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Biomedical subjects

C Schmitz

Publications and source records attributed to C Schmitz.

At least 55 records · Page 3Linked to original sources
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

Mutation in the promoter region of the beta-fibrinogen gene and the risk of future myocardial infarction, stroke and venous thrombosis.

AIM: Polymorphisms in the promoter region of the beta-fibrinogen gene are associated with increased plasma fibrinogen levels. We investigated whether the distribution of the C148T polymorphism is associated with an increase in cardiovascular risk. METHODS AND RESULTS: In a nested case-control design, the distribution of the C148T polymorphism was investigated among 751 participants in the Physicians' Health Study who subsequently developed myocardial infarction, stroke or venous thromboembolism (cases) and among 751 age- and smoking-matched controls over follow-up of 8.6 years. Frequency of the T allele was similar among men who had myocardial infarction (22.7%, P=0.5), stroke (18.4%, P=0.2) or venous thromboembolism (17.0%, P=0.1) compared with those with no cardiovascular events (21.5%). The relative risk for any vascular event among men homozygous or heterozygous for the T allele compared with men homozygous for the C allele was 0.94 (95% CI 0.76-1.16). We found no evidence of an association between the T allele and myocardial infarction (relative risk 1.06; 95% CI 0.82-1.36), stroke (0.87, 0.63-1.21) or venous thromboembolism (0.75; 0.51-1.08). Analysis adjusted for aspirin use and traditional cardiovascular risk factors had no significant effect on these findings. CONCLUSION: In a large prospective cohort, carriage of the T allele for the C148T mutation in the beta-fibrinogen promoter gene was not associated with an increased subsequent risk of cardiovascular events.

Adult↗
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↗
PubMed2001

X-ray-induced chromosome aberrations in human lymphocytes in vitro are potentiated under simulated microgravity conditions (Clinostat).

The influence of simulated microgravity weightlessness on the outcome of radiation-induced chromosomal aberrations was investigated using the clinostat as a tool to simulate weightlessness conditions. Treatments were performed in the G0 phase of human lymphocytes with 1.5 Gy of X-rays alone or in combination with the DNA synthesis inhibitor of 1-beta-D-arabinofuranosylcytosine (ara-C) to check also for possible specific radiation-induced DNA repair processes impairment (excision repair caused by base damage) under microgravity conditions. The results obtained, which confirmed previous findings, showed significantly higher increases of aberrant cells and hence total number of aberrations compared to the parallel treatments performed 'on ground'. For what concern ara-C its contribution in terms of potentiation in the induction of aberrant cells was equivalent in absolute terms under simulated microgravity conditions and 'on ground' indicating that excision repair caused by base damage and inhibited by ara-C is not affected by simulated microgravity. A possible explanation for this outcome could quote two major factors: i) Enhanced probability that under simulated microgravity conditions the reactive DSB are spatially brought together to better interact, hence increasing the probability of mis-rejoining. ii) Alternatively chromatin structure could be modified under simulated microgravity conditions generating different quality and quantities of DNA lesions compared to treatments performed 'on ground'.

Antimetabolites, Antineoplastic↗
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↗
PubMed2000

Use of cryostat sections from snap-frozen nervous tissue for combining stereological estimates with histological, cellular, or molecular analyses on adjacent sections.

Adequate tissue preparation is essential for both modern stereological and immunohistochemical investigations. However, combining these methodologies in a single study presents a number of obstacles pertaining to optimal histological preparation. Tissue shrinkage and loss of nuclei/nucleoli from the unprotected section surfaces of unembedded tissue used for immunohistochemistry may be problematic with regard to adequate stereological design. In this study, frozen cryostat sections from hippocampal and cerebellar regions of two rat strains and cerebellar and cerebral regions from a human brain were analyzed to determine the potential impact of these factors on estimates of neuron number obtained using the optical disector. Neuronal nuclei and nucleoli were clearly present in thin sections of snap-frozen rat (3 microm) and human (6 microm) tissue, indicating that neuronal nuclei/nucleoli are not unavoidably lost from unprotected section surfaces of unembedded tissue. In order to quantify the potential impact of any nuclear loss, optical fractionator estimates of rat hippocampal pyramidal cells in areas CA1-3 and cerebellar granule and Purkinje cells were made using minimal (1 microm) upper guard zones. Estimates did not differ from data reported previously in the literature. This data indicates that cryostat sections of snap-frozen nervous tissue may successfully be used for estimating total neuronal numbers using optical disectors.

Animals↗
PubMed2000

Perinatal asphyxia results in changes in presynaptic bouton number in striatum and cerebral cortex-a stereological and behavioral analysis.

Deficits in cognitive function have been related to quantitative changes in synaptic population, particularly in the cerebral cortex. Here, we used an established model of perinatal asphyxia that induces morphological changes, i.e. neuron loss in the cerebral cortex and striatum, as well as behavioural deficits. We hypothesized that perinatal asphyxia may lead to a neurodegenerative process resulting in cognitive impairment and altered presynaptic bouton numbers in adult rats. We studied cognitive performance at 18 months and presynaptic bouton numbers at 22 months following perinatal asphyxia. Data of the spatial Morris water escape task did not reveal clear memory or learning deficits in aged asphyctic rats compared to aged control rats. However, a memory impairment in aged rats versus young rats was observed, which was more pronounced in asphyctic rats. We found an increase in presynaptic bouton density in the parietal cortex, whereas no changes were found in striatum and frontal cortex in asphyctic rats. An increase of striatal volume was observed in asphyctic rats, leading to an increase in presynaptic bouton numbers in this area. These findings stress the issue that volume measurements have to be taken into account when determining presynaptic bouton density. Furthermore, perinatal asphyxia led to region-specific changes in presynaptic bouton numbers and it worsened the age-related cognitive impairment. These results suggest that perinatal asphyxia induced neuronal loss, which is compensated for by an increase in presynaptic bouton numbers.

Adult↗
PubMed2000

Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device.

We report a 56-year-old male patient developing hypoxemia after surgical replacement of infected valves of a left ventricular assist device (LVAD, Novacor) which had supported him during the previous 15 months. Contrast transesophageal echocardiography (TEE) revealed an atrial septal defect with intermittent right-to-left shunt across a patent foramen ovale. We postulate that the shunt detected in this patient occurred as a consequence of reduced pulmonary vascular compliance due to positive end-expiratory pressure (PEEP) and an increase of mean intrathoracic pressure. Furthermore, we hypothesize that synchronized LVAD operation exacerbates any potential right-to-left shunt due to the profound left ventricular unloading which occurs during LVAD support. In this first report of a right-to-left shunt from a previously unrecognized patent foramen ovale in a Novacor patient, the subsequent transient hypoxemia could be managed by avoiding PEEP of more than 3 mmHg, and mean airway pressure of more than 11 mmHg and by careful volume replacement in order to prevent the pump from completely emptying the left ventricle (LV) and the left atrium (LA). Thus, prior to every LVAD implantation a transesophageal contrast echocardiography with Valsalva maneuver should be performed to identify intracardiac right-to-left shunt.

Heart Septal Defects, Atrial↗