Biomedical subjects

M Vogel

Publications and source records attributed to M Vogel.

At least 73 records · Page 4Linked to original sources

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↗

PubMed2001

Abnormalities of right ventricular long axis function after atrial repair of transposition of the great arteries.

BACKGROUND: While volume derived global indices of right ventricle (RV) function are frequently abnormal after the Mustard procedure, the mechanism for these abnormalities is poorly understood. RV muscle fibres are predominantly arranged longitudinally and thus indices derived in the long axis may better describe RV function. METHODS: 20 survivors of the Mustard operation were studied (age 7.8-37.3 years, median 14.2 years). Long axis recordings from the apical four chamber view were obtained with the M mode cursor positioned through the lateral angle of the tricuspid valve annulus. M mode traces were recorded on paper and later digitised to derive total atrioventricular ring excursion, peak lengthening rate, and peak shortening rate. These data were averaged and compared with control data for the normal RV and left ventricle (LV). RESULTS: RV total atrioventricular ring excursion was lower than that for the RV (p < 0.0001) or LV (p < 0.005) of controls. Peak lengthening rate was lower than the normal RV (p < 0.0001) and LV (p < 0.0001) rates. Furthermore, peak shortening rate was less than that of normal RV (p < 0.0001) and normal LV (p < 0.005) controls. CONCLUSION: Systemic RV long axis function is notably reduced compared with that of either the normal subpulmonary RV or the systemic LV. This presumably reflects the response of the predominantly longitudinally arranged myocardial fibres to increased afterload. However, such measurements may provide a more sensitive marker for progressive changes in global function during long term follow up.

Adolescent↗

PubMed2001

In situ reverse transcriptase-nested polymerase chain reaction to identify intracellular nucleic acids without the necessity of DNAse pretreatment and hybridisation.

In the present study a protocol of in situ reverse transcriptase-nested polymerase chain reaction (in situ RT-nested PCR) was examined based on the following modifications. (i) To exclude false positive signals caused by "DNA repair mechanisms" and "endogenous priming", a two-step PCR was applied after reverse transcription. The first step was performed in the presence of extrinsic primers and unlabeled nucleotides with a maximum of PCR cycles possible without destroying the cell morphology. The second step consisted of only one annealing/elongation reaction, the target sequence marked by addition of digoxigenin-labeled nucleotides and intrinsic primers. (ii) In order to prevent amplifications of genomic DNA nested primer pairs were applied crossing intron sequences. (iii) To minimize the diffusion of PCR products in cells, the extrinsic primers were extended with complementary 5(prime, variant)-tails. This approach results in the generation of high molecular weight concatamers during PCR cycles. By applying this protocol, immunostainings specific for phospholipase A2 of type IIA mRNA were exclusively detectable in the cytoplasm of HepG2 hepatoma cells, which were used as a model system, whereas the nuclei were unstained. Multiple control experiments yielded completely negative results. These data suggest that the in situ RT-nested PCR, which in comparison to the method of in situ RT-PCR-in situ-hybridisation is simpler and less time-consuming, can be used as an alternative approach to identify intracellular nucleic acids.

Blotting, Southern↗

PubMed2001

Producing a multimedia CD-ROM.

The multimedia capabilities of modern computers promise a rich contribution to medical education, integrating video, animation and graphics as a single courseware package. Using the new generation of design tools, computer-assisted learning material can be successfully created in-house.

CD-ROM↗

PubMed2001

Isolation and functional characterization of recombinant GAD65 autoantibodies derived by IgG repertoire cloning from patients with type 1 diabetes.

The generation of human monoclonal autoantibodies is critical for understanding humoral immune responses in autoimmunity. In this study, we isolated the first human recombinant antibodies to glutamate decarboxylase (rGAD65ab) by IgG repertoire cloning, phage display of Fab fragments, and biopanning from two patients at onset of type 1 diabetes. We demonstrate that natural Ig heavy- and light-chain pairings of autoantibodies can be isolated by the recombinant approach and have a major selection advantage over other rGAD65ab. Among eight rGAD65ab, three (rGAD65ab A-C) displayed all functional and structural properties of known disease-related GAD65ab, including reactivity in the enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), islet cell antibody (ICA) test, and variable gene usage. Dominant epitope recognition was directed to the previously defined epitope EP-1 in the middle of GAD65, corroborating its immunodominance in the molecule. New features, such as assay-dependent GAD65 reactivity and new epitope recognition, were observed in two rGAD65ab (D and E). These antibodies were positive in the GAD65 ELISA and ICA test but not in the GAD65 RIA, providing the first examples for ICA with incongruent results in solid-phase and fluid-phase assays. In conclusion, phage display-derived antibodies reflected well the natural autoantibody response in type 1 diabetes and may allow further characterization of assay-dependent features of GAD65ab and the recognition of epitopes in solid- but not fluid-phase assays.

Adult↗

PubMed2001

Cephaibols, new peptaibol antibiotics with anthelmintic properties from Acremonium tubakii DSM 12774.

Two groups of new peptaibol-type antibiotics termed cephaibols have been isolated from the fungus Acremonium tubakii, DSM 12774. These 16- or 17-unit straight-chain peptides, whose structures were characterized by amino acid analyses, 2-D NMR experiments, and by mass spectrometric sequencing, have a high content of the unusual amino acids aminoisobutyric acid and isovaline. The principal constituent of the novel peptaibol mixture is cephaibol A, which is formed in abundance in cultures of the wild strain. The striking biological property of cephaibol A is its pronounced anthelmintic action and activity against ectoparasites.

Acremonium↗

PubMed2001

Memnopeptide A, a novel terpene peptide from Memnoniella with an activating effect on SERCA2.

