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61.
Reduced cell surface levels of GPI‐linked markers in a new case with PIGG loss of function
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Jin James Zhao Jonatan Halvardson Alexej Knaus Patrik Georgii‐Hemming Peter Baeck Peter M. Krawitz Ann‐Charlotte Thuresson Lars Feuk 《Human mutation》2017,38(10):1394-1401
Glycosylphosphatidylinositol (GPI) is a glycolipid that tethers more than 150 different proteins to the cell surface. Aberrations in biosynthesis of GPI anchors cause congenital disorders of glycosylation with clinical features including intellectual disability (ID), seizures, and facial dysmorphism. Here, we present two siblings with ID, cerebellar hypoplasia, cerebellar ataxia, early‐onset seizures, and minor facial dysmorphology. Using exome sequencing, we identified a homozygous nonsense variant (NM_001127178.1:c.1640G>A, p.Trp547*) in the gene Phosphatidylinositol Glycan Anchor Biosynthesis, Class G (PIGG) in both the patients. Variants in several other GPI anchor synthesis genes lead to a reduced expression of GPI‐anchored proteins (GPI‐APs) that can be measured by flow cytometry. No significant differences in GPI‐APs could be detected in patient granulocytes, consistent with recent findings. However, fibroblasts showed a reduced global level of GPI anchors and of specific GPI‐linked markers. These findings suggest that fibroblasts might be more sensitive to pathogenic variants in GPI synthesis pathway and are well suited to screen for GPI‐anchor deficiencies. Based on genetic and functional evidence, we confirm that pathogenic variants in PIGG cause an ID syndrome, and we find that loss of function of PIGG is associated with GPI deficiency. 相似文献
62.
Alexej Ballhausen Prisca Bartels Ines Iacovella Anica Hoegner Alessandro Lorusso Dmitry Bichev Severin Daum Peter Thuss-Patience 《Current oncology (Toronto, Ont.)》2022,29(3):1983
Perioperative chemotherapy is the standard of care for patients undergoing curative resection for gastroesophageal adenocarcinoma. However, less than 50% of patients complete postoperative chemotherapy, and the added benefit to preoperative chemotherapy remains unclear. The aim of this study was to compare disease-free and overall survival (DFS and OS) in patients with perioperative chemotherapy to those who received preoperative chemotherapy only. In addition, a current literature overview is included. This multicenter, retrospective case series included 124 patients with gastroesophageal adenocarcinoma undergoing potentially curative resection and receiving pre- or perioperative chemotherapy between 2006 and 2010. Histopathological, demographic, clinical, and survival data were used to identify the impact of perioperative vs. preoperative chemotherapy on DFS and OS. Patients with perioperative chemotherapy had significantly improved DFS and OS (median DFS 28.0 months; 95%CI 0–62.4 vs. 19.0 months; 95%CI 10.5–27.5; p = 0.008 and median OS 35.7 months; 95%CI 0–73.6 vs. 19.2 months; 95%CI 7.8–30.4; p = 0.002). However, in contrast to patients with tumor-free lymph nodes at the time of resection, patients with positive lymph node status did not significantly benefit from additional postoperative chemotherapy in subgroup analysis. Further studies are encouraged to investigate optimal adjuvant treatment strategies for primary chemotherapy-resistant patients. 相似文献
63.
Wen Ling Ravinder R Regatte Mark E Schweitzer Alexej Jerschow 《Magnetic resonance in medicine》2006,56(5):1151-1155
The onset of cartilage tissue disorders can be characterized by a loss of proteoglycans (PGs) and diagnosed by contrast-enhanced proton ((1)H) MRI techniques, as well as sodium MRI. The behavior of sodium located in anisotropic environments, is examined as a function of cartilage degeneration. PGs are proteolytically depleted from the cartilage samples, which gives rise to a decrease of the ordered sodium content. More surprisingly, however, the residual quadrupolar couplings are shown to increase with increasing depletion levels. Since the residual quadrupolar couplings are intimately related to local order and anisotropic motion, measuring their distribution in cartilage may provide insight into the structural changes that occur within the tissue upon degradation. In this study relatively mild orientational dependence of the couplings was found. Little or no free sodium was observed in the cartilage specimens under study. 相似文献
64.
Hypophyseal-gonadal system during male aging 总被引:1,自引:0,他引:1
The concentration of sex and gonadotropic hormones in blood plasma of 280 reasonably healthy men aged 20-105 was determined using radioimmunoassay kits. Compared to men aged 20-39, the statistically significant decrease in testosterone level was registered in men aged 55-59, the increase in oestradiol in men aged 60-64, progesterone in men aged 55-59, and in LH and FSH in the group aged 65-69. The reactivity of central and peripheral links of the hypothalamic-gonadal system to direct and feed-back control influences alters with age. 相似文献
65.
