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991.
Stephan Kemp Aurora Pujol Hans R. Waterham Bjrn M. van Geel Corinne D. Boehm Gerald V. Raymond Garry R. Cutting Ronald J.A. Wanders Hugo W. Moser 《Human mutation》2001,18(6):499-515
X‐linked adrenoleukodystrophy (X‐ALD) is caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC half‐transporter (ALDP) involved in the import of very long‐chain fatty acids (VLCFA) into the peroxisome. The disease is characterized by a striking and unpredictable variation in phenotypic expression. Phenotypes include the rapidly progressive childhood cerebral form (CCALD), the milder adult form, adrenomyeloneuropathy (AMN), and variants without neurologic involvement. There is no apparent correlation between genotype and phenotype. In males, unambiguous diagnosis can be achieved by demonstration of elevated levels of VLCFA in plasma. In 15 to 20% of obligate heterozygotes, however, test results are false–negative. Therefore, mutation analysis is the only reliable method for the identification of heterozygotes. Since most X‐ALD kindreds have a unique mutation, a great number of mutations have been identified in the ABCD1 gene in the last seven years. In order to catalog and facilitate the analysis of these mutations, we have established a mutation database for X‐ALD ( http://www.x‐ald.nl ). In this review we report a detailed analysis of all 406 X‐ALD mutations currently included in the database. Also, we present 47 novel mutations. In addition, we review the various X‐ALD phenotypes, the different diagnostic tools, and the need for extended family screening for the identification of new patients. Hum Mutat 18:499–515, 2001. © 2001 Wiley‐Liss, Inc. 相似文献
992.
P. Miller P. J. Kemp A. Lewis C. G. Chapman H. J. Meadows C. Peers 《The Journal of physiology》2003,548(1):31-37
Single skeletal muscle fibres from rat and cane toad were mechanically skinned and stimulated either electrically by initiating action potentials in the sealed transverse (t-) tubular system or by ion substitution causing depolarisation of the t-system to pre-determined levels. Depression of mitochondrial ATP-producing function with three diverse mitochondrial function antagonists (azide: 1–10 m m ; oligomycin 1 μg ml−1 and carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP) 1 μ m ), under conditions in which the cytosolic ATP was maintained high and constant, invariably reduced the excitability of rat fibres but had no obvious effect on the excitability of toad fibres, where mitochondria are less abundant and differently located. The reduction in excitability linked to mitochondria in rat fibres appears to be caused by depolarisation of the sealed t-system membrane. These observations suggest that mitochondria can regulate the functional state of mammalian muscle cells and have important implications for understanding how the balance between ATP utilisation and ATP production is regulated at the cellular level in general and in mammalian skeletal muscle fibres in particular. 相似文献
993.
J P Kemp 《Annals of allergy》1992,69(4):276-280
994.
Evaluation of a rapid urease test to detect Campylobacter pylori infection. 总被引:2,自引:6,他引:2
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Seventy-five consecutive patients referred for upper gastrointestinal tract endoscopy were evaluated for Campylobacter pylori infection by pathology, culture, and a biochemical test to detect bacterial urease. Forty-eight patients (64%) had C. pylori present based on pathology or culture or both. Thirty-two urease tests were positive after 1 h, all in patients with C. pylori detected by the two other methods (specificity, 100%; sensitivity, 67%). After 24 h, 47 urease tests were positive, but only 40 had C. pylori present (specificity, 74%; sensitivity, 83%). When read after 1 h, the urease test was highly specific and led to rapid presumptive diagnosis. 相似文献
995.
Expression of parathyroid hormone related protein in normal skin and in tumours of skin and skin appendages 总被引:2,自引:0,他引:2
J A Hayman J A Danks P R Ebeling J M Moseley B E Kemp T J Martin 《The Journal of pathology》1989,158(4):293-296
Parathyroid hormone related protein (PTHrP) has been demonstrated in the tumour cells of squamous cell carcinomas originating in a variety of organs, in undifferentiated small cell tumours of the bronchus, and in carcinoma of the kidney. The protein hormone is thought to produce the hypercalcaemia which may complicate some of these malignancies. By using an antibody raised in rabbits against the N-terminal portion of the molecule, the polypeptide may be demonstrated in cells of the prickle cell layer of normal skin and in the cells of hair follicles. Skin tumours showing squamous or hair follicle differentiation are shown to contain the protein antigen, while basal cell carcinomas and tumours with sweat gland differentiation do not. The hormone may be primordial in origin and the progenitor of parathyroid hormone. 相似文献
996.
