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Biomedical subjects

A Marx

Publications and source records attributed to A Marx.

At least 145 records · Page 8Linked to original sources

[Ischemic preconditioning improves postischemic function, but not energy metabolism of skeletal muscles].

Ischemic preconditioning (IP) refers to a phenomenon whereby short periods of ischemia reduce tissue damage after a subsequent sustained ischemia. The effect of IP before tourniquet ischemia of the extremities has not yet been evaluated. We developed a rat model of skeletal muscle ischemia and measured the effect of IP on postischemic function and high-energy phosphate levels. IP consisted in three cycles of 10 min ischemia and 10 min reperfusion each. IP improved significantly skeletal muscle function after 3 hours of ischemia and 2 hours of reperfusion. High-energy phosphate levels, however, remained unchanged. This study is the first that shows a protective effect of IP in skeletal muscles. These results furthermore suggest that the protection of energy metabolism is not a mechanism of IP in this model. IP could be easily performed before surgery of the extremities under tourniquet ischemia. The protective effect on postischemic skeletal muscle has therefore to be further investigated.

Animals↗

Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure.

We have studied the conformation of tau protein and Alzheimer paired helical filaments (PHF) by several spectroscopic, scattering, and imaging methods revealing the overall shape and the conformation of the polypeptide backbone. Tau protein behaves in solution as if it were denatured; no evidence for compact folding was detected. The protein is highly extended, there is no defined radius of gyration, and the scattering is best described by that of a random ("Gaussian") polymer. CD and Fourier transform infrared spectroscopy show only a minimal content of ordered secondary structure (alpha-helix or beta-sheet). Similarly, PHFs from Alzheimer brain tissue show no detectable secondary structure by x-ray diffraction or spectroscopy. It is thus unlikely that the aggregation of tau into Alzheimer PHFs is based on interactions between strands of beta-sheets (a model currently favored for other disease-related polymers such as beta-amyloid fibers of Alzheimer's disease).

Alzheimer Disease↗

A model of microtubule oscillations.

Simulations of microtubule oscillations have been obtained by a kinetic model including nucleation of microtubules, elongation by addition of GTP-loaded tubulin dimers, disassembly into oligomers, and dissolution of oligomers followed by nucleotide exchange at the free dimers. Dynamic instability is described by the on and off rates for dimer association in the growth phase, the rate of rapid shortening, and the transition rates for catastrophe and rescue. The latter are assumed to be completely determined by the current state of the system ("short cap hypothesis"). Microtubule oscillations and normal polymerizations measured by time-resolved X-ray scattering were used to test the model. The model is able to produce oscillations without further assumptions. However, in order to obtain good fits to the experimental data one requires an additional mechanism which prevents rapid desynchronization of the microtubules. One of several possible mechanisms that will be discussed is the destabilization of microtubules by the products of disassembly.

Animals↗

Thyroid cancer in Belarus post-Chernobyl: improved detection or increased incidence?

There is debate on whether the reported increase in the number of cases of childhood thyroid cancer in Belarus is real and attributable to radiation released following the Chernobyl nuclear accident, or rather an artefact due to incorrect histological diagnosis, more complete case reporting and mass screening of children after the accident. We have scrutinised the histological slides of 120 (75%) of the 160 cases reported among children aged up to 15 years to the Belarus tumour registry from 1986 to 1992 and examined time trends and geographical patterns in incidence and tumour characteristics. Incidence based on reported cases increased from 0.041 per 100,000 in 1986 to 2.548 in 1992. Carcinoma was confirmed in 94% of reviewed tumours. Except for one medullary carcinoma all histologies were of the papillary type. Most of the tumours had spread beyond the organ capsule and measured over 10 mm in diameter. There was a weak and statistically non-significant trend (p = 0.19) towards smaller tumours in the later years. The proportion of cases with lymphnode or distant metastasis remained unchanged. Incidence based on histologically confirmed cases was highest adjacent and to the west and north of Chernobyl, matching best estimates of iodine-131 contamination. Our data thus strongly suggest that the observed increase is real but more data are needed in order to assess the impact of mass screening and to clarify the possible association with radiation released at Chernobyl in 1986.

Adolescent↗

Drug-related mortality in Switzerland from 1987 to 1989 in comparison to other countries.

This article relates to two studies. In the first one all registered drug-related deaths (n = 649) in Switzerland from 1987 to 1989 were analyzed. In Study II a complete regional sample (n = 154) was further investigated. Data linkage to death certificates permitted tabulations according to place of residence and year of death, and the investigation of the migration of addicts. Drug-related mortality rate in urban areas was distinctly higher. Use of morphine/heroin was found in 80%. Consumption of cannabis started at age 11, of IV-applicated drugs at 13 years. Further results pertain to home situation, education, profession, cause, and circumstances of death.

