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11.
Teresa Rodriguez-Calvo Lars Krogvold Natalie Amirian Knut Dahl-Jrgensen Matthias von Herrath 《Diabetes》2021,70(3):752
In type 1 diabetes (T1D), a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against β-cell antigens have been detected in peripheral blood and in the pancreas of patients with short- or long-term disease. In the Diabetes Virus Detection (DiViD) study, researchers collected pancreatic tissue, by pancreatic tail resection, from living patients with recent-onset T1D. These tissues have been extensively studied by the scientific community, but the autoreactive nature of the T-cell infiltrate has remained unexplored. Our objective was to determine the number and localization of these cells in pancreas samples obtained through the DiViD study. Here, we demonstrate the presence of high frequencies of CD8+ T cells reactive against a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue samples from these donors. We also show the heterogeneity of islet distribution and CD8+ T-cell infiltration. Our findings contribute to the current limited existing knowledge of T-cell reactivity in the pancreas of donors with recent-onset T1D and indicate that antigen-specific therapies directed toward preproinsulin could have high clinical impact. 相似文献
12.
Modified multiplex PCR method for detection of pyrogenic exotoxin genes in staphylococcal isolates 总被引:10,自引:0,他引:10 下载免费PDF全文
A modified multiplex PCR method for detection of nine Staphylococcus aureus enterotoxin genes (sea, seb, sec, sed, see, seg, seh, sei, and sej) and one form of immunoreactive toxic shock syndrome toxin based on a previously published method (S. R. Monday and G. A. Bohach, J. Clin. Microbiol. 37:3411-3414, 1999) has been developed. The modified PCR protocol seems robust and gives reliable results. 相似文献
13.
14.
Prolongation of the ejaculation latency in the male rat by thioridazine and chlorimipramine 总被引:1,自引:0,他引:1
Thioridazine (3 mg/kg) and chlorimipramine (1.5–6.0 mg/kg) prolonged the ejaculation latency and increased the number of mounts but did not change the number of intromissions preceding ejaculation. Blockade of peripheral and central noradrenaline receptors by phentolamine and phenoxybenzamine respectively resulted in a suppression of all aspects of the sexual behavior with increasing doses. dl-5-HTP (25–100 mg/kg) in combination with an inhibitor of peripheral 5-HTP decarboxylase (benserazide, 25 mg/kg) produced, like chlorimipramine and thioridazine, a prolongation of ejaculation latency and an increase in the number of mounts preceding ejaculation. Selective inhibition of 5-HT reuptake however, by zimelidine (0–20 mg/kg) or alaproclate (0–20 mg/kg) did not affect the mating behavior. At higher doses of these drugs some animals failed to initiate sexual activities. There was an increase in the postejaculatory interval but no change in the ejaculatory latency.It is concluded that the prolonged ejaculation latencies observed following treatment with thioridazine or chlorimipramine is not due to a blockade of central or peripheral adrenergic -receptors. 相似文献
15.
Differential patterns of circulating adhesion molecules in children with bronchial asthma and acute bronchiolitis 总被引:2,自引:0,他引:2
The object of the study was to assess the levels of circulating forms of the cellular adhesion molecules ICAM-I, VCAM-1, E-selectin, L-selectin and P-selectin in young children with asthma and acute bronchiolitis. Thirty-nine children aged 12 to 84 months with mild or moderate asthma were studied at admission for acute asthma (n = 15) or in a stable phase (n = 24). Ten of the children with acute asthma were seen again after one month. Twenty-two children aged 1 to 17 months with acute bronchiolitis and nine non-atopic controls were also included in the study. In children with acute asthma, the mean concentration of circulating soluble ICAM-1 (SICAM-I) was increased compared to children with stable asthma (mean 442 μg/l versus 363 μg/l; p < 0.001) and to controls (363 μg/l; p < 0.05). The levels of SICAM-1 remained high at follow up. In children with stable asthma, the mean serum concentration of soluble L-selectin (sL-selectin) (2080 μg/l) was significantly higher than in the controls (1664 μg/l; p < 0.05). The levels of circulating cellular adhesion molecules were similar in atopic and non-atopic asthmatics. Children with acute bronchiolitis had increased serum levels of soluble VCAM-1 (sVCAM-I) (1637 μg/l versus 1019 μg/l in the controls; p < 0.01) and sL-selectin (2041 μg/l versus 1664 μg/l in the controls; p < 0.05). There was no difference between the levels of circulating cellular adhesion molecules in children with respiratory syncytial virus (RSV) positive and RSV negative bronchiolitis. Soluble E-selectin (sE-se-lectin) and soluble P-selectin (sP-selectin) in serum were not significantly increased in any of the groups studied. In conclusion, our data suggest differential patterns of circulating cellular adhesion molecules in young children with acute asthma, stable asthma, and acute bronchiolitis, which may reflect differences in the underlying inflammatory processes in these obstructive pulmonary diseases. 相似文献
16.
