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Biomedical subjects

A Schmid

Publications and source records attributed to A Schmid.

At least 55 records · Page 3Linked to original sources
PubMed2001

Cardiovascular, metabolic, and hormonal parameters in professional tennis players.

During the past decade, the physical and mental stress in professional tennis has been constantly increasing. The overall intensity in tennis ranges between 60 and 70% of maximum oxygen uptake and the energy requirements are mainly provided by aerobic energy metabolism. Therefore, particularly with respect to the duration of the tournaments and the length of the matches, a good aerobic capacity promotes continuous success in professional tennis. During frequent periods of high intensity, however, muscular energy is derived from anaerobic glycolysis. Therefore, sports-specific conditioning programs in tennis should improve both glycolytic and oxidative muscular metabolism. Years of training and competition induce a number of cardiovascular and metabolic adaptations: an increase in heart size in terms of an athlete's heart, higher oxygen uptake capacity, improved muscular oxidative enzyme activities, reduced baseline catecholamine levels, and a lower resting heart rate. In addition, tennis induces side-specific increments in bone density, bone diameter, and bone length of the upper extremity. Furthermore, structural and functional adaptations of the conducting arteries in the preferred arm could be demonstrated in professional tennis players. In conclusion, tennis is a very complex sport involving strength, power, speed, agility and explosiveness, as well as endurance components. Scientific data on exercise-related cardiovascular and metabolic parameters in professional tennis are important to evaluate the players individual fitness level and will help to improve sports-specific conditioning programs. This in turn will not only enhance performance but also prevent overstrain and burnout syndromes.

Adaptation, Physiological↗
PubMed2001

Transcriptional organization and dynamic expression of the hbpCAD genes, which encode the first three enzymes for 2-hydroxybiphenyl degradation in Pseudomonas azelaica HBP1.

Pseudomonas azelaica HBP1 degrades the toxic substance 2-hydroxybiphenyl (2-HBP) by means of three enzymes that are encoded by structural genes hbpC, hbpA, and hbpD. These three genes form a small noncontiguous cluster. Their expression is activated by the product of regulatory gene hbpR, which is located directly upstream of the hbpCAD genes. The HbpR protein is a transcription activator and belongs to the so-called XylR/DmpR subclass within the NtrC family of transcriptional activators. Transcriptional fusions between the different hbp intergenic regions and the luxAB genes of Vibrio harveyi in P. azelaica and in Escherichia coli revealed the existence of two HbpR-regulated promoters; one is located in front of hbpC, and the other one is located in front of hbpD. Northern analysis confirmed that the hbpC and hbpA genes are cotranscribed, whereas the hbpD gene is transcribed separately. No transcripts comprising the entire hbpCAD cluster were detected, indicating that transcription from P(hbpC) is terminated after the hbpA gene. E. coli mutant strains lacking the structural genes for the RNA polymerase sigma(54) subunit or for the integration host factor failed to express bioluminescence from P(hbpC)- and P(hbpD)-luxAB fusions when a functional hbpR gene was provided in trans. This pointed to the active role of sigma(54) and integration host factor in transcriptional activation from these promoters. Primer extension analysis revealed that both P(hbpC) and P(hbpD) contain the typical motifs at position -24 (GG) and -12 (GC) found in sigma(54)-dependent promoters. Analysis of changes in the synthesis of the hbp mRNAs, in activities of the 2-HBP pathway enzymes, and in concentrations of 2-HBP intermediates during the first 4 h after induction of continuously grown P. azelaica cells with 2-HBP demonstrated that the specific transcriptional organization of the hbp genes ensured smooth pathway expression.

Amino Acid Sequence↗
PubMed2001

Systemic and local immunosuppression in pancreatic cancer patients.

