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C Schmitz

Publications and source records attributed to C Schmitz.

At least 19 recordsLinked to original sources
PubMed2001

ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology.

Free ADP-ribose (ADPR), a product of NAD hydrolysis and a breakdown product of the calcium-release second messenger cyclic ADPR (cADPR), has no defined role as an intracellular signalling molecule in vertebrate systems. Here we show that a 350-amino-acid protein (designated NUDT9) and a homologous domain (NUDT9 homology domain) near the carboxy terminus of the LTRPC2/TrpC7 putative cation channel both function as specific ADPR pyrophosphatases. Whole-cell and single-channel analysis of HEK-293 cells expressing LTRPC2 show that LTRPC2 functions as a calcium-permeable cation channel that is specifically gated by free ADPR. The expression of native LTRPC2 transcripts is detectable in many tissues including the U937 monocyte cell line, in which ADPR induces large cation currents (designated IADPR) that closely match those mediated by recombinant LTRPC2. These results indicate that intracellular ADPR regulates calcium entry into cells that express LTRPC2.

Adenosine Diphosphate Ribose↗
PubMed2001

N-Nitrosomorpholine induced alterations of unscheduled DNA synthesis, mitochondrial DNA synthesis and cell proliferation in different cell types of liver, kidney, and urogenital organs in the rat.

In order to measure rates of unscheduled DNA synthesis (UDS), mitochondrial DNA synthesis, and cell proliferation, i.e. factors relevant in the early phase of carcinogenesis, young rats received by gavage 200 mg/kg N-nitrosomorpholine (NNM) or vehicle (distilled water), and were injected with 3H-thymidine 24 h later. Autoradiographs from liver, kidney, urethra, prostate, seminal vesicle, and ductus deferens were prepared from deparaffinized sections, using a 250-day exposure time. In the liver, UDS was at least doubled in 2n and 4n hepatocytes. Approximately 3% of these hepatocytes exhibited a fourfold increase in UDS. Such strongly labeled cells were only observed in the liver following NNM exposure. With the exception of renal epithelial cells of the proximal tubule, UDS in epithelial cells of bladder, urethra, ductus deferens, seminal vesicle and prostate was decreased in NNM-exposed rats. Mitochondrial DNA synthesis and cell proliferation were significantly increased only in hepatocytes, and were decreased in all other monitored organs in NNM-exposed rats. The strongly increased UDS and more moderately increased mitochondrial DNA synthesis in a subgroup of hepatocytes suggest that possibly some unrepaired damage persists in the DNA of these cells. The latter cells may be the precursors of so-called foci of hepatocellular alteration, which appear later during the process of carcinogenesis. The increased UDS but decreased rate of proliferation in the renal proximal tubule cells might be related to renal carcinogenesis which is observed in NNM-exposed rats after a long latency period.

Animals↗
PubMed2001

On the impact of calcified deposits within the rotator cuff tendons in shoulders of patients with shoulder pain and dysfunction.

We wanted to prove the hypothesis that calcified deposits within the rotator cuff tendons are merely an epiphenomenon of complex morphological alterations in the shoulders of patients with shoulder pain and dysfunction. The shoulders of 92 patients with calcified deposits within the rotator cuff tendons as noted on plain radiographs were investigated by means of magnetic resonance imaging (MRI; mean age of patient 51.1 years), as well as the shoulders of 28 age- and sex-matched patients with similar clinical symptoms but without any signs of such calcified deposits on plain radiographs. The MRI protocol comprised a coronal, oblique, T1-weighted, spin-echo sequence, a T2-weighted, turbo spin-echo sequence, a sagittal, oblique, T2-weighted, turbo spin-echo sequence, and an axial, T1-weighted, spin-echo sequence. Furthermore, a coronal, oblique, short tau-inversion recovery sequence and a gradient echo sequence were used. The results were compared with data from healthy, asymptomatic volunteers as reported in the literature. The MRI investigations showed no substantial differences between patients with or without calcified deposits within the rotator cuff tendons, but distinct differences between such patients and healthy, asymptomatic volunteers. For patients with shoulder pain, shoulder dysfunction, and calcified deposits within the rotator cuff tendons, these calcified deposits are most probably not the main cause of the clinical symptoms. Rather, it seems to be useful to consider the results of MRI investigations whenever planning therapeutic procedures for patients with shoulder pain and dysfunction, irrespective of whether or not there are signs of calcified deposits within the rotator cuff tendons on plain radiographs.

Adult↗
PubMed2001

Extracorporeal shock-wave therapy for chronic lateral tennis elbow--prediction of outcome by imaging.

