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Biomedical subjects

A Schmid

Publications and source records attributed to A Schmid.

At least 37 records · Page 2Linked to original sources
PubMed2002

PET quantitation and imaging of the non-pure positron-emitting iodine isotope 124I.

A series of PET studies using phantoms is presented to characterize the imaging and quantitative performance of the positron-emitting iodine isotope 124I. Measurements were performed on the 2D-PET scanner GE 4096+ as well as on the Siemens PET scanner HRR+ operated in both 2D and 3D modes. No specific correction was applied for the gamma-rays emitted together with the positrons. As compared to 18F, in studies with 124I there is a small loss of image resolution and contrast, and an increase in background. The quantitative results varied between different scanners and various acquisition as well as reconstruction modes, with an average relative difference of -6 +/- 13% (mean+/-SD) in respect of the phantom radioactivity as measured with gamma-ray spectroscopy. We conclude that quantitation of a radiopharmaceutical labelled with 124I is feasible and may be improved by the development of specific corrections.

Brain↗
PubMed2002

Hematological indices in elite cyclists.

BACKGROUND: Blood testing is a major concern in sports. Sporting federations have introduced cut-off values for hematological variables to limit blood manipulations. To date, no reference margins have been established to adjust single- or multivariable blood tests to the exercise adapted blood cell system of athletes. We studied hemoglobin (Hb), hematocrit (Hct), blood cell variables and changes in vascular volumes in male and female national team cyclists to evaluate the influence of exercise on these variables and the results of blood tests, and to estimate normal ranges in athletes for blood tests. METHODS: 1628 blood samples of 169 male and 55 female athletes were considered. Samples were analyzed automatically, blood cell indices and vascular volumes were calculated. Overall averages and seasonal differences were estimated. RESULTS: Hb-average was: 15.4 +/- 0.8 g dL(-1) for male and 13.9 +/- 0.7 g dL(-1) for female cyclists, Hct: 45 +/- 2.9% and 40.7 +/- 2.7%. Blood variables and vascular volumes showed significant seasonal changes. 1-6% of all samples were found above the currently used limits for blood testing. This is in accordance with the data from the normal population. Nevertheless, EPO misuse or blood manipulations cannot totally be excluded. CONCLUSION: Athletes display seasonal adaptations in their blood profile which should be considered in testing regulations. The presented data might be used as reference values for indirect single- and multivariable blood tests.

Adult↗
PubMed2002

Effects of exercise on soluble transferrin receptor and other variables of the iron status.

BACKGROUND: Soluble transferrin receptor (sTfr) is a new marker of iron status and erythropoietic activity. It has been included in multivariable blood testing models for the detection of performance enhancing erythropoietin misuse in sport. OBJECTIVE: To evaluate the effect of different types and volumes of physical activity on sTfr concentration, variables of iron status (ferritin, transferrin, iron, and protein), and haematological indices. METHODS: Thirty nine subjects were divided into three groups: 1, untrained (n = 12); 2, moderately trained (n = 14); 3, highly trained (n = 13, seven men, six women). Groups 1 and 2 carried out two exercise tests: an incremental running test until exhaustion (test A) and a 45 minute constant speed running test at 70% VO(2)MAX (test B). Group 3 performed three days (women) or four days (men) of prolonged aerobic cycling exercise. The above variables together with haemoglobin and packed cell volume were analysed in venous blood samples before and after exercise. Changes in blood and plasma volume were estimated. RESULTS: sTfr levels were slightly increased in trained and untrained subjects immediately after test A. Test B and aerobic exercise had no significant effect on sTfr. Ferritin levels were increased after the laboratory tests for trained and untrained subjects and after prolonged aerobic exercise in male cyclists. Transferrin was increased significantly in trained and untrained subjects after both laboratory tests, but remained unchanged after prolonged exercise. Plasma and blood volumes were decreased after the laboratory tests but increased after aerobic exercise. No differences in the variables were observed between trained and untrained subjects with respect to response to exercise. CONCLUSION: The changes in sTfr and the variables of iron status can be mainly attributed to exercise induced changes in volume. Taking these limitations into account, sTfr can be recommended as a marker of iron deficiency in athletes.

