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Biomedical subjects

M Vogel

Publications and source records attributed to M Vogel.

At least 451 records · Page 25Linked to original sources
PubMedDate not supplied

Relation between 2- and 3-dimensional architecture of trabecular bone in the human spine.

By means of a new preparation technique which allows the combined 2- and 3-dimensional analysis of trabecular bone we analyzed the vertebral bodies of 22 autopsy cases. None of these cases had any skeletal disease. With increasing age bone volume was decreased in all vertebral bodies (2nd cervical to 5th lumbar body) but this decrease was more pronounced in the lower vertebrae. In the upper cervical spine there was nearly no age-related loss of trabecular bone volume. 3-D analysis demonstrated that the loss of bone tissue is due to a loss of trabecular plates which are transformed to trabecular rods by perforations. The number of plates and rods could be measured directly. In the 2nd lumbar vertebra at the age of 20 years the density of plates was 0.61 mm, the density of rods was 0.2/mm. At the age of 80 years the density of plates was 0.2/mm. The density of rods remained constant at all ages. Perforations could be seen directly. They were located mainly in trabecular plates. At higher ages they occurred in rods either. The number of vertically oriented trabeculae was about twice the number of horizontal ones. The rate of age-dependent reduction of trabeculae was the same in horizontal and vertical trabeculae. It was possible to do real 3-dimensional measurements of the diameter of trabecular rods. These values were compared to the calculated values of trabecular plates. In mean trabecular plates are thinner than rods. It could be demonstrated that microcallus formation is a common feature in the human spine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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Expression of BCL-2 in liver grafts after adenoviral transfer improves survival following prolonged ischemia and reperfusion in rat liver transplantation.

UNLABELLED: Apoptosis represents a crucial mechanism of ischemia-reperfusion injury after liver transplantation. Bcl-2 may inhibit apoptosis. This study investigates the effect on ischemia/reperfusion injury and survival after rat liver transplantation of adenoviral bcl-2 transfer into donor livers. METHODS: A nonreplicative adenovirus, expressing bcl-2 under control of a tetracyclin-inducible promoter (adv TetOn bcl-2) was used to treat male Lewis rats in combination with a second adenovirus transferring the TetOn repressor protein under control of a cytomegalovirus promoter (advCMVRep). Virus induction was achieved by addition of doxycyclin to the drinking water. Controls were pretreated with a control adenovirus (advCMV GFP) or with doxycycline. Liver transplantations were performed after 16-hour graft storage. Bcl-2 expression was evaluated by Western blot and immunohistology. Survival was monitored for 7 days, and tissue specimens were collected at 24 hours and 7 days post reperfusion. RESULTS: After pretreatment with advTetOn bcl-2/adv CMVRep, intrahepatic bcl-2 expression was evident at 24 hours and 7 days but was absent among controls. Bcl-2 expression was detected in hepatocytes and, to a high degree, in sinusoidal lining cells. TUNEL-positive sinusoidal lining cells were strikingly reduced after bcl-2 transfer (0.1 +/- 0.3 cells/hpf, mean +/- SD) compared to control virus (4.8 +/- 2.3) or doxycyclin-treated grafts (1.3 +/- 0.2); P < .05. After bcl-2 treatment, survival after transplantation was 100%, whereas it was 50% in both control groups (P = .035). CONCLUSION: The study shows the feasibility of transient, doxycyclin-controlled adenoviral gene transfer in a transplantation model. Bcl-2 expression increased survival after ischemia/reperfusion in rat liver transplantation, potentially through protection of sinusoidal lining cells.

Adenoviridae↗
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[Femur-fibula-ulna (FFU) complex in the 33rd week of gestation: ultrasonography, radiology, pathology and differential diagnosis. Case report].

We present a case of a 27 year old I. gravida, I. para. Despite of regular ultrasonographic examination the diagnosis of skeletal malformation at the fetus was not before 33. weeks of gestation. It was the rare type of a bothside femur-fibula-ulna (FFU) complex. The FFU-complex is a no lethal malformation with typical unilateral combination from defects of femur and fibula, with contralateral defect of ulna. Dependent to involvement of malformated limbs the FFU-complex is classifiable in four groups. Only in 10 % all limbs are affected. Our case (type IV) showed a peromelia of both upper limbs with stumps of humeri, bothside aplasia of fibula and missing from 4. and 5. toes. There fetus were without nonlimb congenital abnormalities. The etiology of FFU-complex is unknown, the occurrence sporadic. There are never found genetic abnormalities. Familial recurrence is not described. There is no maternal or paternal age effect on FFU-complex. The differential diagnosis must include malformations with reduction anomalies of extremities, like thalidomide syndrome, splenogonadal fusion with limb malformations, Roberts syndrome, oroacral complex or acheiropodia. Mark off are amniotic band too.

