Vacunas contra Hepatitis B/farmacología , Hepatitis B/prevención & control , Adulto , Secuencia de Bases , Portador Sano/epidemiología , Portador Sano/inmunología , Preescolar , Cartilla de ADN/genética , ADN Viral/sangre , ADN Viral/genética , Femenino , Hepatitis B/epidemiología , Hepatitis B/inmunología , Hepatitis B/transmisión , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Inmunidad Materno-Adquirida , Lactante , Masculino , Programas Nacionales de Salud , Cooperación del Paciente , Sudáfrica/epidemiología , Factores de Tiempo , VacunaciónRESUMEN
The birth incidence of neural tube defects (NTDs) in South Africa is threefold to sixfold higher in rural compared with urban blacks. We investigated whether folate deficiency and aberrant homocysteine metabolism could explain the high NTD incidence in rural black populations. Plasma folate and total homocyst(e)ine (tHcy) concentrations were determined in apparently healthy rural black women (n = 107), rural black women with a history of pregnancy complicated by NTDs (n = 54), and urban blacks (n = 101). Methionine load tests were performed on the 54 women with a history of NTD-affected pregnancy and 54 controls matched for age and body mass. The presence of the 677C --> T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene was investigated in both groups by a polymerase chain reaction (PCR) of genomic DNA and HinfI digestion of the PCR product. Apparently healthy urban black women (n = 101) had a lower (P < .001) plasma folate concentration compared with rural black women (n = 107). Women with a history of NTD-affected pregnancy did not differ significantly from controls with respect to plasma folate, fasting homocyst(e)ine, methionine, and the post-methionine load increase in plasma homocyst(e)ine. More than 50% of both of the latter groups had a post-methionine load increase in plasma tHcy less than the fifth percentile as observed in a healthy white control group. No homozygotes for the 677C --> T mutation in the MTHFR gene were found in black mothers with NTD-affected offspring or controls. It is concluded that black urbanization is characterized by a diminished folate status that is paradoxically associated with a lower NTD birth incidence. Homozygosity for the 677C --> T mutation in the gene coding for MTHFR does not constitute a genetic risk factor for NTDs in blacks. No aberrant homocysteine metabolism could be demonstrated in black women with NTD-affected pregnancies.
Asunto(s)
Ácido Fólico/sangre , Homocisteína/metabolismo , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Defectos del Tubo Neural/genética , Complicaciones del Embarazo/enzimología , Adulto , Población Negra , ADN/análisis , ADN/genética , Femenino , Genotipo , Humanos , Metionina , Defectos del Tubo Neural/enzimología , Defectos del Tubo Neural/epidemiología , Estado Nutricional , Embarazo , Complicaciones del Embarazo/epidemiología , Población Rural , Sudáfrica/epidemiologíaRESUMEN
The inhibition of cardiac Na,K-ATPase by 1 alpha,2 alpha-epoxyscillirosidin is the principal cause of poisoning of cattle by the tulip, Homeria pallida. The ultimate goals of this study were to study the interaction between 1 alpha,2 alpha-epoxyscillirosidin and ovine Na,K-ATPase by means of inhibition and displacement binding studies. Ovine cardiac Na,K-ATPase was isolated in membrane-bound form by means of deoxycholate treatment, high-speed ultracentrifugation, NaI treatment and selective solubilization in Lubrol. The inhibition of ovine cardiac and commercial porcine cerebral cortex Na,K-ATPase by 1 alpha,2 alpha-epoxyscilirosidin and ouabain was studied using a discontinuous Na,K-ATPase assay. The binding of 1 alpha,2 alpha-epoxyscillirosidin, ouabain and digoxin to the above enzymes was compared using a displacement binding assay with [3H] oubain. The Lubrol-solubilized ovine cardiac Na,K-ATPase showed a specific activity of 0.3 U/mg with no ouabain insensitive activity. I50 values of 2.1 x 10(-8) and 2.7 x 10(-8) were obtained for the inhibition of this enzyme by 1 alpha,2 alpha-epoxyscillirosidin and ouabain, respectively. 1 alpha,2 alpha-Epoxyscillirosidin has a much higher KD value (1.5 x 10(-7) M), however, than ouabain (9.5 x 10(-9) M) and digoxin (1.7 x 10(-8) M) in displacement binding studies with [3H]ouabain. 1 alpha,2 alpha-Epoxyscillirosidin is a potent inhibitor of ovine cardiac Na,K-ATPase and is a slightly stronger inhibitor of the enzyme than ouabain. The anomalous result for the displacement of 1 alpha,2 alpha-epoxyscillirosidin from its receptor is either a result of different affinities that K+ has for the enzyme ouabain and enzyme-1 alpha,2 alpha-epoxyscillirosidin complexes or because of different complex stabilities of these complexes.
