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Biomedical subjects

T Meyer

Publications and source records attributed to T Meyer.

At least 235 records · Page 13Linked to original sources
PubMed1998

Attachment kinetics, proliferation rates and vinculin assembly of bovine osteoblasts cultured on different pre-coated artificial substrates.

Primary bovine osteoblasts were used to study in-vitro effects of attachment on vinculin assembly in cells cultured on various artificial substrates. Materials coated with fibronectin and bovine serum albumin (BSA) as well as untreated materials (tissue culture polystyrene and Aclar foils) were chosen to investigate substrate-dependent proliferation during the first 3 days of culture. Proliferation was highest on fibronectin-coated substrates, followed by BSA-coated and untreated substrates. During the first 24 h of cultivation, cell attachment kinetics revealed no significant difference between the various substrates. After 24 h detachment rates obtained by calcium depletion with ethylenediaminetetraacetic acid were highest on uncoated materials, followed by BSA- and fibronectin-coated substrates. Phase contrast microscopy revealed typical osteoblast morphology after cell adhesion for 24 h. The dynamic attachment process was concomitant with the reassembly of vinculin into streak-like focal contacts clustered on the ventral side of cells. The kinetics of vinculin reassembly were independent of the underlying coating. Thus, fibronectin coating of artificial substrates increased the attachment strength and proliferation rate of osteoblasts. While the reassembly of vinculin in focal contacts seems to be a prerequisite of osteoblast attachment in vitro, it does not seem to have profound effects on the subsequent cell behaviour on artificial substrates.

Journal Article↗
PubMed1998

Expression of alphav integrins and vitronectin receptor identity in breast cancer cells.

In the present study we have used fluorocytometry and immunoprecipitation to characterize the expression of alphav-containing integrins in a panel of eight human breast cancer cell lines and one normal human mammary epithelial line. We show that the classical vitronectin receptor alphavbeta3 is expressed in only one cell line (MDA-MB-231), whereas alphavbeta5 is expressed on all breast cancer cell lines and alphavbeta1 is expressed on the majority. Using adherence assays to purified ligands in the presence and absence of function-blocking monoclonal antibodies, we have demonstrated that alphavbeta5 mediates adhesion to vitronectin in the majority of these cells. In one cell line, ZR75-1, alphavbeta1 contributes significantly to adhesion to immobilized vitronectin. The formation of focal adhesions containing the alphav and beta1 subunits on vitronectin is also demonstrated by indirect immunofluorescence.

Breast Neoplasms↗
PubMed1998

In vivo and in vitro characterization of the sequence requirement for oligomer formation of Ca2+/calmodulin-dependent protein kinase IIalpha.

Ca2+/calmodulin-dependent protein kinase II (CaMK II) is a multifunctional serine/threonine protein kinase that regulates ion channels, metabolic enzymes, cytoskeletal proteins, and possibly transcription factors. CaMK II holoenzymes have been shown to be large oligomers built from eight or more subunits. The oligomeric structure of CaMK II is required for a critical trans-autophosphorylation step by which each subunit traps bound calmodulin and renders the enzyme partially active in the absence of Ca2+/calmodulin. Here we define a minimal C-terminal domain of alphaCaMK II that is necessary and sufficient for oligomerization. The oligomeric structure of alphaCaMK II deletion mutants was investigated in vitro by gel filtration chromatography and in living cells by measuring nuclear exclusion and diffusion coefficients of green fluorescent protein-tagged mutants. These studies showed that a C-terminal region of alphaCaMK II of 135 amino acids is sufficient for oligomer formation. Oligomer formation was abolished by further C-terminal and N-terminal deletions, indicating that the same region is not only sufficient but also necessary for oligomerization. Thus, an oligomerization domain of only 15 kDa is sufficient to build the circular structure of CaMK II holoenzyme.

Amino Acid Sequence↗
PubMed1998

Endurance training in panic patients: spiroergometric and clinical effects.

