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41.
T. Deufel I. Paetzke D. Pongratz G. Hübner O. H. Wieland 《Journal of molecular medicine (Berlin, Germany)》1984,62(14):651-658
Summary In the diagnosis of metabolic myopathies the use of biochemical methods, in addition to morphological examination of muscle biopsies, is often necessary in order to identify a specific metabolic defect. In order to narrow down the spectrum of biochemical methods, extensive clinical investigation and morphological examination, including histology, enzyme histochemistry and electromicroscopy if necessary have to be done beforehand. Patients are classified in the following groups: 1) progressive muscular weakness and/or muscle wasting with storage of a) glycogen, b) lipid or c) mitochondrial alterations; 2) recurrent rhabdomyolysis induced by fasting or exercise a) with glycogen storage or b) without any specific morphological alterations. The spectrum of metabolic defects comprises disorders of glycogen and glucose metabolism (deficiency of acid maltase, debranching and branching enzyme, phosphorylase, phosphofructokinase and other glycolytic enzymes), lipid metabolism (carnitine deficiency, carnitine palmitoyl transferase deficiency), mitochondria (respiratory chain disorders, pyruvate dehydrogenase deficiency) and others such as adenylate deaminase deficiency. In some of these e.g. infantile acid maltase deficiency and mitochondriopathies, it is clinically more important when organs other than muscle are affected; however, muscle biopsy is a useful substrate for diagnosis of these metabolic disorders.
Mit Unterstützung durch die DFG und die Friedrich Baur Stiftung, München 相似文献
42.
Bettina Wedi MD Ulrike Raap Heitje Lewrick Alexander Kapp MD PhD 《The Journal of allergy and clinical immunology》1998,102(6):1013-1020
Background: The regulation of eosinophil survival and apoptosis may play a major role in diseases demonstrating increased numbers of circulating and tissue eosinophils such as allergic reactions. Because few promoters of eosinophil apoptosis have been described so far, the objective of this study was to elucidate the role of endogenous factors on eosinophil survival and apoptosis. Methods and Results: Highly purified peripheral blood eosinophils were analyzed in the time course from 24 up to 144 hours in culture. Eosinophil survival was assessed with trypan blue dye exclusion and apoptosis was determined by DNA fragmentation gel analysis and ELISA technique with anti-histone antibodies. We confirmed previous results demonstrating prolonged eosinophil survival and inhibited apoptosis by IL-3, IL-5, and GM-CSF. In contrast, eosinophil apoptosis was significantly enhanced by corticosteroids, particularly dexamethasone and hydrocortisone. However, IL-1β, IL-8, IL-12, platelet-activating factor, TNF-α, and eotaxin had no effect on eosinophil survival or apoptosis when compared with culture medium alone. In contrast, IL-4 at concentrations of 100 U/mL or more inhibited eosinophil survival and induced apoptosis. This effect was time dependent and abrogated by preincubation with neutralizing anti–IL-4 antibodies. However, after 96 hours in coincubation, IL-4 did overcome the survival-prolonging effect of IL-3, IL-5, and GM-CSF. IL-4 did not enhance eosinophil surface expression of APO-1/Fas antigen (CD95). In assessing IL-4–mediated effects on eosinophil function, we found no response by means of the release of eosinophil cationic protein or reactive oxygen species. Conclusions: Taken together, our data present direct evidence for the presence of functional IL-4 receptors on human eosinophils and indicate that IL-4 may lead to resolution of chronic inflammation by induction of eosinophil apoptosis. (J Allergy Clin Immunol 1998;102:1013-20) 相似文献
43.