Adult↗
PubMed2001

Increasing the rate of chromatin remodeling and gene activation--a novel role for the histone acetyltransferase Gcn5.

Histone acetyltransferases (HATs) such as Gcn5 play a role in transcriptional activation. However, the majority of constitutive genes show no requirement for GCN5, and even regulated genes, such as the yeast PHO5 gene, do not seem to be affected significantly by its absence under normal activation conditions. Here we show that even though the steady-state level of activated PHO5 transcription is not affected by deletion of GCN5, the rate of activation following phosphate starvation is significantly decreased. This delay in transcriptional activation is specifically due to slow chromatin remodeling of the PHO5 promoter, whereas the transmission of the phosphate starvation signal to the PHO5 promoter progresses at a normal rate. Chromatin remodeling is equally delayed in a galactose-inducible PHO5 promoter variant in which the Pho4 binding sites have been replaced by Gal4 binding sites. By contrast, activation of the GAL1 gene by galactose addition occurs with normal kinetics. Lack of the histone H4 N-termini leads to a similar delay in activation of the PHO5 promoter. These results indicate that one important contribution of HATs is to increase the rate of gene induction by accelerating chromatin remodeling, rather than to affect the final steady-state expression levels.

Acetyltransferases↗
PubMed2001

[Cerebral tuberculosis in a patient with Sharp's syndrome].

HISTORY AND ADMISSION DIAGNOSIS: A 57-year-old female patient with fever and impaired consciousness was admitted to the department of neurology after her first epileptic seizure. She had a 9-year history of mixed connective tissue disease (MCTD, Sharp's syndrome) predominantly presenting with pulmonary symptoms and destructive arthritis. Endoprothetic surgery had to be performed several times and she was given long-term immunosuppressive therapy. INVESTIGATIONS: Cerebrospinal fluid analysis showed pleocytosis (59/mm3), high protein concentration (2540 mg/l) and low glucose level (31 mg/dl) compared to blood glucose level (122 mg/dl) the indicating possible tuberculous meningoencephalitis. DIAGNOSIS, TREATMENT AND COURSE: Tuberculostatic therapy was initiated, but despite extensive testing Mycobacterium tuberculosis could initially not be detected by microscopy, culture or amplification techniques (TMA; transcription mediated amplification). Clinical response to antituberculous therapy was poor and the patient developed cerebral ischaemia and hydrocephalus. Because of earlier histological findings from the synovialectomy showing epitheloid cell granuloma a knee joint specimen from a wound drainage was tested and extracerebral tuberculosis was finally confirmed by mycobacterial culture so that tuberculosis as the reason for the meningoencephalitis became highly probable. Despite slight improvements the patient still had hemiparesis and lethargy as neurological sequalae at the end of therapy. CONCLUSION: The case demonstrates the difficulties in the diagnosis of tuberculosis in patients with signs and symptoms similar for those caused by other multisystemic diseases. When tuberculous meningitis is considered, therapy should be initiated even in cases with negative microbiological tests because of severe consequences when treatment is delayed.

Brain Ischemia↗
PubMed2001

An fMRI study of anticipation and learning of smooth pursuit eye movements in humans.

We studied the neural substrate of anticipation and learning of smooth pursuit eye movements in humans using fMRI. Both predictable and non-predictable eye movements, compared to baseline, activated a common network previously associated with oculomotor function. The temporal dynamics of activity in a subset of these areas suggested a strong correlation with type of condition. Specifically, differential decreases in activity were seen in dorsolateral prefrontal cortex and the intraparietal sulcus during the predictable condition. During the non-predictable condition the same areas exhibited evidence of high levels of activity that further increased throughout the condition. In contrast, differential increases associated with the predictable condition were seen in anterior cingulate and preSMA cortex regions. These changes in activity mirror the time course of the short-term learning of eye movements seen behaviourally, and are congruent with learning-related changes that have been reported for other motor paradigms.

Adult↗
PubMed2001

Arachidonic acid modulates the spatiotemporal characteristics of agonist-evoked Ca2+ waves in mouse pancreatic acinar cells.

