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Biomedical subjects

A Marx

Publications and source records attributed to A Marx.

At least 109 records · Page 6Linked to original sources
PubMed1998

Abnormal thymocyte development and generation of autoreactive T cells in mixed and cortical thymomas.

To gain insight into the pathogenesis of thymoma-associated myasthenia gravis, thymocyte maturation was investigated in mixed and cortical thymomas by three-color flow cytometry. Although we detected cells at all recognizable stages, we noted an unusual increased percentage of early CD4+/CD3- thymocytes--especially in mixed thymoma--and a pronounced decreased percentage of mature CD4+/CD3+ cells in cortical thymomas as well. The percentage of CD3+/CD69+ cells that arose after positive selection was reduced in both thymoma subtypes compared with control thymuses, which suggests differences in the rate or efficiency of positive selection particularly in mixed thymomas. Mature T cells in 10 of 11 thymomas were not activated in situ as shown by the absence of CD25 expression. After stimulation with recombinant human acetylcholine receptor alpha-subunit fragments, thymocytes from 8 of 11 thymomas of both subtypes proliferated more strongly than those from controls, regardless of whether the donors were myasthenic. Responses of residual thymus cells to tetanus toxoid correlated well with those of autologous blood T cells, whereas those from the thymomas clearly did not--implying minimal colonization of thymomas by mature recirculating T cells. In conclusion, our results show that cortical and mixed thymomas exhibited differences in thymocyte maturation. Nevertheless, both thymoma subtypes seem to contribute to the pathogenesis of paraneoplastic myasthenia gravis by generating naive but potentially autoaggressive T cells; in some thymomas, these cells may then be actively immunized inside the tumor.

Autoantigens↗
PubMed1997

The crystal structure of dimeric kinesin and implications for microtubule-dependent motility.

The dimeric form of the kinesin motor and neck domain from rat brain with bound ADP has been solved by X-ray crystallography. The two heads of the dimer are connected via a coiled-coil alpha-helical interaction of their necks. They are broadly similar to one another; differences are most apparent in the head-neck junction and in a moderate reorientation of the neck helices in order to adopt to the coiled-coil conformation. The heads show a rotational symmetry (approximately 120 degrees) about an axis close to that of the coiled-coil. This arrangement is unexpected since it is not compatible with the microtubule lattice. In this arrangement, the two heads of a kinesin dimer could not have equivalent interactions with microtubules.

Adenosine Diphosphate↗
PubMed1997

X-ray structure of motor and neck domains from rat brain kinesin.

We have determined the X-ray structure of rat kinesin head and neck domains. The folding of the core motor domain resembles that of human kinesin reported recently [Kull, F. J., et al. (1996) Nature 380, 550-554]. Novel features of the structure include the N-terminal region, folded as a beta-strand, and the C-terminal transition from the motor to the rod domain, folded as two beta-strands plus an alpha-helix. This helix is the beginning of kinesin's neck responsible for dimerization of the motor complex and for force transduction. Although the folding of the motor domain core is similar to that of a domain of myosin (an actin-dependent motor), the position and angle of kinesin's neck are very different from those of myosin's stalk, suggesting that the two motors have different mechanisms of force transduction. The N- and C-terminal ends of the core motor, thought to be responsible for the directionality of the motors [Case, R. B., et al. (1997) Cell 90, 959-966], take the form of beta-strands attached to the central beta-sheet of the structure.

Amino Acid Sequence↗
PubMed1997

Increased surface expression of CD18 and CD11b in leukocytes after tourniquet ischemia during elective hand surgery.

