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M Ernst

Publications and source records attributed to M Ernst.

At least 73 records · Page 4Linked to original sources
PubMed2000

Human alveolar epithelial cells type II are capable of regulating T-cell activity.

Alveolar epithelial cells type II (AEC-II) express MHC class II on their surface, an important prerequisite for antigen presentation. However, accessory signals are required for an efficient T-cell activation. We therefore isolated AEC-II from tumor-free sections of human lungs obtained by lobectomy/pneumectomy and purified the cells by magnetic-activated cell sorting. Furthermore, we tested the expression of CD54, CD58, CD80, and CD86 on AEC-II and evaluated their accessory function (AF) in cell culture using a coculture of interleukin-2 (IL-2), releasing Jurkat cells and AEC-II. An increased AF is documented by an elevated IL-2 release and expressed as accessory index (AI). In 33 experiments the AF of AEC-II proved to be highly variable. AI ranged between 0.3 and 17.1 with a median of 1.4 (0.3-17.1). Forty-four percent (4-77) of the AEC-II expressed HLA-DR, 44% (12-89%) of the cells expressed CD58, and CD54 was expressed by 55% (16-89%). AEC-II also expressed CD80 and CD86 (38% [0-77%] and 40% [4-68%], respectively). Interestingly, AEC-II released high levels of TGF beta (1730 pg/mL [771-5876]) and the accessory index could be increased (approximately 2-fold) by the addition of neutralizing anti-TGF beta antibodies or radiation. Thus, type II alveolar cells express costimulatory molecules and are able to deliver costimulatory signals for T cells, providing evidence that AEC-II are able to act as antigen-presenting and immunoregulatory cells of the lung. Additionally, the accessory function of AEC-II is under the control of endogenously released TGF beta.

Antigen-Presenting Cells↗
PubMed1999

Interindividual variability in the expression and NNK carbonyl reductase activity of 11beta-hydroxysteroid dehydrogenase 1 in human lung.

The balance between metabolic activation and detoxification is critical in determining the susceptibility to lung cancer upon exposure to the tobacco specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Carbonyl reduction of NNK, followed by glucuronidation, is the main detoxification pathway of this lung carcinogen in humans. Recently, we have identified 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) as microsomal NNK carbonyl reductase in liver and lung. In the present study, the interindividual variability of 11beta-HSD 1 expression and NNK-carbonyl reductase activity was examined in human lung by RT-PCR, Western blot analysis and enzyme activity. Levels of 11beta-HSD 1 mRNA varied over an almost 20-fold range among different subjects. Levels of NNK carbonyl reductase activity in lung microsomes closely resembled the relative amounts of immunoreactive protein as determined by Western blot analysis. In view of the large interindividual differences in the susceptibility of tobacco smoke related lung cancer, we present the first data on the variability of 11beta-HSD 1 expression and NNK carbonyl reduction in human lung.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed1999

Dehydroepiandrosterone replacement in women with adrenal insufficiency.

BACKGROUND: The physiologic role of dehydroepiandrosterone in humans is still unclear. Adrenal insufficiency leads to a deficiency of dehydroepiandrosterone; we therefore, investigated the effects of dehydroepiandrosterone replacement, in patients with adrenal insufficiency. METHODS: In a double-blind study, 24 women with adrenal insufficiency received in random order 50 mg of dehydroepiandrosterone orally each morning for four months and placebo daily for four months, with a one-month washout period. We measured serum steroid hormones, insulin-like growth factor I, lipids, and sex hormone-binding globulin, and we evaluated well-being and sexuality with the use of validated psychological questionnaires and visual-analogue scales, respectively. The women were assessed before treatment, after one and four months of treatment with dehydroepiandrosterone, after one and four months of placebo, and one month after the end of the second treatment period. RESULTS: Treatment with dehydroepiandrosterone raised the initially low serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone into the normal range; serum concentrations of sex hormone-binding globulin, total cholesterol, and high-density lipoprotein cholesterol decreased significantly. Dehydroepiandrosterone significantly improved overall well-being as well as scores for depression and anxiety. For the global severity index, the mean (+/-SD) change from base line was -0.18+/-0.29 after four months of dehydroepiandrosterone therapy, as compared with 0.03+/-0.29 after four months of placebo (P=0.02). As compared with placebo, dehydroepiandrosterone significantly increased the frequency of sexual thoughts (P=0.006), sexual interest (P=0.002), and satisfaction with both mental and physical aspects of sexuality (P=0.009 and P=0.02, respectively). CONCLUSIONS: Dehydroepiandrosterone improves well-being and sexuality in women with adrenal insufficiency.