In pancreatic acinar cells analysis of the propagation speed of secretagogue-evoked Ca2+ waves can be used to examine coupling of hormone receptors to intracellular signal cascades that cause activation of protein kinase C or production of arachidonic acid (AA). In the present study we have investigated the role of cytosolic phospholipase A2 (cPLA2) and AA in acetylcholine (ACh)- and bombesin-induced Ca2+ signaling. Inhibition of cPLA2 caused acceleration of ACh-induced Ca2+ waves, whereas bombesin-evoked Ca2+ waves were unaffected. When enzymatic metabolization of AA was prevented with the cyclooxygenase inhibitor indomethacin or the lipoxygenase inhibitor nordihydroguaiaretic acid, ACh-induced Ca2+ waves were slowed down. Agonist-induced activation of cPLA2 involves mitogen-activated protein kinase (MAPK) activation. An increase in phosphorylation of p38(MAPK) and p42/44(MAPK) within 10 s after stimulation could be demonstrated for ACh but was absent for bombesin. Rapid phosphorylation of p38(MAPK) and p42/44(MAPK) could also be observed in the presence of cholecystokinin (CCK), which also causes activation of cPLA2. ACh-and CCK-induced Ca2+ waves were slowed down when p38(MAPK) was inhibited with SB 203580, whereas inhibition of p42/44(MAPK) with PD 98059 caused acceleration of ACh- and CCK-induced Ca2+ waves. The spreading of bombesin-evoked Ca2+ waves was affected neither by PD 98059 nor by SB 203580. Our data indicate that in mouse pancreatic acinar cells both ACh and CCK receptors couple to the cPLA2 pathway. cPLA2 activation occurs within 1-2 s after hormone application and is promoted by p42/44(MAPK) and inhibited by p38(MAPK). Furthermore, the data demonstrate that secondary (Ca2+-induced) Ca2+ release, which supports Ca2+ wave spreading, is inhibited by AA itself and not by a metabolite of AA.

Acetylcholine↗
PubMed2001

Industrial biocatalysis today and tomorrow.

The use of biocatalysis for industrial synthetic chemistry is on the verge of significant growth. Biocatalytic processes can now be carried out in organic solvents as well as aqueous environments, so that apolar organic compounds as well as water-soluble compounds can be modified selectively and efficiently with enzymes and biocatalytically active cells. As the use of biocatalysis for industrial chemical synthesis becomes easier, several chemical companies have begun to increase significantly the number and sophistication of the biocatalytic processes used in their synthesis operations.

Catalysis↗
PubMed2001

Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors.

BACKGROUND: A major current focus of pharmaceutical research is the development of selective inhibitors of the blood coagulation enzymes thrombin or factor Xa to be used as orally bioavailable anticoagulant drugs in thromboembolic disorders and in the prevention of venous and arterial thrombosis. Simultaneous direct inhibition of thrombin and factor Xa by synthetic proteinase inhibitors as a novel approach to antithrombotic therapy could result in potent anticoagulants with improved pharmacological properties. RESULTS: The binding mode of such dual specific inhibitors of thrombin and factor Xa was determined for the first time by comparative crystallography using human alpha-thrombin, human des-Gla (1--44) factor Xa and bovine trypsin as the ligand receptors. The benzamidine-based inhibitors utilize two different conformations for the interaction with thrombin and factor Xa/trypsin, which are evoked by the steric requirements of the topologically different S2 subsites of the enzymes. Compared to the unliganded forms of the proteinases, ligand binding induces conformational adjustments of thrombin and factor Xa active site residues indicative of a pronounced induced fit mechanism. CONCLUSION: The structural data reveal the molecular basis for a desired unselective inhibition of the two key components of the blood coagulation cascade. The 4-(1-methyl-benzimidazole-2-yl)-methylamino-benzamidine moieties of the inhibitors are able to fill both the small solvent accessible as well as the larger hydrophobic S2 pockets of factor Xa and thrombin, respectively. Distal fragments of the inhibitors are identified which fit into both the cation hole/aromatic box of factor Xa and the hydrophobic aryl binding site of thrombin. Thus, binding constants in the medium-to-low nanomolar range are obtained against both enzymes.