The surface expression of beta2-integrins was investigated in leukocytes from patients undergoing ischemia induced by tourniquet application for elective hand surgery. Blood samples were obtained before initiation, at the end of ischemia, and after 15 minutes of reperfusion from ischemic and contralateral arms of five patients. Comparable expression of CD18, CD11a, CD11b, and CD11c could be detected by immunofluorescence in leukocytes from samples drawn from either arm before tourniquet application. In contrast, a significant increase in the expression of CD18 was detectable in monocytes, granulocytes, and lymphocytes from the ischemic arm compared with that in the nonischemic contralateral control, at the end of the ischemia time (80 +/- 16 minutes). A significantly increased expression of CD11b, but not CD11a or CD11c, determinants was also observed in granulocytes and monocytes. Concomitantly, a significant reduction in the percentages of granulocytes in samples from ischemic areas was detectable. After 15 minutes of reperfusion, differences in the expression of these adhesion molecules were no longer significant. The expression of the genes encoding interleukins IL-1alpha, IL-1beta, and IL-6 and tumor necrosis factor alpha (TNFalpha) proinflammatory cytokines was also studied by reverse polymerase chain reaction (rPCR) in peripheral blood mononuclear cells (PBMCs) obtained from the same samples in three patients. IL-1beta or IL-6 gene expression was never observed. Expression of IL-1alpha and TNFalpha genes, as detected in two patients, was not related with induction of ischemia. However, in these patients expression of one or both these genes was observed in samples derived from the ischemic but not the control arm after 15 minutes of reperfusion. These data document that overexpression of adhesion molecules and sequestration of leukocytes take place following short ischemia times, as routinely applied clinically for minor surgical procedures.

Adult↗
PubMed1997

Pathogenesis of myasthenia gravis.

Various studies over the last 25 years in Man and animal models have revealed many steps in the pathogenesis of myasthenia gravis (MG) which is now considered the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. Though not a disease entity, MG is associated with pathological alterations of the thymus in about 80% of cases. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis, intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and probably involves AChR on myoid cells as the triggering (myasthenogenic) antigen. Genetic factors contribute essentially to the pathogenesis of this form of MG. In thymoma-associated MG genetic factors are probably of marginal significance. Neither intratumour autoantibody production nor T cell activation seem to occur and the AChR is not the myasthenogenic antigen. Instead, abnormal neurofilaments that share epitopes with the AChR and other auto-antigen targets in paraneoplastic MG are expressed in thymomas and may trigger autoantigen-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of most MG cases take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. Where these initial steps occur in MG cases without thymic pathology is not known. Likewise, the factors involved in the initial triggering of MG remain enigmatic in all MG subtypes.

Adolescent↗
PubMed1997

[Fiber optic intubation using a modified laryngeal mask. Report of experiences with use in 105 patients].

PURPOSE: This study was made to investigate the suitability of a modified laryngeal mask airway as an aid for fibreoptic endotracheal intubation in patients with a difficult airway. We used a laryngeal mask airway split lengthwise on its convex site, the incision going from a point corresponding to the teeth down to the base of the cuff. The cuff remains uncut. By this modification it is possible to ventilate an anaesthetised patient and to pass down a fibreoptic bronchoscope via splitting of the laryngeal mask airway into the trachea at the same time. An endotracheal tube of any diameter already mounted over the bronchoscope is then guided into the trachea. The feasibility of this technique was tested and haemodynamic reactions and changes of the parameters of respiration were recorded. METHODS: This technique was used in 105 patients, 68 male and 37 female, mean age 34 years, when difficult intubation was expected or occurred. Blood pressure, pulse rate and peripheral oxygen saturation was recorded on arrival in the anaesthetic room, after induction of anaesthesia, during and after fibreoptic endotracheal intubation. The respiratory minute volume was measured after insertion of the laryngeal mask airway and during the course of fibreoptic intubation. The time needed was recorded. RESULTS: In all cases endotracheal intubation was successful using this technique. The time needed was between 4 and 16 minutes. There was a statistically significant increase in peripheral oxygen saturation and decrease of the pulse rate after induction of anaesthesia. There were no further significant changes of the recorded haemodynamic parameters and the oxygen saturation during and after fibreoptic intubation compared to the results after induction of anaesthesia. CONCLUSION: It could be demonstrated that a fibreoptic intubation is possible in cases of a difficult airway using the technique described here. There is no haemodynamic strain on the patient. This method can be carried out without pressure of time and without to endanger the patient by hypoxia as the patient can be ventilated during the fibreoptic intubation. In cases of impossible intubation and insufficient mask ventilation it can be tried to establish ventilation and to avoid a emergency surgical airway or transtracheal jet ventilation by using this technique.

Adult↗
PubMed1997

Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics.

