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E Mayer

Publications and source records attributed to E Mayer.

At least 37 records · Page 2Linked to original sources

Transfection of E-cadherin cDNA in human lung tumor cells reduces invasive potential of tumors.

Lung cancer is a major health-care problem in industrialized countries. With reference to its therapeutic consequences and major histological variations, it is divided into two subgroups - SCLC (small-cell lung cancer) and NSCLC (non-small-cell lung cancer). As an important factor of cell-cell and cell-substratum interaction, cell adhesion molecules (CAMs) seem to play a key role in tumor-cell migration and invasion that lead to metastases. We investigated human lung tumor cell lines established from histologically documented neoplastic lesions taken in our operating theater. Immunohistological screening showed differences in E-cadherin expression with no clear predominance of SCLC or NSCLC cell lines. Using an invasion model with Matrigel Matrix and a migration assay, we could demonstrate a more aggressive behavior pattern in E-cadherin-negative cell lines. We transfected E-cadherin cDNA into a formerly negative cell line showing strong invasive behavior in the initial tests in order to investigate the role of E-cadherin in this process. In this study, we examined E-cadherin cDNA transfection in human bronchial carcinoma cells. At present, transfection is stable with a follow-up time of one year. We could demonstrate that cell lines were remarkably less invasive after transfection of E-cadherin in the invasion model with Matrigel Matrix. These results indicate that the E-cadherin CAM plays an important role in lung tumor invasion and metastasis. Further studies are in progress to confirm these findings and to describe a possible role of this CAM in tumor therapy.

Cadherins↗

[Chronic thromboembolic pulmonary hypertension: diagnostic impact of Multislice-CT and selective Pulmonary-DSA].

PURPOSE: To evaluate the diagnostic impact of multislice-CT and selective pulmonary DSA in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: 994 vessel segments of 14 consecutive patients with CTEPH were investigated with multislice-CT (slice thickness 3 mm, collimation 2.5 mm, reconstruction intervall 2 mm) and selective pulmonary DSA (posterior-anterior, 45 degrees oblique, and lateral projection. Analysis was performed by 2 investigators independently for CT and DSA. Diagnostic criteria were occlusions and non-occlusive changes like webs and bands, irregularities of the vessel wall, diameter reduction and thromboembolic depositions at different levels from central pulmonary arteries to subsegmental arteries. Reference diagnosis was made by synopsis of CT and DSA by consensus. RESULTS: Concerning patency CT and DSA showed concordant findings overall in 88.9 %, 92.9 % for segmental arteries and 85.4 % for subsegmental arteries. Concerning any thromboembolic changes, multislice-CT was significantly inferior to selective DSA (concordance 67.0 % overall, 70.4 % for segments and 63.6 % for subsegments). Non-occlusive changes of the vessels were significantly underdiagnosed by CT (concordance of CT versus DSA: 23.1 %). CONCLUSION: Multislice-CT and selective pulmonary DSA are equivalent for diagnosis of vessel occlusions at the level of segmental and subsegmental arteries. However, for visualisation of the non-occlusive thromboembolic changes of the vessel wall selective pulmonary DSA is still superior compared to multislice-CT. Multislice-CT and selective pulmonary DSA are complementary tools for diagnosis and treatment planning of chronic thromboembolic pulmonary hypertension (CTEPH).

Angiography, Digital Subtraction↗

Suppression of false recognition in Alzheimer's disease and in patients with frontal lobe lesions.