Animals↗
PubMed2001

Complex genetic interactions among four receptor tyrosine phosphatases regulate axon guidance in Drosophila.

Four receptor-linked protein tyrosine phosphatases are selectively expressed on central nervous system axons in the Drosophila embryo. Published data show that three of these (DLAR, DPTP69D, DPTP99A) regulate motor axon guidance decisions during embryonic development. Here we examine the role of the fourth neural phosphatase, DPTP10D, by analyzing double-, triple-, and quadruple-mutant embryos lacking all possible combinations of the phosphatases. This analysis shows that all four phosphatases participate in guidance of interneuronal axons within the longitudinal tracts of the central nervous system. In the neuromuscular system, DPTP10D works together with the other three phosphatases to facilitate outgrowth and bifurcation of the SNa nerve, but acts in opposition to the others in regulating extension of ISN motor axons past intermediate targets. Our results provide evidence for three kinds of genetic interactions among the neural tyrosine phosphatases: partial redundancy, competition, and collaboration.

Animals↗
PubMed2001

Guanylin in the human pancreas: a novel luminocrine regulatory pathway of electrolyte secretion via cGMP and CFTR in the ductal system.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a channel and regulator protein that is crucially involved in transepithelial ion transport. In the exocrine pancreas, the CFTR-mediated secretion of an electrolyte-rich fluid is a major but as yet incompletely understood function. We show here that the peptide guanylin is a specific activator of CFTR function in the human pancreas implicating regulation of pancreatic electrolyte secretion. Guanylin and its affiliated signaling and effector proteins including guanylate cyclase C, cGMP-dependent protein kinase II, CFTR, and the epithelial Cl-/HCO3- exchanger, anion exchanger 2, are highly expressed in the human pancreas. Guanylin is localized specifically to the typical centroacinar cells and proximal duct cells which, based on its additional presence in the pancreatic juice, is obviously released luminally into the pancreatic ducts. The guanylin receptor and the respective functional downstream proteins are all confined to the apical membrane of the duct cells implicating an as yet unknown route of luminal regulatory pathway of electrolyte secretion in the ductal system. Functional studies in two different human pancreatic duct cell lines expressing the CFTR Cl- channel that is functionally intact in CAPAN-1 cells but defective (delta F508) in CFPAC-1 cells clearly identify guanylin as a specific regulator of pancreatic CFTR channel function. Whole-cell patch-clamp recordings in CAPAN-1 cells revealed that forskolin induces an increase of Cl- conductance mediated by cAMP. In contrast, guanylin increased Cl- conductance in the same cells via cGMP but not cAMP; the respective membrane current was largely blockable by the sulfonylurea glibenclamide. In CFPAC-1 cells, however, neither guanylin nor forskolin produced a current activation. Based on the present findings we conclude that guanylin is an intrinsic pancreatic regulator of Cl- current activation in pancreatic duct cells via cGMP and CFTR. Remarkably, in the pancreas guanylin may exert its function through an intriguing luminocrine mode via the pancreatic juice.

Cyclic GMP↗
PubMed2001

CoenzymeA glutathione disulfide is a potent modulator of angiotensin II-induced vasoconstriction.

CoenzymeA glutathione disulfide (CoASSG) has recently been isolated from bovine adrenal glands and is assumed to play an important role in blood pressure (BP) control. We used the isolated perfused rat kidney to investigate the modulating effects of CoASSG on angiotensin II (AngII)-induced vasoconstriction. Permanent perfusion with CoASSG (1 micromol/L) for 60 min induced a significant (P < .05) shift to the left in the dose-response curve for AngII (about 3.1-fold), whereas the dose-response curve for norepinephrine (NE) was unaffected. During continuous perfusion with 1 micromol/L CoASSG, the repetitive application of 10 pmol AngII significantly increased its vasoconstriction by 170% +/- 14% (P < .05) and 235% +/- 50% (P < .05) for 60 and 120 min, respectively. The potentiation of AngII by permanent perfusion with CoASSG is dose- and time-dependent and shows a plateau at 120 min. Glutathione, oxidized coenzymeA, and coenzymeA (each 1 micromol/L) are not able to enhance the vasoconstriction induced by AngII. We conclude that CoASSG is able to potentiate the vasoactive properties of AngII, and that CoASSG might play an important role in BP regulation via modulating effects of AngII.