Croup is a common manifestation of respiratory tract infection in children, and human parainfluenza virus 1 (HPIV-1) is the agent most commonly associated with croup. In the United States, HPIV-1 produces a distinctive pattern of biennial epidemics of respiratory illness during the autumn months of odd-numbered years. National Hospital Discharge Survey data for croup hospitalizations among patients <15 years old between 1979 and 1993 were examined along with laboratory-based surveillance data on HPIV-1 activity in the United States. The mean annual number of croup hospitalizations was 41,000 (range, 27,000-62,000/year). Ninety-one percent of hospitalizations occurred among children <5 years of age. Minor peaks in croup hospitalizations occurred each year in February, and major peaks occurred in October of odd-numbered years, coincident with peak HPIV-1 activity. Each biennial epidemic of HPIV-1 was associated with 18,000 excess croup hospitalizations nationwide.

Adenovirus Infections, Human↗
PubMed1997

Magnesium in drinking water and ischemic heart disease.

The associations found in the general populations of a number of different countries are suggestive and warrant an integrated program of laboratory and epidemiologic research to reject or confirm the magnesium-IHD hypothesis. Singling out this particular risk factor has two justifications. First, as would be the case with any epidemiologic risk factor for IHD whose attributable risk was large enough to be detectable through epidemiology, applying that attributable risk to the vast annual morbidity and mortality from IHD would translate into tens of thousands of lives benefited and millions of dollars in hospital costs avoided per year. Second, this particular risk factor could conceivably be eliminated by an inexpensive supplementation program. For example, a low-sodium, higher-magnesium and -potassium table salt has been recommended and used in Finland for many years, during a period when the prevalence of hypertension in population surveys was said to decrease (117). Interventions which do not require behavioral change have always been the most cost-effective in public health. We therefore urge funding agencies to give priority to studies determining whether there are unforeseen adverse effects of magnesium for some population subgroups and whether the apparent benefit derived from low doses of magnesium in the development of IHD or IHD death is real. Furthermore, researchers should determine which chemical form of magnesium is best absorbed and most effective. We need to better understand the interrelation of various water and food constituents, as well as individual risk factors, in the pathogenesis of IHD. Susceptible individuals who are at higher risk of being depleted of magnesium need to be identified, and potential untoward effects of magnesium should be studied. Future research must provide better answers about low level waterborne magnesium before recommendations to the public can be made.

Animals↗
PubMed1997

Active fulminant myocarditis characterized by T-lymphocytes expressing the gamma-delta T-cell receptor: a new disease entity?

Lymphocytic myocarditis is thought to be a virus-induced disease. T cells expressing the alpha-beta T-cell receptor seem to play a central role in the pathogenesis and to mediate tissue injury in this disease. A case of active fulminant myocarditis is described, which was analyzed by immunohistochemical, molecular biologic, and serologic methods. Infiltration of the heart tissue predominantly by gamma-delta T cells was detected by immunohistochemistry. No evidence of viral disease could be obtained by in situ hybridization with different enterovirus-specific DNA probes; by reverse-transcriptase polymerase chain reaction using specific primers for enteroviruses, adenoviruses, herpes simplex viruses, influenza A and B viruses, and cytomegaloviruses; or by enzyme-linked immunosorbent assay and electron microscopy. Because gamma-delta T cells may have an autoimmune capacity, we propose that these cells may trigger autoimmune myocarditis. These findings may be important in order to identify subgroups of patients who may benefit from immunosuppressive therapy.

Adult↗
PubMed1997

Kinetics of high-energy phosphates in allopurinol-pretreated ischaemic and post-ischaemic skeletal muscle: an in vivo magnetic resonance spectroscopy study.

