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Biomedical subjects

A Marx

Publications and source records attributed to A Marx.

At least 163 records · Page 9Linked to original sources
PubMed1993

Dynamics of microtubules from erythrocyte marginal bands.

Microtubules can adjust their length by the mechanism of dynamic instability, that is by switching between phases of growth and shrinkage. Thus far this phenomenon has been studied with microtubules that contain several components, that is, a mixture of tubulin isoforms, with or without a mixture of microtubule-associated proteins (MAPs), which can act as regulators of dynamic instability. Here we concentrate on the influence of the tubulin component. We have studied MAP-free microtubules from the marginal band of avian erythrocytes and compared them with mammalian brain microtubules. The erythrocyte system was selected because it represents a naturally stable aggregate of microtubules; second, the tubulin is largely homogeneous, in contrast to brain tubulin. Qualitatively, erythrocyte microtubules show similar features as brain microtubules, but they were found to be much less dynamic. The critical concentration of elongation, and the rates of association and dissociation of tubulin are all lower than with brain microtubules. Catastrophes are rare, rescues frequent, and shrinkage slow. This means that dynamic instability can be controlled by the tubulin isotype, independently of MAPs. Moreover, the extent of dynamic behavior is highly dependent on buffer conditions. In particular, dynamic instability is strongly enhanced in phosphate buffer, both for erythrocyte marginal band and brain microtubules. The lower stability in phosphate buffer argues against the hypothesis that a cap of tubulin.GDP.Pi subunits stabilizes microtubules. The difference in dynamics between tubulin isotypes and between the two ends of microtubules is preserved in the different buffer systems.

Animals↗
PubMed1993

[Pathogenesis of autoimmunity in thymoma].

The analysis of thymic epithelial tumors (TET) with and without myasthenia gravis (MG) has identified both a residual organotypic differentiation of TETs and the aberrant expression of acetylcholine receptor (AChR)-epitopes in TET epithelial cells to be associated with MG. These findings have suggested an abnormal selection of helper T cells as a mechanism of paraneoplastic MG. Here we show by electronmicroscopy that epithelial cells of TETs and normal thymus exhibit the morphological features (autophagic vacuoles) thought to be necessary to process endogenous proteins for presentation by MHC class II molecules to immature T cells.

Autoimmune Diseases↗
PubMed1993

B-cells in thymic epithelial tumours. An immunohistochemical analysis of intra- and extraepithelial B-cell compartments.

A total of 26 thymomas and thymic carcinomas were studied by immunohistochemistry to determine the presence and distribution of intratumoural B-cells. Double staining experiments revealed two distinct B-cell populations in the thymic epithelial tumours. One was found within the perivascular space (PVS), which is separated from the neoplastic epithelium by a basement membrane. In all tumours the PVS contained lymphocytes with the immunophenotype of peripheral B-cells. Large numbers of B-cells with germinal centre formation were found almost exclusively in myasthenia gravis (MG)-associated tumours, mainly in cortical thymomas and well differentiated thymic carcinomas. A second population of B-cells was located in the neoplastic epithelial meshwork, mostly in areas of organoid medullary differentiation characterized by epidermoid cells or Hassall's corpuscules. This population frequently comprised large, CD23+ cells with dendritic features resembling the special type of intramedullary B-cells of the normal human thymus. In contrast, B-cells were uncommon in areas of mixed thymoma showing spindle celled medullary differentiation, and were almost completely absent from tumour areas composed of cortical type epithelium. Hence a medullary microenvironment with epidermoid cells corresponding to Hassall's corpuscules seems to be necessary for specific intrathymic B-cell homing.

Adult↗
PubMed1993

[Quality of emergency admission (resuscitation, REA) and first aid in multiple trauma].

Undue delay between hospital admission and the beginning or urgent operative procedures is considered as a major mortality risk for polytraumatized patients in any trauma center. As part of a quality control study at our institution (Kantonsspital, University of Basel), the time spent for early resuscitation and diagnostic procedures was therefore prospectively recorded in 20 patients (mean age 38 years) with a mean ISS of 26.9 (range: 13 to 43). Time spent in the resuscitation room averaged 31.4 min (range: 10 to 50 min). Conventional radiographic diagnostic procedures took 34.7 more min (range: 20 to 60 min). An additional CT scan was performed in 15 patients requiring 19.5 min per region (head/thorax/abdomen/spine). Four patients underwent angiography necessitating 28 more min (mean). Time elapsed between admission and arrival of the patient in the OR or the ICU respectively accounted for an average of 89 min (range 22 to 200 min). For comparable injury severities this interval was shorter during the day than during the night (77 and 103 min respectively). Diagnoses established during this period were both accurate and comprehensive, as detectable from the low rate of missed diagnosis (three minor fractures). Although our results match favorably with figures reported in the literature we feel that further improvements could be achieved by performing the conventional radiographic procedures simultaneously with the early resuscitation in the resuscitation room. At present time, for reasons of X-ray protection, this is not possible in our institution.

