Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 91 records · Page 5Linked to original sources

PubMed2000

Multiple site silicon-based probes for chronic recordings in freely moving rats: implantation, recording and histological verification.

This paper describes the procedure of assembling a miniature microdrive and silicon probe system for surgical implantation into the adult rat brain. Successful recordings of single and multiunit activity with parallel depth profiles of spontaneous and evoked field potentials are shown. The procedure for histological verification of the position of the silicon probe is described.

Age Factors↗

PubMed2000

A distinct seven-residue trigger sequence is indispensable for proper coiled-coil formation of the human macrophage scavenger receptor oligomerization domain.

We have recently identified a distinct 13-residue sequence pattern that occurs with limited sequence variations in many two-stranded coiled coils but not in trimers, tetramers, or pentamers. This coiled-coil trigger pattern was demonstrated to be indispensable for the assembly of the oligomerization domain of the actin-bundling protein cortexillin I from Dictyostelium discoideum and the leucine zipper domain of the yeast transcriptional activator GCN4. With the aim to extend our knowledge on trigger sequences we have investigated the human macrophage scavenger receptor type A oligomerization domain as a representative of three-stranded coiled coils. We prepared a variety of recombinant N- and C-terminal deletion mutants from the full-length oligomerization domain by heterologous gene expression in Escherichia coli and assessed their ability to form trimeric coiled-coil structures by circular dichroism spectroscopy and analytical ultracentrifugation. Deletion mapping identified a distinct seven-residue sequence that was absolutely required for proper coiled-coil formation, supporting our previous results that heptad repeats alone are not sufficient for oligomerization. The finding that all fragments containing this particular sequence exhibited similar thermal stabilities indicates primarily a stabilizing function of the coiled-coil trigger. Based on sequence similarity, we suggest that functionally related sites are present in other three-stranded coiled-coil proteins.

Amino Acid Sequence↗

PubMed2000

Development of improved soluble inhibitors of FasL and CD40L based on oligomerized receptors.

TNF receptor family members fused to the constant domain of immunoglobulin G have been widely used as immunoadhesins in basic in vitro and in vivo research and in some clinical applications. In this study, we assemble soluble, high avidity chimeric receptors on a pentameric scaffold derived from the coiled-coil domain of cartilage oligomeric matrix protein (COMP). The affinity of Fas and CD40 (but not TNFR-1 and TRAIL-R2) to their ligands is increased by fusion to COMP, when compared to the respective Fc chimeras. In functional assays, Fas:COMP was at least 20-fold more active than Fas:Fc at inhibiting the action of sFasL, and CD40:COMP could block CD40L-mediated proliferation of B cells, whereas CD40:Fc could not. In conclusion, members of the TNF receptor family can display high specificity and excellent avidity for their ligands if they are adequately multimerized.

Animals↗

PubMed2000

[The effect of different volume expanders on neutrophil granulocyte function in vitro].

INTRODUCTION: The influence of kolloids on the immune system is not well documented. In this study we investigated the effects of gelatine, hydroxyethylstarch (HES), human albumine, and dextrane on neutrophil function and receptor expression by flow cytometry. METHODS: Whole blood of healthy volunteers was incubated for 30 minutes with either gelatine, HES (6% and 10%), dextrane 40 and 60, or human albumin 20%. Phagocytic capacity was determined by uptake of fluorescein-isothiocyanate labeled bacteria, the conversion of dihydrorhodamine 123 into fluorescent rhodamine 123 was used for oxidative burst measurements. Expression of complement receptors CD 11b and CD35 was investigated using fluorescein-isothiocyanate labeled antibodies. RESULTS: Incubation with gelatine significantly increased expression of complement receptors and oxidative burst. Dextranes and HES had no influence on neutrophil function. Human albumin reduced the oxidative burst, whereas CD 35 expression was increased. CONCLUSION: The physiological significance of these changes in a range of 10% has to be clarified in further investigations.

Bacteria↗

PubMed2000

[Early detection of breast cancer in Germany. Time to deal with the problem].