Adrenal Insufficiency↗
PubMed1999

Purification of morphologically and functionally intact human basophils to near homogeneity.

Certain studies on basophils require highly purified functionally intact cell preparations. Here, a three-step procedure is described that meets these requirements. The procedure consists of a Ficoll density gradient step, counterflow elutriation and negative selection by magnetic cell sorting (MACS). The mean purity of basophils obtained from 30 donors was 97.6+/-3.96% with a viability of 99.6+/-0.83%. The recovery rate was 49.7+/-15.6%. The cells had a normal morphological appearance as assessed by May-Grünwald-stained cytospins and were functionally intact as shown by their unaltered capacity to release histamine and interleukin 4 (IL-4) following immunological activation. This procedure is a clear improvement over currently available techniques and should facilitate future investigations on basophils.

Basophils↗
PubMed1999

Malignant fibrous histiocytoma of the pancreas: a case report with genetic analysis.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is the most common type of soft tissue sarcoma in adults; it occurs frequently in the extremities, the trunk, or retroperitoneal tissues. MFH rarely is detected in digestive organs, such as the liver or stomach. METHODS: The authors report a patient with MFH of the pancreas who was treated with surgery alone. The tumor was studied for genetic alterations in the p53, p16ink4a, and DPC4 tumor suppressor genes as well as the K-ras oncogene by immunohistochemistry, single strand conformation variant (SSCV) analysis, and direct DNA sequencing. RESULTS: The authors believe that this is the 13th report of primary pancreatic MFH in the world literature and the first genetic analysis of this rare tumor. The patient is alive with no evidence of recurrence 34 months after surgery. Immunohistochemistry revealed no abnormal accumulation of the p53 protein and normal nuclear p16 expression. Mutation analysis of the p53, p16, DPC4, and K-ras genes showed only a polymorphism at codon 72 of the p53 gene and no mutations in any of the genes. CONCLUSIONS: Genotypically, MFH of the pancreas is clearly different from other malignant pancreatic tumors, which further supports the hypothesis that this tumor is a rare but distinct entity.

Aged↗
PubMed1999

Elevated expression of endoglin, a component of the TGF-beta-receptor complex, correlates with proliferation of tumor endothelial cells.

Endoglin/CD105 is a membrane protein involved in the TGF-beta receptor signalling pathway. Endoglin expression has been reported to be selective for a few cell types, in particular endothelial cells, although a number of conflicting reports have been published. In this study, we performed a detailed analysis of endoglin expression in human lung tumors and different tumor and endothelial cell lines, employing reverse-transcriptase-polymerase-chain reaction as well as immunoblotting and immunohistochemistry using verified antibodies to endoglin. Our data show a clearly preferential expression of both endoglin mRNA and protein in endothelial cells. In tumors, endoglin expression was strongly elevated in the angiogenic endothelium at the tumor edges. In agreement with this observation, we find a clear correlation between endoglin expression and markers of proliferation, such as cyclin A and Ki-67, suggesting that endoglin expression is linked to cell-cycle regulation. These findings not only resolve some of the discrepancies in the literature, but also provide the basis for further applications making use of its selective localization and expression in the tumor vasculature.

Antigens, CD↗
PubMed1999

The carboxyl-terminal domains of gp130-related cytokine receptors are necessary for suppressing embryonic stem cell differentiation. Involvement of STAT3.