Angiotensin II↗
PubMed2001

Catecholamines response of high performance wheelchair athletes at rest and during exercise with autonomic dysreflexia.

Autonomic dysreflexia presents a special situation in high-lesion spinal cord injury, however, intentionally or self-induced autonomic dysreflexia directly before or during competition to increase performance, so called 'boosting', is also being reported. In order to examine the influence of autonomic dysreflexia on plasma catecholamines, cardiocirculatory and metabolic parameters, 6 spinal cord injured wheelchair athletes with high-level lesions underwent wheelchair ergometry without (ST1) and with (ST2) autonomic dysreflexia. At the point of exhaustion significantly higher values for norepinephrine and epinephrine were observed in ST2 than in ST1. During autonomic dysreflexia a significantly higher peak performance (77.5 vs. 72.5 watt), higher peak heart rate (161 vs. 149 x min(-1)), and peak oxygen consumption (1.96 vs. 1.85 l x min(-1)), with comparable peak lactate (7.11 vs. 7.00 mmol x l(-1)) were reached on average. The blood pressure values in ST2 were partially hypertensive and higher than in ST1. In conclusion, autonomic dysreflexia, as a sympathetic spinal reflex, leads to a higher release of catecholamines during exercise. This results in higher peak performance, peak heart rate, peak oxygen consumption, and higher blood pressure values. The peak lactate, as an indicator of the anaerobic lactate metabolism, was unchanged. However, autonomic dysreflexia presents an unpredictable risk, caused predominantly by hypertensive blood pressure values, for high-lesion spinal cord injured persons at rest and more so during exercise; it is seen as a prohibited manipulation by the doping guidelines of the International Paralympic Committee.

Adult↗
PubMed2001

Blood volume and hemoglobin mass in elite athletes of different disciplines.

Although it is well known that athletes have considerably larger blood volumes than untrained individuals, there is no data available describing the blood volume variability among differently trained athletes. The first aim of the study was to determine whether athletes from different disciplines are characterized by different blood volumes and secondly to what extent the blood volume can possibly limit endurance performance within a particular discipline. We investigated 94 male elite athletes subdivided into the following 6 groups: downhill skiing (DHS), swimming (S), running (R), triathlon (TA), cycling junior (CJ) and cycling professional (CP). Two groups of untrained subjects (UT) and leisure sportsmen (LS) served as controls. Total hemoglobin (tHb) and blood volume (BV) were measured by the CO-rebreathing method. In comparison to UT (mean +/- SD: tHb 11.0 +/- 1.1 g/kg, BV 78.3 +/- 7.9 ml/kg) tHb and BV were about 35 - 40 % higher in the endurance groups R, TA, CJ, and CP (e. g. in CP: tHb 15.3 +/- 1.3 g/kg, BV 107.1 +/- 7.0 ml/kg). Within the endurance groups we found no significant differences. The anaerobic discipline DHS was characterized by very low BV (87.6 +/- 3.1 ml/kg). S had an intermediate position (BV 97.4 +/- 6.1 ml/kg), probably because of the immersion effects during training in the water. VO(2)max was significantly related to tHb and BV not only in the whole group but also in all endurance disciplines. The reasons for the different BVs are an increased adaptation to training stimuli and probably also individual predisposing genetic factors.

Adult↗
PubMed2001

[CT-guided percutaneous core biopsy: Effective accuracy, diagnostic utility and effective costs].