Previous research has shown that patients with Alzheimer's disease show increasing levels of false recognition across five repeated study-test trials of semantic associates. The present study tested the hypotheses that (i) the increasing false recognition was partly due to the frontal lobe dysfunction of patients with Alzheimer's disease, and (ii) a failure of source monitoring was the central mechanism by which frontal lobe dysfunction led to increasing false recognition across trials. In Experiment 1, patients with frontal lobe lesions and controls were examined in the same repeated trials paradigm as that used previously in patients with Alzheimer's disease. Although controls were able to reduce their false recognition across trials, the patients with frontal lobe lesions were not, and instead showed a constant level of elevated false recognition across the study-test trials. In Experiment 2, two groups of patients with Alzheimer's disease and healthy older adult controls were studied: the first group was given a single study session followed by a recognition test, the second group was given five study sessions followed by a single recognition test. Older adults who were exposed to five study lists demonstrated lower levels of false relative to true recognition, whereas patients with Alzheimer's disease in this condition exhibited levels of false recognition elevated to that of their true recognition, even with the source memory confusion of intervening tests eliminated. The authors suggest that impairment in aspects of frontal lobe function, such as verification-inhibition mechanisms, probably contributes to the inability of patients with Alzheimer's disease to suppress their false recognition across repeated trials. Lastly, it is speculated that one way in which the frontal lobes enable normal episodic memory function is by facilitating the suppression of false recognition and other distortions of memory.

Adult↗

Is the right amygdala involved in visuospatial memory? Evidence from MRI volumetric measures.

Quantitative MRI measurement of hippocampal sclerosis in patients suffering from temporal lobe epilepsy (TLE) have, as yet, failed to evidence any correlation between the right hippocampus and visuospatial memory. In this report, word learning and design learning tasks were carried out as well as MRI volumetric measurements of the hippocampus and amygdala in order to verify possible modality-specific correlations between function and structure. Delayed recall indices in our memory tasks provided significant results. Visuoverbal ratios differed between right and left TLE groups, as did laterality indices of hippocampal and amygdalar volumes. Furthermore, correlations were found between the left hippocampal volume and verbal memory, and between the right amygdala and visuospatial memory. We suggest that the difficulty encountered in establishing a correlation between right temporal structures and visuospatial memory could come both from the type of test employed and the structures considered.

Adult↗

Exocyclic groups in the minor groove influence the backbone conformation of DNA.

Exocyclic groups in the minor groove of DNA modulate the affinity and positioning of nucleic acids to the histone protein. The addition of exocyclic groups decreases the formation of this protein-DNA complex, while their removal increases nucleosome formation. On the other hand, recent theoretical results show a strong correlation between the B(I)/B(II) phosphate backbone conformation and the hydration of the grooves of the DNA. We performed a simulation of the d(CGCGAATTCGCG)2 Drew Dickerson dodecamer and one simulation of the d(CGCIAATTCGCG)2 dodecamer in order to investigate the influence of the exocyclic amino group of guanine. The removal of the amino group introduces a higher intrinsic flexibility to DNA supporting the suggestions that make the enhanced flexibility responsible for the enlarged histone complexation affinity. This effect is attributed to changes in the destacking interactions of both strands of the DNA. The differences in the hydration of the minor groove could be the explanation of this flexibility. The changed hydration of the minor groove also leads to a different B(I)/B(II) substate pattern. Due to the fact that the histone preferentially builds contacts with the backbone of the DNA, we propose an influence of these B(I)/B(II) changes on the nucleosome formation process. Thus, we provide an additional explanation for the enhanced affinity to the histone due to removal of exocyclic groups. In terms of B(I)/B(II) we are also able to explain how minor groove binding ligands could affect the nucleosome assembly without disrupting the structure of DNA.

Binding Sites↗

[Surgical management of pulmonary artery sarcoma].