Cell type-specific responses to the leukemia inhibitory factor (LIF)/interleukin 6 cytokine family are mediated by dimerization of the LIF receptor alpha-chain (LIFRalpha) with the signal transducer gp130 or of two gp130 molecules followed by activation of the JAK/STAT and Ras/mitogen-activated protein kinase cascades. In order to dissect the contribution of gp130 and LIFRalpha individually, chimeric molecules consisting of the extracellular domain of the granulocyte colony stimulating factor receptor (GCSF-R) and various mutant forms of the cytoplasmic domains of gp130 or LIFRalpha were expressed in embryonic stem (ES) cells to test for suppression of differentiation, or in a factor-dependent plasma cytoma cell line to assess for induction of proliferation. Carboxyl-terminal domains downstream of the phosphatase (SHP2)-binding sites were dispensable for mitogen-activated protein kinase activation and the transduction of proliferative signals. Moreover, carboxyl-terminal truncation mutants which lacked intact Box 3 homology domains showed decreased STAT3 activation, failed to induce Hck kinase activity and suppress ES cell differentiation. Moreover, STAT3 antisense oligonucleotides impaired LIF-dependent inhibition of differentiation. Substitution of the tyrosine residue within the Box 3 region of the GSCF-R abolished receptor-mediated suppression of differentiation without affecting the transduction of proliferative signals. Thus, distinct cytoplasmic domains within the LIFRalpha, gp130, and GCSF-R transduce proliferative and differentiation suppressing signals.

Antigens, CD↗
PubMed1999

Retinoic acid effects on an SV-40 large T antigen immortalized adult rat bone cell line.

Clonal cell lines were established from adult rat tibia cells immortalized with SV-40 large T antigen. One clone (TRAB-11), in which retinoic acid (RA) induced alkaline phosphatase (AP) activity, was selected for further study. The TRAB-11 cells express high levels of type I collagen mRNA, type IV collagen, fibronectin, practically no type III collagen, little osteopontin, and no osteocalcin. RA stimulates proliferation of TRAB-11 cells (starting at 10 pM) and survival (starting at 100 pM). TRAB-11 cells synthesize fibroblast growth factor-2 (FGF-2), which has potent autocrine mitogenic effects on these cells and acts synergistically with RA. TRAB-11 cells attach better to type IV collagen than to fibronectin or laminin. Cell attachment to type IV collagen is increased by RA and decreased (65%) by an antibody directed against alpha1beta1 integrin. RA up-regulates steady-state levels of alpha1, mRNA without affecting beta1 mRNA expression. In conclusion, we report the establishment of a clonal cell line from the outgrowth of adult rat tibiae which is highly sensitive to RA in its growth and survival in culture, apparently as a result of integrin-mediated cell interaction with extracellular matrix proteins.

Alkaline Phosphatase↗
PubMed1999

Expression of tumour necrosis factor receptors (CD120a and CD120b) on bronchoalveolar cells.

It is generally accepted that physiological modulators for tumour necrosis factor (TNF) are present in a variety of body fluids including serum. Among these modulators are soluble TNF receptors (TNF-R) that are cleaved from the extracellular domain of the TNF-Rs. Two receptors of different structures with molecular weights of 55 kDa (CD120a) and 75 kDa (CD120b) are known to be expressed on monocytes, lymphocytes, granulocytes and other cells of peripheral blood. The aim of our study was to determine the expression of CD120a and CD120b on bronchoalveolar lavage cells (BAL cells). BAL cells of 14 patients with different pulmonary disorders were stained with anti-CD120a and anti-CD120b monoclonal antibodies and were differentiated by FACS analysis. Both TNF-Rs are expressed on monocytes, macrophages, lymphocytes and granulocytes of the BAL. Although the relation of CD120a to CD120b is individual for a given cell type and an individual patient, strict correlations between both receptors were observed for BAL monocytes and alveolar macrophages. CD120a are expressed on 29.7% of alveolar macrophages; similar data were obtained for CD120b. 24.3% of the BAL monocytes were positive for CD120a and 25.5% for CD120b. 4.1% of the BAL lymphocytes were positive for CD120a whereas the percentage of CD120b positive BAL lymphocytes was approximately six times greater. Analysis of BAL granulocytes revealed 21.2% cells positive for CD120a and 11.6% for CD120b. In contrast to the BAL cells named above there was no positive correlation between CD120a and CD120b expression on BAL lymphocytes and granulocytes. We were able to show that TNF-Rs of BAL cells, like those of blood cells, are shedded in vitro after incubation with or without lipopolysaccharide (LPS), detected as TNFalpha-inhibitor activity in cell culture supernatant. In conclusion, BAL cells express and shed TNF-Rs, as is known for cells of other body compartments.