Abnormalities, Multiple↗
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[X-ray findings in primary bilateral pulmonary hypoplasia-- correlation with pathologico-anatomical findings].

Comparative radiologic/pathologic study of 45 newborns with primary and secondary pulmonary hypoplasia. 43 cases were proven at autopsy. From 9 cases with primary pulmonary hypoplasia, 7 could be identified by 3 independent observers. The roentgen criteria of primary pulmonary hypoplasia are evaluated and should serve in the future to clinically diagnose this condition.

Birth Weight↗
PubMedDate not supplied

[Morphologic study of iliac crest spongiosa in patients with osteoporosis treated according to the ADFR (activation, depression of resorption, formation, repeat the cycle) with parathyroid hormone and diphosphonates (Hannover PTH I study)].

Treatment of osteoporosis with a complete reconstruction of the normal three dimensional architecture of trabecular bone is an unsolved problem. In addition to the well established fluoride therapy new concepts in the treatment of osteoporosis were developed. There is growing interest in the so called ADFR concept (activation, depression of resorption, formation, repeat the cycle) as a physiological stimulation of osteoblastic bone formation. The histological results following ADFR treatment in 8 patients are reported. After 12 months of treatment with parathyroid hormone [1-38)hPTH) (stimulation of the basic metabolic units) and the diphosphonate EHDP (depression of osteoclastic resorption) no change of remodelling processes at the trabecular bone surface could be observed. The results demonstrate many doubts in the importance of the ADFR concept for the treatment of osteoporosis.

Adult↗
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Mimotope and anti-idiotypic vaccines to induce an anti-IgE response.

We have defined epitopes on human IgE by screening different phage display random peptide libraries with a monoclonal anti-IgE antibody termed BSW17. The selected mimotopes and epitopes within the Cepsilon3 and Cepsilon4 region of IgE induced antibodies that were nonanaphylactogenic and had biological activity similar to BSW17. The chemically synthesized and KLH-coupled IgE epitopes or mimotopes were used to induce an anti-IgE response in rhesus monkeys. The immunized rhesus monkeys were subsequently protected in a PCA test when sensitized with human IgE and triggered with the corresponding allergen. Furthermore, using the same monoclonal anti-IgE antibody, we also generated an anti-idiotypic antibody that showed sequence homology with the IgE epitope in the Cepsilon3 domain. This anti-idiotypic antibody as well as the mimotopes were then used in a mouse model to induce orally an anti-IgE immune response. For this purpose mice were fed by intragastric gavages with bacteriophages displaying the small IgE-homologous structures. Orally immunized mice produced serum anti-IgE antibodies that were inhibited by BSW17 suggesting that it may be possible to induce a systemic anti-IgE response orally.

Animals↗
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Allergic manifestations as the results of a conditional autoimmune response.

By means of repertoire cloning we have isolated human anti-IgE antibodies as well as human anti-FcepsilonRI antibodies. Whether the naturally occurring anti-IgE autoantibodies play a pathophysiological role may be disputed, but the beneficial role of recombinant anti-IgE antibodies as a therapeutic agent has been shown. On the other hand, the natural antibodies isolated from an antibody library of a nonallergic individual against the FcepsilonRI alpha-chain are anaphylactogenic, if FcepsilonRI was not occupied. Thus, anti-FcepsilonRI autoantibodies may be part of a conditional autoimmune reaction, leading to urticaria if local IgE is consumed, e.g. after an immediate reaction. Thus, anti-FcepsilonRI antibodies may represent an amplification arm of the late reaction. The normal occurrence of anti-IgE and anti-IgE receptor autoantibodies may suggest that it might also be feasible to induce such autoantibodies by vaccination. In a monkey model using a mimotope of human IgE it was possible to induce a beneficial anti- IgE autoimmune response. The actual epitope of the IgE molecule was then also molecularly reconstructed by generating recombinant anti-idiotypic antibodies. These antibodies also induced effectively an anti-IgE response in monkeys, suggesting that not only mimotopes but also anti-idiotypic antibodies may be used to generate an autoimmune response. Both of our projects suggest that active immunization may be a new form of immunomodulation for the treatment of allergic disease.

Animals↗
PubMedDate not supplied

Fetal autopsy: the most important contribution of pathology in a center for perinatal medicine.