BACKGROUND AND OBJECTIVES: Pulmonary artery sarcoma is a rare neoplasm and possibly unnoticed cause of pulmonary hypertension. The presentation is one of central pulmonary artery obstruction and progressive right-heart failure. In most cases, the diagnosis of malignancy is confirmed post mortem. We report the outcome of eight patients with primary pulmonary artery sarcomas. METHODS: Eight patients (four female, four male, mean age 48,2 years, preop. NYHA functional class III/IV: n = 5/3) were referred for further evaluation of pulmonary hypertension. Malignancy was suspected in six of these patients by means of computed tomography (CT) and magnetic resonance tomography (MRT). In two patients diagnosis was established during pulmonary thromboendarterectomy based on histological examination of frozen sections. Operative procedures consisted of gross tumor resection with prosthetic replacement (n = 3) or reconstruction (n = 5) of central parts of the pulmonary vessels. Additional pneumonectomy was necessary in two patients, resection of metastases in one patient. Seven patients received adjuvant radio- and/or chemotherapy. RESULTS: There were no postoperative deaths. 3 months after surgery, all patients demonstrated improvement in hemodynamics and exercise tolerance. Four patients died 7, 9, 18 and 19 months after surgery, respectively. Two patients are alive 3 and 39 months after primary surgery with evidence of pulmonary metastases. Two patients are alive in complete remission 25 and 65 months postoperatively. CONCLUSIONS: In patients with primary pulmonary artery sarcoma, emphasis must be placed on early identification which can be achieved by CT and MRT. Radical surgical resection currently offers the best chance for survival. Adjuvant therapy might bring additional benefit.

Adult↗

Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome.

Incontinentia pigmenti (IP), or "Bloch-Sulzberger syndrome," is an X-linked dominant disorder characterized by abnormalities of skin, teeth, hair, and eyes; skewed X-inactivation; and recurrent miscarriages of male fetuses. IP results from mutations in the gene for NF-kappaB essential modulator (NEMO), with deletion of exons 4-10 of NEMO accounting for >80% of new mutations. Male fetuses inheriting this mutation and other "null" mutations of NEMO usually die in utero. Less deleterious mutations can result in survival of males subjects, but with ectodermal dysplasia and immunodeficiency. Male patients with skin, dental, and ocular abnormalities typical of those seen in female patients with IP (without immunodeficiency) are rare. We investigated four male patients with clinical hallmarks of IP. All four were found to carry the deletion normally associated with male lethality in utero. Survival in one patient is explained by a 47,XXY karyotype and skewed X inactivation. Three other patients possess a normal 46,XY karyotype. We demonstrate that these patients have both wild-type and deleted copies of the NEMO gene and are therefore mosaic for the common mutation. Therefore, the repeat-mediated rearrangement leading to the common deletion does not require meiotic division. Hypomorphic alleles, a 47,XXY karyotype, and somatic mosaicism therefore represent three mechanisms for survival of males carrying a NEMO mutation.

Alleles↗

Expression of apoptosis-related proteins, p53, and DNA fragmentation in sarcomas of the pulmonary artery.

BACKGROUND: Apoptosis is a common feature in a variety of pathologic conditions. Induction of apoptosis through apoptotic stimuli such as, chemotherapy or radiation, presents new insights into tumor biology and therapy. In particular, members of the Bcl-2 family as well as the Fas system are known to be involved in the regulation of apoptosis in different tumor entities. METHODS: In the current study, the expression of the apoptosis-related molecules p53, Bax, Bcl-2, Fas (CD95), Fas-Ligand and perforin was examined in 7 patients with a sarcoma of the pulmonary artery. Furthermore, the TUNEL-method for the detection of apoptotic cells was applied as well as sequencing of the p53 gene. RESULTS: In the TUNEL assay, approximately 10% of the sarcoma cells displayed DNA fragmentation. In addition, Bax was expressed in tumor cells. Accumulation of p53 was evident in 4 of 7 patients (pAB 240 antibody), and 2 of them were positive for the pAB 1801 antibody. Only 1 case had a point mutation in Exon 5 of the p53 sequence. A few tumor cells showed a double labeling of Bax and p53. Bcl-2 could be detected only in tumor-associated lymphocytes. Finally, several lymphocytes could be stained with perforin, but none of the specimens showed a reactivity for Fas or Fas-Ligand. CONCLUSION: The expression of Bax indicated a possible role of this molecule in programmed cell death in pulmonary sarcomas. The limited coexpression of Bax and p53 suggested that induction of Bax can occur independently of p53. The detection of perforin in lymphocytes suggested a possible role for this molecule in apoptosis of the sarcoma cells. In contrast, the Fas system did not seem to play an essential role in sarcomas of the great vessels.

