Biomedical subjects
Publications and source records attributed to C Schmitz.
We report the case of a 54-year old man with end-stage heart disease in whom the malfunctioning valves of a Novacor LVAS needed to be replaced after 490 days of circulatory support. This procedure could be performed without cardiopulmonary bypass.
Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain. We studied subjects from the Framingham Heart Study to determine (1) the extent to which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD. Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gln homozygous, 82.7+/-2.5%; heterozygous, 92.2+/-0.7%; and Arg homozygous, 100. 5+/-0.4% (P<0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 11.5% of the variance. There was an interaction (P=0.02) between the genotype and total cholesterol on factor VII levels, such that the correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD (P=0.12). In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that genetic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD.
As part of a project to study different methods for the disinfection of effluent water, the inactivation of different microorganisms (Escherichia coli, Deinococcus radiodurans and spores of Bacillus subtilis) using a combination of a photosensitizer (Rose Bengal) with simulated sunlight and oxygen was determined under various environmental conditions (temperature, pH index). In parallel, the singlet-oxygen (1O2) production was also measured under the same conditions. Whereas the vegetative cells could be inactivated much more efficiently at increased temperature and altered index of pH, the production of 1O2 remained essentially the same under these alterations. Additionally, the relations among the sensitivities of different cell types to be killed by our photodynamic treatments (PDT) were opposite to those found after exposure to ionizing radiation. The results of photodynamic experiments do not reflect the cells' capacity to repair DNA strand breaks. Spores of B. subtilis, as a nonvegetative system, could not be inactivated by illuminations up to 100 J cm-2. Together, these findings indicate that DNA is not the primary target, the inactivation of which leads to the killing of our test organisms. Instead, the cellular envelope appears to be the component being assaulted by our PDT.
OBJECTIVE: To clarify morphologic features associated with the clinical outcome of extracorporeal shock wave application (ESWA) in chronic plantar fasciitis. METHODS: In this prospective study 43 patients (48 heels) with chronic courses of plantar fasciitis were clinically examined before and after repetitive low energy ESWA. Standard radiographs of the affected heels were obtained before ESWA to document the existence of a calcaneal heel spur. Magnetic resonance imaging (MRI) was performed before ESWA to evaluate abnormalities of the plantar fascia, the surrounding soft tissue structures, and bone marrow edema of the calcaneus. RESULTS: After ESWA (mean followup 19.3 mo), clinical evaluation of all 48 heels revealed a statistically significant decrease in the mean visual analog scale score from 74.5 to 25.4. Using the Roles and Maudsley score (RM), an established scoring system for categorizing results of treatment following ESWA for patients with plantar fasciitis, patients could be divided into 2 groups, i.e., satisfactory clinical outcome of ESWA (grades 1 and 2 by RM scale; n = 36 heels) and unsatisfactory outcome (grades 3 and 4 by RM scale; n = 12 heels). While thickness of plantar aponeurosis, soft tissue signal intensity changes, and soft tissue contrast medium uptake did not correlate with clinical outcome, the presence of a calcaneal bone marrow edema was highly predictive for satisfactory clinical outcome (positive predictive value 0.94, sensitivity 0.89, specificity 0.8). CONCLUSION: This study indicates that in patients with chronic plantar fasciitis, the presence of calcaneal bone marrow edema on pretherapeutic MRI is a good predictive variable for a satisfactory clinical outcome of ESWA.
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[formula: see text] The controlled and selective synthesis of oligonucleotides on the solid phase is possible under mild aqueous conditions using the enzyme T4 RNA ligase, the resins being tentagel or kieselguhr/polydimethylacrylamide.
In a recent paper (Shankle et al., 1998a), post-natal neurogenesis in the human cerebral cortex was discussed. Based on re-calculations of morphometric data from the literature, the authors concluded an average 1.1% monthly increase in post-natal cortical neuron number between post-natal months 15-72. The present paper makes clear by discussing four main assumptions done by Shankle et al., i.e. shrinkage of the tissue, morphometric features of the neurons under study, conversion of cell densities per area to number per unit volume and estimation of coefficients of variation, that their final conclusion about an increase in neuron number is unsound. Furthermore, five points are discussed here that Shankle et al. had mentioned in order to demonstrate that the pulse thymidine labeling method is less reliable than some have assumed. The present paper refute these assumptions point by point. Thus, the Shankle et al. paper does not provide scientifically valid evidence of a post-natal neurogenesis in the developing human cerebral cortex.