OBJECTIVE: The aim of the current paper is to analyze the significant changes in fetal autopsy made by pathologists in a center for perinatal medicine in response to the recent rapid developments in prenatal medicine. METHODS: We use our technical equipment (interdisciplinary databank, Intranet, fine instruments, imaging techniques) for prenatal diagnostics and fetal pathology in the Center for Perinatal Medicine at the Charité University Medical Center in Berlin, Germany. RESULTS: Our technical setup has made it possible for us to plan autopsies in such a way that rare malformations in special cases can be documented in sectional planes corresponding to the prenatal sonographic images. Before the postmortem examination the pathologist receives all the prenatal findings obtained for the fetus and is able to examine the prenatal images on a monitor. The final diagnosis in the postmortem report includes the results of modern molecular pathology, clinical-genetic examination of the fetus, cytogenetic and molecular-cytogenetic findings and postmortem x-rays. CONCLUSIONS: To be able to incorporate these various results into a final report in routine work the use of an interdisciplinary database is essential. Such a database also ensures faster and more productive interdisciplinary communication in a center of perinatal medicine.

Adult↗
PubMedDate not supplied

Cloning of human anti-IgE autoantibodies and their role in the regulation of IgE synthesis.

In vivo experiments using anti-IgE antibodies have clearly documented that they inhibit IgE production. In vitro experiments showed that not only IgE synthesis but also the effector phase of the allergic response may be influenced, because anti-IgE antibodies can prevent basophil sensitization with IgE or even remove IgE-receptor-bound IgE molecules. However, the question remains whether naturally occurring anti-IgE autoantibodies possess similar biological activity. To generate such antibodies for the necessary in vitro studies, we have cloned human Ig variable genes and selected anti-IgE antibodies using phage display libraries. Most of the human anti-IgE antibodies were anti-idiotypes, but anti-isotypes were also isolated.

Animals↗
PubMedDate not supplied

Can active immunization redirect an anti-IgE immune response?

We used as a template a mouse monoclonal antibody against IgE to isolate peptides from random peptide phage display libraries. Thereby, two types of peptides were isolated that corresponded to two different epitopes on the human IgE molecule. These peptides, also called mimotopes, seem to be a suitable tool in conjunction with carriers to induce an autoimmune response with a beneficial effect in humans, because the originally used template antibody is capable of neutralizing IgE, is nonanaphylactogenic, and inhibits IgE synthesis. The vaccination approach is further supported by the fact that we were capable of isolating anti-idiotypic antibodies from antibody phage display libraries against the template antibody. These anti-idiotypic antibodies were inhibited by both of the isolated IgE mimotopes. Thus, active vaccination with defined IgE mimotopes may represent a follow-up drug for the presently used anti-IgE antibodies.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Pulmonary vascular changes in bronchopulmonary dysplasia: a clinicopathologic correlation in short- and long-term survivors.

Pulmonary vascular findings in infants with bronchopulmonary dysplasia (BPD) are inconsistent. We compared five infants who fulfilled histologic criteria of BPD (group I; survival up to 1 month) with five controls who died of severe neonatal infection without having been ventilated. Nine infants who survived up to 7 months also fulfilled clinical criteria of BPD (group II). These were compared with three term infants who died of nonpulmonary causes. Lung slices were examined qualitatively and by quantitative histomorphometry. The influence of oxygen concentration and positive pressure ventilation on arterial density was studied. Arterial concentration in group I [2.43 (0.63) vessels/mm2, mean +/- SD] increased significantly compared with the controls [1.64 (0.49) vessels/mm2, mean +/- SD]. Most infants in group II who had cor pulmonale at autopsy had decreased arterial density when compared with normal term infants. Postmortem pulmonary angiography was also consistent with this finding. Total oxygen dose was the factor with the greatest influence on reduced arterial density. Relative wall thickness of vessels less than 75 microns in diameter was not significantly reduced in group I (p greater than .05). Infants from group II with cor pulmonale had an increased wall thickness compared with their controls. The proportion of fully muscularized arteries less than 100 microns in diameter was reduced in group I but increased in group II. We conclude that the reduction of cross-sectional perfusion area and abnormal muscularization of more peripheral vessels are important in the pathogenesis of pulmonary hypertension in infants with BPD.

Angiography↗
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Diagnostic aspects of hydatidiform mole with persistence of polymorphic trophoblastic hyperplasia.