Adolescent↗
PubMed1993

[Experience with the AO universal femoral intramedullary nail for management of femur shaft fractures].

57 fractures of the femoral shaft, treated with an AO femoral interlocking nail, have been analysed in a retrospective study. 40 nails have been implanted primarily, 17 as secondary procedures following different operations. In the group of primary nailing 35/40 reached a good or very good result, 8 of them however, following secondary operations. In the group of the secondary nailing, 9/17 patients had a good or a very good result. 3 pseudarthroses persisted. The AO femoral interlocking nail therefore appears to be an adequate implant for the treatment of femoral shaft fractures, but a precise implantation technique is a prerequisite for the successful outcome.

Bone Nails↗
PubMed1993

[The AO universal femur intramedullary nail: problems and their amelioration. Retrospective quality control study of 57 femur shaft fractures].

Today intramedullary nailing is considered the treatment method of choice in fractures of the femoral diaphysis. In this retrospective quality control study 57 femoral fractures treated with the AO-Universal Femoral Nail have been reviewed. The average follow up time was 2.9 years. Intramedullary nailing was done as a primary procedure in 40 cases and in 17 cases as a secondary procedure following various initial operations. The results were evaluated according to the Stromsoe score. 27 of the 40 primary procedures went on to an uneventful healing and showed good to excellent final result. Technical errors (7), non-unions (4) and 1 deep infection required various secondary procedures. Thereafter the final number of good to excellent results amounted to 35 out of 40 patients. In the group with secondary i.m. nailing 9 out of 17 patients showed a good to excellent final result. 2 non unions persisted. In conclusion the AO-Universal Femoral Nail proved to be suited for the treatment of femoral shaft fractures for both primary and secondary procedures. In this series, however, technical imperfections led to a high rate of secondary procedures. Strict observation of the recommended operative technique is therefore mandatory.

Adolescent↗
PubMed1993

[Modification of ischemia and reperfusion damage of skeletal muscles with allopurinol: in vivo 31P MR spectroscopy of the posterior limb of the rat].

The effect of Allopurinol on energy metabolism (re-utilisation of hypoxanthine) was studied in a in vivo skeletal muscle ischemia rat model by 31-P-MR spectroscopy. Allopurinol-treatment showed no benefit to the kinetics of PCr/(Pi + PCr) and ATP/(Pi + PCr). The role of re-utilisation of hypoxanthine has to be further investigated.

Adenosine Triphosphate↗
PubMed1992

Neurofilament epitopes in thymoma and antiaxonal autoantibodies in myasthenia gravis.

Expression by neoplastic thymic epithelial cells of acetylcholine-receptor (AChR) epitopes is associated with the presence of AChR autoantibodies and the development of myasthenia gravis. We studied thymic tumours from patients with and without myasthenia gravis for the expression of neurofilament epitopes by immunohistochemistry with four monoclonal antibodies. There was very little antibody binding in control samples (healthy thymus, or thymitis) or in medullary and mixed thymomas, but neurofilament epitopes were strongly expressed in all cortical thymomas and thymic carcinomas. In addition, the frequency of serum autoantibodies against axons was significantly higher among myasthenic patients with thymic epithelial tumours than among age-matched controls (7/10 vs 3/50; p less than 0.01).

Adolescent↗
PubMed1992

Pathogenetic significance of fetal-type acetylcholine receptors on thymic myoid cells in myasthenia gravis.

To investigate the role of thymic myoid cells in the pathogenesis of myasthenia gravis (MG), mRNA of nonneoplastic thymuses from eight MG patients was analyzed by dot blot hybridization for the occurrence of acetylcholine receptor (AChR) subunit transcripts, using the five AChR-subunit cDNAs (alpha, beta, gamma, delta, and epsilon) as probes. Attention was particularly paid to the gamma- and epsilon-subunit transcripts that specify fetal- or adult-type AChR. In all eight thymuses, transcripts of the alpha-, beta-, gamma-, and delta-subunit genes were detected. Relative autoradiographic signal intensities correlated with the frequencies of thymic myoid cells as determined by immunostaining with anti-AChR monoclonal antibodies. In only one of these thymuses were transcripts of the epsilon-subunit gene detected in addition to those of the other subunit genes. Four MG-associated thymomas without myoid cells were devoid of any AChR-subunit mRNA. Our findings imply that fetal-type AChR is expressed in MG thymuses as a rule, whereas adult-type AChR is coexpressed with it only in a minority of cases. A similar pattern of cotranscription is known to occur at certain stages of muscle development, and can be found in human rhabdomyosarcomas with an intermediate stage of myogenesis. Because the serum autoantibodies of MG patients exhibit preferential reactivity with fetal AChRs, the presence of fetal AChRs in the thymus provides circumstantial evidence for an active involvement of thymic myoid cells in the autoimmune process.

Antibodies, Monoclonal↗
PubMed1992

A striational muscle antigen and myasthenia gravis-associated thymomas share an acetylcholine-receptor epitope.