Endurance capacity was determined by bicycle spiroergometry in patients with panic disorder before (n = 38) and after (n = 10) a 10 week running program and compared to untrained healthy control subjects carrying out the same training (n = 11) and patients receiving clomipramine drug therapy (n = 7) or placebo (n = 7). Before the running program maximal oxygen uptake (VO2peak) and the workload corresponding to a lactate concentration of 4 mmol/l (PLAC4) were significantly reduced in panic patients compared to controls. Patients in the running program and healthy controls improved PLaC4 significantly by running. No significant differences in endurance gains were found between these groups, showing that patients and controls improved equally. At study termination (week 10) running was more efficient than placebo in improving panic symptoms (Bandelow PanicAgoraphobia Scale, Hamilton Anxiety Scale, Clinical Global Impression Scale). Clomipramine treatment was better than placebo (all scales) and running (only Clinical Global Impression). Endurance capacity did not correlate with anxiety scores at baseline, nor did improvement in fitness substantially correlate with changes in psychopathology measures during the study. Panic patients were shown to have a decreased endurance capacity which can be raised by training. Endurance training based on spiroergometric results gives rise to clinical improvement.

Adult↗
PubMed1998

[German version of the Snaith-Hamilton-Pleasure Scale (SHAPS-D). Anhedonia in schizophrenic and depressive patients].

The Snaith-Hamilton-Pleasure-Scale (SHAPS), introduced in English in 1995, assesses self-reported anhedonia in psychiatric patients. It has proven psychometric properties and advantages in applicability compared to other instruments assessing anhedonia. This study presents results of a systematic transcultural protocol translating the SHAPS into German (SHAPS-D). Quality of translation was confirmed on the one hand by bilingual reviewers with regard to equivalence in content and tone. On the other hand stable results were found in a test-retest-design crossing the English and German version with bilingual persons. SHAPS-D was obtained from schizophrenic (n = 50) and depressive (n = 33) patients and from healthy controls (n = 67). Results on applicability, internal consistency and relationship to depression, subjective quality of life, well-being as well as psychopathology indicate that the SHAPS-D is a useful and promising instrument in assessing anhedonia.

Adult↗
PubMed1998

Association of rare human papillomavirus types with genital premalignant and malignant lesions.

Due to the limited number of reports concerning their association with particular dysplastic and neoplastic lesions, the oncogenic potential of so-called rare or novel human papillomavirus (HPV) types is still unclear. Cytologic smears or biopsy specimens from 538 patients were analyzed for dysplastic or neoplastic lesions and HPV infection. The HPV detection and typing system utilized allowed identification of all mucosal HPVs amplifiable by L1 polymerase chain reaction. Considering only patients infected with a single HPV type (n = 329), rare or novel HPVs (HPV-59, HPV-61, HPV-62, HPV-66, HPV-70, HPV-73, MM4, MM7, MM8, CP6108, and CP8304) were detected in 28% of normal specimens (n = 46), none of condylomatous lesions (n = 44), 12% of low-grade squamous intraepithelial lesions (SILs) (n = 42), 8% of high-grade SILs (n = 142), and 4% of cervical cancers (n = 54). Prevalence and oncogenic potential of distinct rare HPV types seems to be higher than previously assumed.

Condylomata Acuminata↗
PubMed1998

Aerosol bolus dispersion in patients with bronchiolitis obliterans after heart-lung and double-lung transplantation. The Munich Lung Transplantation Group.

Bronchiolitis obliterans (BO) is one of the main late complications in patients after lung transplantation. Because BO is located in small airways, conventional lung function tests are supposed to be rather insensitive to detect early stages of this disease. In this study, the capability of the aerosol bolus dispersion test to detect BO was tested in 12 subjects with heart-lung and double-lung transplantation. Four of these patients had histological evidence of BO. The broadening (dispersion) of inhaled boluses consisting of monodispersed inert test particles during respiration was repeatedly measured in each subject. Additional measurements of spirometric and bodyplethysmographic measurements were performed. Patients with evidence of BO showed significantly increased aerosol bolus dispersion and significantly reduced maximal airflow parameters. Calculation of receiver operating characteristics (ROCs) revealed that from all lung function parameters under consideration, aerosol bolus dispersion divided by the maximum expiratory flow rate at 50% of vital capacity (MEF50) and MEI50 had the highest sensitivity and specificity for the detection of BO. Both parameters showed a sensitivity and specificity of 100%. Therefore, it may be speculated that even in early stages of disease, the combination of MEF50 measurement with aerosol bolus dispersion measurements may be a powerful tool for the detection of BO in patients with lung transplantation.