Allopurinol (AP) protects skeletal muscle function against ischaemia-induced injury, but the mechanism is not yet clear. As AP acts as a competitive xanthine oxidase inhibitor, both a reduction of oxygen-derived free radicals and an enhancement of purine resynthesis (salvage pathway) might be involved. We investigated the in vivo kinetics of high-energy phosphates in skeletal muscle after AP pretreatment using 31P-magnetic resonance spectroscopy during 2 h of ischaemia and 3 h of reperfusion in rat hindlimbs. Three animals (group A) were pretreated with a total of 160 mg/kg AP i.p., 3 control animals (group B) received the same amount of 0.9% saline solution. ATP decreased to 18.6 +/- 1.3% of the pre-ischaemic value in group A and to 17.3 +/- 2.8% in group B after 2 h of ischaemia, and rose to only 47.7 +/- 1.5 and 50.5 +/- 1.8%, respectively, after 3 h of reperfusion. Phosphocreatine fell to 7.2 +/- 2.9 and 7.6 +/- 2.2% of pre-ischaemic values after 2 h of ischaemia and rose again to 36.5 +/- 12.9 and 45.4 +/- 20.4% after 3 h of reperfusion. Inorganic phosphate (Pi) increased 5-fold after 2 h of ischaemia, irrespective of the treatment. After 3 h of reperfusion, Pi was still 4 times the pre-ischaemic value. The kinetics of ATP, PCr, and Pi levels were not statistically different between the two groups. These results indicate that the ATP salvage pathway does not play an important role in AP-induced attenuation of ischaemia/reperfusion-induced muscle damage.

Adenosine Triphosphate↗
PubMed1997

Characterization of the human thymic microenvironment: lymphoepithelial interaction in normal thymus and thymoma.

Recent advances in tissue culture technology and molecular biology have extended our understanding of the functional morphology of the thymus. The importance of a crosstalk between lymphoid cells and stroma has been appreciated as a prerequisite for the normal development of both. The network of direct cellular interactions and soluble factors comprising part of the microenvironment is far from being elucidated but the highly ordered thymic architecture clearly plays a pivotal role in normal thymic function. Insight into the genetic control of stroma development is only emerging while knowledge on the genetic control of the various steps in T cell development is already advanced and rapidly expanding. The present paper gives an overview on the cellular components and matrix molecules of the human thymic microenvironment and their development during ontogeny. The intrathymic cytokine network is shortly reviewed. Special emphasis is put on molecules mediating lymphoepithelial interactions that are necessary for the expansion and early selection of immature thymocytes from precursor cells and for the generation of an MHC restricted and self tolerant T cell repertoire by positive and negative selection. Considering these physiological mechanisms we summarize the molecular pathology of the microenvironment and lymphocyte/stroma interactions in thymic epithelial tumors (thymomas). Finally, a pathogenetic model for paraneoplastic myasthenia gravis is given. We suggest abnormal auto-antigen-specific positive selection of naive T cells as the essential molecular mechanism by which thymomas contribute to the autoimmunization against the acetylcholine receptor and other muscle proteins.

Apoptosis↗
PubMed1997

[Carcinoid tumor in Meckel's diverticulum: case presentation and review of the literature].

Meckel's diverticulum is the most common anomaly of the gastrointestinal tract. Neoplasms are extremely rare. We report a case of carcinoid tumor of Meckel's diverticulum in a patient with acute abdominal pain. So far, 111 cases have been reported. Review of the literature reveals that carcinoids are the most common malignant tumors of Meckel's diverticulum. Two thirds of the patients remain asymptomatic. Metastases are seen in 25% at diagnosis. The probability of metastases depends on the size of the primary tumor. Because of the early metastases rate even in small tumors, aggressive surgical management is justified.

Abdomen, Acute↗
PubMed1996

[Bronchus carcinoid tumor in the Tessin canton, retrospective analysis of 13 years and literature review].

Between 1981 and 1993, 27 bronchial carcinoids were diagnosed in patients living in the Swiss Canton of Ticino, with a mean age of 55 (24-78) years. The incidence was 0.79/100,000 inhabitants. Main symptoms were cough (41%), hemoptysis (30%) and bronchial obstruction such as pneumonia or atelectasis (26%). There were no cases with carcinoid crisis. Preoperative evaluation included chest X-ray (100%), bronchoscopic biopsy (84%), computed tomography (44%) and mediastinoscopy (15%). Some 69% of the patients underwent lobectomy and 15% segmental resection. Pneumonectomy was required for curative surgery in 2 patients. One patient underwent bronchoscopic resection. Surgery is generally indicated. The 5-year survival rate for typical carcinoid was 94% and was significantly reduced to 42% in atypical carcinoid cases (p = 0.02). Prognosis after radical surgery is favorable and depends mainly on lymph node involvement and the histological type of carcinoid.