The coincidence of autoantibodies against the acetylcholine receptor (AChR) and muscle striational antigens (SA) is a characteristic finding in thymoma-associated myasthenia gravis (MG), but their origins are still unresolved. Some common muscle antigens that were shown to be targets of anti-SA autoantibodies in thymoma-associated MG have also been detected in normal or neoplastic thymic epithelial cells, suggesting that the release of (eventually altered) antigens from the thymic tumors could elicit SA autoimmunity. In contrast to this model, we report here that titin, which is a recently reported target of SA autoimmunity, is not expressed in thymomas. In addition, we show that skeletal muscle type-II fibers exhibit a striational immunoreactivity with monoclonal antibody mAb155, which was previously identified to label a very immunogenic cytoplasmic epitope of the AChR and neoplastic epithelial cells of MG-associated thymomas. We conclude from these findings that titin autoimmunity in thymoma-associated MG is either due to a molecular mimicry mechanism involving tumor antigens (other than titin) or is a secondary phenomenon following release of titin from muscle. Based on the common immunoreactivity of the AChR, a striational antigen and thymoma, we suggest as the pathogenetic mechanism of thymoma-associated MGa "circulus vitiosus" in which SA autoimmunity could help maintain the AChR autoimmunity that is primarily elicited by the thymomas.

Adult↗
PubMed1992

[B-cells in thymic epithelial tumors: phenotype, distribution and relation to the intramedullary B-cell population of the normal thymus].

Immunohistochemical analysis of 26 thymomas and thymic carcinomas revealed the occurrence of two different intratumoral B-cell populations. High numbers of B-lymphocytes with formation of lymphoid follicles were found in the extra-epithelial perivascular spaces of cortical thymomas and well differentiated thymic carcinomas associated with myasthenia gravis. On the other hand, B-cells within the epithelial meshwork frequently occurred in organoid medullary islands of predominantly cortical and cortical thymomas. In their distribution and phenotype, these cells correspond to the intramedullary B-cell population of the normal thymus, reflecting a specific intratumoral B-cell homing dependent on medullary epithelial differentiation.

Antigens, CD↗
PubMed1992

[Neurofilament expression in thymic epithelial tumors and anti-axonal autoantibodies in myasthenia gravis: a model for autoimmunity by abnormal T cell selection].

Thymic epithelial tumors from myasthenia gravis (MG) patients and non-neoplastic thymuses were investigated by immunohistochemistry for the expression of neurofilament (NF) epitopes. There was little immunoreactivity confined to the medulla in non-neoplastic thymuses and a faint staining only for a 200 kD NF epitope in medullary and mixed thymomas. In contrast, cortical thymomas and well-differentiated thymic carcinomas expressed epitopes of the 68 kD and 160 kD NF. Demonstrating anti-axonal and anti-NF autoantibodies in thymoma patients we conclude that "false-positive T cell selection" is a mechanism of autoimmunity in paraneoplastic MG.

Autoantibodies↗
PubMed1992

Immunocytochemical characteristics of small cell lung carcinoma associated with the Lambert-Eaton myasthenic syndrome.

The Lambert-Eaton myasthenic syndrome (LEMS) is characterized by the presence of IgG antibodies to motor nerve terminals, and associates with small cell lung carcinoma in more than 60% of cases. We have carried out a comparative immunocytochemical study on small cell lung carcinoma (SCLC) in five LEMS cases and six non-LEMS cases, using antibodies to tumor markers, MHC Class I and II, macrophages and lymphocytes. The authors found a reduced expression of the 200Kd neurofilament antigen and of MHC Class I antigens in the LEMS cases as well as a greater infiltration of activated macrophages. It is suggested that these findings are consistent with the view that SCLC antigenic determinants trigger the autoantibody response in SCLC-LEMS.

Antigens, Neoplasm↗
PubMed1992

A shared epitope in the acetylcholine receptor-alpha subunit and fast troponin I of skeletal muscle. Is it important for myasthenia gravis?

The monoclonal antibody MAb 155, isolated by Tzartos et al, recognizes the alpha subunit of acetylcholine receptor (AChR) and stains type II skeletal muscle fibers but does not decorate heart muscle. In addition it reacts with most myasthenia gravis-associated thymomas. The authors show by immunoblotting techniques that the myofibrillar antigen is a 23 kd protein and by partial protein sequence data identify it as fast troponin I. Fast troponin I from various species contains the sequence EEKSGMEGRK close to the C-terminal end at positions 165 to 174. The first lysine (K) is crucial for MAb 155 reactivity since its substitution by methionine and leucine in slow troponin I and cardiac troponin I, respectively, abolishes MAb 155 reactivity. The epitope identified on troponin I is homologous in sequence with the MAb 155 epitope on the AChR alpha subunit established by direct peptide binding as KSAIEGIK (positions 373-380). The authors consider whether fortuitously shared epitopes can be responsible for the high level of autoantibodies to AChR and to muscle proteins seen in many MG patients.

Amino Acid Sequence↗