In Germany there is still an urgent need for action in regard to screening for breast cancer. The announcement of research projects for mammography screening proves this. The following reports the results of the Munich field study. In 2 years, 2489 breast cancer cases were registered (status 6/98). Screening data were available for 1319 patients. The reduction in mortality, found in randomized studies, due to mammography in women over 50 years old was confirmed. A relative reduction of 44.8% in 10-year mortality could be estimated through mammography and 25.1% through palpation, in comparison with "doing nothing." We could also estimate the participation of screening and the used methods in the Munich region. If the mammographies carried out today were used at 2-year intervals for women aged between 50 and 70 years, then the mammography screening could be performed with no additional costs for 70% of the women. The known facts regarding the population-based mortality and regarding the acceptance of the palpation screening and frequency of mammography are additional aspects for inclusion in the discussion of what research projects in Germany are and what they should fulfill.

Breast Neoplasms↗

PubMed2000

Otoscopic findings in relation to tympanometry during infancy.

To determine the value of different otoscopic findings in diagnosing otitis media with effusion, 3,780 otological examinations of 250 infants at ages 0-2 years were compared with tympanometric findings. Otoscopy was performed by an experienced otologist and research-audiologist prior to tympanometry. The following success rates for these procedures were found: otoscopy, 85-91%, tympanometry, 74-94%, either otoscopy or tympanometry, 89-99%. "Glue" was noted as the most frequent abnormal otoscopic feature, i.e., depending on age, 6-32%. Fluid line/ bubbles, bulging/hyperaemia or otorrhoea were rarely (0-5%) observed and contributed little to the diagnosis of otitis media with effusion. No structural changes of the tympanic membrane were observed. Analysis of tympanometric data revealed that the prevalence of tympanogram types B (21-44%), C1 (0.5-16%) and C2 (0-8%) was age-dependent. Comparison of otoscopic and tympanometric findings indicated sufficient diagnostic agreement (Cohen's kappa between 0.41 and 0.74) at age 6-24 months. In conclusion, otoscopy appears to be a valid instrument for diagnosing otitis media with effusion, at least from 6 to 24 months of age. In addition, the results of our study suggest that tuba-dysfunction and otitis media with effusion are age-dependent disorders during infancy, without structural effects on the tympanic membrane.

Acoustic Impedance Tests↗

PubMed2000

Cooperative equilibrium transitions coupled with a slow annealing step explain the sharpness and hysteresis of collagen folding.

Heat and guanidinium-induced denaturation curves of collagen III and its fragments were fitted by theoretical models to explain the extreme sharpness and the hysteresis between unfolding and refolding. It was shown that a recently proposed kinetic model for collagen denaturation does not account for the observed steepness, with physically reasonable values of activation energy and frequency factors in the Arrhenius equation. The extreme slope, which amounts to 0.38 per centigrade for collagen III at the midpoint of its transition, can only be explained by a highly cooperative equilibrium model. The refolding curve is shifted to lower temperatures by 6 degrees C for collagen III and reversible unfolding matching the initial profile of the native protein is observed only after long-time annealing. A simple formalism is proposed by which experimental denaturation and refolding curves are quantitatively described. The transition proceeds via many cooperative steps with slightly different equilibrium constants for unfolding and refolding. Hysteresis and annealing are caused by very slow steps, which are probably connected with a rearrangement of misfolded regions. These slow steps disappear with decreasing size of collagen fragments and hysteresis is not found for collagen model peptides.

Animals↗

PubMed2000

What are oligomerization domains good for?

Collagen triple helices, coiled coils and other oligomerization domains mediate the subunit assembly of a large number of proteins. Oligomerization leads to functional advantages of multivalency and high binding strength, increased structure stabilization and combined functions of different domains. These features seen in naturally occurring proteins can be engineered by protein design by combining oligomerization domains with functional domains.

Animals↗

PubMed2000

Acquiring simultaneous EEG and functional MRI.

