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Biomedical subjects

E Mahler

Publications and source records attributed to E Mahler.

At least 19 recordsLinked to original sources
PubMed2004

Femoral artery infection associated with a percutaneous arterial suture device.

This is a case report of a femoral artery infection with fatal outcome after using a percutaneous suture mediated closure device: A 77-year old patient underwent diagnostic angiography of his thoracic and abdominal aortic aneurysm, the puncture site was closed with the Perclose system. He developed a staphylococcal femoral artery infection with groin abscess, requiring surgical intervention with debridement and removal of the Perclose suture. After stent graft exclusion of the thoracic and abdominal aortic aneurysm a staphylococcal sepsis occurred and the patient died of aneurysm rupture months later despite long term antibiotic therapy. Since the use of the Perclose device carries an increased risk of femoral artery infection with septic endarteritis and bacteremia, it should not be used in routine diagnostic angiography.

Aged↗
PubMed2004

Structural and functional complexity of the humoral response against the Trypanosoma cruzi ribosomal P2 beta protein in patients with chronic Chagas' heart disease.

High levels of antibodies against the C-terminus of the Trypanosoma cruzi TcP2 beta ribosomal protein, defined by the peptide EEEDDDMGFGLFD, named R13, have been measured in sera from patients with chronic Chagas' Heart Disease (cChHD). These antibodies also recognize an epitope on the second extracellular loop of the beta 1-adrenergic receptor, inducing a functional response on cardiomyocytes. The aim of this study was to gain novel insights into the structural basis of this cross-reactivity as well as to evaluate the origin of anti-M2- cholinergic receptor antibodies, which are also commonly found in cChHD patients. To address these questions we immunopurified anti-R13 antibodies and studied the structural requirements of epitope recognition. Results showed that the immunopurified antibodies recognized a conformation of R13 in which the third Glu residue was essential for binding, explaining their low affinity for the mammalian homologue (peptide H13: EESDDDMGFGLFD). Alanine mutation scanning showed individual variations in epitope recognition in each of the studied patients. The importance of a negatively charged residue at position 3 for the recognition of anti-R13 antibodies was further confirmed by competition experiments using a Ser3-phosphorylated H13 analogue, which had 10 times more affinity for the anti-R13 antibody than the native H13 peptide. Moreover, anti-R13 antibodies stimulated either the beta 1-adrenergic or the M2-cholinergic receptor, in strict agreement with the functional properties of the IgG fractions from which they derived, demonstrating that the same parasite antigen may generate antibody specificities with different functional properties. This may be a clue to explain the high variability of electrophysiological disturbances found in cChHD.

Animals↗
PubMed2001

Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction.

BACKGROUND: The relationship between anti-beta-adrenergic (anti-betaR) and anti-M(2)-cholinergic (anti-M2R) receptor antibodies (Abs) and cardiac arrhythmias and their biochemical effects have not been systematically investigated. METHODS AND RESULTS: We studied 41 patients, 28 with ventricular arrhythmias (primary or due to Chagas' heart disease or idiopathic dilated cardiomyopathy; group I), 13 with sinus node dysfunction (primary or caused by Chagas' heart disease; group II), and 10 healthy controls (group III). The chronotropic effects of the IgG and immunopurified anti-beta(1)RAbs or anti-M2RAbs were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The biochemical effects of the IgG from 9 patients from group I, 6 from group II, and 6 controls were evaluated on COS7 cells transfected with genes encoding for beta(1),beta(2)-adrenergic receptors (cAMP increment) or M(2)-cholinergic receptors (phosphatidylinositol increment). The IgG from group I patients exerted a positive chronotropic action, with a high prevalence of anti-betaRAbs (75%) and low prevalence of anti-M2RAbs (10.7%) and induced a clear-cut and long-lasting increment in cAMP. The IgG from group II patients depressed chronotropism, with a high prevalence of anti-M2RAbs (76.9%) and low prevalence of anti-betaRAbs (15.4%) and evoked a marked augmentation of phosphatidylinositol. CONCLUSIONS: Our results demonstrate a strong correlation between anti-betaRAbs and ventricular arrhythmias and anti-M2RAbs and sinus node dysfunction. Anti-betaRAbs increase and anti-M2RAbs inhibit cAMP production. These findings offer new insight into the etiology and pathophysiology of cardiac arrhythmias, with therapeutic implications.

Adult↗
PubMed2001

A monoclonal antibody against the immunodominant epitope of the ribosomal P2beta protein of Trypanosoma cruzi interacts with the human beta 1-adrenergic receptor.