UNLABELLED: The persistence of polymorphic trophoblastic hyperplasia in a hydatidiform mole is an extremely rare condition. Its early recognition is essential since such cases can transform into invasive types of tumors. MATERIALS AND METHODS: The biopsies were routinely processed in paraffin, embedded and stained with HE. Immunohistochemical staining reactions were performed with the following monoclonal antibodies for hydatidiform mole: beta-hCG, HPL, MIB1, CK18, HER-2/neu, p53 and carbohydrate antibodies, Thomsen-Friedenreich antigen, Glycodelin A, Mucl and Mucl-cor. RESULTS: Large villi and hydatidiform villi with wide-ranged syncyctio- and cytotrophoblasts were seen. Intervillous proliferating trophoblasts showed cell- and nuclear polymorphy with a wall invasion of the myometrium. The immunohistochemistry exhibited strong positivity for the membrane-associated HER-2/neu and for the beta-hCG in syncytiotrophoblast and in multinuclear giant cells of intervillus trophoblasts. A weakly positive reaction with hPL was seen in most cells of the trophoblasts. The rest of the immunohistochemistry served as a diagnostic support. CONCLUSION: A complete hydatidiform mole with hyperplasia and proliferation of polymorphic trophoblasts presents a high risk of developing a persistent (eventually metastatic) trophoblastic disorder and, in up to 15% of the cases, an invasive mole. In 2.5% of the cases it can transform into a choriocarcinoma.

Adult↗
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[Umbilical cord complications as a cause of intrauterine fetal death].

In a group of 71 intrauterine fetal deaths in monozygotic pregnancies, umbilical cord complications were the cause of death in 11 cases (16%). These included 5 umbilical knots, 3 loops, and one case each of torsion with constriction, umbilical prolapse and velamentous insertion (with rupture of the umbilical vessels). The relative importance of these umbilical complications is pointed out and discussed in regard to clinical and pathological factors.

Adult↗
PubMedDate not supplied

Expression of inhibin/activin subunits, sialyl-lewis A (CA 19-9, sLea) and sialyl-Lewis X (sLex) carbohydrate antigens in a hydatidiform mole with persistent polymorphic trophoblastic hyperplasia.

UNLABELLED: The persistence of polymorphic trophoblastic hyperplasia in a hydatidiform mole is an extremely rare condition. Its early diagnosis is essential since such cases can transform into invasive tumours. MATERIALS AND METHODS: The paraffin-embedded biopsies were routinely stained with HE. Immunohistochemical staining reactions were performed with monoclonal antibodies against inhibin-alpha, inhibin-betaA and inhibin-betaB subunits. Additional immunohistochemical reaction was performed with, Sialyl-Lewis A and Sialyl-Lewis X and glycodelin. RESULTS: Large villi and hydatidiform villi with ranging syncyctio- and cytotrophoblasts were seen. Intervillous proliferating trophoblasts showed cell- and nuclear polymorphy with invasion of the myometrium wall. The immunohistochemistry exhibited strong positivity for inhibin-alpha, inhibin-betaA and inhibin-betaB subunits in trophoblastic tissue, while the decidua was negative. Sialyl-Lewis A and Sialyl-Lewis X showed no or minimal focal immunohistochemical reaction. CONCLUSION: A complete hydatidiform mole with hyperplasia and proliferation presents a high risk of developing a persistent (eventually metastatic) trophoblastic disorder and, in up to 15% of the cases, an invasive mole. In 2.5% of the cases it can transform into a choriocarcinoma. Since the inhibin/activin subunits reacted positively with trophoblastic tissue, they might be a useful diagnostic marker for hydatidiform mole with persistence of polymorphic trophoblastic hyperplasia.

Activins↗
PubMedDate not supplied

Atrioventricular septal defect complicated by right ventricular outflow tract obstruction. Analysis of risk factors regarding surgical repair.

Eighteen patients with complete atrioventricular septal defect (AVSD) were found to have either associated tetralogy (n = 15) or pulmonary atresia (n = 3). Their pre- and post-operative course was reviewed focusing attention on risk factors for complete repair. These included right ventricular (RV) hypoplasia, identified by cineangiographic volume determinations in two cases (11%) and inadequate pulmonary artery size in one patient. In the 2 cases with RV hypoplasia and in one case, in whom all chordae of the AV valve were connected to a single right ventricular papillary muscle (AVSD type Rastelli B), complete repair was not feasible. In addition, angiography revealed coronary artery variations in 5/18 (28%), which did not preclude surgical repair. Palliative surgery was undertaken in 10 patients and complete repair carried out in five. Six of 18 patients died, 2 among those after complete repair.

Cardiac Volume↗