A total of 278 families of probands with Duchenne or Becker muscular dystrophy has been ascertained and offered genetic counselling. Linkage studies have been performed in these families using polymorphic DNA markers identifying loci linked to Duchenne and Becker muscular dystrophy. The clinical features of the probands are discussed: there was marked intrafamilial resemblance in the severity of the disease. We estimate that a complete study of potential carriers in these families would require analysis of samples from approximately 1400 subjects. The results of linkage studies tended to move women's carrier risk estimates (based on CK and pedigree data) towards the extremes of the risk categories, providing a more definitive risk estimate for 81% of the women who were previously in the middle range of carrier risk probabilities. About 70% of the families had only one affected member. Linkage analysis altered carrier risk estimates in 95% of sisters and aunts of index cases, but only affected estimates of the mother's carrier risks in about 11% of isolated cases. Even where linkage studies were not helpful in elucidating carrier risks, information could usually be obtained for use in prenatal diagnosis if required. We have assessed the attitudes to pregnancy and prenatal diagnosis of women at risk of being carriers of Duchenne or Becker muscular dystrophy and report 17 pregnancies in these women. 相似文献
Severe acute respiratory syndrome (SARS) is an emerging infectious disease. Its etiological agent has been convincingly identified as a new member of family Coronaviridae (SARS-CoV). It causes serious damage to the respiratory system yet the mechanism is not clear. Infection-induced apoptosis or necrosis is suspected but no direct evidence for this yet exists. To date, Vero E6 cells are the only cell line that could be used to replicate the virus with obvious CPE (cytopathic effect) in vitro. It is known for some viruses (including members of family Coronaviridae) that CPE can be caused either by virus-induced apoptosis (active death) or cell necrosis (passive death). In this study, we examined the apoptosis in the SARS-CoV infected Vero E6 cells. Indeed, the results do show that the CPE was induced by apoptosis rather than necrosis, shown by typical DNA fragmentation, through the existence of apoptotic bodies and swollen mitochondria. This observation has some implications for the SARS-CoV pathogenicity: SARS-CoV does induce apoptosis in cell cultures and might have the same effect in vivo, responsible for the severe damage of the respiratory system. 相似文献
Summary Diffuse distribution of small, faintly staining, beaded deposits of rat immunoglobulin M (IgM) around the glomerular capillary blood vessels, and a more intensely staining larger deposition in the mesangium, were observed on the kidney sections of normal rats. As glomerular-fixed nephritogenic antigens are known to be present on the epithelial aspect of the glomerular basement membrane (GBM), especially at the soles of foot processes and at the slit pores, it was assumed that the IgM antibodies were directed against these antigens. Investigation by immunofluorescent antibody double-staining techniques of rat kidney sections obtained from normal and rabbit anti-FX1A-injected rats stained for the nephritogenic antigen showed that a number of antigenic sites in the glomeruli and in the mesangium shared antibody hits by heterologous rabbit IgG and autologous rat IgM antibodies. Most sites in the glomeruli stained specifically for rat IgM or rabbit IgG, but preferentially for the latter. The intensely fluorescent mesangial deposits stained mainly for rat IgM, indicating that at these sites the antigenic material was virtually saturated, while areas at the entry to the mesangial space also stained for rabbit IgG, indicating that at these locations free nephritogenic epitopes were still available for reaction with the anti-FX1A antibody. Western blot analysis have shown that the rabbit anti-rat FX1A IgG and the rat anti-rat KF3 IgM antibodies are directed against the same renal tubular-derived antigen with a molecular weight of 70,000. These experimental findings collectively demonstrate that the heterologous IgG and autologous IgM antibodies are directed against the same nephritogenic antigen, which is found in the glomeruli, the mesangium and the proximal convoluted tubules. Thus, the IgM autoantibody has a possible physiological role but, in addition, there is evidence of active immunophagocytic events, manifested in a rapid and continuous entrapment and expulsion of macromolecules after their processing by the mesangial cells of normal and passive Heymann nephritis rats. 相似文献
It has been speculated that exposure to the chronic stress of racism contributes to the high rates of hypertension among African Americans. Social support may buffer the effects of stress on cardiovascular (CV) health by attenuating stress-induced CV responses that have been linked to hypertension. In this study we investigated the effects of racism and social support on CV reactivity in African American women. Participants showed greater increases in CV and emotional responses while responding and listening to racist provocation. Augmented blood pressure (BP) persisted through recovery following racial stress. Participants receiving no support showed the greatest increases in anger during racist provocation. No significant effects were seen for support on CV reactivity. These results provide some of the first evidence that interactive confrontation with racism elicits significant increases in CV reactivity and emotional distress. Furthermore, individuals receiving less support may be at greater risk for the potentially health-damaging effects of racial stress. These findings may have significant implications for the health of African Americans. 相似文献
Cell proliferation in bronchiolar epithelium of normal mouse lung and of lung chronically exposed to urethane was compared. Animals treated for 10 weeks with drinking water containing 0.1% urethane and their controls were injected with 3H-thymidine; autoradiographs were made of lung tissue and mean grain counts of labeled nuclei in terminal bronchiolar epithelium compared in the control and urethane-treated groups. In controls, the decline in mean grain counts of labeled daughter cells between 24 hours and 4 days after 3H-thymidine injection was compatible with a mean cell cycle time of about 60 hours. In contrast, the hyperplastic bronchiolar epithelium of the urethane-treated animals showed an elevated labeling index and deficient production of labeled cells over the 6-day period as judged by decline in mean grain counts. These findings were interpreted as showing that the hyperplasia and high labeling index did not represent faster turnover or shortened cycle but reflected an increase in cell cycle time or of population renewal time. 相似文献
An early proliferative response measured by [3H] thymidine uptake occurred following mixing and culture in vitro of spleen cell suspensions derived from genetically unrelated rodents. This response reached a maximum value at 40–44 hr. When either component of the mixture in equivalent amounts was cultured alone, only a limited response occurred.