Adult↗

Complex of B-DNA with polyamides freezes DNA backbone flexibility.

The development of sequence-specific minor groove binding ligands is a modern and rapidly growing field of research because of their extraordinary importance as transcription-controlling drugs. We performed three molecular dynamics simulations in order to clarify the influence of minor groove binding of two ImHpPyPy-beta-Dp polyamides to the d(CCAGTACTGG)(2) decamer in the B-form. This decamer contains the recognition sequence for the trp repressor (5'-GTACT-3'), and it was investigated recently by X-ray crystallography. On one hand we are able to reproduce X-ray-determined DNA--drug contacts, and on the other hand we provide new contact information which is important for the development of potential ligands. The new insights show how the beta-tail of the polyamide ligands contributes to binding. Our simulations also indicate that complexation freezes the DNA backbone in a specific B(I) or B(II) substate conformation and thus optimizes nonbonded contacts. The existence of this distinct B(I)/B(II) substate pattern also allows the formation of water-mediated contacts. Thus, we suggest the B(I) <==> B(II) substate behavior to be an important part of the indirect readout of DNA.

Base Sequence↗

Pure representational neglect after right thalamic lesion.

After a right thalamic stroke, an 86-year-old man presented an acute pure left representational neglect in the absence of any perceptual neglect. On spatial mental imagery tasks, the patient systematically omitted items located on his left side, but only when a vantage point was given. This suggests that (1) pure representational neglect is not just a residual finding after recovery from global (perceptual and representational) neglect; (2) space representation can be coded by two independent processes: in viewer-centered or world-based (allocentric) coordinates; and (3) the right thalamus serves as a relay in the processing of spatial visual imagery.

Aged↗

Osteopontin expression in primary sarcomas of the pulmonary artery.

Primary tumors of the great vessels (aorta, pulmonal artery, and inferior vena cava) are rare and represent in most cases vascular leiomyosarcomas. Furthermore, there also exists a group of sarcomas arising from the intima, known as intimal sarcomas, associated with early metastasis and a very poor prognosis. Osteopontin (OPN) is an extracellular matrix protein that binds to alphav integrins, thereby promoting cell attachment, chemotaxis, and signal transduction. The reported association of OPN with malignancy and metastasis prompted us to examine the expression of this protein in seven sarcomas of the pulmonary artery. Strong OPN-specific staining could be detected in tumor cells and the adjacent extracellular matrix. Using a double labeling procedure, proliferating cells showed a strong positive reaction with antibodies against OPN. In addition, this protein could be demonstrated in the cytoplasm of macrophages. CD44, a putative receptor of OPN, was expressed on the cellular surface of tumor-associated lymphocytes. The expression of OPN in macrophages and tumor cells indicates that this molecule could possibly mediate cellular adhesion of both cell types in pulmonary sarcomas. The detection in the extracellular matrix shows that OPN is actively secreted and may interact with the corresponding receptor, CD44, on the surface of lymphocytes. Although the function of OPN is not yet fully understood, our data indicate that strong expression of this molecule in poorly differentiated sarcomas could play a role in the progression of malignancy and metastasis as described previously for carcinomas.

Adult↗

Surface attached ultrathin polymer monolayers for control of cell adhesion.

BACKGROUND: Calcific degeneration is the major drawback of bioprostheses. None of the numerous preventive approaches omitted calcification. Previous studies showed that cellular surface seeding decreases calcium uptake in vitro but achievement of coverage remains problematic. A new approach is presented masking glutaraldehyde residues with a polymer layer allowing cell seeding. The aim of this study was to evaluate different polymers for suitability. METHODS: Ten polymers--covalently bound to glass--were tested for their ability to seed animal and human cells. Quality of coverage was evaluated by light and scanning electron microscopy, and polymers were characterized physicochemically. RESULTS: Quality of cellular growth was similar for canine and human cells. Five polymers allowed excellent surface coverage, two led to a decrease of cell adherence, and four to poor cellular growth. No correlation between molecular weight, thickness, hydrophilicity, or charge of the polymer and cell growth was found. CONCLUSIONS: Polymer monolayers can promote cellular growth but without correlation to physicochemical characteristics. Polymers covalently bound to biologic tissue appear to be a promising approach for achieving cellular coverage of biomaterials.