Pancreatic cancer is characterized by an extremely poor prognosis. For the development of more effective immunotherapies, the systemic and local immunological escape mechanisms need to be further elaborated. These mechanisms may include the secretion of immunosuppressive cytokines, the local hindrance of tumor-infiltrating lymphocytes (TILs), or the loss of the signal transducing CD3 zeta-chain of TILs. In this study, we have analyzed these parameters in 116 patients suffering from pancreatic ductal adenocarcinoma. Mean concentrations of interleukin (IL)-10 and transforming growth factor-beta1/2 were considerably higher than in control sera (P < 0.0001). Disseminated tumor cells were found in 16 of 39 cases. In 28 of 33 surgical specimens, TILs did not reach tumor cells in significant numbers, being "trapped" in the peritumoral tissues. We suggest this as a simple but highly effective tumor escape mechanism. In cases of a TIL/tumor cell contact, CD3 zeta was mostly lost. Overall, 27 of 33 surgical specimens, 9 of 19 peritumoral lymph nodes, and 13 of 25 peritoneal lavage specimens showed significant loss of CD3 zeta (P < 0.02). Elevated concentrations of IL-10/TGF-beta1/2 were, in all but one of three cases, correlated with a CD3 zeta loss in corresponding specimens. Patients with disseminated tumor cells also showed a CD3 zeta loss in all but two corresponding tumor specimens. These results present strong evidence for an active systemic immunosuppression in pancreatic cancer, as shown by elevated IL-10 and TGF-beta1/2 serum levels as well as the presence of disseminated tumor cells. Killing of tumor cells by potentially cytotoxic TILs is obviously suppressed by the prevention of a direct TIL/tumor cell contact and the inactivation of TILs, as shown by a severe loss of CD3 zeta. In addition to active immunization strategies, successful immunotherapies have to focus on restoring in vivo T-cell function to improve the almost always fatal prognosis of pancreatic cancer.

Adult↗
PubMed2001

Sonographic differentiation of stable and unstable lateral condyle fractures of the humerus in children.

Fractures of the lateral humeral condyle in children may cause difficulties in diagnosis and treatment. The fracture line involves the cartilaginous trochlea, which cannot be visualized on conventional radiographs. Therefore, a differentiation is not possible between the conservatively treated stable and the surgically treated unstable fracture, which involves the joint surface but is not dislocated primarily. We performed high-resolution ultrasonography in six children (age, 4-9 years) with a lateral condyle fracture of the humerus and uncertain joint involvement. Ultrasonography was able to visualize the fracture line through the joint surface in two children. Additional three-dimensional information could be gained that helped to plan further surgical procedures. The sonographic findings were confirmed intraoperatively and by magnetic resonance imaging in one child. In the remaining four children, ultrasonography was able to rule out joint involvement, thus classifying the fracture as stable. Conservative treatment was started, and the sonographic findings were confirmed by radiographs 4 days after the trauma to rule out secondary displacement. High-resolution ultrasonography is able to diagnose fracture involvement of the joint forming cartilaginous trochlea humeri in children, thus making further invasive or costly investigations such as magnetic resonance imaging unnecessary.

Cartilage, Articular↗
PubMed2001

[Arthroscopic shoulder stabilization].

Beside electro-thermic procedures (ETACS, LACS) several suture-anchor system for labrum fixation have been developed in the last years. From 4/96 to 10/00 we performed 242 arthroscopic shoulder stabilizations with FASTak-(n = 159) Panalok-(n = 26) and Suretac suture anchors (n = 57) in our clinic. The patients were re-examined with a follow-up of at least 12 months. The best results were in the FASTak-group. After 2 years 4.7% suffered a redislocation. 28.6% (2 patients) needed a revision. The Rowe score was 83.1 +/- 20.9 points. There was a high satisfaction of the patients with the operative result and 60.9% could go back to their pre-op sports level. Compared to open procedures the arthroscopic shoulder stabilization has many advantages. At 24-months follow-up this study demonstrates good results of arthroscopic shoulder stabilisation with FASTak suture anchors.

Adult↗
PubMed2000

Agonist-evoked mitochondrial Ca2+ signals in mouse pancreatic acinar cells.

