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T Schaub

Publications and source records attributed to T Schaub.

At least 19 recordsLinked to original sources
PubMed2004

Threshold extraction in metabolite concentration data.

MOTIVATION: Continued development of analytical techniques based on gas chromatography and mass spectrometry now facilitates the generation of larger sets of metabolite concentration data. An important step towards the understanding of metabolite dynamics is the recognition of stable states where metabolite concentrations exhibit a simple behaviour. Such states can be characterized through the identification of significant thresholds in the concentrations. But general techniques for finding discretization thresholds in continuous data prove to be practically insufficient for detecting states due to the weak conditional dependences in concentration data. RESULTS: We introduce a method of recognizing states in the framework of decision tree induction. It is based upon a global analysis of decision forests where stability and quality are evaluated. It leads to the detection of thresholds that are both comprehensible and robust. Applied to metabolite concentration data, this method has led to the discovery of hidden states in the corresponding variables. Some of these reflect known properties of the biological experiments, and others point to putative new states. AVAILABILITY: An implementation of this approach can be obtained from the authors upon request.

Algorithms↗
PubMed2001

High glucose dialysis solutions increase synthesis of vascular endothelial growth factors by peritoneal vascular endothelial cells.

OBJECTIVE: Increased peritoneal vasculature has been reported in long-term peritoneal dialysis (PD), and vascular endothelial growth factors (VEGFs) have been found in dialysate. High concentrations of glucose or lactate, glucose degradation products (GDPs), and low pH of dialysis solutions are all possible factors in increased peritoneal VEGF synthesis. In this study, we investigated the effects of high glucose dialysis solutions on VEGF synthesis by peritoneal vascular endothelial cells (PVECs). METHODS: The PVECs were isolated from rat omentum and were incubated for 4 hours in three different culture media [M199 media (control), conventional dialysis solutions containing 4.25% glucose diluted with an equal volume of M199 media (HGD), and M199 media containing 118 mmol/L mannitol as an osmolar control (mannitol)]. Levels of VEGF protein in the culture supernatant were measured by ELISA, and mRNA expression was determined by Northern blot analysis. Data are presented as percent of control. RESULTS: After incubation for 4 hours, the number of cells did not differ between the 3 groups. Levels of VEGF in culture supernatant were significantly higher in the HGD group (124% +/- 19%, p = 0.006) as compared with the control and mannitol (85% +/- 10%) groups. The mRNA expression of VEGF appeared to be higher in the HGD group (128% +/- 49%) than in the control and mannitol (94% +/- 18%) groups. CONCLUSION: High glucose dialysis solutions increased VEGF synthesis by PVECs. The relationship between VEGF synthesis by PVECs and neovascularization of the peritoneum observed in long-term peritoneal dialysis patients has to be studied further.

Animals↗
PubMed2000

Developmental regulation of FKBP65. An ER-localized extracellular matrix binding-protein.

FKBP65 (65-kDa FK506-binding protein) is a member of the highly conserved family of intracellular receptors called immunophilins. All have the property of peptidyl-prolyl cis-trans isomerization, and most have been implicated in folding and trafficking events. In an earlier study, we identified that FKBP65 associates with the extracellular matrix protein tropoelastin during its transport through the cell. In the present study, we have carried out a detailed investigation of the subcellular localization of FKBP65 and its relationship to tropoelastin. Using subcellular fractionation, Triton X-114 phase separation, protease protection assays, and immunofluorescence microscopy (IF), we have identified that FKBP65 is contained within the lumen of the endoplasmic reticulum (ER). Subsequent IF studies colocalized FKBP65 with tropoelastin and showed that the two proteins dissociate before reaching the Golgi apparatus. Immunohistochemical localization of FKBP65 in developing lung showed strong staining of vascular and airway smooth muscle cells. Similar areas stained positive for the presence of elastic fibers in the extracellular matrix. The expression of FKBP65 was investigated during development as tropoelastin is not expressed in adult tissues. Tissue-specific expression of FKBP65 was observed in 12-d old mouse tissues; however, the pattern of expression of FKBP65 was not restricted to those tissues expressing tropoelastin. This suggests that additional ligands for FKBP65 likely exist within the ER. Remarkably, in the adult tissues examined, FKBP65 expression was absent or barely detectable. Taken together, these results support an ER-localized FKBP65-tropoelastin interaction that occurs specifically during growth and development of tissues.