Adolescent↗

[Thymus-like expression and molecules accessory to division and of thymocyte-stroma interactions in thymomas: a prerequisite for the establishment of an abnormal T-cell repertoire?].

Costimulatory stromal receptors were identified in thymuses and myasthenia gravis (MG)-associated thymic epithelial tumors (TETs) by immunohistochemistry. ICAM-1 occurred in areas with medullary or cortical differentiation of TETs and thymuses. B7 and LFA-3, absent in the normal cortex, were hyperexpressed in cortical type TETs. VCAM-1, confined to endothelium and dendritic cells in cortex and medulla, was focally expressed by epithelial cells of a medullary thymoma. We suggest that aberrantly expressed costimulatory molecules may contribute to the pathogenesis of paraneoplastic MG by an intratumorous activation of mature T cells.

Antigens, CD↗

Cloning of a cDNA coding for the acetylcholine receptor alpha-subunit from a thymoma associated with myasthenia [correction of myastenia] gravis.

To investigate the role of the acetylcholine receptor (AchR) in the pathogenesis of paraneoplastic Myasthenia gravis (MG), we screened a cDNA library of a MG-associated thymoma with a DNA oligonucleotide coding for aa 371-378, i.e. for part of the very immunogenic cytoplasmatic epitope (VICE-alpha, aa 373-380) of the human AChR alpha-subunit. We isolated two cDNA clones. Analysis of these clones has identified an open reading frame of 1371 bp, coding for the AChR alpha-subunit. No point mutation, insertion or deletion could be detected. Since the thymoma did not contain thymic myoid cells, which normally express AChR, the origin of the AChR transcripts must be the tumor cells itself. These findings confirm former results, where AChR alpha-subunit sequences from MG-thymomas were amplified by PCR.

Base Sequence↗

Distribution of molecules mediating thymocyte-stroma-interactions in human thymus, thymitis and thymic epithelial tumors.

Two findings in thymic epithelial tumors are correlated with the occurrence of myasthenia gravis(MG): (1) the expression of an acetylcholine receptor (AChR)-like-epitope in the neoplastic epithelium, and (2) the preservation of thymus-like features in the neoplasms, indicated by the presence of immature thymocytes. On this background it has been proposed that paraneoplastic MG may start with an intratumorous abnormal T cell selection due to aberrantly expressed AChR-epitopes (self-peptides). As appropriate thymocyte-stroma-interactions are prerequisites for thymocyte development in the thymus (and probably in MG-associated thymic tumors, too), we analyzed the expression of CD28/B7(BB1), CD2/:LFA3, LFA-1/ICAM-1 and VLA-4/VCAM-1 in human thymus and thymomas by immunohistochemistry. In normal thymuses and thymitis the stromal molecules were expressed at higher levels in the medulla than in the cortex. This was particularly true for B7(BB1) that was undetectable by immunoperoxidase techniques in the cortex. In contrast, cortical-type thymic epithelial tumors (cortical thymoma and well differentiated thymic carcinoma), known to exhibit the highest association with myasthenia, expressed the stromal molecules at almost medullary levels. The findings may be a clue to a functional difference between neoplastic and normal cortical epithelial cells: while we find the former to have the capacity to present soluble antigen to antigen-specific CD4+ T cells in vitro, normal cortical epithelium failed to do so. This altered microenvironment in thymomas might contribute to the autoimmunization by stimulating mature recirculating AChR-specific T cells.

CD2 Antigens↗

[The functionally inactive endocrine pancreas tumor].

Endocrine tumors of the pancreas are extremely rare (1-3%). We present two cases with functional inactive tumors--one benign and one malignant--, which were immunohistologically secreting glucagon without having clinical symptoms. Differential diagnosis, operative strategy and therapy of endocrine tumors of the pancreas are discussed.

Adult↗

[Clinical aspects and diagnosis of arterial embolism of the upper extremity].

The upper limb embolus is rarely encountered (upper limb:lower limb emboli 1:4-5). Our problem was to determine in which way the paraclinical investigations influence the operation indication. In 1992, we have seen 10 consecutive patients with an upper limb embolus. The characteristics of our patient group are the advanced age and the cardiovascular morbidity. It was always possible to diagnose the emboli clinically. 7 duplex, 6 Dopplers and 2 angiographies were performed and have confirmed the clinical diagnosis and the clinically suspected localisation of the emboli. All the patients were operated in local anesthesy. An embolectomy with Fogarty catheter was done. After the operation, all our patients were asymptomatic. No amputation was done. We do think that when the clinic is clear enough to diagnose an embolus, no other investigations are necessary to the operation indication.