In the present study we have investigated cytosolic and mitochondrial Ca(2+) signals in isolated mouse pancreatic acinar cells double-loaded with the fluorescent probes fluo-3 and rhod-2. Stimulation of pancreatic acinar cells with 500 nm acetylcholine caused release of Ca(2+) from intracellular stores and produced cytosolic Ca(2+) signals in form of Ca(2+) waves propagating from the luminal to the basal cell pole. The increase in the cytosolic Ca(2+) concentration was followed by Ca(2+) uptake into mitochondria. Between onset of cytosolic and mitochondrial Ca(2+) signals there was a delay of 10.7 +/- 0.4 s. Ca(2+) uptake into mitochondria could be inhibited with Ruthenium Red and carbonyl cyanide m-chlorophenylhydrazone, whereas 2,5-di-tert-butylhydroquinone, which inhibits sarco(endo)plasmic reticulum Ca(2+) ATPases, did not prevent Ca(2+) accumulation in mitochondria. Carbonyl cyanide m-chlorophenylhydrazone-induced Ca(2+) release from mitochondria could only be observed after a preceding stimulation of the cell with a physiological agonist or by treatment with 2, 5-di-tert-butylhydroquinone, indicating that under resting conditions mitochondria do not contain releasable Ca(2+) ions. Analysis of the propagation rate of acetylcholine-induced Ca(2+) waves revealed that inhibition of mitochondrial Ca(2+) uptake did not accelerate spreading of cytosolic Ca(2+) signals. Our experiments indicate that in the early phase of secretagogue-induced Ca(2+) signals, mitochondria behave as passive Ca(2+)-buffering elements and do not actively suppress spreading of Ca(2+) signals in pancreatic acinar cells.

Acetylcholine↗
PubMed2000

Production of enantiopure styrene oxide by recombinant Escherichia coli synthesizing a two-component styrene monooxygenase.

A whole cell biocatalytic process was developed to enable the efficient oxidation of styrene to chiral (S)-styrene oxide with an enantiomeric excess better than 99%. Recombinant Escherichia coli cells were employed to express the genes styAB encoding the styrene monooxygenase of Pseudomonas sp. strain VLB120 from an expression plasmid utilizing the alk regulatory system of P. oleovorans GPo1. The strains reached specific activities of up to 70 U* (g cell dry weight)(-1) in shake-flask experiments with glucose as the carbon source. An efficient two-liquid phase fed-batch process was established for the production of (S)-styrene oxide with hexadecane as an apolar carrier solvent and a nutrient feed consisting of glucose, magnesium sulfate, and yeast extract. Engineering of the phase fraction and the composition of organic phase and feed led to a 2-L scale process with maximal volumetric productivities of 2.2 g (S)-styrene oxide per liter liquid volume per hour. This optimized process was based completely on defined medium and used bis(2-ethylhexyl)phthalate as the apolar carrier solvent, which together with substrate and inducer consisted of 50% of the total liquid volume. Using this system, we were able to produce per liter liquid volume 11 g of enantiopure (S)-styrene oxide in 10 h.

Base Sequence↗
PubMed2000

Xylene monooxygenase catalyzes the multistep oxygenation of toluene and pseudocumene to corresponding alcohols, aldehydes, and acids in Escherichia coli JM101.

Xylene monooxygenase of Pseudomonas putida mt-2 catalyzes the methylgroup hydroxylation of toluene and xylenes. To investigate the potential of xylene monooxygenase to catalyze multistep oxidations of one methyl group, we tested recombinant Escherichia coli expressing the monooxygenase genes xylM and xylA under the control of the alk regulatory system of Pseudomonas oleovorans Gpo1. Expression of xylene monooxygenase genes could efficiently be controlled by n-octane and dicyclopropylketone. Xylene monooxygenase was found to catalyze the oxygenation of toluene, pseudocumene, the corresponding alcohols, and the corresponding aldehydes. For all three transformations (18)O incorporation provided stong evidence for a monooxygenation type of reaction, with gem-diols as the most likely reaction intermediates during the oxygenation of benzyl alcohols to benzaldehydes. To investigate the role of benzyl alcohol dehydrogenase (XylB) in the formation of benzaldehydes, xylB was cloned behind and expressed in concert with xylMA. In comparison to E. coli expressing only xylMA, the presence of xylB lowered product formation rates and resulted in back formation of benzyl alcohol from benzaldehyde. In P. putida mt-2 XylB may prevent the formation of high concentrations of the particularly reactive benzaldehydes. In the case of high fluxes through the degradation pathways and low aldehyde concentrations, XylB may contribute to benzaldehyde formation via the energetically favorable dehydrogenation of benzyl alcohols. The results presented here characterize XylMA as an enzyme able to catalyze the multistep oxygenation of toluenes.