This marked stimulation of DNA synthesis occurred when spleen cells derived from LAF1 mice and a pool of spleen cells from three non-inbred rats were mixed and cultured. No such response occurred in the mouse spleen cultures either in the absence of rat spleen cells, or in the presence of disrupted rat spleen cells. An equally marked response occurred when spleen cells from one rat were mixed and cultured either with C57BL10J or DBA/2J mouse spleen cells, or to a lesser extent with spleen cells from a second unrelated non-inbred rat. A similar marked response occurred with cells derived from C57BL10J and DBA/2J and from BALB/c and C3H/HeJ mice.
The existing data suggest that the response of these rodent spleen cells in the mixed lymphocyte culture (MLC) test is dependent on certain genetic differences inherent in the two cell populations.
The features of a child with osteogenesis imperfecta type III (OI III) resulting from the heterozygous substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen were studied. He was born at term with the clinical features of severe OI, including deep grey-blue sclerae. He had severe osteopenia and all long bones were smaller than normal with cortical thinning, metaphyseal expansion, poor metaphyseal modelling, and multiple fractures. However, the vertebrae, pelvis, and shoulder girdle were of normal shape and there were few rib fractures. Histological examination of the calvarium and tibial shaft showed woven bone without lamellar bone or Haversian systems. The shafts of the long bones were widened owing to repeated fractures. Progressive enlargement of the calvarium occurred between 3 and 4.5 months of age owing to bilateral chronic subdural haematomata and a large arachnoid cyst in the Sylvian fissure. The cyst was probably developmental in origin while the subdural collections were probably the result of perinatal skull trauma. The cyst and the subdural collections resolved following drainage but ventricular dilatation with normal cerebrospinal fluid pressure followed. The proband is the first reported case of OI with a glycine substitution by alanine in the pro alpha 2(I) chain of type I procollagen. 相似文献
Two pairs of isogenic capsulate and noncapsulate and one pair of capsulate fimbriate and nonfimbriate strains of Haemophilus influenzae type b were studied in an organ culture of human respiratory mucosa. Over 24 h, the numbers of recovered bacteria increased from the original inoculum size of 10(5) to 10(8) CFU/ml. Transmission electron microscopy and scanning electron microscopy showed that noncapsulate organisms caused significant epithelial damage, whereas capsulate strains did not. Association of noncapsulate bacteria with damaged epithelial cells was observed by 14 h of incubation. In contrast, capsulate organisms were associated with a dense, thick, gel-like matrix which was observed above the epithelial surface. These capsulate organisms were not seen to associate with the epithelial surface (by transmission electron microscopy), though they were occasionally seen adhering to cells by scanning electron microscopy. Fimbriate capsulate H. influenzae showed increased adherence to buccal cells compared with nonfimbriate capsulate organisms. There was also association of fimbriate capsulate bacteria with damaged organ culture epithelium in one of four experiments. It is concluded that both capsule and fimbriae affect the interaction of H. influenzae with human airway mucosa in vitro by influencing adherence to and damage of the epithelium. 相似文献
Streptococcus pneumoniae infections are common, but how they cause host tissue injury and death is incompletely understood. Immunization with pneumolysin, a thiol-activated toxin produced by the pneumococcus, partially protects animals during subsequent infection. The mechanism by which pneumolysin contributes to disease is not known. The aim of the present investigation was to determine the histologic changes induced by recombinant pneumolysin in the rat lung and to compare them with the changes induced by live organisms. Injection of either toxin (200 or 800 ng) or bacteria into the apical lobe bronchus was associated with the development of a severe lobar pneumonia restricted to the apical lobe. The changes induced by the toxin were greater at the higher concentration, and changes were most severe in those animals in which there was partial ligation of the apical lobe bronchus. The pneumonitis was less severe following injection of a modified toxin with decreased hemolytic activity, generated by site-directed mutagenesis of the cloned pneumolysin gene, indicating that this property of the toxin was important in generating pulmonary inflammation. There was still considerable pneumonitis after injection of a modified toxin with decreased capacity to activate complement. 相似文献