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81.
Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP) 总被引:8,自引:0,他引:8
Rowe PS; Oudet CL; Francis F; Sinding C; Pannetier S; Econs MJ; Strom TM; Meitinger T; Garabedian M; David A; Macher MA; Questiaux E; Popowska E; Pronicka E; Read AP; Mokrzycki A; Glorieux FH; Drezner MK; Hanauer A; Lehrach H; Goulding JN; O'Riordan JL 《Human molecular genetics》1997,6(4):539-549
Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with
homologies to endopeptidases, on the X-chromosome), are responsible for
X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family
of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has
raised important questions regarding PEX function at the molecular level.
The aim of this study was to analyse 99 HYP families for PEX gene
mutations, and to correlate predicted changes in the protein structure with
Zn2+ metallopeptidase gene function. Primers flanking 22 characterised
exons were used to amplify DNA by PCR, and SSCP was then used to screen for
mutations. Deletions, insertions, nonsense mutations, stop codons and
splice mutations occurred in 83% of families screened for in all 22 exons,
and 51% of a separate set of families screened in 17 PEX gene exons.
Missense mutations in four regions of the gene were informative regarding
function, with one mutation in the Zn2+-binding site predicted to alter
substrate enzyme interaction and catalysis. Computer analysis of the
remaining mutations predicted changes in secondary structure,
N-glycosylation, protein phosphorylation and catalytic site molecular
structure. The wide range of mutations that align with regions required for
protease activity in NEP suggests that PEX also functions as a protease,
and may act by processing factor(s) involved in bone mineral metabolism.
相似文献
82.
Adèle R. Weston K. H. Myburgh F. H. Lindsay Steven C. Dennis Timothy D. Noakes J. A. Hawley 《European journal of applied physiology》1996,75(1):7-13
Skeletal muscle buffering capacity (βm), enzyme activities and exercise performance were measured before and after 4 weeks of high-intensity, sub maximal?interval training (HIT) undertaken by six well-trained competitive cyclists [mean maximal oxygen consumption ( O2max)?=?66.2 ml?·?kg?1?·?min?1]. HIT replaced a portion of habitual endurance training and consisted of six sessions, each of six to eight repetitions of 5 min duration at 80% of peak sustained power output (PPO) separated by 1 min of recovery. βm increased from 206.6 (17.9) to 240.4 (34.1) μmol H+?·?g muscle dw?1?·?pH?1 after HIT (P?=?0.05). PPO, time to fatigue at 150% PPO (TF150) and 40-km cycle time trial performance (TT40) all significantly improved after HIT (P?0.05). In contrast, there was no change in the activity of either phosphofructokinase or citrate synthase. In addition, βm correlated significantly with TT40 performance before HIT (r?=??0.82, P?0.05) and the relationship between change in βm and change in TT40 was close to significance (r?=??0.74). βm did not correlate with TF150. These results indicate that βm may be an important determinant of relatively short-duration (60 min) endurance cycling activity and responds positively to just six sessions of high-intensity, submaximal interval training. 相似文献
83.
Snoring and sleep-disordered breathing in young children: subjective and objective correlates 总被引:3,自引:0,他引:3
STUDY OBJECTIVES: We sought to assess the predictive validity of parental report of snoring and other behaviors by comparing such reports with objective findings from overnight polysomnography for the evaluation of sleep-disordered breathing in 2 nonclinical samples, namely, at-risk preschoolers and an older group reflective of the general community. Predictive validity of snoring alone and a score based on multiple child behaviors were compared to outcome at different levels of severity of sleep-disordered breathing. DESIGN: Retrospective observational study. SETTING: Questionnaires were distributed through school programs; polysomnography was performed at Kosair Children's Hospital in Louisville, Kentucky. PARTICIPANTS: One hundred twenty-two preschoolers and 172 5- to 7-year-olds, and their parents, participated in both subjective-report and objective-recording portions of the study. MEASUREMENTS AND RESULTS: Compared to the presence of snoring on polysomnography, parental report of frequent snoring was highly sensitive and specific for both age groups. At all but the lowest level of severity of sleep-disordered breathing, predictive ability was higher for both groups when a parental-report score based on multiple measures of child behavior was applied, compared to parental report of snoring alone. The profiles of these predictive child behaviors differed between the 2 groups, as did their sensitivity and specificity, at their high ranges of parental report. CONCLUSIONS: Scores derived from parental-report questionnaires of children's snoring and other sleep and wake behaviors can be used as surrogate predictors of snoring or sleep-disordered breathing in children. However, design and interpretation should consider age, risk status, and the purpose of the screening assessment. 相似文献
84.
Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1. 总被引:5,自引:2,他引:5 下载免费PDF全文
Y P Shi U Sayed S H Qari J M Roberts V Udhayakumar A J Oloo W A Hawley D C Kaslow B L Nahlen A A Lal 《Infection and immunity》1996,64(7):2716-2723
We have characterized the natural immune responses to the 19-kDa domain of merozoite surface protein 1 in individuals from an area of western Kenya in which malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell proliferative responses in individuals older than 15 years and the profile of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35% of the individuals responded to the E-KNG and E-TSR constructs, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant antigens was observed in different individuals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antibody, IgG1 and IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that IgG1 antibody response may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Furthermore, we observed that although the natural antibodies cross-reacted with all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second epidermal growth factor domain (KNG and TSR) of the antigen. 相似文献
85.
