Biomedical subjects

M Vogel

Publications and source records attributed to M Vogel.

At least 19 recordsLinked to original sources

PubMed2002

Recombinant anti-idiotypic antibodies inhibit human natural anti-glycoprotein (GP)IIb/IIIa autoantibodies.

Anti-idiotypic antibodies (anti-Id) have been described against idiotypes expressed on various autoantibodies. Since an immunoregulatory effect has been postulated for anti-Id, modulation of the anti-Id response in autoimmune disease may be of interest. In chronic immune thrombocytopenic purpura (AITP), autoantibodies directed mainly against platelet membrane glycoprotein (GP) IIb/IIIa cause platelet destruction by Fc-mediated phagocytosis or by complement lysis. We have previously reported on the generation of two recombinant anti-GPIIb/IIIa autoantibody fragments (PDG-X, PDG-B), that are specific for conformationally intact GPIIb/IIIa and inhibit binding of autoantibodies from patients with AITP. In the present study, we show that anti-GPIIb/IIIa specificities are not limited to a single individual by isolating five additional anti-GPIIb/IIIa autoantibody fragments from a second phagemid Fab library of an unrelated healthy donor. Using soluble Fab of PDG-X and PDG-B as antigens for panning Fab phagemid libraries from healthy human individuals, we isolated anti-Id phage clones specific for PDG-X or PDG-B. In addition they inhibited the binding of PDG-X or PDG-B to GPIIb/IIIa. Amino acid sequence comparison between these specific antiId and GPIIb/IIIa was performed. Generation of these anti-Id directed against pathologically relevant anti-GPIIb/IIIa autoantibodies may represent a new suitable and specific therapeutic option for the treatment of antibody-mediated AITP.

Amino Acid Sequence↗

PubMed2001

Model-free determination of dissociation energies of polyatomic systems.

We describe and apply a new procedure that allows a direct determination of dissociation energies of polyatomic systems (clusters, fullerenes, polymers, and other molecules) without any modeling of the systems under investigation. As an example, we have determined the dissociation energies of a series of gold clusters Au(+)n. A comparison with values obtained from statistical models of unimolecular dissociation shows that these models significantly fail to describe the data. In contrast, the new method yields values which are an order of magnitude more accurate, thus allowing one to experimentally set benchmarks for any theory which attempts to describe activated processes.

Journal Article↗

PubMed2001

Regional wall motion and abnormalities of electrical depolarization and repolarization in patients after surgical repair of tetralogy of Fallot.

BACKGROUND: Abnormal depolarization-repolarization in patients with repaired tetralogy of Fallot (TOF) is a risk factor for malignant ventricular tachycardia and sudden death. It is unclear whether ECG abnormalities are associated with abnormal regional right ventricular (RV) function. METHODS AND RESULTS: Seventy-four patients (37 patients <18 and 37 >18 years old) who had had TOF repair at 4.0 years old (0.1 to 47 years old) were examined when they were 18.7 years old (1.7 to 61.1 years old), as were 112 control subjects with normal hearts. Regional function was evaluated with tissue Doppler imaging of the RV and left ventricular (LV) free wall and the septum. Myocardial velocities were sampled continuously from base to apex. Synchronous ECG was analyzed for QRS, QT, and JT duration and QRS, QT, and JT dispersion. All 74 TOF patients had normal LV myocardial velocities. Forty-eight patients (24 patients <18 and 24 >18 years old) had reversed myocardial velocities in diastole in the RV free wall, which were associated with reversed systolic myocardial velocities in 22 and additional reverse diastolic myocardial velocities in the septum in 19. Those 48 patients had a longer QRS duration (151+/-31 versus 124+/-27 ms) and greater QRS (47+/-18 versus 29+/-12 ms), QT (73+/-27 versus 52+/-22 ms), and JT (96+/-31 versus 67+/-35 ms) dispersion. Compared with normal control subjects, all 74 TOF patients had decreased systolic and diastolic myocardial velocities and a longer isovolumic relaxation time. CONCLUSIONS: RV wall-motion abnormalities are a common finding late after TOF repair and are associated with repolarization-depolarization abnormalities. These data further underscore a likely mechanoelectrical interaction as an important part of the pathogenesis of RV disease in these patients.

Adolescent↗

PubMed2001

Cellular mechanisms of depressed atrial contractility in patients with chronic atrial fibrillation.