OBJECTIVE: Electroencephalography (EEG) is a challenge to record simultaneously with functional MRI (fMRI), for it is prone to large artifacts induced by both the static and the time-variant fields of the MR scanner. However, truly concurrent EEG/fMRI recording has great potential for clinical and scientific neurological applications. We have devised a method for acquiring EEG simultaneously with fMRI that minimizes contamination of the EEG signals. METHODS: We recorded EEG differentially during fMRI using special twisted dual-lead electrodes in a bipolar montage, and a combination of analog pre-processing and digital post-processing of the EEG data. We implemented a functional scan protocol that typically yields artifact-free EEG over 87% of the MR scanning period. RESULTS: Our approach greatly reduced gradient, radio frequency, motion and ballistocardiographic artifact in the EEG, and allowed continuous monitoring of the EEG during functional scanning. To illustrate the quality of the EEG following post-processing, we demonstrated that EEG recorded during fMRI retains useful spectral information. CONCLUSIONS: Quality EEG may be recorded simultaneously with fMRI. With this union, activation maps could be made of any relevant changes in the EEG, such as inter-ictal spikes or spectral variations, or of evoked response potentials (ERPs).

Brain↗

PubMed2000

In vivo measurements of glutamine + glutamate (Glx) and N-acetyl aspartate (NAA) levels in human partial epilepsy.

OBJECTIVE: To investigate whether cerebral levels of N-acetyl aspartate (NAA), and glutamine + glutamate (Glx), are interictally altered in the epileptogenic regions of patients with partial seizures. MATERIAL AND METHODS: NAA, Glx, creatine (Cr), choline (Cho) and myo-inositol (mI) was measured in 28 patients with partial epilepsy and 10 healthy controls using localized 1H magnetic resonance spectroscopy. According to the multimethodological consensus, the epileptogenic region was mesial temporal in 18 and neocortical in 10 patients. RESULTS: The Glx/NAA and Glx/Cr ratios in epileptogenic regions were higher, and the NAA/Cr ratios lower than in the homologous regions (P=0.013, P=0.002 and P<0.0001). Applying the 95% confidence interval of controls, 17 of the 20 mesial temporal epileptogenic regions were correctly identified by an increased Glx/NAA and 15 of 20 by a decreased NAA/Cr ratio. Among patients with neocortical epilepsy the Glx/NAA ratio was increased in 8 of the 10 epileptogenic regions, whereas the NAA/Cr ratio was decreased in three. CONCLUSION: Both Glx and NAA are useful to identify the epileptogenic zone. The Glx/NAA ratios may be particularly useful to indentify neocortical epileptogenic regions.

Adolescent↗

PubMed2000

Crystal structure of a naturally occurring parallel right-handed coiled coil tetramer.

The crystal structure of a polypeptide chain fragment from the surface layer protein tetrabrachion from Staphylothermus marinus has been determined at 1.8 A resolution. As proposed on the basis of the presence of 11-residue repeats, the polypeptide chain fragment forms a parallel right-handed coiled coil structure. Complementary hydrophobic interactions and complex networks of surface salt bridges result in an extremely thermostable tetrameric structure with remarkable properties. In marked contrast to left-handed coiled coil tetramers, the right-handed coiled coil reveals large hydrophobic cavities that are filled with water molecules. As a consequence, the packing of the hydrophobic core differs markedly from that of a right-handed parallel coiled coil tetramer that was designed on the basis of left-handed coiled coil structures.

Amino Acid Sequence↗

PubMed2000

Trimerization of cell adhesion molecule L1 mimics clustered L1 expression on the cell surface: influence on L1-ligand interactions and on promotion of neurite outgrowth.

