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Biomedical subjects

A Marx

Publications and source records attributed to A Marx.

At least 127 records · Page 7Linked to original sources
PubMed1996

[Ischemic preconditioning in surgery of extremities: experimental studies].

Ischemic preconditioning (IP), using one or more brief periods of ischemia, each followed by a short reperfusion phase, improves tolerance of subsequent sustained ischemia in different organs. The aim of this experimental study was to evaluate the effects of IP on postischemic function in skeletal muscle. Right hindlimbs of anesthetized rats were pretreated with three cycles each of 10 min of ischemia and 10 min of reperfusion (n = 12). Non-preconditioned animals (n = 12) served as controls. These hindlimbs were then subjected to 3 h of ischemia and 2 h of reperfusion. IP resulted in a significant increase in postischemic skeletal muscle force (240 +/- 47 mN vs 409 +/- 63 mN), force-time integral (1081 +/- 242 mN*s vs 2546 +/- 481 mN*s) and endurance (29.6 +/- 3.4 s vs 48.0 +/- 5.0 s). These data support the potential of IP to reduce postischemic skeletal muscle damage in surgery of the extremities using tourniquet ischemia. The concept deserves clinical evaluation.

Animals↗
PubMed1996

Neuronal targets of serum and cerebrospinal fluid autoantibodies in amyotrophic lateral sclerosis.

Sera and cerebrospinal fluid (CSF) from 25 patients with amyotrophic lateral sclerosis (ALS) were tested by immunofluorescence on fetal, juvenile and adult central and peripheral neuronal (CNS/PNS) tissues and on nerve biopsy material from affected patients for the presence of autoantibodies. Results were compared with control sera from normal blood donors (n = 45) and patients with other neurological diseases (OND) (n = 11). Three different types of tissue reactivity (glial, axonal, and small blood vessels) were found. Antibodies binding to glial and axonal structures were found in 32% of ALS patients as compared to 12% in normal and 27% in OND controls. In contrast, staining of endothelial cells was found with 24% of ALS sera and CSF but not with normal and OND control sera and was demonstrated only with fetal and juvenile nervous tissue and with suralis nerve biopsies of two of five ALS patients. However, normal or inflamed adult CNS/PNS tissue was not stained with these sera. We conclude that ALS is most likely a heterogeneous group of diseases and only a subgroup of ALS may have an autoimmune pathogenesis. These findings may, therefore, have implications for the evaluation of any immunosuppressive treatment in ALS.

Adult↗
PubMed1996

Occurrence of multiple lymphoepithelioma-like carcinomas and MALT-type lymphoma in the stomach: detection of EBV in carcinomas but not in lymphoma.

A multifocal lymphoepithelioma-like carcinoma and a low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-type) were found simultaneously in the stomach of a 65-year-old patient. Carcinoma and lymphoma were intimately associated forming complexes resembling lymphoepithelial lesions at the primary gastric site and in lymph node metastases. The two tumours had developed on a background of severe chronic-atrophic gastritis of the mucosa of antrum and fundus. Autoantibodies to normal gastric glandular tissue could be demonstrated in the patient's sera. Using non-radioactive in situ hybridization (ISH), Epstein-Barr virus (EBV) sequences were detected in virtually all carcinoma cells but neither in the non-neoplastic mucosa nor in the lymphoma. These findings suggest that a focal EBV infection occurred early in the development of the carcinoma followed by a subsequent clonal expansion of the EBV-containing tumour cells. A neoplastic transformation in MALT-type lymphoma is not EBV-related but might be triggered by altered immune mechanisms.

Aged↗
PubMed1996

Effects of verapamil on skeletal muscle function following ischemia and reperfusion.