BACKGROUND: After cardioversion of atrial fibrillation (AF), the contractile function of the atria is temporarily impaired. Although this has significant clinical implications, the underlying cellular mechanisms are poorly understood. METHODS AND RESULTS: Forty-nine consecutive patients submitted for mitral valve surgery were investigated. Twenty-three were in persistent AF (>/=3 months); the others were in sinus rhythm. Before extracorporal circulation, the right atrial appendage was excised. ss-Adrenoceptors were quantified by radioligand binding, and G proteins were quantified by Western blot analysis. The isometric contractile response to Ca(2+), isoproterenol, Bay K8644, and the postrest potentiation of contractile force were investigated in thin atrial trabeculae, which were also examined histologically. The contractile force of the atrial preparations obtained from AF patients was 75% less than that in preparations from patients in sinus rhythm. Also, the positive inotropic effect of isoproterenol was impaired, and Bay K8644 failed to increase atrial contractile force. In contrast, the response to extracellular Ca(2+) was maintained, and the postrest potentiation was preserved. Beta-adrenoceptor density and G-protein expression were unchanged. Histological examination revealed 14% more myolysis in the atria of AF patients. CONCLUSIONS: After prolonged AF, atrial contractility was reduced by 75%. The impairment of beta-adrenergic modulation of contractile force cannot be explained by downregulation of ss-adrenoceptors or changes in G proteins. Dysfunction of the sarcoplasmic reticulum does not occur after prolonged AF. Failure of Bay K8644 to restore contractility suggests that the L-type Ca(2+) channel is responsible for the contractile dysfunction. The restoration of contractile force by high extracellular Ca(2+) shows that the contractile apparatus itself is nearly completely preserved after prolonged AF.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2001

Drosophila rab GDI mutants disrupt development but have normal Rab membrane extraction.

Rab GTPases are essential for vesicular transport. Rab GDP dissociation inhibitor (GDI) binds to GDP-bound rabs, removes rabs from acceptor membranes and delivers rabs to donor membranes. We isolated lethal GDI mutations in Drosophila and analyzed their developmental phenotypes. To learn how these mutations affect GDI structure, the crystal structure of Drosophila GDI was determined by molecular replacement to a resolution of 3.0 A. Two hypomorphic, missense mutations are located in domain II of GDI at highly conserved positions, but not in previously identified sequence conserved regions. The mutant GDIs were tested for ability to extract rabs from membranes and showed wild-type levels of rab membrane extraction. The two missense alleles showed intragenic complementation, indicating that domain II of GDI may have two separable functions. This study indicates that GDI function is essential for development of a complex, multicellular organism and that puparium formation and pole cell formation are especially dependent on GDI function.

Alleles↗

PubMed2001

Mesomelic campomelia, polydactyly and Dandy-Walker cyst in siblings.

The present report describes two fetuses, one female and one male, with thus far undescribed skeletal malformations. The mother was a gravida 2, para 0. Both pregnancies were terminated in the second trimester because of multiple congenital anomalies diagnosed ultrasonographically resembling a short rib-polydactyly syndrome. Both fetuses were found to have postaxial hexadactyly of the hands and feet, marked bilateral campomelia of the forearm and shank bones, and a Dandy-Walker cyst. In addition, the fourth ventricle was dilated in the first sibling and the second sibling had an inverse intestinal malrotation. A literature search failed to reveal similar observations.

Abnormalities, Multiple↗

PubMed2001

Analysis of forced expired volume signals using multi-exponential functions.

Patients with pulmonary disease are often unable to complete forced expiration manoeuvres. The aim of the study is to evaluate whether forced vital capacity (FVC), the volume exhaled at the end of completed forced expiration, can be estimated by extrapolating volume-time curves obtained from uncompleted manoeuvres. The suitability of mono-, bi-, and tri-exponential functions to characterise complete volume-time curves from 50 subjects is investigated. Mono-exponential modelling is insufficient, whereas bi-exponential fitting yields an adequate description for 47 data sets. Tri-exponential models lead to overfitting in all but three cases (normalised sum of least squares: 50.2 +/- 34.5 for mono-, 2.76 +/- 4.11 for bi-, 2.74 +/- 4.19 for tri-exponential modelling; condition number of the correlation matrix: 1.0025 +/- 0.0004 for mono-, 1.08 +/- 0.08 for bi-, 34.7 +/- 100.1 for tri-exponential fitting (mean +/- SD)). Thus, FVC is estimated by the extrapolation of 27 uncompleted spirograms using bi- or tri-exponential models, depending on their accordance with measured data and on the identifiability of their parameters. This algorithm yields unbiased estimates (difference from measured inspiratory vital capacity: 0.01 +/- 0.21 L). This method can be used for investigation of the lung function of subjects who cannot complete the forced expiration manoeuvre.