Today the clinical use of extracorporeal shockwave application (ESWA) for the treatment of lateral tennis elbow is hampered by the lack of results from randomized controlled trials and of predictive parameters of clinical outcome. The present prospective study aimed to provide the latter by means of magnetic resonance imaging (MRI). Twenty-three female and 19 male patients with unilateral chronic tennis elbow of the dominant site were clinically examined before and after repetitive low-energy ESWA. MRI was performed before ESWA to evaluate signal intensity changes or contrast enhancement of the common extensor tendon and the lateral epicondyle. After ESWA (mean follow-up period 18.6 months for all patients), clinical evaluation showed a significantly better mean clinical performance after ESWA than before treatment. Interestingly, male patients showed a significantly better mean clinical performance after ESWA than female patients, and male and female patients differed significantly in the signal intensity of the common extension tendon cross-section and tendon thickening on MRI. For female patients, MRI scans could be applied for predicting a positive clinical outcome of ESWA. This study reports the first indication of predictability of positive clinical outcome of the treatment of chronic lateral tennis elbow by ESWA using imaging prior to treatment. This may serve as an important step towards overcoming the therapeutic nihilism with respect to the non-operative management of this condition recently in the literature.

Adult↗
PubMed2001

Impaired tensile strength after shock-wave application in an animal model of tendon calcification.

Extracorporeal shock-wave application facilitates dissolution of rotator cuff calcifications. Therefore, disappearance or disintegration of tendon calcifications by shock waves might be appropriate for any kind of tendon calcification. Here, shock waves with various energy flux densities were applied to the mineralized medial gastrocnemius tendon of turkeys as an animal model. After application of shock waves in vivo, with energy flux density of 0.6 mJ/mm(2), histologic examination and microradiography did not show dissolution or disintegration of tendon calcifications. After shock-wave application in vitro, even for energy flux density of 1.2 mJ/mm(2) neither dissolution nor disintegration of tendon calcifications were observed. Biomechanical testing revealed significant impairment of tensile strength following shock-wave application in vitro, with energy flux density of 1.2 mJ/mm(2), but not with 0.6 mJ/mm(2). These results are important for considerations of clinical extracorporeal shock-wave application on tendon calcifications, as well as on tendon ossifications.

Animals↗
PubMed2001

International Council of Emboli Management (ICEM) Study Group results: risk adjusted outcomes in intraaortic filtration.

BACKGROUND: The Multicenter Study of Perioperative Ischemia (McSPI) developed and validated a Stroke Risk Index for estimating the likelihood that patients undergoing isolated coronary artery bypass grafting will experience major perioperative neurologic events. The International Council of Emboli Management (ICEM) Study Group has suggested that use of intraaortic filtration reduces adverse neurologic events. OBJECTIVE: The objective of the present study was to compare predicted and observed neurologic outcomes in patients receiving intraaortic filtration. PATIENTS AND METHODS: From February 1999 to August 2000, 962 patients were enrolled consecutively in a prospective, nonvoluntary registry of intraaortic filtration in 15 European centers. Of these, 447 underwent isolated coronary artery bypass grafting, the target population for applying the McSPI Stroke Risk Index. Forty-five had incomplete data, yielding a study group of 402 patients. The Stroke Risk Index was calculated for each patient, and the sum across patients yielded an expected number of neurologic events. These were compared to observed events by confidence limits and goodness of fit. RESULTS: Six neurologic events were observed (1.5%; 95% confidence limits 0.6-3.4%), roughly half the 13.7 predicted by the Stroke Risk Index (3.4%; 95% confidence limits 2.0-5.8%), P=0.03. CONCLUSIONS: Adverse neurologic events associated with coronary artery bypass grafting in which intraaortic filtration was used were rare and fewer than expected on the basis of the Stroke Risk Index. Rare occurrence of clinically relevant events precludes their use as primary endpoints for randomized clinical studies; however, the Stroke Risk Index provides a valuable benchmark in the absence of such studies.

Aorta↗
PubMed2001

Neuron loss during early adulthood following prenatal low-dose X-irradiation in the mouse brain.

PURPOSE: Apart from subsequent cell death, little is known about long-term effects of a prenatal low-dose X-irradiation (PLDI) on nuclear (n) and mitochondrial (mt) DNA, and whether these effects are connected with reduced neuron numbers in the adult brain. MATERIALS AND METHODS: Pregnant mice were X-irradiated with 0, 10 or 50cGy at day 13 (E13) of pregnancy. One day after (E14), or postnatally at day 25 (P25) or P180, the brains of the offspring were analysed concerning the extent of nDNA repair, mt biogenesis, and the relative content of nDNA single strand breaks (SSB). Stereology was applied for evaluating neuronal loss. RESULTS: One day after irradiation no unrepaired SSB were detected. Significant results were mainly obtained for hippocampal pyramidal cells at P180, particularly cell loss following 50 cGy PLDI, increased SSB content and mt biogenesis (0 vs. 10cGy) but decreased mt biogenesis for 10 vs. 50 cGy. CONCLUSIONS: A hypothesis closely related to that regarding molecular events during aging is presented for explaining this second wave of cell death in adult mice following PLDI as a result of accumulated mtDNA damage caused by PLDI. A possible relation to the neurodegenerative hypothesis of schizophrenia is discussed.