Adolescent↗
PubMed1998

Expression of porcine major histocompatibility antigens in cardiac tissue.

In this study we have used monoclonal antibodies directed against antigens of the major histocompatibility complex (MHC) class I and class II to reveal the detailed cellular distribution of swine lymphocyte alloantigens (SLA) in cardiac tissue. By applying a sensitive immunophosphatase staining reaction we detected the ubiquitous expression of SLA class I and class II on the vascular endothelium. Endothelial cells of capillaries and blood vessels were intensely stained structures in the examined swine hearts. Similar staining patterns were observed in control experiments with anti-von Willebrand factor serum and Dolichus biflorus lectin used as immunohistochemical markers for endothelial cells. The luminal layer of studied pulmonary valves exhibited a strong staining reaction with anti-SLA class I and class II antibodies. In contrast, normal cardiac myocytes failed to express immunodetectable amounts of either of the SLA determinants. Intercalated discs in porcine heart tissue did not react with either anti-SLA class I or class II antibodies. Our data showing the abundant expression of SLA molecules on endothelial cells in normal swine heart may have physiological implications in cell-mediated rejection occurring in xenotransplanted hearts.

Animals↗
PubMed1998

Mice are protected from Helicobacter pylori infection by nasal immunization with attenuated Salmonella typhimurium phoPc expressing urease A and B subunits.

Live Salmonella typhimurium phoPc bacteria were tested as mucosal vaccine vectors to deliver Helicobacter pylori antigens. The genes encoding the A and B subunits of H. pylori urease were introduced into S. typhimurium phoPc and expressed under the control of a constitutive tac promoter (tac-ureAB) or a two-phase T7 expression system (cT7-ureAB). Both recombinant Salmonella strains expressed the two urease subunits in vitro and were used to nasally immunize BALB/c mice. The plasmid carrying cT7-ureAB was stably inherited by bacteria growing or persisting in the spleen, lungs, mesenteric or cervical lymph nodes, and Peyer's patches of immunized mice, while the plasmid carrying tac-ureAB was rapidly lost. Spleen and Peyer's patch CD4+ lymphocytes from mice immunized with S. typhimurium phopc cT7-ureAB proliferated in vitro in response to urease, whereas cells from mice given S. typhimurium phoPc alone did not. Splenic CD4+ cells from mice immunized with phoPc cT7-ureAB secreted gamma interferon and interleukin 10, while Peyer's patch CD4+ cells did not secrete either cytokine. Specific H. pylori anti-urease immunoglobulin G1 (IgG1) and IgG2A antibodies were detected following immunization, confirming that both Th1- and Th2-type immune responses were generated by the live vaccine. Sixty percent of the mice (9 of 15) immunized with S. typhimurium phoPc cT7-ureAB were found to be resistant to infection by H. pylori, while all mice immunized with phoPc tac-ureAB (15 of 15) or phoPc (15 of 15) were infected. Our data demonstrate that H. pylori urease delivered nasally by using a vaccine strain of S. typhimurium can trigger Th1- and Th2-type responses and induce protective immunity against Helicobacter infection.

Animals↗
PubMed1998

Immunization of pigs with a particle-mediated DNA vaccine to influenza A virus protects against challenge with homologous virus.

Particle-mediated delivery of a DNA expression vector encoding the hemagglutinin (HA) of an H1N1 influenza virus (A/Swine/Indiana/1726/88) to porcine epidermis elicits a humoral immune response and accelerates the clearance of virus in pigs following a homotypic challenge. Mucosal administration of the HA expression plasmid elicits an immune response that is qualitatively different than that elicited by the epidermal vaccination in terms of inhibition of the initial virus infection. In contrast, delivery of a plasmid encoding an influenza virus nucleoprotein from A/PR/8/34 (H1N1) to the epidermis elicits a strong humoral response but no detectable protection in terms of nasal virus shed. The efficacy of the HA DNA vaccine was compared with that of a commercially available inactivated whole-virus vaccine as well as with the level of immunity afforded by previous infection. The HA DNA and inactivated viral vaccines elicited similar protection in that initial infection was not prevented, but subsequent amplification of the infection is limited, resulting in early clearance of the virus. Convalescent animals which recovered from exposure to virulent swine influenza virus were completely resistant to infection when challenged. The porcine influenza A virus system is a relevant preclinical model for humans in terms of both disease and gene transfer to the epidermis and thus provides a basis for advancing the development of DNA-based vaccines.