Adolescent↗

PubMed2001

Structural analysis of high resolution in vitro MR images compared to stained grindings.

The recent advancement of high resolution magnetic resonance imaging has opened up new avenues for the determination of structural characteristics of the trabecular network, which may significantly improve the diagnosis of osteoporosis. An analysis of the calcaneus in healthy women has shown similar age-related changes when comparing structural parameters in high resolution MR images and BMD as measured by DXA [1]. Here we undertook an in vitro study to further compare structural measurements in MR images with those from stained grindings. A 3D gradient echo sequence on a 1.5 T scanner was used to obtain four contiguous sagittal MR images with a slice thickness of 1 mm and an in plane pixel size of 195 microns. Twenty-one stained grindings with a slice thickness of 1 micron each were obtained from a 3 mm thick slab of the same volume investigated by MR. The stack of stained grindings was also used to simulate the influence of variations in slice thickness and in plane resolution. Results for structural parameters derived from the high resolution MR images differed considerably from those derived from the stained grindings because the MR images are heavily influenced by partial volume artifacts. This finding was supported by simulations which also revealed that even at a slice thickness of 500 microns and an in plane pixel size of 13 microns, accurate results could not be obtained when a histomorphometric type analysis was applied. Results also depended strongly on the segmentation method. However, contrary to the stained grindings, images averaged over several slices reveal the three-dimensional network character of the trabecular structure. New efforts should be undertaken to develop analysis strategies that are more adequate for in vivo high resolution images instead of using analysis techniques applied in classical histomorphometry.

Cadaver↗

PubMed2001

[Intracorneal granulomatous inflammation].

INTRODUCTION: We report a patient suffering from lattice corneal dystrophy and with a corneal granuloma 8 months after phototherapeutic keratectomy (PTK). CASE REPORT: PTK was performed in a 33-year-old man with hereditary lattice corneal dystrophy. An intracorneal tumor was found in the right eye 8 months after treatment. There was no indication of previous foreign body injury. Detailed clinical examinations yielded no evidence of the cause or nature of the tumor. For this reason an excision was performed. RESULTS: Histological examination revealed a dense inflammatory infiltration of the deeper corneal stroma with epithelioid cells, histiocytes, lymphocytes, eosinophilic leukocytes, and giant cells of the Touton type. There was no indication of a generalized granulomatous inflammation. CONCLUSION: A monosymptomatic, intracorneal, granulomatous infiltration is very rare and has not previously been described in a case of lattice corneal dystrophy. This may have been a case of xanthogranuloma or sarcoidosis. Strangely, the granuloma occurred only several months after PTK; nevertheless, a pathogenetic connection seems unlikely.

Adult↗

PubMed2001

Numerical analysis of Ca2+ depletion in the transverse tubular system of mammalian muscle.

Calcium currents were recorded in contracting and actively shortening mammalian muscle fibers. In order to characterize the influence of extracellular calcium concentration changes in the small unstirred lumina of the transverse tubular system (TTS) on the time course of the slow L-type calcium current (I(Ca)), we have combined experimental measurements of I(Ca) with quantitative numerical simulations of Ca2+ depletion. I(Ca) was recorded both in calcium-buffered and unbuffered external solutions using the two-microelectrode voltage clamp technique (2-MVC) on short murine toe muscle fibers. A simulation program based on a distributed TTS model was used to calculate the effect of ion depletion in the TTS. The experimental data obtained in a solution where ion depletion is suppressed by a high amount of a calcium buffering agent were used as input data for the simulation. The simulation output was then compared with experimental data from the same fiber obtained in unbuffered solution. Taking this approach, we could quantitatively show that the calculated Ca2+ depletion in the transverse tubular system of contracting mammalian muscle fibers significantly affects the time-dependent decline of Ca2+ currents. From our findings, we conclude that ion depletion in the tubular system may be one of the major effects for the I(Ca) decline measured in isotonic physiological solution under voltage clamp conditions.