Animals↗

Significance of ligand tails for interaction with the minor groove of B-DNA.

Minor groove binding ligands are of great interest due to their extraordinary importance as transcription controlling drugs. We performed three molecular dynamics simulations of the unbound d(CGCGAATTCGCG)(2) dodecamer and its complexes with Hoechst33258 and Netropsin. The structural behavior of the piperazine tail of Hoechst33258, which has already been shown to be a contributor in sequence-specific recognition, was analyzed. The simulations also reveal that the tails of the ligands are able to influence the width of the minor groove. The groove width is even sensitive for conformational transitions of these tails, indicating a high adaptability of the minor groove. Furthermore, the ligands also exert an influence on the B(I)/B(II) backbone conformational substate behavior. All together these results are important for the understanding of the binding process of sequence-specific ligands.

Base Sequence↗

Hyperbaric oxygen--an effective tool to treat radiation morbidity in prostate cancer.

PURPOSE: We report the results of hyperbaric oxygen therapy (HBO) used in the treatment of radiation cystitis and proctitis following irradiation of prostate cancer. MATERIALS AND METHODS: Between June 1995 and March 2000, 18 men (median age 71 years) with radiation proctitis (n=7), cystitis (n=8), and combined proctitis/cystitis (n=3) underwent HBO therapy in a multiplace chamber for a median of 26 sessions (range 2-60). The treatment schedule (2.2-2.4 atmospheres absolute, 60 min bottom time, once-a-day, 7 days a week) was set at a lower limit of 20 sessions; the upper limit was left open to symptom-related adjustment. Prior to HBO treatment, RTOG/EORTC late genitourinal (GU) morbidity was Grade 2 (n=3), Grade 3 (n=6) or Grade 4 (n=2); modified RTOG/EORTC late gastrointestinal (GI) morbidity was either Grade 2 (n=4) or Grade 3 (n=6). RESULTS: Sixteen patients underwent an adequate number of sessions. RTOG/EORTC late GU as well as modified GI morbidity scores showed a significant improvement after HBO (GI, P=0.004; GU, P=0.004; exact Wilcoxon signed rank test); bleeding ceased in five out of five patients with proctitis and in six out of eight patients with cystitis; one of those two patients, in whom an ineffective treatment outcome was obtained, went on to have a cystectomy. CONCLUSIONS: HBO treatment seems to be an effective tool to treat those patients with late GI and GU morbidity when conventional treatment has led to unsatisfactory results. Particularly in patients with radiation cystitis, HBO should not be delayed too long, as in the case of extensive bladder shrinkage improvement is hard to achieve.

Aged↗

Serial STIR magnetic resonance imaging correlates with clinical score of activity in thyroid disease.

PURPOSE: To assess the correlation between inflammatory activity in extraocular muscles measured with serial short tau inversion recovery (STIR) sequence magnetic resonance imaging (MRI) scans and clinical disease activity in thyroid eye disease. METHODS: In this retrospective study, 22 patients with thyroid eye disease who had undergone serial MRI scans using the STIR sequence were assessed. The signal intensity ratio (SIR) of the most inflamed extraocular muscle was compared with the Mourits score (a clinical measure of thyroid eye disease activity). RESULTS: The SIR value has previously been shown to correlate with clinical activity of thyroid eye disease. In a particular patient the SIR value increases in proportion with the clinical features of the disease as assessed by the Mourits rating system. When the change in STIR sequence MRI is compared with the change in Mourits score rating for a given patient the correlation is highly significant (p < 0.001). CONCLUSIONS: This study confirms that serial STIR sequence MRI scans correlate with clinical disease activity. Inflammatory activity in the most inflamed muscle (as measured by SIR) reflects overall disease activity. SIR values obtained from MRI scans provide a useful measure of disease activity and may help in the monitoring and treatment of this condition.