Animals↗
PubMed1998

Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.

Tie2 is an endothelium-specific receptor tyrosine kinase that is required for both normal embryonic vascular development and tumor angiogenesis and is thought to play a role in vascular maintenance. However, the signaling pathways responsible for the function of Tie2 remain unknown. In this report, we demonstrate that the p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase) associates with Tie2 and that this association confers functional lipid kinase activity. Mutation of tyrosine 1101 of Tie2 abrogated p85 association both in vitro and in vivo in yeast. Tie2 was found to activate PI3-kinase in vivo as demonstrated by direct measurement of increases in cellular phosphatidylinositol 3-phosphate and phosphatidylinositol 3, 4-bisphosphate, by plasma membrane translocation of a green fluorescent protein-Akt pleckstrin homology domain fusion protein, and by downstream activation of the Akt kinase. Activation of PI3-kinase was abrogated in these assays by mutation of Y1101 to phenylalanine, consistent with a requirement for this residue for p85 association with Tie2. These results suggest that activation of PI3-kinase and Akt may in part account for Tie2's role in both embryonic vascular development and pathologic angiogenesis, and they are consistent with a role for Tie2 in endothelial cell survival.

3T3 Cells↗
PubMed1998

The EAAT2 (GLT-1) gene in motor neuron disease: absence of mutations in amyotrophic lateral sclerosis and a point mutation in patients with hereditary spastic paraplegia.

OBJECTIVES: To investigate if sequence alterations of the excitatory amino acid transporter gene EAAT2 (GLT-1) may be a contributory factor to the pathogenesis of motor system degeneration. EAAT2 serves as a candidate gene as its reduced expression was reported in patients with amyotrophic lateral sclerosis (ALS). Furthermore, neurolathyrism, a motor neuron disease clinically related to hereditary spastic paraplegia (HSP), has been associated with an exogenous excitotoxin. METHODS: Sequence alterations were screened for in the coding region of EAAT2 in 55 patients with ALS and one family with autosomal dominant HSP (AD-HSP). RESULTS: In ALS, no sequence alteration in the EAAT2 gene have been found. Interestingly, a heterozygous A79G mutation of the EAAT2 gene was detected in two of seven affected patients with AD-HSP in the same kindred. The absence of cosegregation with the familial disease showed that the detected variant was not the cause of disease. The A79G sequence variant was not found in 55 patients with ALS or in 50 non-neurological controls. CONCLUSION: The allelic variant of the EAAT2 gene in conjunction with the primary gene defect may be a modifying factor for the highly variable AD-HSP phenotype.

Adult↗
PubMed1998

Superiority of combined CK-MB and troponin I measurements for the early risk stratification of unselected patients presenting with acute chest pain.

BACKGROUND: Recent studies have suggested that positive troponin I tests are associated with an increased risk of cardiac death during short-term follow-up. However, it is unknown if troponin I tests alone or in addition to CK-MB measurements are superior to predict unfavorable outcome during long-term follow-up. PATIENTS AND METHODS: In a prospective, double-blind study we assessed the prevalence and prognostic value of combined troponin I and CK-MB tests in an unselected cohort of patients (n = 292) admitted to the emergency department for acute chest discomfort. Patients were grouped according to the diagnosis on discharge in those with acute myocardial infarction (1), unstable angina (2), and noncardiac chest pain (3). Six months after enrollment, death rates were obtained and follow-up interviews were performed with respect to survival, recurrence of chest pain, and myocardial infarction. RESULTS: In patients with evidence of coronary heart disease, the mortality rate for abnormal troponin I and normal CK-MB levels was 5.0%. Baseline troponin I and elevated CK-MB levels were associated with a mortality rate of 4.0%. However, the mortality rate was significantly higher (11.1%) in patients presenting with elevated troponin I and CK-MB values. In patients without myocardial infarction on admission, 10.5% with positive troponin I tests died compared to 1.6% with negative tests. The mortality rate in patients without myocardial infarction was 2.7% for patients with elevated CK-MB but normal troponin I values. In patients with both markers elevated a significantly higher mortality rate (16.7%) was found, representing a 6-fold increase in the death event rate. With the additional knowledge of troponin I values, it could be demonstrated that certain cases were misclassified as having noncardiac chest pain. At least some of the latter patients with above-normal values of troponin I were retrospectively to be reclassified as unstable angina. Acute non-Q-wave myocardial infarctions were occasionally misdiagnosed as either angina pectoris or nonischemic chest pain. CONCLUSIONS: Our data suggest the superiority of combined CK-MB and troponin I measurements in clinical practice for the early risk stratification of patients presenting with acute chest pain. In nonmyocardial infarctions, both CK-MB and troponin I convey independent prognostic information with regard to fatal outcome. Troponin I tests in addition to CK-MB measurements contribute to a lower rate of misdiagnoses.