Amino Acid Sequence↗
PubMed1999

Characterization of an in vitro model of elastic fiber assembly.

Elastic fibers consist of two morphologically distinct components: elastin and 10-nm fibrillin-containing microfibrils. During development, the microfibrils form bundles that appear to act as a scaffold for the deposition, orientation, and assembly of tropoelastin monomers into an insoluble elastic fiber. Although microfibrils can assemble independent of elastin, tropoelastin monomers do not assemble without the presence of microfibrils. In the present study, immortalized ciliary body pigmented epithelial (PE) cells were investigated for their potential to serve as a cell culture model for elastic fiber assembly. Northern analysis showed that the PE cells express microfibril proteins but do not express tropoelastin. Immunofluorescence staining and electron microscopy confirmed that the microfibril proteins produced by the PE cells assemble into intact microfibrils. When the PE cells were transfected with a mammalian expression vector containing a bovine tropoelastin cDNA, the cells were found to express and secrete tropoelastin. Immunofluorescence and electron microscopic examination of the transfected PE cells showed the presence of elastic fibers in the matrix. Biochemical analysis of this matrix showed the presence of cross-links that are unique to mature insoluble elastin. Together, these results indicate that the PE cells provide a unique, stable in vitro system in which to study elastic fiber assembly.

Animals↗
PubMed1993

[Computed tomography following extracorporeal shockwave lithotripsy of the kidneys. III. A prospective CT study of 105 patients and a 3-year follow-up of 23 patients using CT and 99mTc-MAG3 clearance].

In 105 patients CT studies were done prospectively after renal ESWL with a second generation lithotripter. 33 (31%) of the patients had renal oedema (n = 8), renal (n = 20) or extrarenal (n = 31) bleeding. Three of the 23 patients who had a three year follow-up had chronic renal changes, 10 had renal stones. As blunt renal trauma can be the cause of renal hypertension a longterm follow-up is necessary in ESWL patients, particularly if there was renal bleeding after treatment. Further studies are needed to determine the exact risk of renal hypertension after ESWL.

Adult↗
PubMed1992

[99m-Technetium-mercaptoacetyltriglycine (MAG3) for the demonstration of the kidney changes following extracorporeal shockwave lithotripsy. A prospective study of 117 patients].

Extracorporeal shock wave lithotripsy (ESWL) has become the treatment of choice for urinary calculi. 117 patients were studied prospectively with 99mTc mercaptoacetyltriglycine (MAG3) before and after ESWL. 79 (66%) of the 119 kidneys treated had abnormal findings. Of these 63/119 (53%) had abnormal scans. 41 (65%) had focal lesions with a delayed intrarenal transport. The remaining 22 had a diffuse delay of intrarenal transport. A loss of relative renal function of 3% and more compared to the pretreatment values was observed in 50/119 (42%) patients. 99mTc MAG3 should be done routinely together with radiologic tests (CT or MRI) before and after ESWL to select the patients at risk for post ESWL hypertension.

Female↗
PubMed1991

ATP-dependent leukotriene export from mastocytoma cells.

The biosynthesis of leukotrienes (LT) C4 and B4 is followed by an export of these mediators into the extracellular space. This transport was characterized using plasma membrane vesicles prepared from mastocytoma cells and identified as an ATP-dependent primary active process. The apparent Km-values were 110 nM for LTC4 and 48 microM for ATP. The transport rate was highest for LTC4, whereas LTD4, LTE4, and N-acetyl-LTE4 were transported with relative rates of 31, 12 and 8%, respectively, at a concentration of 10 nM. LTB4 transport was also dependent on ATP. LTC4 transport was inhibited by LTD4 receptor antagonists (IC50 = 1.0 microM for MK-571 and 1.3 microM for LY245769) and by the inhibitor of leukotriene biosynthesis MK-886 (IC50 = 1.8 microM). The ATP-dependent export carrier for leukotrienes in leukotriene-synthesizing cells represents a novel member of the family of ATP-dependent exit pumps.

Adenosine Triphosphate↗
PubMed1991

[Computed tomography following extracorporeal shockwave lithotripsy (ESWL) of the kidneys. I: Correlation with acute histopathological findings in experimental animals].