Verapamil (VRP) improves ischemic tolerance of different organs including brain, kidney, liver and heart. We report here on the effects of preischemic VRP treatment on skeletal muscle function following 3 h of tourniquet ischemia and 2 h of reperfusion using a rodent model. Postischemic and contralateral limbs were evaluated. Fast (musculi peronei)- and slow-twitch muscles (musculus soleus) of both limbs were excised and electrically stimulated in vitro. VRP pretreatment was found to significantly decrease tetanic peak tension of both contralateral nonischemic m. soleus and mm. peronei. Furthermore, VRP improved fatigability of slow-twitch muscles of both ischemic and contralateral limbs [increase of fatigue index from 0.04 +/- 0.009 (0 mg/kg) to 0.10 +/- 0.019 (4 mg/kg)], but not of fast-twitch muscles. These data indicate that the effects of VRP on postischemic skeletal muscle function depend on fiber composition.

Animals↗
PubMed1996

Ischemic preconditioning improves post-ischemic skeletal muscle function.

Ischemic preconditioning (IP), using one or more brief periods of ischemia before a sustained ischemia, represents a new approach to reduce tourniquet ischemia-induced skeletal muscle damage. The aim of this study was to investigate the effect of IP on skeletal muscle function and high-energy phosphate tissues levels in a rodent model. IP protocols using one, two, or three preconditioning cycles were compared. IP was found to significantly improve force, performance, endurance, and contractility of postischemic skeletal muscle. The efficacy of IP-induced protection was correlated with the number of preconditioning cycles. Preconditioning with three cycles resulted in a more effective protection as compared to one or two cycles. Three cycles of IP significantly improved force (409 +/- 63 versus 240 +/- 47 mN), performance (2546 +/- 481 versus 1081 +/- 242 mN*sec), endurance (46.7 +/- 5.0 versus 29.6 +/- 3.4 sec) and contractility (59.9 +/- 4.2 versus 38.7 +/- 5.1) in postischemic m.extensor dig. long. when compared to nonpreconditioned muscles. In contrast, high-energy phosphate tissue levels remained unchanged after three cycles of preconditioning. Altogether, this study describes, for the first time, the efficacy of IP to improve postischemic muscle function. The respective clinical potential warrants further exploration.

Animals↗
PubMed1996

Thymoma-associated myasthenia gravis. Transplantation of thymoma and extrathymomal thymic tissue into SCID mice.

To study the possible role of thymomas and of extrathymomal thymic tissue in the development and maintenance of myasthenia gravis, we transplanted fragments of either tissue into SCID mice and monitored the production of anti-acetylcholine receptor antibodies in the recipients. Furthermore, the transplants were characterized by immunohistochemistry. Unlike after transplantation of thymus with lymphofollicular hyperplasia that induced high titers of anti-acetylcholine receptor antibodies, thymoma transplants never produced autoantibodies. Mice transplanted with extrathymomal thymic tissue also failed to produce anti-acetylcholine receptor antibodies except one group that received transplants containing hyperplastic extrathymomal tissue. These findings may explain the refractoriness of thymomatous myasthenia to thymectomy.

Adult↗
PubMed1996

Expression of neurofilaments and of a titin epitope in thymic epithelial tumors. Implications for the pathogenesis of myasthenia gravis.

Autoantibodies against both striated muscle proteins, particularly titin, and the acetylcholine receptor are a hallmark of thymoma-associated myasthenia gravis. However, the stimulus for these responses remains enigmatic as whole titin is not detectable in these tumors. This study reports that in thymomas with cortical differentiation many of the neoplastic epithelial cells expressed low and medium molecular weight neurofilaments detected with several antibodies (on selections and blots) and at the RNA level (by reverse transcriptase polymerase chain reaction). Moreover, higher molecular weight forms sharing at least one epitope with titin were detectable slightly less frequently, as were the more strongly phosphorylated epitopes. In stark contrast, in medullary and mixed thymomas, and especially in the normal thymus, immunoreactivity with anti-neurofilament antibodies was rare. This aberrant overexpression of a titin epitope by epithelial cells with antigen-presenting phenotype in an inappropriate cortical microenvironment suggests that they might autosensitize maturing T cells there and so initiate anti-titin autoimmunity in these patients.