Aged↗
PubMed1998

Comparison of aerobic exercise, clomipramine, and placebo in the treatment of panic disorder.

OBJECTIVE: The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo. METHOD: Forty-six outpatients suffering from moderate to severe panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to a 10-week treatment protocol of regular aerobic exercise (running), clomipramine (112.5 mg/day), or placebo pills. RESULTS: The dropout rate was 31% for the exercise group, 27% for the placebo group, and 0% for the clomipramine group. In comparison with placebo, both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures (analysis of variance, last-observation-carried-forward method and completer analysis). A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively. Depressive symptoms were also significantly improved by exercise and clomipramine treatment. CONCLUSIONS: These results suggest that regular aerobic exercise alone, in comparison with placebo, is associated with significant clinical improvement in patients suffering from panic disorder, but that it is less effective than treatment with clomipramine.

Adult↗
PubMed1998

Diagnosis of emphysema in patients with chronic bronchitis: a new approach.

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (D) are altered in patients or animal models with lung emphysema. This study was performed to examine the sensitivity and specificity of ADAM and D in the detection of emphysema in vivo compared with conventional lung function parameters. The study comprised patients with chronic obstructive bronchitis (COB) without emphysema (group COB; n=19, age 56+/-8 yrs, forced expiratory volume in one second (FEV1)/vital capacity (VC) 66+/-12% predicted) and patients with chronic bronchitis with high-resolution computed tomography-confirmed emphysema (group COB-E; n=20), age 65+/-7 yrs, FEV1/VC 44+/-16% pred). Using monodisperse aerosol particles ADAM assessed the calibres of peripheral airspaces, while D measured convective gas mixing. Among all lung function parameters, ADAM and D showed the highest sensitivity and specificity for separating patients with COB from those with COB-E (area under the receiver operating characteristics curve (pROC) 0.99 and 1.0, respectively). In patients with COB aerosol parameters did not differ from those found in the control group, whereas patients with COB-E exhibited a two-fold increase in peripheral airspace dimensions compared with subjects with COB (0.86+/-0.07 versus 0.37+/-0.02 mm, p=0.0001) and an increase in D by >50% (541+/-74 versus 345+/-42 cm3, p=0.0001). In conclusion, aerosol-derived airway morphometry and aerosol bolus dispersion are powerful tools in the differential diagnosis of chronic obstructive pulmonary disease.

Administration, Inhalation↗
PubMed1998

Combined operative and endovascular treatment of a post-traumatic embolizing aneurysm of the subclavian artery.

PURPOSE: To describe a combined endovascular and surgical approach for an embolizing subclavian artery aneurysm as an alternative to conventional reconstructive surgery. METHODS AND RESULTS: A 39-year-old woman presented with a post-traumatic aneurysm of the left subclavian artery and occlusion of the brachial artery due to embolization. Exclusion of the aneurysm was achieved by intraoperative implantation of a covered stent during simultaneous reconstruction of the brachial artery by a venous bypass graft. The patient is well and free of symptoms 24 months after the operation. CONCLUSIONS: Repeat operative trauma to the supraclavicular region was avoided by transluminal implantation of a covered stent-graft in combination with an axilloulnar bypass procedure for chronic embolic occlusion of the brachial artery.

Adult↗