Several studies indicate that cell adhesion molecules have to be clustered on the cell surface to engage in adhesive functions. We investigated adhesive functions of clustered versus monomeric L1 extracellular parts in vitro to distinguish how clustering affects ligand binding and promotion of neurite outgrowth. Trimeric L1 was recombinantly expressed and covalently assembled by the cartilage matrix protein's coiled-coil domain. Trimeric L1 has an apparent molecular mass of approximately 380 kDa in the nonreduced form and approximately 130 kDa in the reduced form. Rotary shadowing electron micrographs of trimeric L1 revealed a rod-like shape terminating in three globular domains. Monomeric L1 assumes a horseshoe shape of domains Ig I-IV followed by a rod-like structure consisting of Ig V and VI and fibronectin type III 1-5. Circular dichroism measurements showed that the secondary structure consists of beta-sheets. Trimeric L1 binds to itself, to monomeric L1, to laminin-1, and to alpha5beta1 integrin in a concentration-dependent manner. In contrast, binding of monomeric L1 could only be saturated with itself but not with laminin-1 and with alpha5beta1 integrin. Promotion of neurite outgrowth from PC12 cells cultured on adsorbed trimeric L1 was increased by 100%, whereas on monomeric L1 the increase was only 50% over the control value. Promotion of neurite outgrowth from PC12 cells was specifically inhibited in a concentration-dependent manner by a polyclonal antibody against L1. These findings show that clustering of only three extracellular domains increases considerably L1's binding affinity to different ligands and enhances neurite outgrowth, suggesting that adhesive functions of L1 on the cell surface depend on cluster formation.

Animals↗

PubMed2000

[Population-related findings and treatment results and clinic variations in the Munich field study of rectal carcinoma].

BACKGROUND: Different approaches for an effective quality management are funded by the Ministry of health to verify, and if necessary to optimize, the quality of health care using the tracer diagnosis breast, rectal and lung cancer in 8 regions in Germany. The aim of the study is to develop a model for description and support of high quality health care for cancer patients. The conception, initial findings and inter-hospital variations are shown for some aspects of the primary therapy of rectal cancer in the region of Munich (population 2.3 million). PATIENTS AND METHODS: The field study is a population based cohort study. The recruitment phase started in April 1996 and finished March 1998. Established documentation sheets of the tumor registry along with original reports (reports of the doctors, pathologists etc.) are used for documentation. RESULTS: 26 surgical departments, 12 pathology departments, 9 radiotherapy departments and about 300 general practitioners have documented for this study. So far a sample of 809 have been analyzed. After an almost complete documentation the crude incidence will be about 23/100.000. 57% of all patients were men and 43% were women. 765 patients have been operated, 44 not. PT-categories (for the operated patients) are distributed as follows: pTis and pT1 10.7%, pT2 25%, pT3 54.5%, pT4 9.8%. Distribution of tumor localization: < 4 cm 6.7%, 4 bis < 8 cm 36.2%, 8 bis < 12 cm 30.8%, > or = 12 cm 26.3%. Local excision was performed in 4%, sphincter conserving therapy (SCT) in 71.5% (protective stoma: 23.7%), not sphincter conserving therapy (nSCT) in 18.4% and a palliative operation in 6%. The large surgical departments (> 25 patients per year) treated 53.8% of all patients. The proportion of older patients is significant higher in the smaller departments (< 10 patients per year). There are no differences in pTNM-distribution. No variations exist in the operation method between the department groups. More or less varying inter-hospital differences exist between the individual departments for all epidemiological and therapeutical parameters. CONCLUSIONS: Variations of medical care exist more between the individual hospitals than between department groups, divided by workload. To support the quality of health care a feedback of the results has to be available for each physician and each department.

Female↗

PubMed2000

Pituitary and gonadal endocrine effects and pharmacokinetics of the novel luteinizing hormone-releasing hormone antagonist teverelix in healthy men--a first-dose-in-humans study.

