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71.
Andreas Recke Cassian Sitaru Gestur Vidarsson Mirja Evensen Mircea T. Chiriac Ralf J. Ludwig Detlef Zillikens 《Journal of autoimmunity》2010,34(4):435-444
In different autoimmune diseases, tissue damage is mediated by the Fc portion of autoantibodies. These include autoimmunity to type VII collagen, a major hemidesmosomal skin constituent, where autoantibodies activate both complement and leukocytes, leading to separation within the dermal–epidermal junction. Fc-dependent effector functions differ among IgG subclasses. To elucidate the still controversial role of IgG subclasses in the pathogenesis of autoimmunity to type VII collagen, we generated a unique set of V gene-matched recombinant chimeric anti-type VII collagen autoantibodies of the four human IgG subclasses. Binding specificities and avidities of all four autoantibodies were comparable. Using ex vivo models, our results demonstrate that a monoclonal autoantibody is sufficient to activate complement and to induce dermal–epidermal separation. However, only IgG1 and IgG3, but not IgG2 and IgG4 against type VII collagen, were pathogenic in our ex vivo model systems. To our knowledge, this is the first time that a full-length recombinant disease-related human autoantibody has been investigated. Our results demonstrate the usefulness of recombinant antibody technology to dissect the contribution of F(ab′)2 and Fc portions of autoantibodies to their biological effects. These findings may eventually contribute to novel diagnostic tools for monitoring disease and to the development of more specific therapies in autoantibody-mediated diseases, i.e. the generation of subclass-specific adsorbers, used for extracorporal immunoapheresis, or the shifting of the autoimmune response to production of non-pathogenic autoantibodies. 相似文献
72.
Puesken M Fischbach R Wenker M Seifarth H Maintz D Heindel W Juergens KU 《European radiology》2008,18(10):2087-2094
The purpose was to compare global left-ventricular (LV) function parameters measured with cine MRI with results from multiphase dual-source CT (DSCT) using 10 and 20 reconstruction phases. Twenty-eight patients with suspected or known CAD underwent DSCT coronary angiography. LV end-diastolic (EDV), end-systolic (ESV) and stroke volumes (SV), and ejection fraction (EF) were determined using LV segmentation and selection of specific phases from DSCT image sets reconstructed either at 5% or 10% steps through the R-R interval. Cine MRI served as the reference investigation. Threshold-based 3D-segmentation was feasible in all DSCT data sets. EDV and ESV were underestimated by DSCT, but showed excellent correlation (Pearson's correlation coefficient 0.95/0.97) to values obtained with MRI. Using data from 5% DSCT image reconstructions instead of 10% phase reconstructions, the position of the ED and ES phase was changed in 16 of 28 patients; ESVs were to found to be slightly smaller, whereas EDV were slightly larger, resulting in a systematic overestimation of LV EF by 1.9% (p = 0.56). Threshold-based 3D segmentation enables accurate and reliable DSCT determination of global LV function with excellent correlation to cine MRI. Minor differences in LV EF indicate that both modalities are virtually interchangeable, even if the number of reconstructed phases is limited to 10% phase reconstructions. 相似文献
73.
Valkama AM Laitakari KT Tolonen EU Väyrynen MR Vainionpää LK Koivisto ME 《European journal of pediatrics》2000,159(6):459-464
The aim of this series was to assess hearing screenings; auditory brainstem responses (ABR), transient evoked otoacoustic
emissions (TEOAE) and free field auditory responses (FF) for the prediction of permanent bilateral hearing loss in high-risk
preterm infants at term post-conceptional age. A total of 51 preterm infants (gestational age <34 weeks, birth weight <1500 g)
underwent examinations at term and hearing, speech and neurological development were followed up until a corrected age of
18 months. Significant hearing defects were verified by broader ABR examinations under sedation and by clinical ward observation
including responsiveness to sounds and enhancement of hearing using an amplification device. Seven bilateral fails in ABR
were found, together with nine bilateral fails in TEOAE and four fails in FF screening at term age. Six preterm infants were
later confirmed to have a significant permanent bilateral hearing loss, four of whom had also cerebral palsy. Bilateral failure
in ABR screening predicted hearing loss with a sensitivity of 100% and a specificity of 98%, TEOAE with a sensitivity of 50%
and a specificity of 84% and in the FF examination at the levels of 50% and 98%, respectively.
Conclusion Transient evoked otoacoustic emissions alone seem not to be so applicable to the neonatal screening of hearing in high-risk
preterm infants as shown earlier in full-term infants, possibly because a hearing defect may be due to retrocochlear damage.