Alcohols↗
PubMed2000

Gonadotropin-releasing hormone receptor initiates multiple signaling pathways by exclusively coupling to G(q/11) proteins.

The agonist-bound gonadotropin-releasing hormone (GnRH) receptor engages several distinct signaling cascades, and it has recently been proposed that coupling of a single type of receptor to multiple G proteins (G(q), G(s), and G(i)) is responsible for this behavior. GnRH-dependent signaling was studied in gonadotropic alphaT3-1 cells endogenously expressing the murine receptor and in CHO-K1 (CHO#3) and COS-7 cells transfected with the human GnRH receptor cDNA. In all cell systems studied, GnRH-induced phospholipase C activation and Ca(2+) mobilization was pertussis toxin-insensitive, as was GnRH-mediated extracellular signal-regulated kinase activation. Whereas the G(i)-coupled m2 muscarinic receptor interacted with a chimeric G(s) protein (G(s)i5) containing the C-terminal five amino acids of Galpha(i2), the human GnRH receptor was unable to activate the G protein chimera. GnRH challenge of alphaT3-1, CHO#3 and of GnRH receptor-expressing COS-7 cells did not result in agonist-dependent cAMP formation. GnRH challenge of CHO#3 cells expressing a cAMP-responsive element-driven firefly luciferase did not result in increased reporter gene expression. However, coexpression of the human GnRH receptor and adenylyl cyclase I in COS-7 cells led to clearly discernible GnRH-dependent cAMP formation subsequent to GnRH-elicited rises in [Ca(2+)](i). In alphaT3-1 and CHO#3 cell membranes, addition of [alpha-(32)P]GTP azidoanilide resulted in GnRH receptor-dependent labeling of Galpha(q/11) but not of Galpha(i), Galpha(s) or Galpha(12/13) proteins. Thus, the murine and human GnRH receptors exclusively couple to G proteins of the G(q/11) family. Multiple GnRH-dependent signaling pathways are therefore initiated downstream of the receptor/G protein interface and are not indicative of a multiple G protein coupling potential of the GnRH receptor.

Adenylyl Cyclases↗
PubMed2000

Role of muscles accumbens dopamine D1 and D2 receptors in instrumental and Pavlovian paradigms of conditioned reward.

RATIONALE: This study investigated the role of nucleus accumbens dopamine D1 and D2 receptors in two different paradigms of conditioned reward. OBJECTIVE: We addressed the question whether accumbal dopamine is important for the motor or for the motivational components of reward. METHODS: We compared the effects of intra-accumbal infusion of the dopamine D1 receptor antagonist SCH23390 (0.3, 1.0, 3.0 microg) and the D2 receptor antagonist sulpiride (0.3, 1.0, 3.0 microg) on conditioned lever pressing for food, with the effects on the inhibition of the startle response by a conditioned reward signal. RESULTS: Both the D1 and the D2 antagonist dose-dependently attenuated conditioned lever pressing for reward under a fixed-ratio of responding and increased the consumption of freely available lab chow. However, the preference for freely available pellets, and the attenuation of the startle response in the presence of a conditioned stimulus predicting reward were not impaired by blockade of accumbal dopamine receptors. CONCLUSIONS: Our data support the idea that dopamine in the nucleus accumbens is necessary for instrumental response selection in the context of reward rather than for the mere motor performance of behavior or for the evaluation of the hedonic properties of rewarding stimuli.