UNLABELLED: BACKGROUND. Teverelix is a novel synthetic peptidic luteinizing hormone-releasing hormone (LHRH) antagonist. METHODS: Single subcutaneous morning doses of teverelix acetate (either 0.5, 1, 2, 3, or 5 mg base) were investigated in a randomized, single-blind, placebo-controlled, dose-escalating parallel-group design in healthy men. Six subjects received teverelix, and two subjects received placebo per dose level. Blood samples for lutropin, luteinizing hormone (LH), and follitropin, follicle-stimulating hormone (FSH), and testosterone, as well as for pharmacokinetics, were withdrawn up to 120 hours after dosing. Serum hormone levels were determined by electrochemicoluminescence immunoassays, and plasma teverelix concentrations were determined by radioimmunoassay. RESULTS: Teverelix led to a rapid, marked suppression of LH, testosterone and, to a lesser extent, FSH. Median maximum suppressions compared with predose levels were -93% for LH and -54% for FSH after teverelix 5 mg, and -93% for testosterone after teverelix 3 mg, respectively. After 5 mg teverelix, testosterone suppression <1 ng/mL started a median of 12 hours after dosing and lasted for a median of 33 hours. The duration of testosterone suppression increased with dose. Geometric means of peak teverilix plasma concentrations were 4.5 ng/mL (0.5 mg teverelix) to 49.0 ng/mL (5 mg teverelix) and tmax occurred between 1 and 4 hours after dosing. Geometric means of the area under the teverelix plasma concentration-time course from zero to time of the last quantifiable plasma concentration [AUC(O-tlast)] were 54.9 ng x h/mL (0.5 mg teverelix) to 881.8 ng x h/mL (5 mg teverelix). Median values for apparent terminal half-lives ranged from 24 to 75 hours. The most frequently reported adverse events were short-lasting mild injection-site reactions. CONCLUSIONS: Teverelix showed pronounced LH and testosterone suppressive effects after single subcutaneous doses in healthy men. Duration of hormone suppression increased with dose. Teverelix was well tolerated. This profile indicates potential for further clinical use.

Adult↗

PubMed2000

Predictive value of parent-reported symptoms in the assessment of otitis media with effusion during infancy.

OBJECTIVE: To determine the predictive value of parent-reported symptoms in the assessment of otitis media with effusion (OME) during infancy. DESIGN: Prospective longitudinal study that compared the results of questionnaire-based parental reports with the state of the middle ear assessed by otoscopy and tympanometry at 3-month intervals from birth to the age of 2 years. SETTING: Outpatient Department, University Hospital Maastricht, The Netherlands. SUBJECTS: One hundred and fifth healthy-born infants. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values of parent-reported ear infection, hearing loss, mouth breathing, snoring and common cold. RESULTS: Prevalence rates showed the following ranges: OME, 39%-53%, parent-reported ear infection, 2%-20%, hearing loss 2%-7%, mouth breathing, 30%-41%, snoring, 31%-41% and common cold, 65%-81%. Common cold demonstrated the highest sensitivity (83%) with a low specificity of 36%. Hearing loss gave the highest positive predictive value (PPV) (70%) with a moderate negative predictive value (NPV) (54%). PPV increased with the number of anamnese questions answered positively. CONCLUSIONS: The diagnostic value of parent-reported ear infection, hearing loss and common cold was found to be limited. Combinations of positively-reported symptoms gives increased diagnostic validity while the absence of parent-reported symptoms does not necessarily indicate the absence of OME.

Ambulatory Care↗

PubMed2000

BBID: the biological biochemical image database.

The Biological Biochemical Image Database is a WWW accessible relational database of archived images from research articles that describe regulatory pathways of higher eukaryotes. Pathway information is annotated and can be queried in the study of complex gene expression. In this way, complex regulatory pathways can be tested empirically in an efficient manner in the context of large-scale gene-expression systems.

Computer Graphics↗

PubMed2000

Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group.

In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.

Adult↗

PubMed2000

Texture analysis for classification of cervix lesions.

This paper presents a generalized statistical texture analysis technique for characterizing and recognizing typical, diagnostically most important, vascular patterns relating to cervical lesions from colposcopic images. The contributions of the research include: 1) the introduction of a generalized texture analysis technique based on the combination of the conventional statistical and structural textural analysis approaches by using a statistical description of geometric primitives; 2) the introduction of a set of textural measures that capture the specific characteristics of cervical textures as perceived by human. Experimental study with real images demonstrated the feasibility and promising of the proposed approach in discriminating between cervical texture patterns indicative of different stages of cervical lesions.

Female↗