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Biomedical subjects

E Mayer

Publications and source records attributed to E Mayer.

At least 19 recordsLinked to original sources

Pure imagery hemi-neglect of far space.

Patients with hemispatial neglect restricted to near (within reaching distance) or to far space (beyond reaching distance) have been described. This constitutes a double-dissociation considered by current neurocognitive thinking as compelling evidence for separate networks. However, a similar double-dissociation exists with respect to perceived as opposed to imagined space. If the organization of represented space was similar to that of perceived space, it should contain a far/near dissociation as well. This paper describes a patient with pure representational neglect restricted to far space.

Aged↗

Expression of drug resistance related proteins in sarcomas of the pulmonary artery and poorly differentiated leiomyosarcomas of other origin.

Sarcomas are known to develop resistance to current chemotherapeutic strategies, displaying a multidrug-resistant phenotype. Mechanisms involved in drug resistance include reduced cellular drug accumulation, drug detoxification as well as alterations in drug target specificity. In seven sarcomas of the pulmonary artery (SPA) and ten leiomyosarcomas of other origin, we studied the immunohistochemical expression of P-glycoprotein (P-gp), multidrug-resistance protein (MRP), lung resistance protein (LRP), metallothionein (MT) and topoisomerase IIalpha. Upregulation was found in tumour cells for P-gp but not for MRP in SPA and other leiomyosarcomas. Topoisomerase IIalpha was expressed at high levels in tissue of primary tumours as well as recurrent tumours. Both P-gp and topoisomerase IIalpha were present in numerous tumour-associated vessels. LRP was expressed at high levels in SPA but to a lesser extent in the other leiomyosarcomas. MT was expressed at low levels but was markedly present at the border of necrosis. The overall survival and the relapse-free survival did not correlate with the expression of these factors. There was no significant relationship between treated and non-treated patients with respect to the expression of the examined molecules. P-gp, but not MRP, may play a role in the development of drug resistance. P-gp, LRP and topoisomerase IIalpha contribute to drug resistance through expression in tumour-associated vessels. Unique high levels of topisomerase IIalpha reflect the high proliferation rate of these tumours. MT seems to serve as a detoxifying agent of metabolites at the border of necrosis. Our findings underline the fact that multiple factors contribute to chemoresistance and that examination of a spectrum of relevant molecules is probably necessary to plan the best therapy.

ATP Binding Cassette Transporter, Subfamily B↗

Representation of anatomical constraints in motor imagery: mental rotation of a body segment.

Classically, the mental rotation paradigm has shown that when subjects are asked to judge whether objects that differ in orientation are spatially congruent, reaction times increase with angular discrepancy, although some reports have shown that this is not always the case. Would similar results be obtained with realistic figures of body segments? In this work, the mental rotation of a hand attached to its forearm and arm in anatomically possible and impossible starting positions is compared with the mental rotation of a hammer. The main results show that reaction times increase monotonically with the angle of discrepancy for both stimuli and that the speed of rotation is higher for anatomically possible orientations in the case of the hand. Thus, mental rotation of body segments follows the same empirical rules as objects of another nature, and biomechanical constraints imposed to the motility of these segments can be considered as attributes of the mental representation.

Adult↗

Pulmonary balloon angioplasty of chronic thromboembolic pulmonary hypertension (CTEPH) in surgically inaccessible cases.

The clinical course of patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) depends on the distribution pattern of the thromboembolic material. In patients with thromboembolic findings in the central pulmonary segments pulmonary thrombendarterectomy (PTE) has excellent results and acceptable operative risk. This paper presents two surgically inaccessible cases that were successfully treated with balloon pulmonary angioplasty. Balloon angioplasty improved parenchymal perfusion, increased cardiac index (Delta CI +19.2 % [Case 1], and +15.4 % [2]), reduced pulmonary vascular resistance during follow-up (Delta PVRI -25.0 % [1] and -15.9 % [2]), and is discussed as an alternative treatment option for cases not suited for surgery.

Adult↗

Pure global acalculia following a left subangular lesion.

We describe the case of a right-handed patient who presented a severe acalculia in the context of a pure Gerstmann syndrome following a subangular lesion that spared the left inferior parietal lobule (IPL). The patient showed impairments in Arabic and verbal codes, in number production and comprehension, as well as in numerical facts and problem solving. By using the EC301 calculation battery, semantic and syntactic tasks in Arabic and verbal codes, we tested the different hypotheses raised by the cognitive neuropsychological models of acalculia. The patients' difficulties, which were not associated with a general intellectual deterioration, and those affecting number processing as a particular semantic class, were indicative of a "global acalculia". This deficit, which exceeded the anarithmetia usually described in Gerstmann syndrome following left IPL lesion, suggested that the isolation of this area may constitute a sufficient condition for producing such a global acalculia. These results are discussed in terms of a disorder in the manipulation of mental images of spatially related objects.

Brain↗

A 10 year retrospective survey of cataract surgery and endophthalmitis in a single eye unit: injectable lenses lower the incidence of endophthalmitis.