Pediatric sleep-disordered breathing (SDB) is known to negatively impact home and classroom behavior. Preschool-age Hispanic children from Spanish-speaking households are at elevated risk for poor school readiness. The authors used a multi-informant approach to assess home and preschool behavior among Hispanic children at risk for SDB (n = 67). Higher parent-reported SDB risk and elevated snoring were associated with parent- and teacher-reported problem behaviors and poorer teacher-reported classroom executive function among boys; elevated snoring was associated with internalizing behaviors among girls. Elevated snoring may be associated with problems related to impaired inhibitory self-control, suggesting the need for early intervention in order to improve school readiness among these a priori defined at-risk Hispanic children. 相似文献
86.
87.
BACKGROUND: Exposure to Aspergillus fumigatus allergens results in enhanced total serum IgE and peripheral blood eosinophils in mice. The associated pulmonary inflammation and immunologic responses are comparable to those detected in human allergic bronchopulmonary aspergillosis. Allergen-induced cytokines are thought to regulate the inflammatory and immune responses in these animals. METHODS: In the present study, we exposed C57BL/6 and BALB/c mice to A. fumigatus antigen. Both wild-type and IL-4 knockout phenotypes of animals of both strains were used. Some animals were also treated with anti-IL-5 or anti-IFN-gamma. Total serum IgE, Aspergillus species IgG subclass, peripheral blood eosinophils, and lung histology were studied. RESULTS: The results demonstrate similar lung inflammation in all wild-type and IL-4-/- animals exposed to A. fumigatus antigen. Similarly, in spite of the diverse immune response produced by the anticytokine treatment, no major differences were detected among any of the animal groups studied. CONCLUSIONS: It can be concluded that A. fumigatus exposure in an immunologically unaltered host is predominantly of a Th2 type, and that depletion of the Th2 cytokine leads to a similar lung inflammation but with a characteristic Th1 response, suggesting that the pathogenesis of allergic aspergillosis is the result of multiple induction pathways. 相似文献
88.
Robert G Rivard Suzanne McCall Matthew E Griffith Joshua S Hawley Roseanne A Ressner Himabindu Borra James E Moon Miriam L Beckius Clinton K Murray Duane R Hospenthal 《Medical mycology》2007,45(8):685-689
Disseminated phaeohyphomycosis is an uncommon infection affecting immunocompetent and immunocompromised individuals in which response to older antifungal agents has been variable. We compared the effect of six days of therapy with caspofungin, posaconazole, and amphotericin B in parallel studies of survival and fungal burden in an immunocompromised mouse model of Exophiala infection. Mice immunocompromised with cyclophosphamide were treated for 6 days starting one day after initiation of infection. Treatment regimens included amphotericin B, caspofungin, and posaconazole. In the survival studies, experimental animals were observed for 14 days. In the fungal burden tests the experimental animals were sacrificed 7 days after infection and brain and kidney burden determined. Treatment with any agent decreased mortality (P < 0.05), with 40%, 30%, and 80% observed survival of the animals treated with amphotericin B, caspofungin, and posaconazole, respectively. Amphotericin B and posaconazole treatment resulted in a decrease in fungal burden compared to untreated controls (P < 0.05). No reduction in fungal burden was noted in the caspofungin group. All three antifungals evaluated improved survival of immunocompromised mice in this otherwise fatal disseminated phaeohyphomycosis. Amphotericin B and posaconazole reduced fungal burden. Posaconazole and caspofungin appear to have potential for use in treatment of this rare infection. 相似文献
89.
P Masoko JN Eloff 《African journal of traditional, complementary, and alternative medicines》2007,4(2):231-239
The dried leaves of Combretum and Terminalia species (Combretaceae) were extracted with acetone, hexane, dichloromethane and methanol. Thin layer chromatography (TLC) plates were developed under saturated conditions and sprayed with 0.2% 2,2-diphenyl-1-picryl hydrazyl (DPPH) in methanol for antioxidant screening. Visualization of separated bands exhibiting antioxidant activities enabled the localization and the subsequent identification of the potential active compounds. The acetone and methanol extracts displayed the presence of antioxidant activity after spraying the chromatogram with DPPH. Hexane and dichloromethane extracts did not have any antioxidant activity. C. hereroense had the highest number of active compounds, followed by C. collinum ssp. taborense, which were 16 and 10, respectively. Acetone extracts of all tested Combretum species had 53 active bands and methanol had 55. All Terminalia species extracted with acetone and methanol had antioxidant activity. T. gazensis and T. mollis methanol extracts had 11 and 14 active compounds respectively in one of the solvent systems used. The qualitative DPPH assay on TLC was successfully used in this study to systematically assess the total antioxidant activity of the Combretum and Terminalia species extracts. 相似文献
90.
Our present scientific knowledge of the effects of specific training interventions undertaken by professional cyclists on selected adaptive responses in skeletal muscle and their consequences for improving endurance performance is limited: sport scientists have found it difficult to persuade elite cyclists to experiment with their training regimens and access to muscle and blood samples from these athletes is sparse. Owing to the lack of scientific study we present a theoretical model of some of the major training-induced adaptations in skeletal muscle that are likely to determine performance capacity in elite cyclists. The model includes, but is not limited to, skeletal muscle morphology, acid-base status and fuel supply. A working premise is that the training-induced changes in skeletal muscle resulting from the high-volume, high-intensity training undertaken by elite cyclists is at least partially responsible for the observed improvements in performance. Using experimental data we provide evidence to support the model. 相似文献