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11.
Burkhard J Manfras William A Rudert Massimo Trucco Bernhard O Boehm 《Journal of immunological methods》1997,210(2):305
The characterization of the human T-cell receptor (TCR) repertoire in various physiological and pathological conditions has become an important tool in studies of the immune response. Therefore, a number of PCR based strategies for the semiquantitative analysis of the TCR repertoire have been described. Family specific amplification of TCR cDNA has been employed in a number of studies often with contradictory results. We have developed a strategy utilizing exogenous standards with homologous primer binding sites for the quantitative analysis of the α/β T-cell receptor repertoire. This system allows the detection of even minute differences in T-cell populations based on quantitative PCR (Q-PCR) and competitive PCR (C-PCR). Results presented here demonstrate that expansions of T-cell subsets as defined by the specificity of the variable gene segments can be readily monitored when exceeding 1% of the total repertoire. In addition, the proposed method reveals direct information of CDR3 size heterogeneity and can be used to estimate the T-cell repertoire complexity and monitor clonal expansions. We discuss variables such as cell number and experimental conditions influencing accuracy and reproducibility of the analyses. We have used this protocol based on non-radioactive techniques for characterization of the fine specificity of the T-cell repertoire in peripheral and organ-infiltrating T-lymphocytes. The analyses revealed information about polyclonal or clonal expansion of T-cells in vivo and in vitro following various stimuli such as superantigenic stimulation of T-cell subsets as well as antigen-driven shaping of the α/β T-cell repertoire in autoimmune and infectious diseases. 相似文献
12.
13.
G. Aumüller Paul-Martin Holterhus Lutz Konrad Burkhard von Rahden Olaf Hiort Murielle Esquenet Guido Verhoeven 《Anatomy and embryology》1998,197(3):199-208
As it is suggested that the androgen receptor mechanism is required for prostatic development, we attempted to determine
the appearance, expression and distribution of the androgen receptor in embryonic, infantile and pubertal human prostate.
Using mono- and polyclonal antibodies and a digoxigenin-labeled 713 bp riboprobe, the androgen receptor expression in paraffin
sections of fetal, infantile, and pubertal prostates was studied at the protein and RNA level. Under highly standardized conditions,
application of the polyclonal antibodies resulted in a weak cytoplasmic and nuclear labeling of the epithelium of fetal glands.
No immunoreaction was obtained with monoclonal antibodies. Applying the polyclonal antibody to pubertal and adult specimens,
immunoreactivity of the androgen receptor was positive in nuclei of adluminal and basal epithelial cells, in interstitial
and vascular smooth muscle cells and vascular endothelium, whereas ganglionic cells and enteroendocrine cells were negative.
In situ hybridization with the digoxigenin-labeled riboprobe gave clear positive results already in epithelium of very young
fetal specimens. A semiquantitative visual evaluation of in situ hybridizations showed that intermediate intensity of expression
was increased in pubertal and adult specimens, whereas strong expression was reduced in prostatic epithelium. Conclusions:
The essential findings are: (1) an early expression of androgen receptor mRNA in the fetal prostate; (2) no immunoreaction
of monoclonal antibodies against the androgen receptor in the same specimens, (3) a decrease of androgen receptor mRNA expression,
but increase in immunoreactivity of the androgen receptor protein with the onset of glandular maturation during puberty.
Accepted: 29 September 1997 相似文献
14.
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
15.
Effect of intracerebral norepinephrine depletion on outcome from severe forebrain ischemia in the rat 总被引:3,自引:0,他引:3
Nellgård BM Miura Y Burkhard Mackensen G Pearlstein RD Warner DS 《Brain research》1999,847(2):174-269
Manipulations of plasma catecholamine concentrations influence outcome from ischemic brain insults. It has been suggested that these effects are mediated by influences on brain catecholamine concentrations. This study examined whether major changes in brain norepinephrine concentrations can alter outcome from severe forebrain ischemia. Sprague-Dawley rats were administered 50 mg/kg i. p. N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or were left untreated (control). One week later, these rats were subjected to either 7 or 8 min of normothermic forebrain ischemia (bilateral carotid occlusion and MABP=30 mmHg) and allowed to recover for 4 days. Histologic damage was then evaluated. In other control and DSP-4-treated animals, hippocampal microdialysate norepinephrine concentrations were measured before, during and after 8 min of forebrain ischemia. Norepinephrine concentrations were also determined in brain homogenates from non-ischemic DSP-treated and control rats. A 95% depletion of norepinephrine was observed in brain homogenates from non-ischemic DSP-4-treated rats compared with control. During ischemia, microdialysate norepinephrine concentrations increased in control but not in DSP-4-treated rats (P=0.002). For plasma, intra-ischemic epinephrine concentrations increased 8-10-fold and returned to baseline values post-ischemia with no differences between groups. Plasma norepinephrine values remained unchanged in both groups. Histologic damage resulting from either 7 or 8 min of ischemia in hippocampal structures, caudoputamen, and neocortex was similar between DSP-4-treated and control groups. This study could not identify any effect of major changes in brain norepinephrine concentrations on ischemic brain damage. These data indicate that peripheral catecholamine effects on near-complete forebrain ischemic outcome are unlikely to be mediated by effects on central catecholamine concentrations. 相似文献
16.