Animals↗
PubMed2000

Osseous overgrowth after post-traumatic amputation of the lower extremity in childhood.

Severe accidents in children may cause extreme destruction of the lower extremities. In some cases, there is no possibility to preserve the limbs. Initially, a weight-bearing stump cannot be achieved after amputation due to unstable local and soft tissue conditions. This critical situation is often complicated by one of the leading problems in the limb-deficient child - the development of osseous overgrowth. Bizarre overgrowth of the stump may lead to skin perforation, pressure ulcers, and difficulties with the prosthesis. Since 1993, we have been able to follow five pediatric and adolescent patients (2 years to 17 years old) with six post-traumatic amputations of the lower extremities. Four of these cases developed osseous overgrowth. One child treated with initial autologous stump-capping had excellent soft tissue conditions and no problems with the artificial limb. We also report on a case of bizarre and extensive new bone formation. We conclude that close follow-up visits after post-traumatic amputations in children are essential because of new bone formation which may endanger the soft tissue situation of the stump. Unfortunately, surgical revisions have to be performed quite often. To avoid several surgical corrections, an initial stump-capping with autologous material from the injured limb can be performed. Thus, the number of secondary procedures may be reduced drastically.

Adolescent↗
PubMed2000

Characterization of channel-forming activity in muscle biopsy from a porin-deficient human patient.

A bioptic specimen from the muscles of a patient suffering from severe myopathy was inspected for the presence of human porin 31HL. Western blotting suggested that the specimen was free of the most abundant eukaryotic porin 31HL (HVDAC1). The specimen was treated with detergent and the soluble protein fraction was passed through a dry hydroxyapatite column. The passthrough of this column was inspected for channel formation in artificial lipid-bilayer membranes. The channel observed under these conditions had a single-channel conductance of about 2.5 nS in 1 M KCl, was cation selective, and was found to be virtually voltage independent. Experiments with a control specimen from a healthy human being, without any indication for muscle myopathy, revealed the presence of the voltage-dependent porin 31HL in the sample. It is discussed whether the patient's bioptic specimen contained another human porin, which has not been studied to date in its natural environment.

Biopsy↗
PubMed2000

[Epidemiology of obesity].

Obesity is a well-recognized health hazard in affluent societies. The prevalence of overweight and obesity are high and still increasing consistently in industrialized countries. The body mass index (BMI) is an internationally accepted index to estimate body weight. The recent published WHO-classification of body weight allows the worldwide comparison of obesity prevalences. The WHO-MONICA study revealed different obesity prevalences in several European countries. The lowest prevalence of obesity was found in Sweden and Northern France (7-14%) whereas the highest prevalence (40%) was reported from East-European countries. The results of the DHP-survey suggest that 50% of the adult German population are overweight and 20% are obese. Data from the MONICA-study show lower prevalences for Switzerland, where 38% of the adult population are considered to have overweight and 11% are obese. By the way the prevalence of obesity is still increasing with a renewed acceleration during the last two decades. Obesity is starting to get the status of a main health problem not only in western countries but also in less developed countries of Middle- and South-America. In Germany obesity and the obesity-related morbidity and mortality caused costs of nearly 20.7 Mrd. DM in 1995. Therefore obesity is a major economic burden for the society. Like in other developed countries the costs attributable to obesity correspond to 2-8% of total health care expenditure.

Adult↗
PubMed2000

Lipoproteins and free plasma catecholamines in spinal cord injured men with different injury levels.

