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31.
Ferrer I Kapfhammer JP Hindelang C Kemp S Troffer-Charlier N Broccoli V Callyzot N Mooyer P Selhorst J Vreken P Wanders RJ Mandel JL Pujol A 《Human molecular genetics》2005,14(23):3565-3577
ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2-/- mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascade. 相似文献
32.
Baeyens A Claes K Willems P De Ruyck K Thierens H Vral A 《Cancer Genetics and Cytogenetics》2005,163(2):106-112
Recently, multiple studies have shown that a sequence variant in CHEK2 (CHEK2 1100delC) plays a role in the susceptibility to breast cancer. This mutation should confer about a twofold increased breast cancer risk in women and a 10-fold increased risk in men. Because the CHEK2 gene plays a critical role in DNA damage repair and the CHEK2 1100delC variant confers susceptibility to breast cancer, we investigated if patients carrying the CHEK2 1100delC mutation are characterized by an enhanced chromosomal radiosensitivity. To this end, familial breast cancer patients, sporadic breast cancer patients, and healthy women, considered in our previously studied to determine their chromosomal radiosensitivity with the G2 and G0-MN assay, were all tested in present study for the presence of the CHEK2 1100delC variant. The 1100delC variant was detected in none of the 100 healthy individuals, in 1 of 100 (1%) unselected breast cancer patients and in 3 of 78 (3.8%) breast cancer patients with a family history of breast cancer. The breast cancer patients with the CHEK2 1100delC genotype had a mean radiation-induced yield of chromatid breaks that was not significantly different from that of the healthy control group. Although the mean yield of micronuclei (MN) was significantly higher compared to the healthy control group, this higher mean MN yield was due to a single patient who had a very high number of MN compared to the parallel control. Our data suggest that breast cancer patients with a CHEK2 1100delC mutation are in general not characterized by a distinct enhanced chromosomal radiosensitivity. These conclusions are, however, very preliminary, because of the small numbers of CHEK2 1100delC breast cancer patients studied. 相似文献
33.
H. Blumberg Petra Haupt W. Jänig W. Kohler 《Pflügers Archiv : European journal of physiology》1983,398(1):33-40
Afferent fibres, in the inferior splanchnic nerves and lumbar white rami, which supply the colon and its mesentery in the cat, were investigated for their responses to distension and contraction of the colon and to local pressure applied to colon and its mesentery. 1) 63% (177 out of 287) of the axons had resting activity (median 0.3 imp/s). These axons were either unmyelinated (conduction velocity below 2 m/s) or thin myelinated (conduction velocity below 18 m/s). Most axons without resting activity (N=95 out of 106 axons) conducted at less than 1.4 m/s, and most were probably sympathetic efferents. 2) 76 out of 80 afferent units with resting activity (95%) and 8 out of 27 units without (30%) were excited by distension of the colon. The thresholds were largely at intraluminal pressures of around 25 mm Hg or higher. 3) Most afferent units (87%) responded with an increased steady state discharge throughout the distension with or without initial dynamic response. The rest of the afferent units responded only with a transient discharged to distension. 4) Most afferent units reacted in a graded manner to variable intraluminal pressures. 5) In only 43% of the distension-sensitive afferent units could mechanoreceptive sites be located on the wall of the colon or in the mesentery. The majority of the afferent units had one mechanoreceptive site only, some had two. 6) Afferent units reacting to colon distension were also excited by contraction of the colon. 7) The excitability spectrum of visceral afferent fibres in the inferior splanchnic nerves, which are activated by colon distension, suggests that these units are involved in visceral nociception from the colon. 相似文献
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35.
Seiler Petra; Fischer Bernd; Lindenau Antje; Beier Henning M. 《Human reproduction (Oxford, England)》1994,9(10):1920-1926
The commercial polychlorinated biphenyl (PCB) formulation Aroclor1260 (4 mg/kg body weight), technical grade dichlorodiphenyltrichloroethane(DDT; 3 mg) and Lindane (-hexachlorocyclohexane; 0.8 mg) wereadministered orally, either separately or in combination, tosexually mature female rabbits three times per week for 1215weeks. Oviductal and uterine luminal fluid, cleavage stage embryos(day 1 post coitum), blastocysts (day 6), fetuses, exocoelicfluid and placentae (day 11) were analysed, firstly for chlorinatedhydrocarbon residues, and secondly for embryonic and fetal development.The doses applied were well tolerated by the treated animals.PCB and DDT accumulated in uterine secretions (day 6) but notin oviductal luminal fluid (day 1). Both chlorinated hydrocarbonswere found in preimplantation blastocysts. Residues in day 11fetuses were 16- (DDT) or 18-fold (PCB) higher than in day 6blastocysts. Significant amounts were also detected in placentaltissue and in exocoelic fluid. A specific accumulation of thehighly chlorinated biphenyl congener no. 180 was noted in fetuses,placentae and exocoelic fluid. The clear accumulation of thechlorinated hydrocarbon compounds in luminal fluid and embryonictissue is contrasted by rather weak effects on fertility. Nostatistically significant differences between treated animalsand controls were observed for fertilization rate and pre- andpost-implantation (up to day 11 post coitum) losses. However,in females exposed to PCB, a 20% higher loss of blastocystswas noticed, as compared with controls (P > 0.05). This effectwas shown on day 6 of embryonic development and may be due tothe embryotoxic activities of PCB. 相似文献
36.
