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排序方式: 共有3342条查询结果,搜索用时 15 毫秒
41.
K Suzuki T Ezoe J Tohyama J Matsuda MT Vanier K Suzuki 《Acta paediatrica (Oslo, Norway : 1992)》2003,92(S443):54-62
Spontaneously occurring genetic lysosomal storage diseases are as rare in other mammalian species as in man. However, the advent of gene targeting technology has revolutionized the state of animal models of genetic diseases. Nearly all lysosomal storage diseases known in man have been duplicated in the mouse. The technology now allows, not only complete inactivation of endogenous genes, but also the introduction of essentially any type of mutation. These animal models can overcome many of the limitations inherent in studies of human patients - rarity of the disease, extremely complex genetic background and logistical and ethical constraints in the design and execution of experiments with human subjects. For example, genetic manipulations of germ cells or cross-breeding experiments between two mutants are readily feasible with animal models. Two major areas of the utility of animal models are the clarification of the pathophysiology/pathogenetic mechanism of disease and the exploration of therapeutic approaches. Examples of experiments using animal models of lysosomal storage disease are presented, primarily from studies undertaken in our own laboratory.
Conclusion : Animal models have proved invaluable in extending our knowledge of the lysosomal storage diseases and exploring potential therapies. 相似文献
Conclusion : Animal models have proved invaluable in extending our knowledge of the lysosomal storage diseases and exploring potential therapies. 相似文献
42.
Hemoglobin and albumin adducts of benzene oxide among workers exposed to high levels of benzene 总被引:3,自引:0,他引:3
Yeowell-O'Connell K; Rothman N; Smith MT; Hayes RB; Li G; Waidyanatha S; Dosemeci M; Zhang L; Yin S; Titenko-Holland N; Rappaport SM 《Carcinogenesis》1998,19(9):1565-1571
Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and
albumin (Alb) to form protein adducts (BO-Hb and BO-Alb), which are
presumed to be specific biomarkers of exposure to benzene. We analyzed
BO-Hb in 43 exposed workers and 42 unexposed controls, and BO-Alb in a
subsample consisting of 19 workers and 19 controls from Shanghai, China, as
part of a larger cross-sectional study of benzene biomarkers. The adducts
were analyzed by gas chromatography-mass spectrometry following reaction of
the protein with trifluoroacetic anhydride and methanesulfonic acid. When
subjects were divided into controls (n = 42) and workers exposed to < or
=31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO-Hb levels were
32.0, 46.7 and 129 pmol/g globin, respectively (correlation with exposure:
Spearman r = 0.67, P < 0.0001). To our knowledge, these results
represent the first observation in humans that BO-Hb levels are
significantly correlated with benzene exposure. Median BO-Alb levels in
these 3 groups were 103 (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb,
respectively, also reflecting a significant correlation with exposure
(Spearman r = 0.90, P < 0.0001). The blood dose of BO predicted from
both Hb and Alb adducts was very similar. These results clearly affirm the
use of both Hb and Alb adducts of BO as biomarkers of exposure to high
levels of benzene. As part of our investigation of the background levels of
BO-Hb and BO-Alb found in unexposed persons, we analyzed recombinant human
Hb and Alb for BO adducts. Significant levels of both BO-Hb (19.7 pmol/g)
and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of the
observed background adducts reflect an artifact of the assay, while other
portions are indicative of either unknown exposures or endogenous
production of adducts.
相似文献
43.
Increased aneusomy and long arm deletion of chromosomes 5 and 7 in the lymphocytes of Chinese workers exposed to benzene 总被引:4,自引:1,他引:4
Zhang L; Rothman N; Wang Y; Hayes RB; Li G; Dosemeci M; Yin S; Kolachana P; Titenko-Holland N; Smith MT 《Carcinogenesis》1998,19(11):1955-1961
Two of the most common cytogenetic changes in therapy- and chemical-
related leukemia are the loss and long (q) arm deletion of chromosomes 5
and 7. The detection of these aberrations in lymphocytes of individuals
exposed to potential leukemogens may serve as useful biomarkers of
increased leukemia risk. We have used a novel fluorescence in situ
hybridization (FISH) procedure to determine if specific aberrations in
chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of
workers exposed to benzene. Forty-three healthy workers exposed to a wide
range of benzene concentrations (median 31 p.p.m., 8 h time-weighted
average) and 44 unexposed controls from Shanghai were studied. Whole blood
was cultured and metaphase spreads were harvested at 72 h. Benzene exposure
was associated with increases in the rates of monosomy 5 and 7 but not
monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and
with increases in trisomy and tetrasomy frequencies of all three
chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a
dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the
exposed workers. These results demonstrate that leukemia-specific changes
in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of
otherwise healthy benzene-exposed workers. We suggest that aberrations in
chromosomes 5 and 7 may be useful biomarkers of early biological effect for
benzene exposure.