Triple resin casts were made of the pulmonary arteries, veins, and airways from six dog lungs. The airways were cast at a pressure of 25 cm resin in all six. In the first three, both vessels were cast at a pressure of 30 cm resin, and in the second three, arteries were at 10 cm resin and veins at 5 cm resin. Measurements were made of luminal airway diameters down to 1 mm and of the luminal diameters of the corresponding segments of the vascular trees. The relation of one to the other was shown by calculating the regression lines for the corresponding diameters. Intrapulmonary arteries and veins are of approximately equal diameter when cast at 30 cm resin, while the veins are 20% larger than the arteries when cast at 5 cm and 10 cm of resin, respectively. Both vessel diameters are 75% of bronchial at the higher pressure, while at the lower pressures arteries are 59%, and veins 71% of bronchial. In any individual, vessel diameters are a relatively constant proportion of airway diameter. This constant of proportionality varies considerably between dogs, its value ranging from 0.48 to 1.03. It is concluded that in any individual all three trees have similar diameter ratios--that is, the ratio between mean diameters of branches in successive orders. 相似文献
997.
998.
Evaluation of staining methods for identifying Campylobacter pylori 总被引:11,自引:0,他引:11
E Madan J Kemp T U Westblom M Subik S Sexton J Cook 《American journal of clinical pathology》1988,90(4):450-453
Campylobacter pylori has been implicated in the pathogenesis of peptide ulcer disease. The rapid identification of this organism may depend upon histologic diagnosis, because culture methods are complex and require a minimum of seven days in order to identify a negative specimen. The purpose of this study was to determine which stain used to identify this organism was the most cost-effective and easiest to perform and interpret on a routine basis. Sixty-one consecutive gastric antral biopsies were stained with hematoxylin and eosin, Giemsa, Brown-Brenn, and Warthin-Starry, with 23 of the cases stained by Brown-Hopps. Of the stains tested, the Wright-Giemsa was the easiest to perform. The organisms on the Wright-Giemsa showed a smooth, uniform purple color, whereas the Warthin-Starry gave the organism a granular appearance that at times could be confused for silver precipitate. Both the Wright-Giemsa and Brown-Hopps stain had the highest degree of identification of the organism (defined by percent positivity). The routine use of the Wright-Giemsa stain for identification of C. pylori in antral biopsies is recommended. 相似文献
999.
1000.
Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid oxidation in L6 myotubes 总被引:2,自引:0,他引:2
Matthew J. Watt Gregory R. Steinberg Zhi-Ping Chen Bruce E. Kemp Mark A. Febbraio 《The Journal of physiology》2006,574(1):139-147
We investigated the role of fatty acid availability on AMPK signalling and fatty acid oxidation in skeletal muscle. Incubating L6 skeletal muscle myotubes with palmitate (a saturated fatty acid) or linoleate (a polyunsaturated fatty acid) increased AMPK activity by 56 and 38%, respectively, compared with untreated cells. Consistent with these changes, AMPK Thr172 and acetyl-CoA carboxylase β Ser218 phosphorylation were increased in fatty acid treated cells. Pre-incubating cells with palmitate or linoleate increased subsequent fatty acid oxidation by 86 and 92%, respectively. The enhanced AMPK signalling occurred in the absence of detectable changes in free AMP and glycogen content. The activity of the upstream kinase LKB1 was decreased by fatty acid treatment indicating that AMPK activation was not a consequence of LKB1 activation. Instead, fatty acids enhanced LKB1 phosphorylation of AMPK. Fatty acids did not alter LKB1 activity when either synthetic peptide or AMPK α(1–312) catalytic fragment was used as substrate indicating that the βγ subunits were required for the fatty acid activation. Infection of cells with a dominant-negative AMPK adenovirus reduced basal fatty acid oxidation and inhibited the stimulatory effects of fatty acid pretreatment on fatty acid oxidation. These results indicate that increasing fatty acid availability increases AMPK activity independent of changes in the cellular energy charge and support the view that fatty acids may modulate AMPK allosterically, making it a better substrate for LKB1. 相似文献