Animals↗

PubMed2001

Rescue by birth: defective placental maturation and late fetal mortality.

OBJECTIVE: To estimate the incidence and lethality of placental maturation defect, and to determine the impact of the pattern of placental dysfunction on the risk of recurrent stillbirth or maternal disease in later life. METHODS: Questionnaire and archival analysis of fetal deaths from placental dysfunction at 32-42 weeks (1975-1995 in Zurich), classified as chronic (parenchyma loss) or acute (maturation defect of the terminal chorionic villi). Population survey of 17,415 consecutive unselected singleton placentas (1994-1998 in Berlin). RESULTS: Of the 71 stillbirths, 34 were due to parenchyma loss and 37 to maturation defect. Parenchyma loss predominated in the first pregnancy (73.5% compared with 43.2%; P <.05). The risks of recurrent stillbirth and subsequent childlessness did not differ between the two groups. Eleven percent of mothers whose placenta had maturation defect had diabetes in the index pregnancy; none of the other women in the group developed diabetes over the 5-20-year observation period. In the population survey, incidence of maturation defect was 5.7%, and was associated with fetal death in 2.3% of cases. Normal placentas were associated with fetal death in 0.033%. CONCLUSION: Placental maturation defect can be a cause of fetal hypoxia. Although the risk of stillbirth is 70-fold that of a normal placenta, few affected fetuses actually die. The risk of recurrent stillbirth is tenfold above baseline and occurs mostly after 35 weeks' gestation.

Adult↗

PubMed2001

In vivo comparison of bioactive glass particles in rabbits.

Bioglass particles of the compositions 45s5, 52s and 55s were implanted in the distal femoral epiphysis of rabbits. Animals were sacrificed at 7, 28, and 84 d postoperatively and specimens investigated using light microscopy and histomorphometry. Bone bonding occurred in a zentripetal fashion and fastest for 45s5. Bone formation was hampered at the core of the implantation bed where bone bonding showed a peak at 28d and diminished at 84d (except for 55s). This went along with a significant increase in numerous multinuclear giant cells (MNGC). Implantation model, particle size and surface-area-to-volume ratio are discussed as possible parameters determining bone regeneration.

Animals↗

PubMed2001

Quantification of morphologic and hemodynamic severity of coarctation of the aorta by magnetic resonance imaging.

OBJECTIVE: As the morpholgic severity of coarctation of the aorta is difficult to assess, especially after previous repair, the value of the technique of multiplanar reconstruction of magnetic resonance imaging data to achieve a 3-dimensional reconstruction of the aortic arch was evaluated and compared to hemodynamic measurements. METHODS AND RESULTS: We performed 30 examinations in 27 patients aged from 6 to 54 years, with a mean of 21 years, by magnetic resonance imaging using a 1.5Tesla scanner with a standard body coil. Measurements of flow across the coarctation were performed using phase shift velocity mapping, and peak velocity was calculated at the site of stenosis. Aortic cross-sectional area before, at, and beyond the stenosis was reconstructed 3-dimensionally to calculate a percentage degree of stenosis. Morphologic severity of stenosis was correlated to invasively assessed hemodynamic gradients and morphologic data from biplane angiography in 23 patients. Among the 30 examinations, 24 patients had been previously treated by either surgery, in 17 patients, or balloon dilation, while 6 had native coarctation. 3-dimensional reconstruction was possible in all and better delineated the anatomy concerning the hemodynamic relevance of stenoses even as compared with biplane angiography. The correlation between severity of narrowing assessed by diameter measurements in the biplane angiography and 2-dimensional magnetic resonance imaging was r = 0.94, and multiplanar reformation with 2-dimensional magnetic resonance imaging was r = 0.87 with a tendency of higher grading with the 3-dimensional technique (p = 0.0001). The correlation of 2-dimensional magnetic resonance imaging with invasively measured hemodynamic gradients was r = 0.67 versus r = 0.74 for the areas assessed by multiplanar reformation, indicating that the hemodynamic relevance of a morphological approach to evaluate the degree of a stenosis should better be assessed 3-dimensionally. CONCLUSIONS: The 3-dimensional reconstruction of the morphologic severity of coarctation offers additional information over conventional imaging especially in patients with kinking, complex geometry, or collaterals, in whom hemodynamic measurements can become unreliable.

Adolescent↗

PubMed2001

Conditional autoantibodies in urticaria patients: a unifying hypothesis.