相似文献
44.
Neuropsychological functioning in end-stage renal disease. 总被引:2,自引:0,他引:2
H N Bawden P Acott J Carter D Lirenman G W MacDonald M McAllister M C McDonnell S Shea J Crocker 《Archives of disease in childhood》2004,89(7):644-647
AIMS: To compare the neuropsychological functioning and behaviour of children with non-syndromic end-stage renal disease (ESRD) and sibling controls. METHODS: The study was carried out at two tertiary care paediatric teaching hospitals, in Halifax and Vancouver, Canada. Children with ESRD were on a renal transplant waiting list and either pending dialysis or on dialysis therapy. Twenty two patient-sibling pairs were evaluated. Neuropsychological assessments consisting of measures of intelligence, academic achievement, memory, and motor abilities were carried out. Maternal ratings of behaviour and self-report rating of self-esteem were collected. RESULTS: The Verbal, Performance, and Full Scale IQs of patients with ESRD were significantly lower than the IQs of the sibling controls. The mean differences were 8.6, 11.7, and 10.9 points, respectively. ESRD patients also had significantly more difficulty on measures of fine motor coordination and ability to copy geometric designs than sibling controls. There were no differences between groups on measures of academic achievement, memory, behaviour, or self-esteem. CONCLUSIONS: Although children with ESRD exhibited mild deficits on measures of intelligence and some measures of motor abilities, their neuropsychological outcome was more favourable than earlier reports indicated. 相似文献
45.
Recent advances in modern perinatal and neonatal intensive care have led to an increase in the survival of premature infants. This increased survival, unfortunately, has not been accompanied by an improvement in neurodevelopmental outcomes. Premature infants, especially those with an extremely low birth weight (less than 1000 g) or those born at less than 28 weeks’ gestation, are at increased risk of major disabilities and complex, ‘low severity’ dysfunctions that have significant, lasting effects on their school function, academic performance and behaviour, as well as on family function. Neonatal follow-up programs provide a number of functions to centres providing neonatal intensive care, including quality assurance and audits, research and follow-up clinical care to neonatal intensive care unit survivors and their families. The challenge for neonatal follow-up programs is to meet the often competing objectives of providing clinical services to children and their families while providing quality assurance and audits, and high-quality long-term outcome research components, given the available resources. There is also a need for ongoing research to develop and evaluate effective postdischarge intervention programs to improve the long-term outcome of prematurity and other neonatal complications. Developmental paediatricians – with their background and training in the provision of specialized health care to children and their care-givers with respect to developmental and psychosocial well-being, and in conducting developmental and behavioural disabilities research – play a valuable role in the follow-up assessment and care of neonatal intensive care unit graduates, and strengthen the multidisciplinary research groups necessary to assess long-term outcomes and the effects of perinatal and postdischarge interventions. 相似文献
46.
Hanin Rashid Robert Lebeau Norma Saks Anthony R. Artino Judy A. Shea 《Teaching and learning in medicine》2016,28(4):353-357
This Conversation Starters article presents a selected research abstract from the 2016 Association of American Medical Colleges Northeast Region Group on Educational Affairs annual spring meeting. The abstract is paired with the integrative commentary of three experts who shared their thoughts stimulated by the pilot study. These thoughts explore the metacognitive, social, and environmental mechanisms whereby advice plays a role in self-regulated learning. 相似文献
47.
48.
Wesley H. Self MD MPH Joyce Mickanin MSN RN Carlos G. Grijalva MD MPH Freda H. Grant MT ASCP Michelle C. Henderson MSN RN Glenda Corley MT ASCP D. Glen Blaschke II MD Candace D. McNaughton MD MPH Tyler W. Barrett MD MSCI Thomas R. Talbot MD MPH Barbara R. Paul MD 《Academic emergency medicine》2014,21(3):274-282
49.
50.