In an experimental study on pigs, 28 stone-free kidneys were treated with a second generation lithotripter. Histologically, acute bleeding was seen after ESWL in 23 (82%) of the 28 treated kidneys. CT studies before and after contrast were correct in 20/28 (74%) cases. It was shown that extracorporeal shock waves cause renal bleeding that is only partially detected by computed tomography. It can be concluded that the CT findings seen in a high percentage of renal stone patients after ESWL represent bleeding. The incidence of renal bleeding after ESWL and thus the possible risk of hypertension has obviously been underestimated so far in clinical studies.

Animals↗
PubMed1991

[Computed tomography after extracorporeal shockwave lithotripsy (ESWL) of the kidneys. II. A correlation with the histopathologic findings 3 weeks later in an animal experiment].

In a pig model, 13 kidneys were treated with a second generation lithotripter and examined by CT immediately and three weeks after ESWL. 9 (69%) acute traumatic lesions were seen in CT without, and 10 (77%) in CT with contrast in the 13 treated kidneys. After 3 weeks only 1 residual lesion persisted in CT contrast studies. On the histopathologic specimens residuals of bleeding were found in 3 (23%) of the 13 kidneys treated, which could not be seen in CT studies. CT is accurate in monitoring acute traumatic renal lesions after ESWL, but appears less reliable in chronic ones. Three weeks after ESWL traumatic renal lesions show marked regression.

Animals↗
PubMed1990

[Acute effects of the natural atmospheric ozone exposure on lung function of clinically normal smokers and non-smokers].

The influence of moderate ambient ozone exposure on spirometric lung function and bronchial responsiveness was analyzed in 13 healthy adult nonsmokers and 11 asymptomatic smokers. The study was divided into an initial investigation at low atmospheric ozone concentrations of about 80 (range 68-102) micrograms/m3 and a subsequent similar testing at moderately elevated ozone concentrations above 140 (range 145-205) micrograms/m3. Overall there was a slight but significant impairment in forced expiratory volumes (p less than 0.002) at elevated compared with low ozone concentrations. Furthermore, a significant increase in bronchial responsiveness was shown, with a decrease in threshold dose for inhaled metacholine to produce a 50% fall in specific airway conductance (p less than 0.02). In both smokers and nonsmokers there was a similar change in lung function at ambient ozone concentrations, with more pronounced bronchial irritation in the smokers group. It is concluded that even moderately elevated ambient ozone concentrations can induce slight but significant ventilatory obstruction and an obvious increase in bronchial responsiveness in healthy adults. Although the minor impairment of lung function did not cause manifest acute respiratory problems, it still reduced maximal physical ventilation capacity. The results further support the assumption that air pollution may act as a primary trigger in the development of obstructive airway disease.

Airway Obstruction↗
PubMed1990

ATP-dependent primary active transport of cysteinyl leukotrienes across liver canalicular membrane. Role of the ATP-dependent transport system for glutathione S-conjugates.

The liver is the major organ which eliminates leukotriene C4 (LTC4) and other cysteinyl leukotrienes from the blood circulation into bile. Transport of LTC4 was studied using inside-out vesicles enriched in canalicular and sinusoidal membranes from rat liver. The incubation of canalicular membrane vesicles with [3H]LTC4 in the presence of ATP resulted in an uptake of LTC4 into vesicles. The initial rate of ATP-stimulated LTC4 uptake was about 40-fold higher in canalicular than in sinusoidal membrane vesicles. When liver plasma membrane vesicles were incubated in the absence of ATP, an apparent transient uptake of LTC4 was observed which was temperature-dependent and not affected by the osmolarity. This indicates that LTC4 was bound to proteins on the surface of plasma membrane vesicles. Two proteins with relative molecular weights of 17,000 and 25,000 were detected by direct photoaffinity labeling as major LTC4-binding proteins. One protein (Mr 25,000) was ascribed to subunit 1 (Ya) of glutathione S-transferase which was associated with the membrane. LTD4, LTE4, N-acetyl-LTE4, and omega-carboxy-N-acetyl-LTE4 were also transported into liver plasma membrane vesicles in an ATP-dependent manner with initial rates relative to LTC4 (1.0) of 0.46, 0.11, 0.35, and 0.22, respectively. Mutual competition between the cysteinyl leukotrienes and S-(2,4-dinitrophenyl)-glutathione for uptake indicated that they are transported by a common carrier. Apparent Km values of the transport system for LTC4, LTD4, and N-acetyl-LTE4 were 0.25, 1.5, and 5.2 microM, respectively. The ATP-dependent transport of LTC4 into vesicles was not inhibited by doxorubicin, daunorubicin, or verapamil, or by the monoclonal antibody C219, suggesting that the transport system differs from P-glycoprotein. Liver plasma membrane vesicles prepared from mutant rats deficient in the hepatobiliary excretion of cysteinyl leukotrienes lacked the ATP-dependent transport of cysteinyl leukotrienes and S-(2,4-dinitrophenyl)-glutathione. These results demonstrate that the ATP-dependent carrier system is responsible for the transport of cysteinyl leukotrienes and glutathione S-conjugates from the hepatocytes into bile.