Antibodies, Monoclonal↗
PubMed1999

2D exchange NMR spectra under slow MAS: A simplified scheme to obtain pure-phase spectra without unwanted cross peaks

A simplified method for acquiring pure-phase two-dimensional exchange spectra under slow magic-angle spinning (MAS) is introduced. It combines rotor-synchronized 2D exchange spectroscopy with whole-echo acquisition leading to a simplification in data acquisition and data processing compared to the States-type data sampling using "time reversal" (A. Hagemeyer et al., Adv. Magn. Reson. 13, 85 (1989)). As an added benefit, it allows for well-defined mixing times of an arbitrary integer multiple of the MAS rotor period. The proposed method is, however, only applicable to samples where an echo of the free-induction decay can be obtained, i.e., where the inhomogenous linewidth is larger than the homogeneous linewidth. This is, for example, the case in rare-spin spectroscopy of samples with natural isotopic abundance. The usefulness of the new method is demonstrated, using 13C spectroscopy, on two model compounds. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Pharmacological modulation of the IFNgamma-induced accessory function of alveolar macrophages and peripheral blood monocytes.

OBJECTIVE AND DESIGN: Although alveolar macrophages (AM) are poor accessory cells, alveolar macrophages of patients with sarcoidosis or tuberculosis show an elevated accessory function indicating that the accessory function (AF) of AM can be upregulated. MATERIALS AND METHODS: We examined whether the AF of AM and peripheral blood monocytes (PBM) can be increased by interferon-gamma (IFNgamma) and whether immunomodulating drugs like cyclosporine A, cyclophosphamide, dexamethasone, and ambroxol are able to modulate the accessory function and the expression of accessory molecules. RESULTS: IFNgamma increased the AF of AM and PBM up to 309 +/- 122% and 152 +/- 25%, respectively (p < 0.02, unstimulated control = 100%, in all cases). In alveolar macrophages this increase is most efficiently prevented by cyclosporine A (31 +/- 13%), followed by cyclophosphamide (64 +/- 20%) and dexamethasone (66 +/- 20%). In monocytes the IFNgamma-induced increase in accessory function is prevented only by cyclosporine A (17 +/- 7%) and dexamethasone (59 +/- 9%). Cyclosporine A was also the most effective drug downregulating the expression of accessory molecules (CD54, CD58, CD80 and CD86). CONCLUSIONS: In summary, the accessory function of alveolar macrophages and monocytes is upregulated by IFNgamma and can be controled by immunomodulating drugs.

Aged↗
PubMed1999

[Thoracoscopic therapy of pleural empyema after pneumonectomy].

In a 4-year period two right-sided empyemas occurred following a total of 39 pneumonectomies for lung cancer. In another case pneumonectomy was performed for left-sided lung cancer with concomitant empyema as an emergency procedure in a patient referred from an outside hospital. Empyema was treated with repeated thoracoscopic debridements and intermittent lavage with polyvinylpyrrolidine-iodine solution and streptocinase/streptodornase. Three to seven thoracoscopies were required to sterilize the pleural cavity. After a median follow-up of 14 months all three patients are well and without any evidence of infection. VATS is suitable for definitive treatment of postpneumonectomy empyema and is associated with excellent functional and cosmetic results.

Adult↗
PubMed1999

PET in child psychiatry: the risks and benefits of studying normal healthy children.

1. Inclusion of children, particularly healthy control children, is a continuing debate. 2. Why involve children in PET research? The assumption is that the knowledge gained from such studies is critical for the advance of prevention and treatment of psychiatric illnesses. 3. What are the risks of PET procedures? Radiation exposure poses the most difficult problem. The assessment of this risk needs to separate the emotional reaction at the mention of "radiation" from the consideration of objective data of large studies of health hazards associated with low-level radiation exposure. 4. The assessment of the benefit/risk ratio is critical to the conduct of research, and requires the evaluation of risks according to the ambiguous definition of "minimal risk".

Brain↗
PubMed1999

Both atrial resection and superior vena cava replacement in sleeve pneumonectomy for advanced lung cancer.

Extended sleeve pneumonectomy including removal of the superior vena cava, right atrium and parts of left atrium on cardiopulmonary bypass was successfully performed in a 40-year-old man. The tumour was histologically proven a T4 N1 stage with margins free from tumour. Adjuvant radiochemotherapy was administered postoperatively on an outpatient base. The patient did well for 7 months then he died from myocardial infarction due to metastatic infiltration of the right coronary artery. Other metastatic deposits were not found at autopsy. More data from extended pulmonary resections are required to demonstrate a benefit.