The terpene peptide memnopeptide A (1), C76H108N16O18S, MW 1564, was isolated from a culture of the fungus Memnoniella echinata FH 2272 on casein peptone. The structure of the novel compound was elucidated with the aid of 2D NMR experiments and from amino acid analysis and mass spectrometric sequencing of the peptide. The compound consists of a known phenylspirodrimane subunit linked to the decapeptide Met-His-Gln-Pro-His-Gln-Pro-Leu-Pro-Pro. This proline-rich peptide is a subsequence of beta-casein. From the observed absence in the literature of any other highly significant sequence homologues, memnopeptide A can be assumed to arise from metabolic products of the fungus with direct incorporation of constituents of the nutrient medium. The formation of memnopeptide A suggests this may be a mechanism for storage of amines by the fungus. Memnopeptide A has weak antibacterial activity against gram-positive bacteria and effects half-maximal activation of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2) at a concentration of 12.5 microM.

Antiporters↗

PubMed2001

[Role of Herpes simplex virus in the immune stromal keratitis].

BACKGROUND: Herpes simplex virus (HSV) infection of the cornea is a leading cause of blindness in occidental countries and a common recurrent manifestation of it is the immune stromal keratitis (ISK). However, it is not known whether active viral replication occurs during the acute phase of the disease, because isolation of the virus by conventional culture techniques has not been accomplished. AIM: To establish the presence of HSV in patients with ISK. MATERIAL AND METHODS: Fourteen corneal swabbing samples, from active diseased eyes of patients with clinical diagnosis of ISK, were submitted to Herpchek and PCR for the identification of HSV antigens and genome. RESULTS: All ISK samples were negative by both techniques. CONCLUSIONS: It was not possible to identify HSV antigens nor their genome by the methodology used. It is likely that, they can't be detected in corneal superficial layers or probably there is no viral replication at this stage of the disease, so antiviral therapy should be reconsidered.

Acute Disease↗

PubMed2001

Natural anti-FcepsilonRIalpha autoantibodies isolated from healthy donors and chronic idiopathic urticaria patients reveal a restricted repertoire and autoreactivity on human basophils.

The role of autoantibodies against the alpha-subunit of the human high-affinity IgE receptor (FcepsilonRIalpha) in the pathogenesis of chronic idiopathic urticaria (CIU) is controversial. We have shown that these antibodies are widespread, apparently non-pathogenic and belong to the natural antibody repertoire. To clarify this controversy, we constructed antibody libraries from both healthy donors and CIU patients with active disease. Here we describe the first three high affinity IgM anti-FcepsilonRIalphaautoantibodies isolated from normal and urticaria libraries. Sequence analysis revealed germline VH in both cases paired with a slightly mutated VL, thus supporting their classification as natural antibodies. Strikingly, one major IgM clone was present in both CIU patients and normal donors. The anti-FcepsilonRIalpha autoantibodies recognize FcepsilonRIalpha on cells, but are non-anaphylactogenic on blood basophils, except when IgE is removed from the receptor. Based on their functional activities we propose a concept of "conditional autoimmunity" where natural anti-FcepsilonRIalphaautoantibodies can become pathogenic dependent on the state of occupancy of the FcepsilonRIalpha by its natural ligand IgE.

Animals↗

PubMed2000

Characterization of a chemical artifact in the liquid chromatographic determination of 3-butyn-2-one using the 2,4-dinitrophenylhydrazine method.

This study reports the identification of a chemical artifact occurring in the liquid chromatographic analysis of 3-butyn-2-one by means of the 2,4-dinitrophenylhydrazine (DNPH) method. Besides the expected derivatization reaction to the corresponding butynone DNPhydrazone, a rearrangement was observed, thus leading to the formation of 3-methyl-1-(2',4'-dinitrophenyl)pyrazol (DNPP). Although the rearrangement product and the hydrazone can easily be separated by means of liquid chromatography, problems arise from coelution of the pyrazol with the formaldehyde DNPhydrazone. Identification of the artifact by means of UV-Vis spectroscopy using dual wavelength or diode array detection is discussed.

Artifacts↗

PubMed2000

Molecular basis for nonanaphylactogenicity of a monoclonal anti-IgE antibody.

IgE Abs mediate allergic responses by binding to specific high affinity receptors (FcepsilonRI) on mast cells and basophils. Therefore, the IgE/FcepsilonRI interaction is a target for clinical intervention in allergic disease. An anti-IgE mAb, termed BSW17, is nonanaphylactogenic, although recognizing IgE bound to FcepsilonRI, and interferes with binding of IgE to FcepsilonRI. Thus, BSW17 represents a candidate Ab for treatment of IgE-mediated disorders. By panning BSW17 against random peptide libraries displayed on phages, we defined mimotopes that mimic the conformational epitope recognized on human IgE. Two types of mimotopes, one within the Cepsilon3 and one within the Cepsilon4 domain, were identified, indicating that this mAb may recognize either a large conformational epitope or eventually two distinct epitopes on IgE. On the basis of alignments of the two mimotopes with the human IgE sequence, we postulate that binding of BSW17 to the Cepsilon3 region predominantly blocks binding of IgE to FcepsilonRI, leading to neutralization of IgE. Moreover, binding of BSW17 to the Cepsilon4 region may explain how BSW17 recognizes FcepsilonRI-bound IgE, and binding to this region may also interfere with degranulation of IgE sensitized cells (basophils and mast cells). As a practical application of these findings, mimotope peptides coupled to a carrier protein may be used for the development of a peptide-based anti-allergy vaccine by induction of anti-IgE Abs similar to the current approach of using humanized nonanaphylactogenic anti-IgE Abs as a passive vaccine.

Amino Acid Sequence↗