RESUMEN
The Cockayne syndrome B protein (CSB) has long been known to be involved in the repair of DNA modifications that block the RNA polymerase in transcribed DNA sequences (transcription-coupled repair). Recent evidence suggests that it also has a more general role in the repair of oxidative DNA base modifications such as 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG). In mammalian cells, 8-oxoG is a substrate of the repair glycosylase OGG1. Mice without this enzyme accumulate 8-oxoG in the genome and have elevated spontaneous mutation rates. To elucidate the role of CSB in the prevention of mutations by oxidative DNA base damage, we have generated mice that are deficient in Csb or Ogg1 or both genes and carry a non-transcribed bacterial lacI gene for mutation analysis (Big Blue mice). Our results indicate that the overall spontaneous mutation frequencies in the livers of Csb(m/m)/Ogg1-/- -mice are elevated not only compared with heterozygous control mice (factor 3.3), but also with Ogg1-/- -animals (factor 1.6). Sequence analysis revealed that the additional mutations caused by CSB deficiency in an Ogg1-/- background are mostly G:C to T:A transversions and small deletions. For all mouse strains, the background levels of oxidative purine modifications in the livers correlate linearly with the numbers of G:C to T:A transversions observed. The data indicate that CSB is involved in the inhibition of mutations caused by spontaneous oxidative DNA base damage in a non-transcribed gene.
Asunto(s)
Daño del ADN , Enzimas Reparadoras del ADN/genética , Inestabilidad Genómica/genética , Mutación , Animales , Proteínas Bacterianas/genética , ADN Glicosilasas/deficiencia , ADN Glicosilasas/genética , Enzimas Reparadoras del ADN/deficiencia , Femenino , Represoras Lac , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos , Ratones Noqueados , Ratones Transgénicos , Mutagénesis Insercional , Estrés Oxidativo , Mutación Puntual , Proteínas de Unión a Poli-ADP-Ribosa , Proteínas Represoras/genética , Eliminación de SecuenciaRESUMEN
The purpose of the present investigation was to study the role of two potential contributory factors, hyperphagia and alterations in fuel metabolism, on the development of tissue trace element accumulation in the experimentally induced diabetic rat. The role of increased mineral intake associated with diabetic hyperphagia on tissue trace element accumulation was evaluated by feeding control and diabetic rats high-carbohydrate (HC) diets which varied in Zn, Cu, Mn, and Mg concentrations. Diabetic rats were hyperphagic and had lower plasma Mg, and higher liver Zn, Cu, and Mn concentrations than control rats, regardless of dietary mineral intake. In a second study, diabetic hyperphagia was reduced by feeding control and diabetic rats a HC, high-fat (HF), or high-protein (HP) diet; the effects of altering diabetic metabolism on trace element status was studied. Liver Mn and Zn concentrations of diabetic rats fed the HF diet were lower than diabetic rats fed the HC diet and HP diet, and were similar to control rats. Liver Cu concentrations of diabetic rats fed the HF and HP diets were lower than diabetic rats fed the HC diet and were similar to control rats. While diabetic rats, in general, had higher plasma glucagon concentrations and lower percent body fat than control rats, diabetic rats fed the HF diet had similar plasma glucagon and percent body fat to control rats. These data suggest that tissue-specific biochemical needs, such as the need for metals as cofactors for enzymes, rather than hyperphagia per se, may drive the accumulation of trace elements in the diabetic animal.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Oligoelementos/metabolismo , Animales , Glucemia/metabolismo , Composición Corporal , Peso Corporal , Dieta , Femenino , Glucagón/sangre , Hematócrito , Hiperfagia/metabolismo , Insulina/sangre , Hígado/metabolismo , Magnesio/sangre , Masculino , Ratas , Ratas Sprague-DawleyAsunto(s)
Síndromes de Inmunodeficiencia/etiología , Trastornos Nutricionales/inmunología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adolescente , Adulto , Anciano , Envejecimiento/inmunología , Avitaminosis/complicaciones , Avitaminosis/inmunología , Niño , Grasas de la Dieta/efectos adversos , Susceptibilidad a Enfermedades/inmunología , Femenino , Enfermedades Fetales/etiología , Humanos , Síndromes de Inmunodeficiencia/prevención & control , Lípidos/deficiencia , Neoplasias/etiología , Trastornos Nutricionales/complicaciones , Trastornos Nutricionales/terapia , Obesidad/complicaciones , Obesidad/inmunología , Embarazo , Complicaciones del Embarazo , Oligoelementos/deficienciaRESUMEN
The cariogenic bacteria Streptococcus sobrinus and S. cricetus were shown to have an absolute requirement for manganous ion in order to bind glucans or to adhere to glass in the presence of sucrose. The bacteria possessed a reasonably high affinity transport system for 54Mn2+, yielding a Km of about 12 microM. The Vmax for uptake of 54Mn2+ in S. sobrinus was increased when the bacteria were grown in Mn-depleted medium, but the Km remained the same. There was no evidence for two Mn2+ uptake systems, commonly observed for many bacteria. Ions such as Ca2+, Co2+, Co3+, Cu2+, Fe2+, Fe3+, Hg2+, Mg2+, Ni2+, and Zn2+ did not inhibit the uptake of 54Mn2+ by the bacteria, although Cd2+ was a potent inhibitor. Fractionation experiments showed that manganese was distributed in protoplasts (67%) and in the cell wall (33%). Approximately 80% of the 54Mn2+ in S. sobrinus was rapidly exchangeable with nonradioactive Mn2+. Electron spin resonance experiments showed that all of the manganese was bound or restricted in mobility. Proton motive force-dissipating agents increased the acquisition of 54Mn2+ by the streptococci, probably because the wall became more negatively charged when the cell could no longer produce protons.