Whenever using modern stereological methods for estimating number-weighted or volume-weighted mean volumes of biological particles such as cell nuclei, either 'isotropic uniform random' (IUR) tissue sections or 'vertical' ones had to be used. However, with the currently available procedures and tools it was virtually impossible to prepare such sections from small specimens such as the mouse brain. Here, a modification of the 'isector' is presented, which allows the embedding of mouse brain halves into paraffin spheres as a useful basis for preparing IUR sections. By using this modified isector it could be shown for various types of neurons in the hippocampus and cerebellum of young adult mice, that there are no differences between estimated mean nuclear volumes obtained on IUR sections and those obtained on conventional frontal or sagittal ones. This result may be used to expand the interpretation of estimated mean nuclear volumes of the types of neurons investigated here.
Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults' level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.
Anticipatory adjustments of forearm posture are associated with a voluntary load-lifting movement in bimanual load-lifting tasks. Three aspects of these adjustments are analyzed: their goal, their central organization, and their acquisition. The goal of the anticipatory adjustment in this task is to minimize the perturbation of forearm posture that occurs during unloading. The central organization is based on two parallel controls responsible, respectively, for the lifting movement of the moving forearm and the anticipatory postural adjustment of the postural forearm, their coordination depending on a central timing signal. The acquisition of the anticipatory postural adjustment was tested using a paradigm where the voluntary movement performed by one hand triggered, via an electronic switch, the load release of the postural forearm. It was achieved after 40-60 trials and was not graded as a function of the voluntary movement parameters, but of the disturbance of the postural arm about to occur. The learned anticipation was not transferred when, after a first acquisition session with one forearm as the postural forearm, a second learning session was performed with the other forearm as the postural forearm. The acquisition was tested in Parkinsonian and in hemiparetic patients with capsular lesion. The highest acquisition deficit was observed in hemiparetic patients, when the contralateral forearm was the postural forearm; the deficit was less important when the ipsilateral arm was postural. Surprisingly, the anticipatory postural adjustments in hemiparetic patients were rather well preserved when the natural load-lifting task was tested. These results suggest that the basal-ganglia SMA circuit and M1 premotor areas are important in the acquisition process.
Using quantitative autoradiography, both nuclear DNA repair - measured as nuclear unscheduled DNA synthesis (UDS) - and mitochondrial (mt) DNA synthesis were evaluated in situ for several types of cells in the brains of untreated mice of various age. It was found that distinct types of neuronal cells showed a decline of both UDS and mtDNA synthesis with age, whereas - except for glial cells of the cerebral cortex - no glial or endothelial cells showed age-related alterations of UDS. Together with various data reported in the literature, these patterns of a cell type-specific decrease of UDS and mtDNA synthesis with age in the mouse brain lead to an improved understanding of the complex interrelationships between the molecular events associated with the phenomenon of aging as well as to a new idea regarding the cause of the specific distribution pattern of those cells in the human brain that are affected by the formation of paired helical filaments in Alzheimer's disease.
We estimated the total neurone number, glial number, and glial index (ratio glial cells/neurone) in the thalamic mediodorsal nucleus (MD) in seven patients suffering from Huntington's disease (HD; four males, three females, mean age 52.4 +/- 13.6 years) and age- and sex-matched controls (four males, three females, mean age 53.6 +/- 12.1 years) by means of a stereological protocol. The mean total neurone number (N(T)) in the MD of controls was 2,985,188 +/- 174,710, the mean glial number (G(T); astrocytes, oligodendrocytes) 21,785,008 +/- 2,986,678, and the glial index 7.29 +/- 0.88. In HD, the average neurone number was decreased by 23.8% to 2,275,321 +/- 247,162 (Mann-Whitney U-test P < 0.05), the mean glial number by 29.7% to 15,318,895 +/- 1,722,524 (Mann-Whitney U-test P < 0.05), the glial index was slightly reduced to 6.81 +/- 1.06. Gallyas' impregnation for the demonstration of fibrous astroglia gave strongly positive results in all cases with HD and negative results in the controls. The morpho-functional correlation of the results is complicated because individual variability, presence of segregated and parallel neuronal circuits, and plasticity of the adult human CNS must be considered.
This study provides the theoretical background of the decision to count approximately 750-1,300 neurons per individual in the preceding study of Heinsen et al. [6] finding a significant (P < 0.05) nerve cell loss in the thalamic mediodorsal nucleus in Huntington's disease with the so-called V(Ref) x N(V) method. Using a computer simulation of the study of Heinsen et al., it was shown that the legitimation for counting only 100-200 neurons per individual in previous studies comparable to that carried out by Heinsen et al. was based on incorrect assumptions. In this context it was of particular importance to confirm the theoretical prediction in the literature that the random error of total neuron number estimates obtained with the V(Ref) x N(V) method is actually greater than assumed in current stereological studies. In summary, this study revives the question of how many individuals need to be investigated and how many neurons (or other cell types, respectively) need to be counted per individual in studies comparable to that carried out by Heinsen et al.