Torsten Kuwert Carlo Morgenroth Burkhard Woesler Peter Matheja Stefan Palkovic Bernhard Vollet Samuel Samnick Ulrich Maasjosthusmann Hartmut Lerch Franz-Josef Gildehaus Hansdetlef Wassmann Otmar Schober 《European journal of nuclear medicine and molecular imaging》1996,23(10):1345-1353
Using single-photon emission tomography (SPET), the radiopharmaceuticall,-3-iodine-123--methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours. 相似文献
17.
Burkhard F. Spiekermann David J. Stone David L. Bogdonoff Terrance A. Yemen 《Journal canadien d'anesthésie》1996,43(8):820-834
Purpose
Airway management in neurosurgical patients pre sents unique challenges to the anaesthetist. This review will consider specific approaches to numerous problems in airway management related to logistical, physiological and anatomi cal concerns. The goal is to provide a clinically oriented and practical discussion regarding issues of airway management in neurosurgical patients.Source
The recent literature has been reviewed regarding airway management options and related perioperative complications in the neurosurgical population. This is interlaced with approaches to many of the problems and their solutions based on experience gained in a very busy university neurosurgical practice over the past decade.Principal findings
Specific pathophysiological alterations in the neurosurgical patient influence the technique chosen for securing an airway. These relate to the presence of increased intracranial pressure, intracranial aneurysms or arteriovenous malformations. Other important disordes influencing airway management include severe coronary artery disease, acromegaly and congenital airway difficulties. Stereotactic neurosurgery and conscious sedation for various neurosurgical procedures also provide unique challenges. There are other considerations unique to the neurosurgical patient such as intra- and postoperative airway obstruction and the timing of postoperative extubation.Conclusion
The demands for airway management in neu roanaesthesia require expertise in the various modes of secur ing the airway while considering the patient’s physiological requirements as well as the unique surgical demands. 相似文献18.
Thomas Lehrnbecher Andreas Trusen Frank Deinlein Burkhard Hcht Alexander Marx Joachim Kühl 《Pediatric blood & cancer》2003,40(1):13-17
Lymphoproliferative disorder (LPD) is described in only a few children receiving chemotherapy for cancer. In all of them, an association between LPD and EBV (Epstein‐Barr Virus) was found. We report on a patient who developed LPD not associated with EBV while receiving chemotherapy for relapsed acute lymphoblastic leukemia (ALL). Despite discontinuation of chemotherapy, administration of intravenous immunoglobulins and surgery the patient died. Growing experience with this disorder may allow better treatment options in the future and will show whether LPD not associated with EBV requires different therapeutic strategies. Med Pediatr Oncol 2003;40:13–17, © 2003 Wiley‐Liss, Inc. 相似文献
19.
Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance. 总被引:2,自引:0,他引:2
Peter Jantscheff Luigi Terracciano Adam Lowy Katharina Glatz-Krieger Fritz Grunert Burkhard Micheel Jens Brümmer Urs Laffer Urs Metzger Richard Herrmann Christoph Rochlitz 《Journal of clinical oncology》2003,21(19):3638-3646
PURPOSE: CEACAM6, CEACAM1, and human carcinoembryonic antigen (CEA) are coexpressed in normal colorectal epithelia, but show deregulated expression in colorectal cancers (CRC). Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors. The aim of our study was to evaluate the prognostic relevance of CEACAM6, CEACAM1, and CEA tissue expression in patients with CRC. PATIENTS AND METHODS: Immunohistochemical analysis was carried out on tissue microarrays from 243 paraffin-embedded biopsies from a randomized controlled clinical trial (Swiss Group for Clinical Cancer Research [SAKK] 40/81) of adjuvant fluorouracil-based chemotherapy with CEACAM-specific monoclonal antibodies. The median follow-up was 8 years. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier estimates and hazard ratios (HRs) estimated using Cox proportional hazards models. RESULTS: Tissue expression of CEACAM6, CEACAM1, and CEA was enhanced in 55%, 58%, and 94% of patients, respectively. Multivariate Cox analysis including sex, age, tumor site, stage, differentiation grade, treatment, and nodal status as covariates showed that CEACAM6 overexpression independently predicted poor OS (HR, 1.86; P =.0100) and DFS (HR, 2.00; P =.0028), whereas CEACAM1 or CEA were not significantly related to these outcomes. The data did not provide evidence for or against the hypothesis that the CEACAM6 effect on survival differs according to treatment. CONCLUSION: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups. Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear. 相似文献
20.