Adolescent↗
PubMed1996

Myasthenia gravis.

Myasthenia gravis (MG) is the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. It is almost invariably associated with pathological alterations of the thymus. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis B cells are increased in the medulla forming germinal centers or diffuse B cell infiltrates. Intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and involves AChR on myoid cells as the triggering (myasthenogenic) antigen. In thymomas no intratumorous immune reaction occurs and the AChR is not the myasthenogenic antigen. Instead, an abnormal neurofilament that shares epitopes with the AChR is expressed in thymomas and may trigger AChR-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of MG take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. The etiology of MG remains enigmatic.

Adolescent↗
PubMed1996

[CD40 as a mediator of proliferation in normal ans neoplastic thymic epithelium].

AIMS AND METHODS: While CD40 is a costimulatory molecule of utmost importance for B-cell proliferation and Ig class switch its role has not been elucidated in the human thymus and in thymic epithelial tumors. To investigate, whether CD40 is functionally active there, we investigated the proliferative response by 3H-Thymidin incorporation of primary normal and neoplastic thymic epithelial cell cultures to CD40 triggering by soluble CD40 ligand (CD40L). RESULTS: Normal thymic epithelial cells exhibited proliferation in response to CD40 ligand in a dose dependent manner, while a CD40 ligand specific monoclonal antibody prevented this effect. This response was not significantly different from the response of neoplastic thymic epithelial cells derived from myasthenia gravis-associated thymomas. CONCLUSION: Our data demonstrate that CD40 is expressed on the surface of normal and neoplastic epithelial cells of the thymus and is a functional molecule in terms of epithelial cell proliferation in vitro. Given the differential expression of CD40 in the various histological thymoma subtypes in vivo, the finding suggests a role of CD40 in the different mechanisms of tolerance breakdown in thymomas.

Antigens, CD↗
PubMed1996

[Abnormal T cell maturation in myasthenia gravis associated thymomas].

AIMS AND METHODS: Paraneoplastic myasthenia gravis is a thymoma-associated autoimmune disease, characterized by autoantibodies against the acetylcholine receptor (AChR). CD4+ AChR-specific T cells play a pivotal role in the production of autoantibodies. However, it is not known how the tumor is involved in the pathogenesis of autoimmunity. To address this question thymocyte maturation was followed in medullary, mixed and cortical thymomas using three-color FACS analysis. RESULTS: Compared to normal thymuses medullary thymomas were almost devoid of immature T cells and most intratumorous lymphocytes appeared to be of peripheral origin. In mixed and cortical thymomas maturation of thymocytes took place from the most immature precursors to thymomcytes with a mature phenotype. Only in the latter tumor subtypes immature CD4+/CD8-/CD3-thymocytes were significantly increased. In addition, a reduced production of mature CD4+ T cells suggests ineffective positive selection. Activated T cells were present in one medullary but none of the mixed or cortical thymomas. CONCLUSION: Each histological thymoma subtype is associated with a characteristic defect of T cell maturation. The contribution of medullary thymomas to the pathogenesis of myasthenia gravis (MG) might be a pathological intratumorous T cell activation. By contrast, an abnormal antigen-specific T cell selection may be the contribution of cortical and mixed thymomas to anti-AChR autoimmunity.

Antigens, CD↗
PubMed1996

[Molecular mimicry between neurofilaments and titin as the basis for autoimmunity towards skeletal muscle in paraneoplastic myasthenia gravis].

AIMS AND METHODS: Autoantibodies against striated muscle proteins, particularly titin, characteristically distinguish thymoma-associated from non-paraneoplastic myasthenia gravis (MG) patients. However, the stimulus for this autoimmunity remains enigmatic since whole titin is not detectable in these tumors. Since Neurofilaments (NF) contain titin epitopes, MG-associated thymomas were investigated for NF expression using immunohistochemistry and Western blotting. RESULTS: In thymomas with cortical differentiation many of the neoplastic epithelial cells expressed medium molecular weight NF at the protein level. In sharp contrast, in medullary and mixed thymomas and in normal thymuses immunoreactivity with anti-NF antibodies was rare. CONCLUSION: The overexpression of NFs with titin epitopes by neoplastic cells in an inappropriate cortical environment may be the basis for the autosensitization of developing T-cells against titin in MG-associated cortical type thymomas.