Asunto(s)
Glicósidos Cardíacos/farmacología , Colenos/farmacología , Inhibidores Enzimáticos/farmacología , Miocardio/enzimología , Polietilenglicoles , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , ATPasa Intercambiadora de Sodio-Potasio/aislamiento & purificación , Animales , Unión Competitiva , Bovinos , Corteza Cerebral/enzimología , Estabilidad de Enzimas , Ouabaína/metabolismo , Ovinos , Yoduro de Sodio/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Solubilidad , PorcinosRESUMEN
STUDY OBJECTIVE: To ascertain the incidence and spectrum of congenital anomalies in neonates born in a rural hospital. DESIGN: This was a prospective, hospital-based study, undertaken on liveborn neonates over the period 12 June 1989 - 31 December 1992. SETTING: Mankweng Hospital, Sovenga, Northern Transvaal. MAIN RESULTS: Of a total of 10,380 neonates born during this period, 7,617 (73.4%) were examined within the first 24 hours of life. On the basis of published observations, only 26.2% of severe congenital anomalies diagnosable by age 5 years are diagnosable at birth. In this South African study the finding at birth of severe, externally visible congenital anomalies in 14.97 per 1,000 livebirths could mean that by age 5 years the minimum cumulative incidence of severe congenital anomalies may involve 57.14 per 1,000 children. Extrapolating from other Third-World studies, the cumulative incidence of severe congenital anomalies in such communities may affect up to 84.85 per 1,000 children by the age of 5 years. High incidences of neural tube defects (3.55 per 1,000 livebirths) and Down syndrome (2.10 per 1,000 livebirths), both conditions which can be prevented by prenatal screening, were recorded. CONCLUSIONS: These figures indicate the necessity for inclusion of appropriate prenatal, genetic, family planning and paediatric facilities into the primary health care delivery system of rural areas, to manage such problems and to initiate programmes to reduce the incidence of selected congenital anomalies such as Down syndrome and neural tube defects.
Asunto(s)
Negro o Afroamericano , Anomalías Congénitas/epidemiología , Anomalías Múltiples/epidemiología , Anomalías Múltiples/etnología , Población Negra , Sistema Nervioso Central/anomalías , Anomalías Congénitas/etnología , Anomalías del Sistema Digestivo , Hospitales/estadística & datos numéricos , Humanos , Incidencia , Recién Nacido , Anomalías Musculoesqueléticas , Estudios Prospectivos , Población Rural , Sudáfrica/epidemiología , Sudáfrica/etnología , Anomalías UrogenitalesAsunto(s)
Países en Desarrollo , Genética Médica , Atención Primaria de Salud , Lactancia Materna , Servicios de Salud del Niño/organización & administración , Preescolar , Anomalías Congénitas/prevención & control , Servicios de Planificación Familiar , Genética Médica/organización & administración , Necesidades y Demandas de Servicios de Salud , Humanos , Lactante , Recién Nacido , Atención Primaria de Salud/organización & administraciónRESUMEN
We describe two mentally retarded brothers with craniofacial anomalies, polydactyly, and other clinical manifestations compatible with the acrocallosal syndrome (ACS). These are the first black patients from Africa with this diagnosis. They are also the fourth set of sibs described with ACS, and together with the parental consanguinity documented in this family, confirm autosomal recessive inheritance of this syndrome. The clinical manifestations in our patients confirm the intrafamilial variability of the syndrome. Postnatal onset of growth retardation is proposed as an additional manifestation of ACS.
Asunto(s)
Anomalías Múltiples/genética , Consanguinidad , Huesos Faciales/anomalías , Polidactilia/genética , Cráneo/anomalías , África , Niño , Humanos , Lactante , Masculino , SíndromeRESUMEN
Down's syndrome (DS) is the most common chromosomal cause of metal retardation, and amniocentesis is the most significant factor affecting its prevalence. In South Africa, prenatal cytogenetic diagnoses have been available for just over a decade and the utilisation and effect of this procedure in the white population born between 1980 and 1984 was evaluated. On the basis of pooled data involving 4,939,640 births, an overall world mean rate for DS of 1,34/1,000 live births (mainly Caucasian) for single-year maternal ages was calculated. Accordingly, 58 cases of DS were expected in the 40-year and older maternal age group in South Africa. Only 34 cases (59%) were detected prenatally, and a further 3 cases were identified by the notification system during the same period and in the same maternal age group. Another 24 DS cases in the maternal age group of 40 years and over could thus potentially have been detected prenatally and prevented, while 21 cases in this age group (36%) could not be accounted for at all. Cost-benefit analyses are shown and the number of amniocenteses required for various maternal age groups to affect the prevention of DS is calculated.
Asunto(s)
Síndrome de Down/epidemiología , Adulto , Factores de Edad , Amniocentesis/estadística & datos numéricos , Síndrome de Down/diagnóstico , Síndrome de Down/economía , Humanos , Masculino , Edad Materna , Sudáfrica/epidemiología , Población BlancaRESUMEN
A national screening programme was introduced in 1980 when the first cases with the Martin-Bell syndrome were diagnosed in South Africa. This survey includes patients from all the major population groups in South Africa. One thousand patients, who include 354 relatives of 21 index cases, were investigated cytogenetically. About 75% of the 354 relatives were either affected males or obligate or possible carriers. The segregation pattern of the fragile site was investigated in 271 offspring of 58 carrier women. At least 30% of the carriers were mildly mentally retarded with most expressing the fragile site. Various other investigations, such as measurements of testes, speech, verbal and IQ evaluations and hormone studies were done on several affected males. No fragile site could be demonstrated in 57 unselected autistic children. The results of this programme show that this syndrome is a common cause of mental retardation and that prevention of mental retardation is possible if all the involved families could be identified.