Adult↗
PubMed1999

[Intra- and postoperative airway management of tracheal carina ruptures from bilateral endobronchial intubation].

OBJECTIVE: Carina near tracheal ruptures following blunt chest trauma or endotracheal intubation are rare, but lifethreatening events. Both early diagnosis by fibreoptic bronchoscopy and immediate surgical treatment are essential. There is no uniform recommendation for airway-management concerning the tube. Standard tracheal- and double-lumen tubes position the cuff at the site of the injury and tracheostomy tubes are too short to protect the lesion from positive airway pressure. We discuss the causes, diagnosis, and treatment of tracheal ruptures, reviewing the recent literature. METHODS: We analysed data from three female patients who sustained carina near tracheal ruptures. They underwent selective endobronchial intubation with two tubes, both under fibreoptic control. Following the surgical repair the tubes were then introduced via tracheostomy. Because of severe respiratory failure (aspiration pneumonia, mediastinitis, status asthmaicus, ARDS) independent lung ventilation was performed for 9-14 days. Obviously the fixation of the tubes is most essential and their correct position was confirmed by daily fibreoptic or radiologic control. Then a single tracheostomy tube was inserted. RESULTS: The patients respiratory functions improved and they were discharged from ICU after 21-36 days, breathing spontaneously with closed tracheostoma. No long-term complications were noted. CONCLUSION: Maintaining the safety procedures the bilateral endobronchial intubation is an important and successful method in carina near tracheal rupture, perioperatively and for long-term ventilation.

Adult↗
PubMed1999

Inhaled nitric oxide as a prophylactic treatment against reperfusion injury of the lung.

BACKGROUND: Inhaled Nitric Oxide (NO) has been found to be effective in clinical treatment of reperfusion injury after lung transplantation. This study was designed to determine a possible prophylactic role to reduce severe reperfusion injury. METHODS: In 12 minipigs the left lung was selectively perfused with cold Euro-Collins solution. After 90 minutes of warm ischemia the lungs were reperfused and the contralateral pulmonary artery and main bronchus clamped. Hemodynamic and respiratory parameters were monitored for 7 hours. 6 animals were used as controls. 6 pigs formed the NO group and were ventilated continuously with 40 ppm nitric oxide (NO) starting 30 minutes prior to reperfusion. RESULTS: In the control group right heart failure developed within 1.9 +/- 0.8 hours of reperfusion. Lung compliance was significantly reduced. A significant increase of pulmonary vascular resistance (PVR) was found. All animals of the NO group survived the reperfusion period of 7 hours. PVR was decreased compared to controls (p = 0.03). AaDO2 was lower, but not significantly different. The dynamic compliance of the lung was significantly higher (p = 0.007) in the NO group. CONCLUSIONS: The prophylactic institution of inhaled NO reduces reperfusion injury of the lung. Short-term use of inhaled NO should be adopted as a prophylactic agent after transplantation of lungs preserved in Euro-Collins solution.

Administration, Inhalation↗
PubMed1999

High presynaptic dopaminergic activity in children with Tourette's disorder.

OBJECTIVE: Tourette's disorder is characterized by chronic fluctuating motor and vocal tics. Despite extensive investigation of the neuropathophysiology of the disorder by a wide array of methodologies, its neurobiochemical substrate is still unclear. Converging evidence, however, suggests a primary role of the dopaminergic system, particularly within the basal ganglia. METHOD: This study examined the integrity of presynaptic dopaminergic function in children with Tourette's disorder, using positron emission tomography and the tracer [18F]fluorodopa (FDOPA). Accumulation of FDOPA in synaptic terminals, a measure of DOPA decarboxylase activity, was quantified in caudate nucleus, putamen, frontal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum). RESULTS: Subjects with Tourette's disorder showed higher FDOPA accumulation than controls in the left caudate nucleus (by 25%; p = .03) and right midbrain (by 53%; p = .08). CONCLUSION: These findings provide evidence of dopaminergic dysfunction in children with Tourette's disorder which affects both cell nuclei and nerve terminals. Based on the known regulation of DOPA decarboxylase activity by post- and presynaptic receptors, and by extracellular dopamine concentration, abnormal activity in this enzyme may reflect deficits in a variety of functional elements of the dopamine system. The precise mechanism underlying an up-regulation of DOPA decarboxylase activity needs to be identified in future studies.

Adolescent↗