PURPOSE: The value of a diagnostic technique does not only depend on its sensitivity, specificity and accuracy, but also on how its results affect clinical management. This effect is represented by the values effective accuracy and the diagnostic utility which were determined for CT-guided coaxial core biopsies in this study. MATERIALS AND METHODS: 180 consecutive biopsies were analyzed. The results were analyzed with the help of a logistic regression analysis with regard to the organ regions biopsied, the size of the needle used, and the number of tissue cores taken. Correct results that were not accepted as diagnostic clinically and resulted in additional biopsies were scored together with the false results under negative utility coefficients. RESULTS: The sensitivity, specificity and accuracy of all the tests amounted to 91.1 %, 100 %, and 93.3 %, respectively. The diagnostic utility of the biopsies varied between 66 % for the liver and pancreatic lesions, and 88 % for the non-organ related retroperitoneum. In those cases where more than three tissue cores were taken the results were statistically significantly better in terms of effective accuracy and diagnostic utility. No significant differences were found with regard to different needle sizes in the biopsied organ regions. The lowest clinical acceptance was observed for the histological findings "scar tissue" and "inflammation". CONCLUSION: CT-guided coaxial biopsies offer a high degree of sensitivity, specificity and accuracy, as well as a low rate of therapeutically relevant complications. With increasing use of differentiated strategies in therapy for malignomas percutaneous biopsies play a very important role in the management of these diseases. Prospective studies should further evaluate the effective accuracy and diagnostic utility of core biopsies also in comparison to fine needle aspiration biopsies (FNAP).

Adult↗
PubMed2001

Artificial oxygen carriers--the new doping threat in endurance sport?

Maximal oxygen uptake is the major performance limiting factor in endurance sports. Sophisticated training methods have been developed to increase this variable. On the other hand, attempts have been made to improve maximal oxygen uptake by artificial means: blood doping and the misuse of recombinant human erythropoietin have beneficial effects on aerobic exercise capacity. Both methods have been banned by international sporting federations. A new class of substances might represent the next step of fraudulent improvement of the maximal oxygen uptake: artificial oxygen carriers, such as solutions based on recombinant, bovine or human hemoglobin and perfluorocarbon-emulsions have been shown to improve oxygen delivery to the muscle. Hemoglobin-based solutions improve aerobic exercise capacity in animal and human testing. Both substances have potentially lethal side effects including renal toxicity, increased systemic and pulmonary blood pressure and impairment of the immune system. Hemoglobin-based carriers can be detected in drug testing with routine laboratory tests based on the detection of free hemoglobin. Perfluorocarbon is not metabolized by the body and exhaled through the lung and can be measured with chromatography. No screening for these substances in drug tests has been performed so far. International sporting federations should be aware of this new, emerging doping threat.

Biological Transport↗
PubMed2001

Left ventricular wall motion during diastolic filling in endurance-trained athletes.

PURPOSE: The purpose of this study was to assess left ventricular (LV) wall motion in highly endurance-trained athletes to evaluate LV diastolic function in physiologically hypertrophied hearts. BACKGROUND: Diastolic filling dynamics have previously been examined in endurance-trained athletes by measuring pulsed-wave mitral inflow velocities during the early and atrial filling phase, indicating an unimpaired LV function. Assessment of LV wall motion may give additional information about the LV diastolic function in endurance-trained athletes. METHODS: Left ventricular mass (LVM) and volume (LVV) were determined by M-mode echocardiography. Peak LV wall motion in the region of the basal septum close to the mitral anulus were measured during the early rapid and atrial filling phase by tissue Doppler in 30 endurance-trained athletes (T) and 16 sedentary control subjects (C) presumed to be healthy. RESULTS: Myocardial LVM and LVV in T (LVM 159.4 +/- 18.0 g.m(-2), LVV 100.4 +/- 13.0 mL.m(-2)) were significantly higher than in C (LVM 105.7 +/- 12.0.m(-2), LVV 70.1 +/- 11.9 mL.m(-2)), and heart rate (HR) was significantly lower (HR C: 69.6 +/- 11.0 bpm, T 50.9 +/- 8.7 bpm),which is consistent with endurance training (P < 0.01 for both). Peak LV wall motion during the early rapid filling phase did not differ significantly between the groups (T: 10.69 +/- 1.46 cm.(s-)1; C: 10.61 +/- 1.52 cm.(s-)1). Peak atrial wall motion was significantly lower in T (4.53 +/- 0.84 cm.s-1) versus C (5.74 +/- 0.75 cm.s(-1)), and the ratio of peak early diastolic to atrial wall motion was consequently higher in athletes (P < 0.01 for both). CONCLUSION: Regional wall motion at the basal septum near the mitral anulus during the early rapid filling phase is not altered by an increase in LVM or LVV when associated with endurance training.

Adult↗