Chronic urticaria may be characterized by conditional autoantibodies against the alpha-chain of the high-affinity receptor for IgE (FcepsilonRI). These autoantibodies are termed conditional as they only recognize unoccupied FcepsilonRI. The same conditional reactivity pattern has also been found in sera of atopic and normal healthy donors. Any condition resulting in accessibility of FcepsilonRI will render these autoantibodies anaphylactogenic. This finding offers a unifying hypothesis for the manifestation of different forms of urticaria. Non-immunologic triggers may thereby influence directly or indirectly the number of accessible FcepsilonRI allowing the conditional autoantibodies to induce urticaria symptoms.

Autoantibodies↗

PubMed2001

Dopamine and noradrenaline efflux in the rat prefrontal cortex after classical aversive conditioning to an auditory cue.

We used bilateral microdialysis in the medial prefrontal cortex (PFC) of awake, freely moving rats to study aversive conditioning to an auditory cue in the controlled environment of the Skinner box. The presentation of the explicit conditioned stimuli (CS), previously associated with foot shocks, caused increased dopamine (DA) and noradrenaline (NA) efflux. This conditioned response was dependent on the immediate pairing of the two stimuli; in the pseudoconditioned group that received an equal number of both stimuli, but in an unpaired fashion, no conditioned increases in efflux were observed.

Acoustic Stimulation↗

PubMed2001

Isolated fetal ascites caused by primary lymphangiectasia: a case report.

We present a case of isolated fetal ascites diagnosed by ultrasonography at 29 weeks' gestation. Cordocentesis revealed a normal karyotype and negative viral titers. Postnatally, the diagnosis of primary lymphangiectasia was made by intestinal biopsy. To our knowledge this is the first description of prenatal manifestation of primary lymphangiectasia.

Adult↗

PubMed2001

Mitochondrial single-stranded DNA-binding protein is required for mitochondrial DNA replication and development in Drosophila melanogaster.

The discovery that several inherited human diseases are caused by mtDNA depletion has led to an increased interest in the replication and maintenance of mtDNA. We have isolated a new mutant in the lopo (low power) gene from Drosophila melanogaster affecting the mitochondrial single-stranded DNA-binding protein (mtSSB), which is one of the key components in mtDNA replication and maintenance. lopo(1) mutants die late in the third instar before completion of metamorphosis because of a failure in cell proliferation. Molecular, histochemical, and physiological experiments show a drastic decrease in mtDNA content that is coupled with the loss of respiration in these mutants. However, the number and morphology of mitochondria are not greatly affected. Immunocytochemical analysis shows that mtSSB is expressed in all tissues but is highly enriched in proliferating tissues and in the developing oocyte. lopo(1) is the first mtSSB mutant in higher eukaryotes, and its analysis demonstrates the essential function of this gene in development, providing an excellent model to study mitochondrial biogenesis in animals.

Animals↗

PubMed2001

Conditional autoimmunity mediated by human natural anti-Fc(epsilon)RIalpha autoantibodies?

Natural antibodies provide an early defense mechanism against pathogens, show a frequent self-reactivity, and are present throughout life. Two questions concern the physiological control of self-reactivity and the pathogenetic link to autoimmune disease. Here we propose a concept of conditional autoimmunity involving natural antibodies against the alpha chain of the high-affinity receptor for IgE (Fc(epsilon)RIalpha ). Like other natural antibodies, anti-Fc(epsilon)RIalpha antibodies are found in sera of healthy donors. We now report the first human recombinant anti-Fc(epsilon)RIalpha autoantibodies isolated by repertoire cloning from a human tonsillar IgM library. These high-affinity antibodies recognize Fc(epsilon)RIalpha on cells and trigger histamine release from freshly isolated blood basophils. However, the latter effect requires IgE removal from the Fc(epsilon)RI. The same conditional histamine release is seen when using sera from individual normal donors and affinity-purified anti-Fc(epsilon)RIalpha antibodies isolated from multidonor therapeutic IgG preparations. We propose that such anti-Fc(epsilon)RIalpha antibodies can become pathogenic and that this is dependent on the state of occupancy of the Fc(epsilon)RIalpha by its natural ligand IgE. We suggest that an imbalance between Fc(epsilon)RIalpha occupancy and natural anti-Fc(epsilon)RIalpha antibodies may be implicated in the pathogenesis of autoimmune urticaria.

Amino Acid Sequence↗