Animals↗
PubMed2001

Advanced glycation end products (AGEs)-induced expression of TGF-beta 1 is suppressed by a protease in the tubule cell line LLC-PK1.

BACKGROUND: Advanced glycation end products (AGEs) are assumed to play a key role in diabetic nephropathy (DN). Since little is known about their action in tubule cells, we investigated in LLC-PK1 cells: (i) whether AGE-bovine serum albumin (AGE-BSA) affects cell proliferation and expression of transforming growth factor-beta (TGF-beta 1); and (ii) whether the AGE-induced effects can be modulated by trypsin due to interference with its binding proteins at the cell surface. METHODS: Arrested cells were exposed to vehicle (control), AGE-BSA (19--76 microM) and BSA (38 microM) in the presence or absence of trypsin (0.625--5.0 microg/ml) (2.5 microg/ml) for 24 h. We evaluated cell proliferation by cell count and by [(3)H]thymidine incorporation, TGF-beta 1 expression by reverse transcription-polymerase chain reaction (RT-PCR), and TGF-beta 1 protein by ELISA. In addition, cell accumulation of AGEs was studied by immunohistochemical staining of the AGE imidazolone. RESULTS: AGE-BSA inhibited [(3)H]thymidine incorporation, lowered cell number and increased cell protein content as well as TGF-beta 1 mRNA and protein as compared with control and BSA. Immunohistochemical staining revealed a marked intracellular accumulation of the AGE imidazolone. Co-incubation of AGE-BSA with trypsin ameliorated the impaired thymidine incorporation, the decreased cell count and the enhanced cell protein content. TGF-beta 1 overexpression was normalized, while TGF-beta 1 protein declined insignificantly. Intracellular imidazolone accumulation was strikingly suppressed. CONCLUSIONS: In the tubule cell line LLC-PK1, AGE-BSA exerts an antiproliferative effect, most probably due to TGF-beta 1 overproduction. The co-administration of trypsin abrogated this alteration, very likely as a result of an interaction with AGE-binding protein(s), which is supported by the decreased intracellular AGE accumulation. These findings may be the starting point for the development of specific proteolytic enzymes to interfere with the interaction between AGEs and their receptors/binding proteins.

Animals↗
PubMed2000

More cerebellar granule cells following prenatal low-dose X-irradiation.

It was the aim of this study to estimating and comparing the total number of granule and Purkinje cells in the cerebellum of 180-day-old mice following a prenatal low-dose X-irradiation (50 cGy) at day 13 of gestation. Using the optical fractionator we found an expected, significant decrease of the total number of Purkinje cells (-21.1%; P=0.041) and a surprising, significant increase of the total number of granule cells (+23.1%; P=0.026) if comparing prenatally irradiated with sham-irradiated mice. The possible molecular basis of these seemingly paradoxical results is discussed.

Animals↗
PubMed2000

Stereological quantification of carboxyfluorescein-labeled rat lung metastasis: a new method for the assessment of natural killer cell activity and tumor adhesion in vivo and in situ.

The function of natural killer (NK) cells is often studied by assessing in vitro levels of NK cell mediated lysis of target cells, or by assessing in vivo levels of lung tumor cell retention or metastatic colonization of intravenously injected tumor cells. However, these methods do not permit direct quantification and visualization of NK cells and their targets in vivo and in situ. Here, a new approach is described to visualize effector-to-target interactions as well as to estimate total numbers of targets in the lung, in vivo and in situ. MADB106 tumor cells were vitally labeled using carboxyfluorescein (CFSE) and intravenously (i.v.) injected into Fischer 344 rats (10(6) cells/rat). This mammary adenocarcinoma derived cell line is syngeneic to the inbred Fischer 344 rat and highly sensitive to NK cell activity in vivo. Effector-to-target interactions were visualized by immunostaining. Using the optical fractionator method, total numbers of CFSE-labeled MADB106 tumor cells were estimated in the left lung of the animals 5 min after tumor inoculation. To further demonstrate the usefulness of this approach in reflecting in vivo processes, rats were inoculated with MADB106 cells and simultaneously with a single i.v. bolus of either 1 microg/kg adrenaline or saline. Both lungs were removed 5 min later. Adrenaline caused a significant 80% reduction in the total number of lung CFSE-labeled MADB106 tumor cells, suggesting a rapid modulation of metastasis by stress hormones. This new approach facilitates the monitoring of effector-to-target interactions and the quantification of immune cell function or tumor adhesion in vivo and in situ.