Monoclonal antibodies were raised against a recombinant ribosomal P2beta protein of Trypanosoma cruzi. One of these reacted with the C terminus of this protein (peptide R13, EEEDDDMGFGLFD) and epitope mapping confirmed that this epitope was the same as the one defined by the serum of immunized mice, and similar to the previously described chronic Chagas' heart disease (cChHD) anti-P epitope. Western blotting showed that the monoclonal antibody recognized the parasite ribosomal P proteins, as well as the human ribosomal P proteins. Electron microscopy showed that it stained different structures in parasite and human cells. Interestingly, surface plasmon resonance measurements indicated that the affinity for the parasite ribosomal P protein epitope (R13) was five times higher than for its human counterpart (peptide H13, EESDDDMGFGLFD). Since the human epitope contained an acidic region (EESDD) similar to the AESDE peptide recognized by cChHD patients in the second extra-cellular loop of the human beta1-adrenergic receptor, the biological activity of the antibody was assessed on neonatal rat cardiomyocytes in culture. The monoclonal antibody had an agonist-like effect. These results, together with the fact that the monoclonal reacted in Western blots with the different isoforms of the heart beta1-adrenergic receptor, confirm the possible pathogenic role of antibodies against the parasite ribosomal P protein based on their cross-reaction with the human beta1-adrenergic receptor.

Animals↗
PubMed2001

Why are NICU infants at risk for chronic otitis media with effusion?

Newborns in a Neonatal Intensive Care Unit (NICU) and even later have a high incidence of otitis media with effusion (OME). It is unclear which aspects play a role in the incidence of chronic OME during infancy. In order to investigate the effect of nasally-placed tubes, cranial growth, immune system, and neuromotor function on the occurrence of chronic OME, 83 NICU patients were observed prospectively for middle ear status. Duration and type of treatment with nasal tubes were obtained from the NICU notes. At the NICU, and 1 and 2 years of age the cranial circumference and neuromotor function were assessed. As a proxy for disturbed local immune system parental reports of snoring, mouth breathing and common cold were used. Multivariate analysis revealed that infants treated with nasotracheal and nasopharyngeal tubes showed a marginally significant increased risk for chronic OME (OR=3.2 [95% CI 0.5--21.2]). Treatment with nasogastric tubes appeared to have a lower risk for chronic OME (OR=1.5 [95% CI 0.1--25.1]). No significant effect was found for cranial circumference. Signs of disturbed local immunity during the first 6 months of life (OR=1.4 [95% CI 0.4--4.7]), as well as impaired neuromotor function (OR=1.9 [95% CI 0.5--6.8]), showed also a marginally significant increased risk for chronic OME. The cohort of NICU patients might be relatively too small in order to find significant effects. Although the results of this study should be interpreted cautiously, it is suggested that nasally-placed tubes for ventilatory assistance, disturbed local immunity and impaired neuromotor function are associated with chronic OME.

Chronic Disease↗
PubMed1997

Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus.

Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the beta1-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the beta1 adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-beta1 receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.

Amino Acid Sequence↗
PubMed1995

[Love for radical responsibility. Comments on crisis and and chances of the German Psychoanalytic Society].

The author describes the situation prevailing within the German Psychoanalytic Association, drawing upon his experiences as a long-standing member and looking at the historical development of the Association, its progress and aberrations, from the earliest beginnings up to the present professional policy debate on the frequency and duration of psychoanalytic psychotherapies.

Appointments and Schedules↗
PubMed1986

Possible associations among plasma prolactin levels, tardive dyskinesia, and paranoia in treated male schizophrenics.

To determine whether there is an association between prolactin (PRL) levels and psychopathology or tardive dyskinesia during neuroleptic treatment, we measured plasma prolactin levels and neuroleptic activity (NA) in 33 chronically treated male schizophrenics. Neuroleptic dose, plasma NA, and PRL were significantly intercorrelated. Plasma PRL levels were also measured in 8 male schizophrenics recently withdrawn from neuroleptics and in 18 normal male controls. In treated patients, but not in controls, PRL levels decreased with age and duration of illness, two variables that we interpreted as indirect measures of neuroleptic exposure. PRL levels in patients recently withdrawn from neuroleptics were lower than in treated patients or controls, which was suggestive of rebound hypoprolactinemia. A prolactin index, calculated as the ratio of PRL levels to NA, was inversely correlated with paranoid symptoms and tardive dyskinesia in younger treated patients. These results lead to speculation that tuberoinfundibular dopaminergic supersensitivity develops in chronically treated schizophrenics and that it is associated with nigrostriatal supersensitivity, manifested by tardive dyskinesia, and paranoid symptoms, which may reflect mesolimbic supersensitivity.

Adult↗