Consequently, auditory brainstem response screening seems to be more suitable for very low birth weight preterm infants.
Received: 21 September 1999 / Accepted: 5 January 2000 相似文献
74.
75.
Mirja Neizel Wiebke Kaestner Malte Kelm Harald P. Kühl 《Current cardiovascular imaging reports》2009,2(2):124-129
Identification of the functional severity of intermediate coronary artery lesions is challenging for the interventional cardiologist.
Functional severity can be measured invasively using the fractional flow reserve (FFR). However, FFR has the disadvantage
of being invasive and associated with radiation exposure. Cardiac MRI (CMR) offers the opportunity to assess myocardial perfusion
noninvasively. A semiquantitative index of myocardial perfusion (perfusion reserve index or PRI) can be obtained from the
first-pass of a bolus of gadolinium through the myocardium. Studies comparing the invasive FFR to CMR perfusion imaging in
patients with coronary artery stenosis of undefined significance have demonstrated that CMR first-pass perfusion imaging may
be useful for the assessment of their functional significance. However, in patients with a high prevalence of microvascular
dysfunction, the value of this method may be limited because the PRI may be influenced by both the epicardial conductance
vessel function as well as microvascular function. 相似文献
76.
Patients with coronary artery disease (CAD) undergoing noncardiac surgery (NCS) pose a special challenge for the anaesthesiologist, as the risk of serious perioperative cardiac complications, which represent a significant cause of morbidity and mortality, is increased in this population. Here we report about a patient with a solitary liver metastasis, who was admitted for hemihepatectomy. The patient with a known single vessel CAD, reporting no current cardiac problems, was cleared for the surgical procedure which carries a high risk of cardiac complications. Cardiology reports were present for evaluation. After an unremarkable placement of the peridural catheter and endotracheal intubation the patient presented with bradycardia and hypotension. Pharmacological resuscitation was initiated. After the patient was stabilized and the differential diagnosis suggested a cardiac problem, surgery was postponed. Following the end of anaesthesia, the patient remained in stable condition without catecholamine support. Coronary angiography on the next day revealed a progression of the CAD. The peridural catheter was removed before the intervention, Aspirin and clopidogrel were given on the same day. The patient was operated successfully without complications six weeks after the coronary intervention. 相似文献
77.
Migraine in children and adolescents: a guide to drug treatment 总被引:2,自引:0,他引:2
Hämäläinen ML 《CNS drugs》2006,20(10):813-820
Migraine is a common disorder in children and adolescents, with a prevalence of 5 and 10%, respectively. Some patients may have recognisable factors that trigger or aggravate migraine attacks, such as flickering or bright lights, strong smells and noise, and where possible these should be avoided. It is also wise to maintain a lifestyle where children receive regular meals and get sufficient sleep. If used, acute pharmacological treatment should be given at the onset of an attack, followed by a rest or sleep. According to recent literature, paracetamol (acetaminophen) and ibuprofen can be recommended for the acute treatment of migraine attacks in children and adolescents, and sumatriptan nasal spray can be recommended for adolescents. The oral formulation of sumatriptan has not shown efficacy in paediatric patients, and the subcutaneous injection, although somewhat effective, is not an ideal formulation for this patient group. There are too few data on the efficacy of the other 'triptans' to recommend their use in children and adolescents. There are less data on the use of prophylactic drugs in paediatric patients. In systematic studies, only flunarizine, which is not available in many countries, and propranolol have been found to be effective. A pilot placebo-controlled study suggests that topiramate might also be effective. Several other agents are commonly used to prevent migraine attacks in children (e.g. amitriptyline, valproic acid [sodium valproate]) despite a lack of robust research into their efficacy. 相似文献
78.
The higher toxicity of cereulide relative to valinomycin is due to its higher affinity for potassium at physiological plasma concentration 总被引:5,自引:0,他引:5
Teplova VV Mikkola R Tonshin AA Saris NE Salkinoja-Salonen MS 《Toxicology and applied pharmacology》2006,210(1-2):39-46
Valinomycin and cereulide are bacterial toxins with closely similar chemical structure and properties but different toxic effects. Emetic poisoning is induced by cereulide but not by valinomycin. Both are specific potassium ionophores. Such compounds may affect mitochondrial functions. Both compounds cause a potassium-dependent drop in the transmembrane inner membrane potential due to the uptake of K+ as positively charged ionophore complex. Valinomycin is more potent than cereulide at high [K+] (>80 mM), whereas cereulide in contrast to valinomycin is active already at <1 mM. With cereulide, there is a substantial lag, while valinomycin acts without lag. Both ionophores induce mitochondrial swelling in the presence of K+, in the case of cereulide with a lag. These toxins strongly inhibited respiration at the level of complex IV when used at higher concentrations than that used for detection of ionophoretic transport of K+. At high [KCl] (120 mM), valinomycin was more potent than cereulide both as ionophore and inhibitor, but at low [KCl] (2.5 mM), cereulide was much more potent. Thus, valinomycin needed 20-30 mM KCl for substantial effects, cereulide only 1-3 mM K+, which is close to its level in blood serum. This explains the higher toxicity of cereulide at low concentrations with the positively charged potassium complex being accumulated in the cell by transport through the plasma membrane driven by the membrane potential. Furthermore, with similar concentrations, the final concentration of cereulide in the cells may become higher than that of valinomycin. 相似文献
79.