Asunto(s)
Manganeso/metabolismo , Streptococcus sobrinus/metabolismo , Adhesión Bacteriana , Transporte Biológico , Espectroscopía de Resonancia por Spin del Electrón , Glucanos/metabolismo , Cinética , Lectinas/metabolismo , Streptococcus sobrinus/efectos de los fármacosRESUMEN
Mobile encapsulated lipomas are a benign neoplastic process with pronounced mobility in the subcutaneous plane. Characteristic clinical and histologic features differentiate this distinctive entity from similar reactive adipose processes.
Asunto(s)
Lipomatosis/patología , Neoplasias Cutáneas/patología , Anciano , Necrosis Grasa/patología , Femenino , Humanos , MuñecaRESUMEN
This paper presents the demographic and clinical data necessary to define the population of children and adolescents served in a model day treatment program. On the day of admission, patients (N = 204) and parents complete a batter of instruments designed to measure reliably characteristics of the patient's system at three levels: individual, parental, and family. Design of the assessment establishes comparisons among self-report, parent/other report, and clinician report measures at each subsystem level. Results of the CBCL, YSR, PIC, Piers-Harris, MCMI, DAS, and FES indicate moderate levels of disturbance, usually consistent with norms reported on referred or clinical populations. Patients are being treated for a wide variety of childhood disorders within systems demonstrating dysfunction at parental, marital, and familial levels.
Asunto(s)
Centros de Día/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Adolescente , Niño , Trastornos de la Conducta Infantil/epidemiología , Demografía , Estudios de Evaluación como Asunto , Familia , Femenino , Humanos , Masculino , Tennessee/epidemiologíaRESUMEN
This investigation was a study of the free radical concentration of a living system, Drosophila melanogaster, by electron spin resonance spectroscopy. The paramagnetic content of the organism was measured as a function of age, mutant strain, and diet (normal vs. carcinogenic). In all cases, 4 to 6 days after ecdysis the free radical concentration decreased to approximately 70% of its value as measured shortly after ecdysis. The different mutant strains exhibited distinctly different free radical concentrations in accord with visual observations of the degree of pigmentation. Drosophila raised on a carcinogenic diet always showed a lower concentration of free radicals than the control groups on a normal diet.
Asunto(s)
Carcinógenos/metabolismo , Dieta , Drosophila melanogaster/metabolismo , Radicales Libres , Animales , Drosophila melanogaster/genética , Espectroscopía de Resonancia por Spin del Electrón , MutaciónRESUMEN
The authors report 3 cases of herpes encephalitis in children aged respectively 15 days, 12 months and 18 months. In all 3 cases E.E.G. activity of a periodic nature was noted, which was continuous or intermittent, lateralised or focal in the temporal region, appearing from the 4th to 7th day. The periodicity (of the E.E.G. complex) was short and their stereotyped appearance particularly unusual in babies. In all 3 children convulsive seizures occurred before the discovery of the periodic activity. The latter was found to change in morphology and timing during the seizures. The disease process led to death of the neonate, and recovery with serious sequellae in the other two children. Possible relationships between the transitory nature of the periodic acitivity, the age and the eventual course of the disease, were discussed.
Asunto(s)
Electroencefalografía , Encefalitis/fisiopatología , Infecciones por Herpesviridae/fisiopatología , Enfermedades del Recién Nacido/fisiopatología , Encefalitis/microbiología , Femenino , Infecciones por Herpesviridae/complicaciones , Humanos , Lactante , Recién Nacido , Masculino , Meningitis/microbiología , Meningitis/fisiopatología , Convulsiones/etiologíaRESUMEN
The authors report electroclinical changes observed during Enflurane anaesthesia, at various concentrations, in 25 children aged 4 to 14 years. EEG features are described from induction to surgical anesthesia (concentration 3-3.5%) and during overdoses (4-4.5%) with or without hyperventilation. Groups of spikes, low voltage sequences and electroclinical "seizures" (2 cases) only occur if the concentration of enflurane is not kept below 3.5%. A longitudinal study (24th hour, 3rd and 6th day) shows, by comparison with the pre-anaesthetic EEG, persistence in all cases of EEG slowing 24 hours after the anaesthesia, and in some patients EEG disturbances continue until the 6th day. These results are discussed in relation to data on the biodegradation of enflurane.
Asunto(s)
Electroencefalografía , Enflurano/farmacología , Éteres Metílicos/farmacología , Adolescente , Anestesia , Niño , Relación Dosis-Respuesta a Droga , Humanos , Factores de TiempoRESUMEN
The authors compare recovery and the post-anaesthetic period in 45 patients anaesthetised with a combination of either pentothal, nitrous oxide, fluothane and dolosal (group 1, 24 subjects), or of pentothal, nitrous oxide and phenoperidine (group 2, 21 subjects). The quality of recovery was judged at the end of anaesthesia by determining of occurrence of the first response to 3 types of stimulation (calling the name, noise and pain) and the density of these responses during each minute. During the post-anaesthetic period the respective percentages of wakefulness and sleep were calculated. In this way the authors demonstrate a significant (P less than 0.01) shortening in recovery time for group 2, reactivity to own name occurring first in both groups, and a very significant (P less than 0.001) increase in the percentage of physiological sleep in subjects of group 2 during the post-anaesthetic stage.