AIM: To study the incidence of endophthalmitis following cataract surgery over a 10 year period, and to examine ways in which this may be related to changes in surgical technique. METHODS: All cases of endophthalmitis occurring over a 10 year period within a single ophthalmic unit in the United Kingdom were reviewed, and possible risk factors identified. RESULTS: During the study period, as the technique of extracapsular cataract surgery was replaced by phacoemulsification, there was a commensurate reduction in the incidence of endophthalmitis. Injectable IOLs were associated with the lowest risk of postoperative endophthalmitis (0.028%). CONCLUSIONS: Injectable intraocular lenses do not make contact with the ocular surface and this may result in the observed lower rate of endophthalmitis. This, and the ease with which they can be inserted through small incisions, support their use as the first line method of lens insertion.

Acute Disease↗

Structure of a new dense amorphous ice.

The detailed structure of a new dense amorphous ice, VHDA, is determined by isotope substitution neutron diffraction. Its structure is characterized by a doubled occupancy of the stabilizing interstitial location that was found in high density amorphous ice, HDA. As would be expected for a thermally activated unlocking of the stabilizing "interstitial," the transition from VHDA to LDA (low-density amorphous ice) is very sharp. Although its higher density makes VHDA a better candidate than HDA for a physical manifestation of the second putative liquid phase of water, as for the HDA case, the VHDA to LDA transition also appears to be kinetically controlled.

Journal Article↗

3He-MRI-based vs. conventional determination of lung volumes in patients after unilateral lung transplantation: a new approach to regional spirometry.

BACKGROUND: To use 3Helium (3He)-MRI in patients with unilateral lung grafts to assess the contributions of graft and native lung to total ventilated lung volume, and second to compare conventional measurements of intrapulmonary gas volume (spirometry, body plethysmography) with image-based volumetry of ventilated lung parenchyma visualized by hyperpolarized 3He-MRI. METHODS: With Ethics Committee approval, five patients with single lung transplantation (SLTX) for idiopathic pulmonary fibrosis (IPF) underwent both conventional pulmonary function testing (PFT) and 3He-MRI of the lung. Intrapulmonary gas volume (GV) during the inspiratory breathhold for 3He-MRI was calculated from measured functional residual capacity (corrected for supine position) and inspired tidal volume. Image-based global and regional lung volumetries (LV) were performed in three-dimensionally reconstructed 3He-MR images (corrected for the fraction of tissue and blood). RESULTS: Transplanted lungs were characterized by a homogeneous distribution of signal intensity, whereas the native lungs of the patients suffering from IPF displayed an inhomogeneous signal distribution pattern with numerous round or wedge-shaped ventilation defects. Total ventilated lung volume determined by 3He-MRI correlated well with PFT-based measurements, but with a systematic overestimation of the 3He-based lung volumetry of approximately 20%. Functioning lung grafts contributed 66+/-6% and their corresponding native IPF lungs 34+/-6% to total ventilated volume (P<0.05; mean+/-SD). CONCLUSION: 3Helium-MRI of the lung offers a novel approach to regional determination of ventilated lung volume, including its blood and tissue compartments. The advantage of this technique over computed tomography or ventilation scintigraphy is the lack of radiation exposure, and hence its repeatability. Follow up of SLTX patients with this new technique may allow the monitoring of functional and structural developments of grafted lungs with better sensitivity and specificity than PFT.

Female↗

Quantitative assessment of right ventricular volumes in severe chronic thromboembolic pulmonary hypertension using transthoracic three-dimensional echocardiography: changes due to pulmonary thromboendarterectomy.

AIMS: Evaluation of a three-dimensional reconstruction method to show the changes of right ventricular volume and systolic function when patients undergo pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: In the examination of 11 patients (four female, seven male; age 56+/-10 years) before and after pulmonary thromboendarterectomy, end-diastolic and end-systolic right ventricular volumes were determined as a sum total of the calculated volumes of derived parallel slices of the right ventricle. Using a Tomtec workstation and a Vingmed CFM 800 echocardiography device, the acquired data were ECG-and respiration-triggered in the course of transthoracic examination, using step intervals of 5 degrees. The ventricular outline was traced manually on 5mm slices from longitudinal cut planes. For subsequent correction, their area measurements were displayed and the volume cross-checked against the volume from orthogonal cut planes. End-diastolic and end-systolic volumes could be quantified in 11/11 cases before surgery, but data could only be attained for 9/11 patients after surgery, because a limited apical window rendered the postoperative three-dimensional reconstruction impossible in two cases. Before surgery, right ventricular size was larger than normal and systolic function was clearly impaired in all of the patients (end-diastolic volume: 121+/-37 ml; end-systolic volume 91+/-30 ml; ejection fraction 25+/-8%). The decrease in mean pulmonary artery pressure after surgery was significant (47+/-8 vs 26+/-8 mmHg; P<0.05). End-diastolic and end-systolic right ventricular volumes had been reduced (80+/-33 ml and 54+/-31 ml respectively), and the ejection fraction had increased (36+/-9%). CONCLUSIONS: Successfully performed pulmonary thromboendarterectomy leads to a significant reduction of right ventricular chamber size and improvement of systolic function, which can be determined with great precision and quite easily, using transthoracic three-dimensional echocardiography. Published by Elsevier Science Ltd. All rights reserved.

Adult↗

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↗