Mitochondrial polarisation status and [Ca2+]i signalling in rat cerebellar granule neurones aged in vitro 总被引:1,自引:0,他引:1
Mitochondrial membrane potential is a major factor that controls, ultimately, the cellular energy supply. By use of a mitochondrial membrane potential dye (rhodamine 123, R123) and image analysis we show that during long-term (>3 weeks) culture of primary neurones (cerebellar granule neurones) there is a gradual and time-dependent depolarisation of neuronal mitochondria. This process was demonstrated by analysing the changes in the heterogeneity of the cytosolic rhodamine 123 fluorescent signal as a function of the age in culture and by measuring the amplitude of the rhodamine 123 fluorescence evoked by the addition of a mitochondrial protonophore (FCCP). The relationship between cytosolic [Ca(2+)](i) and mitochondrial membrane potential was assessed by recording both parameters simultaneously, in neurones loaded with fura-2 and rhodamine 123. Neuronal stimulation (KCl-evoked depolarisation) induced a mitochondrial depolarisation response resulting from the entry of cytosolic Ca(2+) into mitochondria. In young cultures (10 DIV), the mitochondrial membrane potential recovered fully within 30s from the start of the stimulation, despite the continuous presence of the depolarisation stimulus and the maintained cytosolic [Ca(2+)](i) signal. In contrast, in older neurones (DIV 22), the mitochondrial response was of smaller amplitude and displayed a much longer repolarization period. Also, in these older neurones, the threshold [Ca(2+)](i) level required for the initiation of the mitochondrial depolarisation response was increased by 50%. Thus, the present results indicate that neuronal maturation and ageing in conditions of long-term in vitro culture determine significant changes in the mitochondrial polarisation status that are manifest both in resting conditions and during stimulation and could explain some of the reported changes in neuronal homeostasis in long-term neuronal cultures. 相似文献
66.
A dual role for interleukin-1 in LTP in mouse hippocampal slices 总被引:4,自引:0,他引:4
Interleukin-1 (IL-1) exerts numerous effects in the central nervous system and has been implicated in synaptic plasticity. The objective of this study was to investigate the role of endogenous as well as exogenous IL-1 on long-term potentiation (LTP). Hippocampal slices incubated at 34-36 degrees C show enhanced levels of IL-1alpha and IL-1beta compared to slices incubated at 21-24 degrees C. IL-1 inhibits LTP induced by theta-burst stimulation (TBS) at either temperature. IL-1 receptor antagonist (IL-1ra) had no effect on LTP at 21-24 degrees C, but displayed a concentration-dependent inhibition of LTP at 34-36 degrees C. Under control conditions, the magnitude of LTP was not temperature dependent. These data suggest that IL-1 is required for LTP under physiological conditions but at higher doses, as encountered in pathological conditions, IL-1 inhibits LTP. 相似文献
67.
To determine the heating effects of magnetic resonance imaging (MRI) on non-ferromagnetic total hip endoprostheses, hip endoprostheses were tested in vitro and in an ex vivo animal model. The MRI protocol on a 1.5 T scanner consisted of five sequences with a total duration of 23 min. The maximum heating of prosthetic material was 0.17 K in vitro and 0.90 K ex vivo; the maximum heating of bone surrounding tissue was 0.73 K ex vivo. Slight heating of the prostheses and the surrounding tissue was noted, which should not have any side effects in patients with titanium total hip endoprostheses. 相似文献
68.
Using the example of sodium/proton antiporter from Escherichia coli NhaA, we review the capabilities of single-molecule atomic force microscopy and force spectroscopy to observe structural and functional insights of a membrane protein, which are not attainable by other traditional methods. While atomic force microscopy provides high-resolution topographs of single membrane proteins, their oligomeric state and assembly, single-molecule force spectroscopy experiments detect molecular interactions of the protein. The sensitivity of this method makes it possible to detect and locate interactions that stabilize secondary structures such as transmembrane alpha-helices, polypeptide loops and segments within them. Controlled refolding experiments using single-molecule force spectroscopy observed individual secondary structure segments folding into the functional protein. Various folding pathways of NhaA were detected, each one exhibiting a certain probability to be taken. Time-lapse refolding experiments enabled determining the folding kinetics and hierarchy of individual secondary structural elements. Recent examples detected and located the ligand binding of an antiporter. Similarly, inhibitor binding and location can be detected which in future may guide towards comparative studies of agonist and antagonist altering the functional state of a membrane protein. We review current and future potentials of these approaches to characterize the action of pharmacological molecules on the antiporter function. 相似文献
69.
V V Frolkis V G Shevtchuk N S Verkhratsky A S Stupina S M Karpova T Y Lakiza 《Experimental aging research》1979,5(5):441-477
Changes in hemodynamics and myocardial contractile capacity following the stimulation of extracardial nerves and administration of various doses of acetylcholine, norepinephrine, propranolol, phentolamin, atropine, serpasil and benzohexonium were studied in albino rats, rabbits and cats of various age. The shifts in cardiac acetylcholine and norepinephrine content and the activity of some enzymes of their catabolism were determined as well. Functional changes were compared with the structural shifts in intramural nervous system. In old animals there was a rise in threshold of voltage, which induced threshold reaction at stimulation of n. vagus and n. sympaticus and there was a change in heart sensitivity to acetycholine and norepinephrine, propranolol, atropine, serpasil and benzohexonium. A relationship was shown between age changes in nervous regulation of heart and transmitter metabolism. The intensity of acetylcholine and norepinephrine synthesis was decreased in old age, the transmitter metabolism in various parts of the heart was not uniformly altered, the sensitivity of epicardial chemoreceptors to nicotine, veratrum, acetylcholine was increased. The reflexes from cardiac mechanoreceptors were diminished. 相似文献
70.