Asunto(s)
Síndrome del Cromosoma X Frágil/epidemiología , Aberraciones Cromosómicas Sexuales/epidemiología , Adolescente , Adulto , Factores de Edad , Trastorno Autístico/genética , Niño , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Tamización de Portadores Genéticos , Pruebas Genéticas , Hormonas/sangre , Humanos , Discapacidad Intelectual/genética , Inteligencia , Masculino , Embarazo , Diagnóstico Prenatal , Sudáfrica , Testículo/patologíaRESUMEN
A comprehensive genetic/diagnostic survey was undertaken at a special school for the mentally retarded involving 105 patients. Cytogenetic, biochemical and clinical investigations were undertaken to establish the contribution of the genetic factors to the problem of mental retardation. Apart from obtaining information about specific children, identifying families at risk, and providing genetic counselling in nearly 50% of cases, data was obtained which could be compared with other similar surveys. According to the aetiological groupings of the patients, 6.7% could be attributed to perinatal damage, 17.1% to chromosomal defects, 4.8% to biochemical disorders, 5.7% to other genetic causes, 12.4% to other prenatal damage, 1.9% to infections, and 51.4% to unknown causes. No individual with the marker X syndrome was found in this group.
Asunto(s)
Discapacidad Intelectual/genética , Adolescente , Adulto , Errores Innatos del Metabolismo de los Aminoácidos/genética , Aminoácidos/orina , Niño , Preescolar , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Síndrome de Down/genética , Epilepsia/genética , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Aberraciones Cromosómicas Sexuales/genética , Sudáfrica , Cromosoma XAsunto(s)
Marcadores Genéticos , Cromosoma X , Femenino , Heterocigoto , Humanos , Discapacidad Intelectual/genética , MasculinoAsunto(s)
Trastorno Autístico/genética , Marcadores Genéticos , Cromosoma X , Niño , Femenino , Humanos , Masculino , Aberraciones Cromosómicas SexualesRESUMEN
We present here a familial case of a paracentric inversion in man with a short review of the literature. A paracentric inversion of chromosome 10(q11q26) was found in the amniocytes drawn for advanced maternal age. The presence of the inversion was investigated in 35 family members in three generations. No recombinants were recognized. The significance of these data for appropriate genetic counselling and possible reproductive risks is discussed.
Asunto(s)
Inversión Cromosómica , Cromosomas Humanos 6-12 y X , Adulto , Bandeo Cromosómico , Femenino , Tamización de Portadores Genéticos , Asesoramiento Genético , Degeneración Hepatolenticular/genética , Humanos , Masculino , Edad Materna , Linaje , Embarazo , Recombinación Genética , RiesgoRESUMEN
Cytogenetic investigations of mentally retarded patients at the care and rehabilitation centres of the Department of Health and Welfare and at special schools have been in progress since 1972. A total of 2533 cytogenetic investigations have been carried out. A chromosomal abnormality was found in 20,6% of individuals investigated. Next to Down syndrome the Martin-Bell syndrome with the marker X chromosome occurred most frequently. This syndrome is found in the White, Black, Indian and Coloured population groups. In 15 families that have been identified, 56 males and 35 females (carriers) have the marker X chromosome. The importance and role of diagnostic/genetic investigations in mentally retarded individuals is outlined.
Asunto(s)
Aberraciones Cromosómicas/complicaciones , Marcadores Genéticos , Discapacidad Intelectual/complicaciones , Aberraciones Cromosómicas Sexuales/complicaciones , Cromosomas Sexuales , Cromosoma X , Trastornos de los Cromosomas , Femenino , Humanos , Masculino , Estadística como AsuntoRESUMEN
This report describes the first cases of X-linked mental retardation with a marker X chromosome seen in South Africa, and forms part of an ongoing study. The marker was found in 11 affected males and 1 carrier female in 4 families investigated. The demonstration of the marker X chromosome characterized by a fragile site at the long arm (fra(X) (q27) in association with nonspecific X-linked mental retardation heralds a new era in cytogenetics. The attention of human geneticists everywhere is focused on various aspects of this fascinating phenomenon. It has now become possible to diagnose an apparently common familial cytogenetic condition with a high risk of recurrence and to identify female carriers; perhaps in time we will be able to provide prenatal diagnosis. Because of the familial involvement through X-linked inheritance the syndrome is believed to be more common than trisomy 21. The nature of the association of mental retardation with the marker X chromosome is unknown, but it could be related to close linkage with abnormal gene(s) or due to faulty transcription of the genes beyond the fragile site.