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81.
PD Dr. I. Kurth 《Medizinische Genetik》2011,23(1):15-20
The sensory nervous system detects pressure, touch, stretching, heat, and cold and translates these stimuli into action potentials. To protect the body from tissue damage acute pain is felt when a stimulus gains a critical intensity. The combination of impaired nociception and autonomic dysfunction is the hallmark of hereditary sensory and autonomic neuropathies (HSAN). Sensory loss in HSAN patients results in ulcerations of hands and feet and may necessitate amputations. Congenital onset of HSAN leads to self-mutilating behavior in affected children. Degeneration of motor neurons can complicate the disease. HSAN is divided into five groups according to clinical symptoms. So far, nine genes have been identified as causative for the disorder. The present article reviews the clinical, genetic, and pathophysiological aspects of HSAN. 相似文献
82.
Mosaicism is defined as the simultaneous presence of cells with different genotypes that originate from a common zygote. Mutations can either be present in germline or somatic cells. Monogenic disorders apparently caused by a de novo mutation may show a recurrence risk due to germline mosaicism in a parent. Duchenne muscular dystrophy is a well investigated example with a high frequency of germline mosaicism and the estimation for the risk of recurrence is based on theoretical models and empirical data. Recently, somatic mutations have been uncovered in various syndromic disorders, such as Proteus syndrome or hemimegalencephaly and respective mutations often show gain-of-function properties. Genetic testing is mainly based on next generation sequencing technologies but still remains challenging; however, detection of somatic mosaicism is expected to be of increasing relevance in the diagnosis of monogenic disorders. Somatic mosaicism may also play a hitherto underestimated role in common disorders. 相似文献
83.
With an incidence of approximately 0.2?% in newborns gonosomal chromosome aberrations are of major relevance for clinical genetics. They frequently occur as numerical and/or structural gonosomal mosaicism. The correlation between genotype and phenotype is poor most probably due to different levels of mosaicism in different tissues and they represent a great challenge especially in prenatal diagnostics, requiring genetic counseling by an experienced clinical geneticist. Postnatally, gonosomal mosaicism in females often leads to the clinical symptoms of Turner’s syndrome (especially short stature and infertility) with an potentially increased risk for gonadoblastoma if an XY cell line is present. In males with Klinefelter’s syndrome mosaicism is also frequent (up to 20?%). Mosaicism in 47,XYY and 47,XXX karyotypes is rarely reported perhaps due to the innocuous phenotype seldom being an indication for chromosome analysis. 相似文献
84.
Valerie Leblanc Marie-Claude Dery Carl Shooner Eric Asselin 《Reproductive biology and endocrinology : RB&E》2003,1(1):59
During rat estrous cycle, the endometrium proliferates in response to sex steroids and specific endometrial epithelial cells
undergo apoptosis in absence of embryonic factors. The central executioner of apoptosis is a family of aspartic acid-specific
cysteine proteases known as caspases. Smac/DIABLO is released from the mitochondria during apoptosis and its stimulation promotes
caspases activation by neutralizing members of the inhibitor of apoptosis proteins (IAPs) family, such as X-linked inhibitor
of apoptosis protein (XIAP). The aim of this study was to investigate the involvement of Smac/DIABLO and XIAP in the control
of caspases activation in endometrium of cycling rats. Polyoestrus female rats were sacrificed at each stage of estrous cycle
(diestrus, proestrus, estrus, and metestrus). Endometrial protein extracts were collected to perform Western Blot analysis.
Alternatively, uterine horns were sectioned for immunohistochemistry (IHC). We and others showed previously the presence of
apoptosis at estrus in rat uterine epithelium. In the present study, cleaved caspase-3, -6, and -7 fragments were detected
at estrus. IHC confirmed that caspase-3 was present only in luminal and glandular epithelium at estrus. XIAP was highly expressed
at estrus in both epithelial and stromal cells. In contrast, expression of Smac/DIABLO was elevated at diestrus, proestrus
and metestrus but was minimal at estrus. Treatment of ovariectomized rats with 17β-estradiol induced XIAP expression and inhibited
Smac/DIABLO protein expression in the endometrium. Cleaved caspase-3, -6, and -7 fragments increased in endometrial protein
extracts following 17β-estradiol treatment. Expression of NF-κB and IκB proteins, and IκB phosphorylation status were detected
in the endometrium but were not influenced by the estrous cycle. These findings suggest that Smac/DIABLO and XIAP are regulated
differently and may play important roles in the regulation of endometrial cell fate. Moreover, this study confirms a key role
for executioner caspases in the control of apoptotic processes at estrus in the rat uterus. 相似文献
85.
86.
PD Dr. Hermann Rink Dipl.-Biol. H. -J. Partke 《Radiation and environmental biophysics》1975,12(2):119-125
Yeast cells, Saccharomyces uvarum, were irradiated with X-rays and grown in liquid suspension. Glucose as the only carbon source was limited to 12.5 mM. Under these conditions giant cells are formed. Cell number, glucose utilization, ethanol production and oxygen consumption are measured during the time of growth. The mean weight of single cells in the stationary phase increases up to 75 krad and is not due to an uptake of water. In irradiated cultures oxygen consumption and glucose utilization per cell are higher than in control cells. The data demonstrate that synthesis- and energy-metabolism during the formation of non-dividing, radiation-induced giant cells is increased. 相似文献
87.