Persons with spinal cord injury (SCI) are especially prone to atherogenesis. This is partly explained by an unfavourable lipoprotein profile in these individuals. The impairment of the sympathetic nervous system, and the fact that SCI subjects are subject to extreme physical inactivity, may have an influence on their lipid profile and lipoprotein(a) concentration. We made a detailed investigation of the lipid profile as well as serum levels of adrenaline and noradrenaline in 80 men with SCI ranging from tetraplegia to low paraplegia and in 16 control subjects. The lipid profile of tetraplegics was characterized by elevated very low-density lipoprotein cholesterol and triglyceride levels and reduced high-density lipoprotein levels. In contrast, paraplegics had significantly higher low-density lipoprotein and total cholesterol levels. Tetraplegics had lower and the low-lesion paraplegics had higher adrenaline and noradrenaline levels than the high-lesion paraplegics and the control subjects. High-lesion SCI subjects also showed an extreme reduction in VO2max. The lipoprotein profile was dependent on the injury level and serum catecholamine concentrations. The lower the noradrenaline values, the lower the high-density lipoprotein cholesterol. The low-density lipoprotein also correlated to catecholamines and particularly adrenaline values. Despite the correlation between lipoprotein(a) and adrenaline, no significant differences in lipoprotein(a) were found within SCI individuals as well as between SCI individuals and control subjects, indicating the predominantly genetic determination of lipoprotein(a) and thus the cardiovascular risk. Different serum catecholamine levels due to impairment of sympathetic nervous system and VO2max levels were observed in SCI subjects. This was associated with a higher lipid risk profile for cardiovascular diseases; however, the risk profile is dependent on the lesion level.

Adult↗
PubMed2000

Haemoglobin, haematocrit and red blood cell indices in elite cyclists. Are the control values for blood testing valid?

BACKGROUND: In international cycling and cross-country skiing competitions, blood tests are used to unmask the performance enhancing misuse of erythropoietin. Haematocrit (cycling) and haemoglobin (cross-country skiing) limits have been set by international sporting federations (haematocrit 50%, haemoglobin 18.5 g/dl). Athletes tested above these cut-off values are declared unfit for competition. To investigate the validity of these regulations, we studied haemoglobin, haematocrit and red blood cell indices of elite cyclists before erythropoietin became commercially available. MATERIAL AND METHODS: We investigated 523 blood samples of 92 male elite cyclists (age 16-31 years) from 1978 to 1987. Haematocrit, haemoglobin and red blood cell count were analysed automatically, erythrocyte indices were calculated. RESULTS: Haemoglobin (-0.3 +/- 1 g/dl), haematocrit (-1.2 +/- 2.8%) and red blood cell count (-0.2 +/- 0.4 x 10(6)/mm3) decreased significantly (p < 0.05) with increasing training workload. The erythrocyte indices showed no significant change. Fifty-four blood samples (10.3%) showed a haematocrit above 50%, one sample presented a haemoglobin mass higher than 18.5 g/dl. During periods of increased workload, less athletes tested above the haematocrit limit. CONCLUSION: The current haematocrit limit used in blood tests might lead to a high number of false positive tests.

Adolescent↗
PubMed2000

Elevation of plasma prolactin in patients undergoing autologous blood stem-cell transplantation for breast cancer: is its modulation a step toward posttransplant immunotherapy?

Prolactin is a suspected promotor of breast cancer cell growth, and it shares pleiotropic immunoregulatory properties. We studied plasma prolactin and its drug-induced modulation in 20 women with breast cancer undergoing high-dose chemotherapy and autologous blood stem-cell transplantation. Plasma prolactin levels were serially assayed before and during conditioning and within and beyond 30 days after transplant. Before transplant, prolactin plasma levels were in the age-adjusted range of normal women. During conditioning and within 30 days after transplant, prolactin levels increased in all patients (p < 0.0001), but remained in the normal range. Antiemetic drugs such as metoclopramide and phenothiazines, known to enhance pituitary prolactin secretion, further elevated prolactin plasma levels (p < 0.00001). Patients remaining in continuous complete remission after transplant (median follow-up, 3 years) disclosed higher prolactin levels compared with those obtaining only partial remission or ensuing early relapse. Prolactin levels are regularly elevated during conditioning and within 30 days after autologous transplantation for breast cancer. Further elevations of prolactin plasma levels are induced by metoclopramide and other antiemetic drugs. Elevated plasma prolactin had no adverse effect on disease-free survival after transplant. We propose to investigate further the upregulation of prolactin after transplant aiming to induce a posttransplant consolidative immune reaction.

Adult↗