Resolution and conservation of mismatches in DNA end joining 总被引:1,自引:1,他引:1
Pfeiffer Petra; Thode Silke; Hancke Juliane; Keohavong Phouthone; Thilly William G. 《Mutagenesis》1994,9(6):527-535
DNA end joining is a major pathway for the elimination of double-strandbreaks from chromosomal DNA of higher eucaryotic cells. Extractsof Xenopus laevis eggs rejoin such breaks even when their shortsingle-stranded termini are expected to form imperfectly matchedoverlaps. However, end-joined products cloned in Escherichiacoli, necessarily give rise to perfectly matched products. Thereforeit has not been possible to determine whether the end joiningprocess creates mismatched products, perfectly matched (resolved)products or both. To investigate whether mismatch resolutionwas the result of the X. laevis end joining process or of activitiesof the bacterial host we used denaturing gradient gel electrophoresisto analyse joined products. We found that the end joining processdoes include mismatch resolution, the degree of which varieswith regard to the nature of the original overlap structure.Mismatches 3' to a gap are completely resolved, mismatches 3'to a nick and 5' to a nick or gap are resolved to some extentbut are generally conserved. Mismatches between base matchesare always conserved. These findings suggest competing processesof ligation, DNA fill-in synthesis or exonucleolytic excisionof mismatched bases next to a gap or nick. At mismatches 3'to a nick the probability of ligation is greater than that ofexcision while at mismatches 3' to a gap the probability ofexcision is greater than elongation of a given mismatch. Atmismatches 5' to nicks or gaps it appears that ligation or elongationand ligation, respectively, are the most probable pathways butproducts resulting from mismatch excision, elongation and ligationare also detected.
5To whom correspondence should be addressed 相似文献
37.
Resistance of pathogenic bacteria to antibiotics leads scientists to discover new antibacterial drugs. Ninety samples of wood-colonizing fungi were cultivated on agar plates, and their extracts tested for antibacterial activity using the Vibrio fischeri bioluminescence test. Two fungi species, Serpula lacrymans and Nectria vilior, were found to be a potential new source of thermostable antibiotics. Vibrio fischeri bioluminescence test was found to be a useful method for antibacterial activity screening from the samples of natural origin. 相似文献
38.
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40.
Wolfgang Müller-Felber Klaus Küllmer Petra Fischer Carl-Detlev Reimers Stefan Wagner Ullrich Harland Martin Schmidt-Achert Dieter Pongratz 《Virchows Archiv : an international journal of pathology》1993,422(4):277-283
Leu-19 antigen, which seems to be identical with neural cell adhesion molecule (N-CAM), plays a major role in the innervation of muscle cells, and in adult muscle appears after denervation and during regeneration of muscle fibres, where it acts as part of a signalling system increasing the probability of re-innervation. This combined enzyme-histochemical and immunohistochemical study examined whether this signalling process was regulated in a uniform or differential pattern for type 1 and type 2 muscle fibres. The subscapular nerve of 18 rabbits was transsected with subsequent complete denervation of the supraspinatus muscle. Leu19 and N-CAM immunohistochemistry was performed 2 to 64 days after surgery. Whereas in normal muscle there are virtually no Leu-19/N-CAM positive muscle fibres; from day 2 after denervation an increasing proportion of fibres expressed Leu-19/N-CAM, prior to any neurogenic atrophy. In the early stage of denervation Leul9/N-CAM expression was confined to type 1 fibres. After 11 days nearly all fibres were Leul9/N-CAM positive irrespective of their fibre type. Sixty-four days after denervation type 1 fibres became Leu19/N-CAM negative, while atrophic type 2 fibres showed intensive staining. Thus, expression of Leu-19 antigenity is differently regulated in both fibre types. 相似文献