Tiikkainen M Häkkinen AM Korsheninnikova E Nyman T Mäkimattila S Yki-Järvinen H 《Diabetes》2004,53(8):2169-2176
Both rosiglitazone and metformin increase hepatic insulin sensitivity, but their mechanism of action has not been compared in humans. The objective of this study was to compare the effects of rosiglitazone and metformin treatment on liver fat content, hepatic insulin sensitivity, insulin clearance, and gene expression in adipose tissue and serum adiponectin concentrations in type 2 diabetes. A total of 20 drug-naive patients with type 2 diabetes (age 48 +/- 3 years, fasting plasma glucose 152 +/- 9 mg/dl, BMI 30.6 +/- 0.8 kg/m2) were treated in a double-blind randomized fashion with either 8 mg rosiglitazone or 2 g metformin for 16 weeks. Both drugs similarly decreased HbA1c, insulin, and free fatty acid concentrations. Body weight decreased in the metformin (84 +/- 4 vs. 82 +/- 4 kg, P < 0.05) but not the rosiglitazone group. Liver fat (proton spectroscopy) was decreased with rosiglitazone by 51% (15 +/- 3 vs. 7 +/- 1%, 0 vs. 16 weeks, P = 0.003) but not by metformin (13 +/- 3 to 14 +/- 3%, NS). Rosiglitazone (16 +/- 2 vs. 20 +/- 1 ml.kg(-1).min(-1), P = 0.02) but not metformin increased insulin clearance by 20%. Hepatic insulin sensitivity in the basal state increased similarly in both groups. Insulin-stimulated glucose uptake increased significantly with rosiglitazone but not with metformin. Serum adiponectin concentrations increased by 123% with rosiglitazone but remained unchanged during metformin treatment. The decrease of serum adiponectin concentrations correlated with the decrease in liver fat (r = -0.74, P < 0.001). Rosiglitazone but not metformin significantly increased expression of peroxisome proliferator-activated receptor-gamma, adiponectin, and lipoprotein lipase in adipose tissue. In conclusion, rosiglitazone but not metformin decreases liver fat and increases insulin clearance. The decrease in liver fat by rosiglitazone is associated with an increase in serum adiponectin concentrations. Both agents increase hepatic insulin sensitivity, but only rosiglitazone increases peripheral glucose uptake. 相似文献
80.
Puomila A Huoponen K Mäntyjärvi M Hämäläinen P Paananen R Sankila EM Savontaus ML Somer M Nikoskelainen E 《Acta ophthalmologica Scandinavica》2005,83(3):337-346
PURPOSE: To assess the clinical picture and molecular genetics of 14 Finnish families with dominant optic atrophy (DOA). METHODS: The clinical status of family members was based on the assessment of visual acuity, colour vision, visual fields and optic nerve appearance; 31 individuals were affected, two suspect and 21 unaffected. A total of 30 coding exons and exon- intron boundaries of the OPA1 gene were sequenced in order to detect mutations. RESULTS: Half the patients were diagnosed at the age of < or = 20 years. Ten out of 20 affected individuals followed up for > or = 6 years had a progressive disease and 10 had a stable disease. According to WHO criteria, 36% of the affected patients were visually handicapped. Eight OPA1 pathogenic mutations, all but one novel, and 18 neutral polymorphisms were detected. CONCLUSION: The most sensitive indicators of DOA were optic disc pallor and dyschromatopsia. With molecular genetic analysis, asymptomatic mutation carriers and DOA cases with a mild clinical outcome were ascertained. No mutational hotspot or Finnish major mutation in the OPA1 gene could be demonstrated as most families carried a unique mutation. No obvious genotype- phenotype correlation could be detected. Detailed clinical assessment and exclusion of non-DOA families prior to mutation screening are necessary for obtaining a high mutation detection rate. 相似文献