Adult↗
PubMed1996

Ischemic preconditioning--a new concept in orthopedic and reconstructive surgery.

The duration of tourniquet-induced ischemia during orthopedic and reconstructive surgery is limited by the risk of ischemia and reperfusion injury to skeletal muscle. This study evaluated the potential of ischemic preconditioning (short periods of ischemia with intermittent reperfusion) to improve skeletal muscle function after ischemia and reperfusion in a rodent model. Preconditioning was found to improve force, contractility, and performance and to decrease fatigue of skeletal muscle. In contrast, energy-rich phosphates, measured concurrently, were not affected by preconditioning, suggesting mechanisms other than energy preservation to be involved. In summary, preconditioning may enable prolongation of orthopedic and reconstructive procedures.

Animals↗
PubMed1996

The myelin basic protein-specific T cell repertoire in (transgenic) Lewis rat/SCID mouse chimeras: preferential V beta 8.2 T cell receptor usage depends on an intact Lewis thymic microenvironment.

In the Lewis rat, myelin basic protein (MBP)-specific, encephalitogenic T cells preferentially recognize sequence 68-88, and use the V beta 8.2 gene to encode their T cell receptors. To analyze the structural prerequisites for the development of the MBP-specific T cell repertoire, we reconstituted severe-combined immunodeficient (SCID) mice with fetal (embryonic day 15-16) Lewis rat lymphoid tissue, and then isolated MBP-specific T cell lines from the adult chimeras after immunization. Two types of chimera were constructed: SCID mice reconstituted with rat fetal liver cells only, allowing T cell maturation within a chimeric SCID thymus consisting of mouse thymic epithelium and rat interdigitating dendritic cells, and SCID mice reconstituted with rat fetal liver cells and rat fetal thymus grafts, allowing T cell maturation within the chimeric SCID and the intact Lewis rat thymic microenvironment. Without exception, the T cell lines isolated from MBP-immunized SCID chimeras were restricted by MHC class II of the Lewis rat (RT1.B1), and none by I-Ad of the SCID mouse. Most of the T cell lines recognized the immunodominant MBP epitope 68-88. In striking contrast to intact Lewis rats, in SCID mice reconstituted by rat fetal liver only, MBP-specific T cell clones used a seemingly random repertoire of V beta genes without a bias for V beta 8.2. In chimeras containing fetal Lewis liver plus fetal thymus grafted under the kidney capsule, however, dominant utilization of V beta 8.2 was restored. The migration of liver-derived stem cells through rat thymus grafts was documented by combining fetal tissues from wild-type and transgenic Lewis rats. The results confirm that the recognition of the immunodominant epitope 68-88 by MBP-specific encephalitogenic T cells is a genetically determined feature of the Lewis rat T cell repertoire. They further suggest that the formation of the repertoire requires T cell differentiation in a syngeneic thymic microenvironment.

Amino Acid Sequence↗
PubMed1996

Isolated dihydroxyacetonephosphate-acyl-transferase deficiency in rhizomelic chondrodysplasia punctata: clinical presentation, metabolic and histological findings.

UNLABELLED: Rhizomelic chondrodysplasia punctata (RCDP) is clinically characterized by symmetrical shortening of the proximal limbs, contractures of joints, a characteristic dysmorphic face, and cataracts. In the classical form an impairment of several peroxisomal functions and enzymes (plasmalogen synthesis, phytanic acid oxidation, 3-oxoacyl-CoA thiolase) has been repeatedly shown. Recently a variant involving only the peroxisomal dihydroxyacetonephosphate acyltransferase (DHAP-AT) has been described. We present a patient with isolated DHAP-AT deficiency and all clinical, radiological and pathological features of classical RCDP. For the first time, microscopy and immunocytochemistry of hepatocytes could be performed. CONCLUSION: In contrast to studies on classical rhizomelic chondrodysplasia punctata which have shown enlarged peroxisomes in numbers varying from hepatocyte to hepatocyte, the peroxisomes in our patient seem to be normal in size, number and shape.

Acyltransferases↗