Implanted biomaterials are coated immediately with host plasma constituents, including extracellular matrix (ECM); this reaction may be undesirable in some cases. Poly(L-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG) has been shown to spontaneously adsorb from aqueous solution onto metal oxide surfaces, effectively reducing the degree of non-specific adsorption of blood and ECM proteins, and decreasing the adhesion of fibroblastic and osteoblastic cells to the coated surfaces. Cell adhesion through specific peptide-integrin receptors could be restored on surfaces coated with PLL-g-PEG functionalized with peptides of the RGD (Arg-Asp-Gly) type. To date, no study has examined the effect of surface modifications by PLL-g-PEG-based polymers on bacterial adhesion. The ability of Staphylococcus aureus to adhere to the ECM and plasma proteins deposited on biomaterials is a significant factor in the pathogenesis of medical-device-related infections. This study describes methods for visualizing and quantifying the adhesion of S. aureus to smooth and rough (chemically etched) titanium surfaces without and with monomolecular coatings of PLL-g-PEG, PLL-g-PEG/PEG-RGD and PLL-g-PEG/PEG-RDG. The different surfaces were exposed to S. aureus cultures for 1-24h and bacteria surface density was evaluated using scanning electron microscopy and fluorescence microscopy. Coating titanium surfaces with any of the three types of copolymers significantly decreased the adhesion of S. aureus to the surfaces by 89-93% for PLL-g-PEG, and 69% for PLL-g-PEG/PEG-RGD. Therefore, surfaces coated with PLL-g-PEG/PEG-RGD have the ability to attach cells such as fibroblasts and osteoblasts while showing reduced S. aureus adhesion, resulting in a selective biointeraction pattern that may be useful for applications in the area of osteosynthesis, orthopaedic and dental implantology. 相似文献
44.
Zeeb Hajo Ahrens Wolfgang Haug Ulrike Grabenhenrich Linus Pigeot Iris 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2021,64(9):1076-1083
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Epidemiologie als wissenschaftliche Disziplin ist prädestiniert dafür, Kernfragen der COVID-19-Pandemie zu... 相似文献
45.
Carlos R Ferreira Kristina Kintzinger Mary E Hackbarth Ulrike Botschen Yvonne Nitschke M Zulf Mughal Genevieve Baujat Dirk Schnabel Eric Yuen William A Gahl Rachel I Gafni Qing Liu Pedro Huertas Gus Khursigara Frank Rutsch 《Journal of bone and mineral research》2021,36(11):2193-2202
Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA. 相似文献
46.
Andrea Franz Daniel Herz Jens Raabe Ulrike Seeberger Christine Bollmann 《Foot and Ankle Surgery》2021,27(4):389-394
BackgroundFlatfoot is a frequent skeletal deformity in childhood that can be minimally invasively treated by arthroereisis. Question: Does the motion of juvenile flexible flatfoot normalize after arthroereisis?MethodPedographic measurements were obtained from 39 patients preoperatively, six months postoperatively and compared to a healthy group. The footprints were divided into 8 areas. The selected parameters were: contact area and force-time-integral.ResultsAfter surgery, a load shift from the medial to the lateral areas was detected under the midfoot and forefoot. The force-time-integral under the hallux normalized. However, under the lateral midfoot, the postoperative force-time-integral was significantly higher than in the control group.SignificanceThe study shows that arthroereisis is able to correct the medially displaced load distribution of juvenile flexible flatfoot. However, further investigations are required to find out if the higher punctual loading under the lateral midfoot may cause problems in the long term. 相似文献
47.
Rachel Wuerstlein Nadia Harbeck Eva-Maria Grischke Dirk Forstmeyer Raquel von Schumann Petra Krabisch Kerstin Lüdtke-Heckenkamp Andrea Stefek Oliver Stoetzer Andrea Grafe Gabriele Kaltenecker Helmut Forstbauer Doris Augustin Iris Schrader Joke Tio Ulrike Nitz Oleg Gluz Ronald E. Kates Monika Karla Graeser 《Breast care (Basel, Switzerland)》2021,16(1):50
BackgroundProtroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT).Patients and MethodsOf the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed.ResultsNine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim.ConclusionsApplication of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer. 相似文献
48.
A. Wolkin E. Duncan M. Sanfilipo S. Wieland T. B. Cooper J. Rotrosen 《Journal of neural transmission (Vienna, Austria : 1996)》1994,95(1):49-61
Summary The purpose of this study was to evaluate the hypothesis that neuroleptic non-response in the face of adequate DA post-synaptic receptor blockade reflects failure of regulatory mechanisms to decrease DA pre-synaptic activity. Eight chronic schizophrenics, meeting rigorous criteria for neuroleptic non-response, were treated for four weeks with alpha-methylparatyrosine as an adjunct to their previously stable neuroleptic dose. Treatment with AMPT produced a prompt decrease in plasma HVA that was, on average, 72% lower at the end of the study. While there was also strong clinical evidence of reduction in central dopaminergic activity (both a significant reduction in dyskinetic movements and increase in extrapyramidal symptoms), there was virtually no change in severity of psychotic symptoms. Thus, in this group of non-responders, psychotic symptoms persisted despite both extensive dopamine post-synaptic receptor blockade and marked reduction of presynaptic activity. These symptoms may not be directly DA dependent. 相似文献
49.