Female↗

[Acute or chronic transplant rejection - high resolution CT of the chest in lung transplant recipients].

PURPOSE: Aim of the study was to evaluate the postoperative changes in patients with single (SLTX) or double lung transplantation (DLTX) with HRCT and to correlate those findings with the clinical diagnosis. MATERIAL AND METHODS: 29 patients with SLTX (n = 14) or DLTX (n = 15) were observed for more than 6 years after transplantation by HRCT (n = 82). CT examinations were performed in inspiration and expiration (n = 70) with a slice thickness of 1 mm and a feed of 10 mm. The image material was evaluated by 2 experienced radiologists in consensus. Criteria for acute rejection at HRCT were: ground glass opacities and focal air trapping in expiration. Criteria for chronic transplant rejection were: bronchial dilatation, bronchial wall thickening and thickening of interlobar septae. The clinical evaluation consisted of laboratory tests, lung function tests, and bronchoscopy including bronchial lavage in special cases. RESULTS: 20/29 patients are still alive (mean 21 months). 5/9 patients died because of chronic transplantant rejection, 1 patient suffered from a non-Hodgkin's lymphoma localised at the right hilus. Severe threatening pneumonia occurred in 13 cases. 10/29 patients showed symptoms of acute rejection. Expiratory HRCT found a focal air trapping in all cases and extended ground glass opacities in 11/14 cases. Also a bronchial dilatation was observed in more than 50 % (9/14). 12/29 patients suffered from chronic transplant rejection. HRCT showed bronchial dilatation in 26/27 investigations and severe ground glass opacities in 21/27 investigations. Thickening of the interlobal septa as well as centrilobular opacities were found in more than 50 % of the examinations. CONCLUSION: High resolution CT of the chest in patients after lung transplantation is able to show numerous pathological alterations. Without clinical information a confident differentiation in acute or chronic transplant rejection or pneumonia can be difficult or impossible.

Acute Disease↗

Surgical treatment of pulmonary artery sarcoma.

OBJECTIVE: Pulmonary artery sarcomas are rare and usually fatal tumors. The diagnosis is difficult and delayed in most cases. Newer imaging techniques could allow early diagnosis in patients with symptoms of pulmonary vascular obstruction. Surgical resection improves clinical symptoms and offers the only chance of cure. We report the case histories of 7 patients with primary pulmonary artery sarcomas treated by surgical resection with or without adjuvant therapy. METHODS: Seven patients (3 women and 4 men; mean age, 52.3 years; preoperative New York Heart Association functional class III/IV, n = 5/2) underwent operations. Malignancy was preoperatively suspected in 5 patients, and 2 patients had a presumptive diagnosis of chronic pulmonary embolism. Tumor resection with partial or total prosthetic replacement (n = 2), reconstruction (n = 5), or both, of central parts of the pulmonary arteries was performed in 6 patients. Thromboendarterectomy was necessary in 4 patients, and pneumonectomy was necessary in 2 patients. Six patients received adjuvant therapy. RESULTS: There was no perioperative mortality. All patients had a substantial improvement in exercise tolerance and hemodynamics 3 months after their operations. Four patients died 7, 9, 18, and 19 months after their operations because of recurrent tumor or pulmonary metastases. Two patients are alive 21 and 35 months after primary surgical repair, with pulmonary metastases detected by computed tomographic scans. One patient is alive 62 months after resection without clinical or radiologic signs of tumor recurrence or metastasis. CONCLUSIONS: Early diagnosis of primary pulmonary artery sarcomas can be improved by computed tomography and magnetic resonance scanning. Radical surgical resection probably presents the only chance for cure. The role of neoadjuvant or adjuvant treatment modalities has to be defined. Pulmonary artery sarcoma need not necessarily be a fatal diagnosis.

Adult↗