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BACKGROUND: Minimally invasive coronary surgery has gained more and more clinical acceptance. A clear contrast to the minimally invasive idea is the highly invasive pulmonary artery catheter used for hemodynamic monitoring during the operation. We evaluated a less invasive device which calculates cardiac output (CO) and hemodynamics based on arterial pulse-contour analysis. METHODS: In 20 patients revascularized by the off-pump technique with the octopus system, agreement of CO by pulse-contour was compared to pulmonary arterial and femoral arterial thermodilution and hemodynamic alterations during the operation were recorded. Pulse-contour CO is computed by measuring the area under the arterial pressure waveform and dividing it by aortic impedance. Aortic impedance is determined by an arterial thermodilution at the onset of the system. RESULTS: Correlation of pulmonary arterial and arterial thermodilution CO to pulse-contour CO was 0.91 and 0.90 respectively (both p<0.01). Coefficients of variations were 6.2% and 6.7%. The bias was 0.1 L per minute and standard deviations were 0.42 L per minute and 0.55 L per minute. Hemodynamic changes during the operations were seen mainly during the distal anastomosis of the first diagonal branch; only slight changes occurred during the anastomosis of the left anterior descending coronary artery. CONCLUSIONS: Arterial pulse-contour analysis is easy to use and minimally invasive, thus qualifies as a reliable routine monitoring tool during minimally invasive coronary surgery with tissue stabilizers.
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To investigate possible effects of injections of tritiated thymidine ([3H]dThd) into pregnant mice or the injection procedure itself on the proliferation of neuronal precursor cells in the fetuses, pregnant mice received intraperitoneal injections of either [3H]dThd or saline on embryonic days 12, 14, and 19, while their offspring remained untreated. A second group of dams was not injected but their male offspring received a subcutaneous injection of again either [3H]dThd or saline on postnatal day 10. Then total numbers of hippocampal pyramidal cells (areas CA1 to CA3) and granular cells (dentate gyrus) were determined stereologically for 20-day-old as well as for 80-day-old male pups. No significant differences were found for the mean total number of pyramidal cells between the investigated groups of pups. However, the mean total number of granular cells was significantly reduced in those groups in which the dams had received an intraperitoneal injection, irrespective of whether [3H]dThd or saline was injected. This revives the repeated warning in the literature to consider the effect of the injection procedure on the developing brain when interpreting possible effects of agents administered during pregnancy.
The Chinese hamster cell lines E36 and CHOK1 dramatically differ in susceptibility to amphotropic murine leukemia virus (A-MuLV) and gibbon ape leukemia virus (GALV); E36 cells are highly susceptible to both viruses, CHOK1 cells are not. We have previously shown that GALV can infect E36 cells by using both its own receptor, HaPit1, and the A-MuLV receptor, HaPit2. Given that the two cell lines are from the same species, the loss of function of both of these receptors in CHOK1 cells is surprising. Other studies have shown that CHOK1 cells secrete proteins that block A-MuLV entry into CHOK1 as well as E36, suggesting the two A-MuLV receptors are functionally identical. However, CHOK1 conditioned medium does not block GALV entry into E36, indicating the secreted inhibitors do not block HaPit1. HaPit1 and ChoPit1 therefore differ as receptors for GALV; ChoPit1 is either inactivated by secreted factors or intrinsically nonfunctional. To determine why GALV cannot infect CHOK1, we cloned and sequenced ChoPit1 and ChoPit2. ChoPit2 is almost identical to HaPit2, which explains why CHOK1 conditioned medium blocks A-MuLV entry via both receptors. Although ChoPit1 and HaPit1 are 91% identical, a notable difference is at position 550 in the fourth extracellular region, shown by several studies to be crucial for GALV infection. Pit1 and HaPit1 have aspartate at 550, whereas ChoPit1 has threonine at this position. We assessed the significance of this difference for GALV infection by replacing the aspartate 550 in Pit1 with threonine. This single substitution rendered Pit1 nonfunctional for GALV and suggests that threonine at 550 inactivates ChoPit1 as a GALV receptor. Whether native ChoPit1 functions for GALV was determined by interference assays using Lec8, a glycosylation-deficient derivative of CHOK1 that is susceptible to both viruses and that has the same receptors as CHOK1. Unlike with E36, GALV and A-MuLV exhibited reciprocal interference when infecting Lec8, suggesting that they use the same receptor. We conclude both viruses can use ChoPit2 in the absence of the inhibitors secreted by CHOK1 and ChoPit1 is nonfunctional.