J?rn-Uwe Piesold Bilal Al-Nawas Knut A Gr?tz 《Mund-, Kiefer- und Gesichtschirurgie》2006,10(5):287-300
For several decades bisphosphonates have been used to reduce skeletal related events in patients with both osteoporosis or bone metastases. Under long term application, besides the known therapy side effects, a new clinical picture has been described within the last few years. This is osteonecrosis of the jaws, which is characterized by its difficulty in treatment. Besides exposed jaw bone, the start of the disease usually lacks any symptoms. The typical clinical symptoms then are foetor ex ore, swelling, exsudation, loosening of teeth, pain or paresthesia. Later oro-antral/nasal or oro-cutaneous fistula can develop. The X-ray shows persisting tooth sockets after extractions and later cloudy radio-lucency, sequestra or fractures. The patient exposed to bisphosphonate can be grouped according to the risk for osteonecrosis: high risk patients with intravenous bisphosphonate therapy and additional chemo-, radiation or corticoid therapy--predominantly patients with a malignant underlying disease and bone metastases low risk patients with an oral bisphosphonate therapy without additional chemo-, radiation or corticoid therapy--preferably patients with non-corticoid-induced osteoporosis. Before starting a bisphosphonate therapy possible causes of infection should be treated and risk of injuries to the mucosa should be reduced according to the individual risk profile. This is supplemented by information of the patient about the risk of necrosis and the possibilities for prevention. Regular dental recall under bisphophonate therapy is emphasised for early recognition of possible problems. Prophylaxis is recommended for the prevention of periodontal infection combined with a follow up of removable denture for possible ulcera. Generally, conservative treatment measures are preferred to surgical ones. Inevitable operations are carried out non-traumatically using broad spectrum antibiotic prophylaxis until the day of suture removal (not before day 10). Long term follow up examinations are recommended.Patients with dental implants inserted before a bisphophonate therapy should be subject to intensive recall examinations. For patients undergoing or following a bisphosphonate therapy the indication for dental implants should be as strict as for patients following head and neck radiation therapy. In the present for patients with osteonecrosis, even after healing, dental implants are regarded as contra-indication. Therapy of the necrosis often requires general anaesthesia, hospitalisation, naso-gastral feeding tube and intravenous, systemic antiinfective treatment. The necrosis is removed completely and a tension free wound closure with vascularised tissue is intended. A literature review shows the metabolic effect of biphosphonates, the known pathogenesis of the bisphosphonate-induced jaw necrosis. It is essential to develop interdisciplinary communication, aiming at a joint care for this group of concerned patients and involving not only those medical disciplines, which order and use bisphosphonates, but especially dentists and maxillofacial surgeons. 相似文献
17.
Mark DeLong Jim Wright Mat Dawson Thomas Meyer Knut Sommerer Craig Dunbar 《Journal of aerosol medicine》2005,18(4):452-459
The purpose of this study was to evaluate the in vitro and in vivo dose delivery characteristics of the AIR pulmonary delivery system over a range of flow rates. A 5-mg placebo powder of engineered particles with low densities (<0.4 g/cc) and large geometric diameters (>5 microm) was delivered via a simple, capsule based, passive dry powder inhaler. The emitted dose, geometric and aerodynamic particle size distributions (aPSDs) were obtained over a range of flow rates (15-60 LPM). The in vitro results demonstrated improved powder dispersion with increasing flow rate through the inhaler. The in vivo dose delivery characteristics were obtained by gamma scintigraphy. Twelve healthy subjects performed the following three inhalation maneuvers: (i) a targeted peak inspiratory flow rate (PIFR) of 20 +/- 10 LPM, (ii) a deep comfortable inhalation, and (iii) a deep forced inhalation. PIFR and inhaled volume were obtained during the inhalation of the dose using a spirometer. In vivo dose delivery was characterized by high and reproducible emitted doses (mean = 87%; inter and intra-subject CV = 5%) and high lung deposition (mean = 51% of the total dose), with low inter and intra-subject CVs (18% and 13%, respectively) across a range of PIFRs (12-86 LPM). Lung deposition of the total dose was shown not to be dependent on PIFR by analysis of variance across the range of inspiratory flow rates (p = 0.29). This was due to the competing effects of smaller aPSDs, increased extrathoracic deposition and higher emitted doses with increasing PIFR. Fully characterizing the effect of inspiratory flow rate requires analysis of the therapeutic response, as well as in vitro dose delivery and lung deposition. 相似文献
18.
Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). 总被引:4,自引:0,他引:4
Beate Kempf-Bielack Stefan S Bielack Heribert Jürgens Detlev Branscheid Wolfgang E Berdel G Ulrich Exner Ulrich G?bel Knut Helmke Gernot Jundt Hartmut Kabisch Mathias Kevric Thomas Klingebiel Rainer Kotz Rainer Maas Rudolf Schwarz Michael Semik J?rn Treuner Andreas Zoubek Kurt Winkler 《Journal of clinical oncology》2005,23(3):559-568
PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome. 相似文献
19.
Iodinated contrast media (ICM) have become one of the major causes of drug hypersensitivity reactions (HSRs) related to increasing numbers of ICM-based radiological imaging procedures. Strategies for diagnosing and preventing ICM-induced HSRs have not been uniformly standardized yet. However, advances have been made based on the results of recent research. A previous history of hypersensitivity to ICM is the most significant risk factor for developing HSR by ICM. Avoidance of culprit agents and premedication is the main strategy to prevent recurrences of HSRs in high-risk patients. In addition, we strongly recommend identifying sensitized ICM using skin tests to determine immunoglobulin E-mediated or delayed-type allergy and to guide the choice of an alternative contrast agent. ICM provocation test procedures have been established and are helpful in selected cases. In this paper, we review how to evaluate patients who have experienced immediate or delayed HSRs caused by ICM to minimize the risk of recurrence and discuss unmet needs that require further research. 相似文献
20.
Using administrative data from Norway, we examine the extent to which family doctors influence their clients’ propensity to claim sick-pay. The analysis exploits exogenous switches of family doctors occurring when physicians quit, retire, or for other reasons sell their patient lists. We find that family doctors have significant influence on their clients’ absence behavior, particularly on absence duration. Their influence is stronger in geographical areas with weaker competition between physicians. We conclude that it is possible for family doctors to contain sick-pay expenditures to some extent, and that there is a considerable variation in the way they perform this task. 相似文献