Adenosine Triphosphate↗
PubMed1990

Nuclear medicine studies in the differential diagnosis of diseases with spinal involvement.

Plain X-rays computed tomographic and magnetic resonance images all yield information on the pathophysiology of diseases with spinal involvement. Descriptions of the following nuclear medicine methods are presented: Bone scanning with 99 m-technetium labeled phosphonate complexes used for the evaluation of skeletal metastases, primary bone tumors, traumatic, degenerative, and postoperative changes as well as in inflammatory conditions. Specific radionuclides used for the localization of inflammatory conditions are radioactive labeled leucocytes. Iodine total body scans used to detect spinal metastases of follicular and papillary thyroid carcinoma. 201-thalliumchloride is used as a tumor-marker with high affinity and sensitivity in malignant thyroid tumors. 131- or 123-iodine-meta-iodobenzylguanidine scans used in the detection of metastases of pheochromocytoma and neuroblastoma. Immunoscintigraphy with radioactive labeled anti-CEA antibodies used for the specific labelling of metastases of gastrointestinal tract tumors, melanoma, breast, and ovarian carcinoma. The value of the various nuclear medicine methods in the diagnostic schedule is illustrated in case reports.

Humans↗
PubMed1990

[Melorheostosis, osteopoikilosis and ostiopathia striata. Their clinical significance and the value of scintigraphy in the differential diagnosis].

Melorheostosis, Osteopoikilosis and Osteopathia striata Clinical Relevance and Bone Scintigraphy Melorheostosis, Osteopoikilosis and Osteopathia striata are rare conditions. Although there is no casual therapy for any of the three diseases, differential diagnosis is important because concomitant or resulting impairments deserve orthopaedic or medical treatment. The analysis of typical cases with their clinical, roentgenological and radionuclide presentation shows the need of an accurate diagnosis to prevent senseless treatment or lost therapeutic opportunities.

Adult↗
PubMed1989

[The place of bone scintigraphy in the diagnosis and follow-up of Ewing's sarcoma].

The radiological and scintigraphic findings of 26 patients with histologically proven Ewing's sarcoma were analysed. Three-phase bone scan should be done early in patients presenting with pain and normal radiographs. Perfusion and metabolism of a bone lesion can be assessed by skeletal scintigraphy. Bone metastases are first seen on bone scan. In the follow-up of the patient bone scans at regular intervals are essential to detect bone metastases and tumour recurrence. The scintigraphic findings have to be correlated with radiographs and if these are negative a short-term control is indicated. Three-phase bone scans can assess the tumours response to therapy.

Adolescent↗
PubMed1989

[A computed tomographic analysis of vertebral rotation before and after surgical correction of idiopathic scoliosis].

Preoperative and postoperative computer tomographs in 24 patients suffering from idiopathic scolioses who were treated by CD (Cotrel-Dubousset) surgery, showed a mean correction of the rotatory angle in the apex vertebra amounting to 28.5% in relation to the anterior midline of the body, and 23.8% in relation to the sagittal plane. Best results were seen in lumbar curves and in the lumbar curves of double major curves. In thoracic curves only minor corrections were observed. CD instrumentation is the first dorsal procedure that allows a three-dimensional correction of the scoliotic spine.

Adolescent↗