Autoantibodies↗
PubMed1996

[Absence of herpesvirus saimiri STPC oncogene in salivary gland tumors and epithelial thymus tumors].

AIM AND METHODS: The oncoprotein STP-C-488 induces salivary gland and thymic epithelial tumours when expressed as a transgene in mice (MURPHY et al. 1994). Given the enigmatic tumorigenesis of corresponding tumours in humans, we now investigated genomic DNA and RNA from 11 thymomas, 5 pleomorphic adenomas and control autopsy material (n = 8) for the occurrence of the STP-C-488 sequences by Southern-blotting, Northern-blotting and PCR. RESULTS: All tumor samples and control tissues were negative for the STP-C-488 in Southern-blot and Northern-blot-hybridization. PCR analyses did not reveal amplification products of the length expected for STP-C-488. However, a PCR fragment of a different size was found in 50% of the thymomas and pleomorphic adenomas, but in only one of 8 controls. The sequence of this PCR product revealed local homologies with various herpesviruses. CONCLUSION: The oncoprotein STP-C-488 is not involved in the tumorigenesis of human thymomas and salivary gland tumours. Whether the novel sequences amplified preferentially from these tumours play a role in pathogenesis needs further investigation.

Animals↗
PubMed1995

Superfetation occurring in connection with gamete intrafallopian transfer: a case report.

This observation reports a case of susperfetation which occurred in connection with gamete intrafallopian transfer (GIFT). The macroscopic and histological examination of a spontaneous abortion from a 33-year-old woman (15th week of pregnancy) revealed the existence of two embryos with a monochorionic diamniotic placenta (developmental age approximately 41 days) and two fetuses and a fetal remnant with a trichorionic and triamniotic placenta (developmental age approximately 98 days). The large developmental age difference of embryos and fetuses cannot be explained by retardation, because the embryos showed adequate development with the development of their placenta. Moreover, the usual causes of intrauterine growth retardation could be excluded as could retention of the embryos since the tissues showed no autolytic changes. Consequently the large developmental age difference is explained by assuming that the embryos developed from successive ovulations. A second nidation of blastocysts had occurred after the GIFT concurrently with the clinically reported hyperstimulation syndrome.

Abortion, Spontaneous↗
PubMed1995

[Detection of GABA(A) receptor mRNA in cochlear tissue. An in situ hybridization study].

Gamma-aminobutyric acid (GABA) and the GABAergic system play an important role in the efferent modulation of cochlear function. We examined surface preparations of guinea pig and mouse cochleae by in situ hybridization using radioactive labelled oligonucleotides for several subunits of the GABAA receptor. Frozen sections of rat and guinea pig brain (cortex, hippocampus, cerebellum) served as controls. In the mouse cochlea the mRNA of the alpha-1 and alpha-5, beta-1 and gamma-1 subunit were detected, while in guinea pig cochlea mRNA of the alpha-1, alpha-4, alpha-5, and gamma-1 subunit of the GABAA receptor were found. Positive signals were located in the regions of the outer hair cells and had a weaker intensity in the inner hair cells. In the brain sections the several subunits were detected in a variable distribution in the cerebellum, hippocampus and cortical regions. Rat specimens exhibited stronger signals than guinea pig brain sections. These investigations have extended previous results of immunocytochemical experiments from our laboratory demonstrating mRNA sequences of GABAA receptor subunits in the mammalian inner ear. Detection of these nucleotide sequences using surface preparations of the cochlea on a molecular level by in situ hybridization supports the importance of GABA as a cochlear neurotransmitter. Furthermore, it can be concluded that the mammalian cochlea is able to express a GABA-dependent neurotransmission system.

Animals↗