Tammo von Schrenck Burkhard Mackensen Ulrike Mende Wilhelm Schmit Jörg Sievers Silvia Mirau Andreas Raedler Heiner Greten 《Naunyn-Schmiedeberg's archives of pharmacology》1994,349(4):346-354
In gallbladder smooth muscle, carbachol interacts with M3 receptors to mediate contraction. To examine components of the intracellular second messenger system that is coupled to these receptors we have tested whether carbachol stimulates the formation of inositol phosphates (IP) to cause contraction. Guinea pig gallbladder muscle strips were prelabeled with [3H]inositol and were incubated with 0.1 mmol/l carbachol, a concentration causing maximal contraction. [3H]inositol monophosphates, [3H]inositol bisphosphates and [3H]inositol trisphosphates and contraction were measured at various times (0–90 s). To examine whether a pertussis toxin-sensitive guanine nucleotide binding protein is coupled to the muscarinic receptors, guinea pigs were pretreated with pertussis toxin (180 g/kg i.v./24 h). The effectiveness of pertussis toxin treatment was determined by measuring [32P]ADP-ribosylation of a –40/41 kDa protein from gallbladder homogenates. Carbachol caused a significant time-dependent increase in the formation of [3H]inositol monophosphates, [3H]inositol bisphosphates and [3H]inositol trisphosphates. The time course of [3H]inositol trisphosphate turnover caused by carbachol was biphasic, and was detectable at 15 s and maximal at 60 s; at 75 s and 90 s formation of [3H]inositol trisphosphates decreased, whereas the time course of carbachol-induced contraction of the gallbladder smooth muscle strips reached a plateau after 90 s. The effects of carbachol on [3H]inositol trisphosphates and on contraction were abolished by atropine. Pretreatment with pertussis toxin resulted in ADP-ribosylation of a 40/41 kDa protein from gallbladder cell membranes but did not affect the concentration-response or time course of carbachol-induced contraction. These results indicate that carbachol-induced contraction of gallbladder smooth muscle cells is accompanied by the activation of inositol phosphate turnover and does not involve a pertussis toxin-sensitive G-protein.This article is based in part on the doctoral thesis of Burkhard Mackensen at the Faculty of Medicine, University of Hamburg, Germany. Some of the results were presented at the meeting of the American Gastroenterological Association (AGA) in San Francisco 1992 (von Schrenck et al. 1992)
Correspondence to: T. von Schrenck at the above address 相似文献
50.
Thomas Wieland Klaus Liedel Sylvia Kaldenberg-Stasch Dagmar Meyer zu Heringdorf Martina Schmidt Karl H. Jakobs 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(4):329-336
Receptor-induced binding of the stable GTP analogue, guanosine 5-[-thio]triphosphate (GTP [S]), to guanine nucleotide-binding regulatory proteins (G proteins) was measured in various permeabilized cells. In myeloid differentiated human leukemia (HL-60) cells, permeabilized with either digitonin, streptolysin O or Staphylococcus aureus -toxin, binding of GTP [S] induced by three distinct chemoattractant receptors was observed. The extent of receptor-stimulated GTP [S] binding (maximally about 2-fold) was independent of the type of permeabilizing agent used. In human erythroleukemia cells permeabilized with digitonin, agonist activation of thrombin and neuropeptide Y receptors increased GTP [S] binding by 1.8- and 1.5-fold, respectively. Finally, in adherently grown human embryonic kidney cells permeabilized with digitonin, activation of the stably expressed human muscarinic m3 receptor increased GTP[S] binding by about 1.6-fold. In digitonin-permeabilized HL-60 cells, a quantitative analysis of formyl peptide receptors and interacting G proteins was performed. About 50,000 formyl peptide receptors per cell were detected. Agonist binding to these receptors was fully sensitive to regulation by guanine nucleotides and pertussis toxin. The number of high-affinity GTP [S] binding sites, most likely representing heterotrimeric G proteins, was calculated to be about 670,000 per cell. Stimulation of formyl peptide receptors led to the activation of about 130,000 of high-affinity GTP [S] binding sites, indicating a ratio of about three activated G proteins per one agonist-activated receptor.Overall, this study indicates that receptor-stimulated GTP [S] binding to G proteins in permeabilized cells is a sensitive and rapid method for analyzing receptor-G protein interactions, which can be applied to a variety of cultured cells and for various receptor systems. 相似文献