Aged↗

Myogenesis in thymic transplants in the severe combined immunodeficient mouse model of myasthenia gravis. Differentiation of thymic myoid cells into striated muscle cells.

Thymic myoid cells (TMCs) bearing acetylcholine receptors (AchR) on their surface have a central role in the concept of intrathymic autosensitization in the pathogenesis of myasthenia gravis. In a SCID mouse model of myasthenia gravis, solid pieces of thymuses with lymphofollicular hyperplasia were transplanted into SCID mice. The chimeric mice displayed long-term secretion of anti-AchR antibodies. Here, we traced the fate of TMCs contained in transplanted myasthenia gravis thymuses. Unexpectedly, the number of thymic TMCs in transplanted tissue was slightly higher than in untransplanted thymus. More strikingly, the transplanted TMCs were more highly differentiated than their nontransplanted counterparts. This was demonstrated by a more than 10-fold increase of AchR-main immunogenic region epitopes recognized by monoclonal antibody 198. Some TMCs had even differentiated into striated muscle cells. The abundance of AchRs in human thymic transplants in the SCID mouse model of myasthenia gravis may help to study the mechanisms of autosensitization against the AchR in vivo.

Animals↗

[Simultaneous surgical and technical catheter revascularization of the lower extremity].

Intraoperative balloon angioplasty was performed on 17 patients and 19 arteries undergoing a concomitant vascular reconstructive procedure during the past 24 months. All angioplasties were performed with the aid of digital substraction angiography (DSA) in the operating room. The primary purpose of intraoperative angioplasty was mainly to increase outflow (18) or inflow (1) in conjunction with a planned vascular procedure. Dilatation obviated the need of more extensive vascular reconstruction in these elderly patients.

Aged↗

[The importance of surgical assistants from the viewpoint of the heads of surgery].

60 heads of surgical units of non-university hospitals in Switzerland were questioned about their opinion about their assistants. The questionnaire was divided into: general data about hospital size and number of assistants, employment criteria, further education, operative activities and working hours of assistants. The answers are representative for the situation in non-university hospitals in Switzerland.

Clinical Competence↗

[Stable joint-bridging extension of malleolar dislocations and pilon fractures with the AO pinless external fixator].

The pinless external fixator, introduced into clinical practice for open tibial fractures, suggested itself for use as a traction substitute because of its pinless frame. The aim of this feasibility study was to replace the conventional calcaneal pin traction by a joint-bridging pinless fixator, inserted under local anesthesia. 10 patients with 6 malleolar dislocation fractures, 3 pilon tibial and 1 open distal tibial fracture were immobilised by a joint-bridging pinless fixator during 10.4 days (5-16 days) till swelling had subsided and definitive fracture treatment, consisting of plate fixation, took place. The implantation of the joint-bridging pinless fixator in local anaesthesia was well tolerated by all patients. This traction substitute offered good patient comfort and easy care. Although the provided stability was less than a conventional fixator, all patients were able to lift up their fractured extremity without pain.

Aged↗

Idiotype identity in a MALT-type lymphoma and B cells in Helicobacter pylori associated chronic gastritis.

BACKGROUND: To investigate the mechanisms triggering MALT-lymphoma development, we examined the occurrence of normal B cells in lymphoid tissue and chronic gastritis with the same idiotype as an IgA-positive MALT lymphoma. EXPERIMENTAL DESIGN: Lymphoma idiotype IgA was produced by monoclonal human antibody technology. Against this idiotype a murine monoclonal antibody 27/165 with anti-idiotypic (alpha Id) specificities was raised, and applied immunohistochemically to identify the non-neoplastic precursor B cells in non-neoplastic human tissues. RESULTS: alpha Id 27/165 reacted exclusively with the IgA expressing MALT lymphoma but not with 20 other MALT-type gastric lymphomas nor with 26 nodal lymphomas and was not reactive with normal and inflamed lymph nodes. alpha Id 27/165 immunoreactivity was also absent from MALT of different mucosal sites but was readily encountered on a substantial number of lymphocytes and plasma cells in 95% cases of chronic gastritis associated with Helicobacter pylori (H.p.). The target antigen of the lymphoma IgA was found to be a common antigen of IgA and IgM plasma cells of MALT but not a constituent of bacteria commonly involved in the pathogenesis of gastritis. CONCLUSIONS: The distinct binding of alpha Id 27/165 to only reactive mucosal B cells is a first direct evidence for the evolution of MALT-type lymphoma from chronic gastritis. Since the target antigen of the lymphoma IgA has been found to be an autoantigen of MALT plasma cells it is suggested that this MALT-type lymphoma may have arisen after triggering by an autoimmune response resulting from H.p.-induced gastritis.

Antibodies, Monoclonal↗