Adenocarcinoma↗
PubMed2000

Normal blood pressure and plasma renin activity in mice lacking the renin-binding protein, a cellular renin inhibitor.

In renal extracts, some renin is present as "high molecular weight renin," a heterodimeric complex of renin with the 46-kDa renin-binding protein (RnBP), also known as N-acyl-D-glucosamine 2-epimerase. Because RnBP specifically inhibits renin activity, the protein was proposed to play an important role in the regulation of the renin-angiotensin system (RAS). Using gene targeting, we have generated mice lacking RnBP and tested this hypothesis in vivo. In particular, we analyzed biosynthesis, secretion, and activity of renin and other components of the RAS in mice lacking RnBP. Despite extensive investigations, we were unable to detect any major effects of RnBP deficiency on the plasma and renal RAS or on blood pressure regulation. Contrary to previous hypotheses, we conclude that RnBP does not play a significant role in the regulation of renin activity in plasma or kidney. However, RnBP knockout mice excrete an abnormal pattern of carbohydrates in the urine, indicating a role of the protein in renal carbohydrate metabolism.

Animals↗
PubMed2000

Competition between n-alkane-assimilating yeasts and bacteria during colonization of sandy soil microcosms.

An n-alkane-assimilating strain of Candida tropicalis was selected in sandy soil inoculated with microorganisms from contaminated sites. Competition experiments with n-alkane utilizers from different strain collections confirmed that yeasts overgrow bacteria in sandy soil. Acidification of the soil is one of the colonization factors useful for the yeasts. It can be counteracted by addition of bentonite, a clay mineral with high ion exchange capacity, but not, however, by kaolin. Strains of different yeast species showed different levels of competitiveness. Strains of Arxula adeninivorans, Candida maltosa, and Yarrowia lipolytica overgrew strains of C. tropicalis, C. shehatae or Pichia stipitis. Two strains of C. maltosa and Y. lipolytica coexisted during several serial transfers under microcosm conditions.

Alkanes↗
PubMed2000

Switch from a BIVAD to a LVAD in a boy with Kawasaki disease.

A 9-year-old boy with Kawasaki disease survived after two severe myocardial infarctions. Thereafter pharmacologically untreatable ventricular arrhythmia and rapidly deteriorating heart failure developed in the patient. After 19 days of biventricular and a further 27 days of left univentricular mechanical circulatory support with the Berlin Heart (Cardiotechnica, Berlin, Germany) assist device the boy successfully underwent heart transplantation. At a follow-up of 54 months, the boy is leading an active and unrestricted life.

Arrhythmias, Cardiac↗
PubMed2000

Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach.

Any investigation of the total number of neurons in a given brain region must first address the following questions. What is the best method for estimating the total number of neurons? What are the validity and the expected precision of the obtained data? What precision must the estimates attain with respect to the scientific question? In the present study, these questions were addressed using a computer simulation. Virtual brain regions with various spatial distributions of virtual neurons were modeled. The total numbers of virtual neurons in the modeled brain regions were repeatedly estimated by simulation of modern design-based stereology, either by using the 'fractionator' method or by the established method based on the product of estimated neuron density and estimated volume of the reference space. We show that estimates of total numbers of neurons obtained using the fractionator are from a statistical and economical standpoint more efficient than corresponding estimates obtained using the density/volume procedure. Furthermore, the use of two simple prediction methods (one for homogeneous and the other for clustered neuron distributions) permits satisfactory predictions about the variation of presumably any estimates of total numbers of neurons obtained using the fractionator. Finally, we show that assessing the reliability of estimates of mean total neuronal numbers using the ratio between the mean of the squared coefficients of error of the estimates and the squared coefficient of variation of the estimated total neuronal numbers, a frequently employed method in stereological studies, is neither useful nor informative. The present results may constitute a new set of recommendations for the rigorous usage of design-based stereology. In particular, we strongly recommend counting considerably more neurons than is currently done in the literature when estimating total neuronal numbers using design-based stereology.

Algorithms↗
PubMed2000

Celloidin mounting (embedding without infiltration) - a new, simple and reliable method for producing serial sections of high thickness through complete human brains and its application to stereological and immunohistochemical investigations.

Celloidin mounting (embedding without infiltration) of the human central nervous system (CNS) proved to be superior to gelatin embedding for the production of serial sections ranging in thickness from 220 to 500 microm. After gallocyanin-staining, a comprehensive neuroanatomical as well as neuropathological survey of the human brain is possible, including diagnosis of Alzheimer's disease. Details of a fractionator analysis of the total striatal neuron number are described and the possible quantitative analysis of parallel immunohistochemically stained sections is discussed.

Adult↗