PD Dr. Karl Zilles Axel Schleicher Hans -Joachim Kretschmann 《Cell and tissue research》1978,190(2):285-299
Summary The grey level index (= GLI) and the fresh volume were determined with the image analyser Micro-Videomat for the nucl. n. facialis after axotomy of the left n. facialis. The experiments were performed on 10 rats in different stages of ontogenesis. The GLI is a quantitative parameter which could be quickly obtained and which demonstrated quantitative changes during retrograde reaction in the respective centres. A decrease in the fresh volumes of the affected nucl. n. facialis could also be demonstrated. The meaning of GLI is discussed.Supported by Deutsche Forschungsgemeinschaft grants Kr 289/10 and Zi 192/1Dedicated to Prof. Dr. H. Leonhardt on the occasion of his 60th birthday 相似文献
88.
Dery Olivier; Corvera Carlos U.; Steinhoff Martin; Bunnett Nigel W. 《American journal of physiology. Cell physiology》1998,274(6):C1429
Although serineproteases are usually considered to act principally as degradativeenzymes, certain proteases are signaling molecules that specificallyregulate cells by cleaving and triggering members of a new family ofproteinase-activated receptors (PARs). There are three members of thisfamily, PAR-1 and PAR-3, which are receptors for thrombin, and PAR-2, areceptor for trypsin and mast cell tryptase. Proteases cleave withinthe extracellular NH2-terminus oftheir receptors to expose a newNH2-terminus. Specific residueswithin this tethered ligand domain interact with extracellular domainsof the cleaved receptor, resulting in activation. In common with many Gprotein-coupled receptors, PARs couple to multiple G proteins andthereby activate many parallel mechanisms of signal transduction. PARsare expressed in multiple tissues by a wide variety of cells, wherethey are involved in several pathophysiological processes, includinggrowth and development, mitogenesis, and inflammation. Because thecleaved receptor is physically coupled to its agonist, efficientmechanisms exist to terminate signaling and prevent uncontrolledstimulation. These include cleavage of the tethered ligand, receptorphosphorylation and uncoupling from G proteins, and endocytosis andlysosomal degradation of activated receptors. 相似文献
89.
Rhizobium leguminosarum bv. trifolii produces an acidic exopolysaccharide (EPS) which plays an important role in the development of nitrogen-fixing nodules. Tn5 mutant of R. trifolii 93 defective in EPS production (Exo-) forms ineffective (Fix-) nodules on red clover. This Exo- mutation is complemented by the pARF1368 and pARF25 cosmids isolated from gene bank of Rhizobium trifolii TA1, but the complementation is not correlated with restoration of Fix+ phenotype. Furthermore, these cosmids introduced to wild-type of R. trifolii 24 repress its ability to form nitrogen-fixing nodules. These results might suggest that bacteria with cosmids carrying the exo region form EPS of altered structure. It has been shown by 1H-n.m.r. that exopolysaccharides produced by R. trifolii 93pARF-1368 and 93pARF25 contain less non-carbohydrate residues (acetyl, pyruvyl and 3-hydroxybutanoyl) than the wild type EPS. These data suggest that the biological activity of the exopolysaccharide of R. trifolii depends on the contents of the non-carbohydrate substitutions. 相似文献
90.
Schmidlin F Dery O DeFea KO Slice L Patierno S Sternini C Grady EF Bunnett NW 《The Journal of biological chemistry》2001,276(27):25427-25437
Understanding the molecular mechanisms of agonist-induced trafficking of G-protein-coupled receptors is important because of the essential role of trafficking in signal transduction. We examined the role of the GTPases dynamin 1 and Rab5a in substance P (SP)-induced trafficking and signaling of the neurokinin 1 receptor (NK1R), an important mediator of pain, depression, and inflammation, by studying transfected cells and enteric neurons that naturally express the NK1R. In unstimulated cells, the NK1R colocalized with dynamin at the plasma membrane, and Rab5a was detected in endosomes. SP induced translocation of the receptor into endosomes containing Rab5a immediately beneath the plasma membrane and then in a perinuclear location. Expression of the dominant negative mutants dynamin 1 K44E and Rab5aS34N inhibited endocytosis of SP by 45 and 32%, respectively. Dynamin K44E caused membrane retention of the NK1R, whereas Rab5aS34N also impeded the translocation of the receptor from superficially located to perinuclear endosomes. Both dynamin K44E and Rab5aS34N strongly inhibited resensitization of SP-induced Ca(2+) mobilization by 60 and 85%, respectively, but had no effect on NK1R desensitization. Dynamin K44E but not Rab5aS34N markedly reduced SP-induced phosphorylation of extracellular signal regulated kinases 1 and 2. Thus, dynamin mediates the formation of endosomes containing the NK1R, and Rab5a mediates both endosomal formation and their translocation from a superficial to a perinuclear location. Dynamin and Rab5a-dependent trafficking is essential for NK1R resensitization but is not necessary for desensitization of signaling. Dynamin-dependent but not Rab5a-dependent trafficking is required for coupling of the NK1R to the mitogen-activated protein kinase cascade. These processes may regulate the nociceptive, depressive, and proinflammatory effects of SP. 相似文献