Biomedical subjects

T Fischer

Publications and source records attributed to T Fischer.

At least 73 records · Page 4Linked to original sources

PubMed2000

Trapping an atom with single photons

The creation of a photon-atom bound state was first envisaged for the case of an atom in a long-lived excited state inside a high-quality microwave cavity. In practice, however, light forces in the microwave domain are insufficient to support an atom against gravity. Although optical photons can provide forces of the required magnitude, atomic decay rates and cavity losses are larger too, and so the atom-cavity system must be continually excited by an external laser. Such an approach also permits continuous observation of the atom's position, by monitoring the light transmitted through the cavity. The dual role of photons in this system distinguishes it from other single-atom experiments such as those using magneto-optical traps, ion traps or a far-off-resonance optical trap. Here we report high-finesse optical cavity experiments in which the change in transmission induced by a single slow atom approaching the cavity triggers an external feedback switch which traps the atom in a light field containing about one photon on average. The oscillatory motion of the trapped atom induces oscillations in the transmitted light intensity; we attribute periodic structure in intensity-correlation-function data to 'long-distance' flights of the atom between different anti-nodes of the standing-wave in the cavity. The system should facilitate investigations of the dynamics of single quantum objects and may find future applications in quantum information processing.

Journal Article↗

PubMed2000

Calnuc, an EF-hand Ca(2+) binding protein, specifically interacts with the C-terminal alpha5-helix of G(alpha)i3.

Calnuc (nucleobindin) was previously shown to be present both in the cytosol and in the Golgi and to be the major Golgi Ca(2+) binding protein. In this study we verified the existence of the cytosolic pool of calnuc and investigated its interaction with G(alpha)i3. Cytosolic calnuc was released by mild digitonin permeabilization. In pulse-chase experiments, the two pools of calnuc had different mobilities, suggesting different posttranslational modifications. That calnuc interacts with G(alpha)i3 in vivo was verified by the finding that G(alpha)i3 could be crosslinked intracellularly to calnuc and co-immunoprecipitated from NIH 3T3 cells stably overexpressing either activated (Q204L) or inactivated (G203A) G(alpha)i3. Binding was Ca(2+) and Mg(2+)-dependent. Calnuc and G(alpha)i3-GFP codistributed primarily in the Golgi region. By yeast two-hybrid analysis, the binding site on G(alpha)i3 for calnuc was mapped to the C-terminal region because removal of the last 12 amino acids (but not 11) abolished the interaction. Peptide competition indicated that calnuc, with its coiled-coil domain constituted by the two EF-hands, binds to G(alpha)i3's C-terminal alpha5-helix. These results demonstrate that calnuc may play an important role in G protein- and Ca(2+)-regulated signal transduction events.

3T3 Cells↗

PubMed2000

Autologous transplantation of in vivo purged PBSC in CML: comparison of FISH, cytogenetics, and PCR detection of Philadelphia chromosome in leukapheresis products.

To determine the effectiveness of different methods for the detection of tumor cell contamination of collected peripheral stem cells, we performed a study on 39 chronic myelogenous leukemia (CML) patients who were consecutively treated at our department. Analyses of tumor cell contamination by fluorescence in situ hybridization (FISH), conventional cytogenetics, and polymerase chain reaction (PCR) showed marked differences in the percentage of evaluable results: Quantitative analysis of tumor cell contamination was feasible in 60 of 105 (57%) samples evaluated with the use of conventional cytogenetic analysis and in 105 of 107 (98%) samples analyzed by FISH. PCR was evaluable in all 85 samples tested (100%). Both methods were shown to be adequate overall in determining the number of BCR-ABL positive cells, although cytogenetics tended to produce slightly higher percentages. Based on these results, we conclude that FISH performed on leukapheresis products is a rapid and reliable method for assessing the quality of these products and should be used for routine evaluation of tumor cell contamination of CML stem cell products.

Adult↗

PubMed2000

Correction of cor triatriatum sinistrum in a Jehovah's Witness infant.

A cor triatriatum sinistrum was successfully treated by operation in a 14-week-old infant of a Jehovah's Witness family. The child was pretreated with erythropoietin until a hemoglobin level of 14 g/dl was obtained. There was no cardiac catheterization before the operation. The operation was performed with cardiopulmonary bypass. No blood products were transfused and the hemoglobin level after performing modified ultrafiltration was 11.5 g/dl. The infant was extubated on the same day and discharged from our institution on the eighth day after surgery. Two years after surgery the child is in sinus rhythm and is developing well.

Cardiac Surgical Procedures↗

PubMed2000

Decline of caries prevalence after the cessation of water fluoridation in the former East Germany.

In contrast to the anticipated increase in dental caries following the cessation of water fluoridation in the cities Chemnitz (formerly Karl-Marx-Stadt) and Plauen, a significant fall in caries prevalence was observed. This trend corresponded to the national caries decline and appeared to be a new population-wide phenomenon. Additional surveys (N=1017) carried out in the formerly-fluoridated towns of Spremberg (N=9042) and Zittau (N=6232) were carried out in order to support this unexpected epidemiological finding. Pupils from these towns, aged 8/9-, 12/13- and 15/16-years, have been examined repeatedly over the last 20 years using standardised caries-methodological procedures. While the data provided additional support for the established fact of a caries reduction brought about by the fluoridation of drinking water (48% on average), it has also provided further support for the contention that caries prevalence may continue to fall after the reduction of fluoride concentration in the water supply from about 1 ppm to below 0.2 ppm F. Caries levels for the 12-year-olds of both towns significantly decreased during the years 1993-96, following the cessation of water fluoridation. In Spremberg, DMFT fell from 2.36 to 1.45 (38.5%) and in Zittau from 2.47 to 1.96 (20.6%). These findings have therefore supported the previously observed change in the caries trend of Chemnitz and Plauen. The mean of 1.81 DMFT for the 12-year-olds, computed from data of the four towns, is the lowest observed in East Germany during the past 40 years. The causes for the changed caries trend were seen on the one hand in improvements in attitudes towards oral health behaviour and, on the other hand, to the broader availability and application of preventive measures (F-salt, F-toothpastes, fissure sealants etc.). There is, however, still no definitive explanation for the current pattern and further analysis of future caries trends in the formerly fluoridated towns would therefore seem to be necessary.

Adolescent↗

PubMed2000

Effect of dark test-substance pigmentation on skin perfusion assessments and effect of test technique on balsam of Peru patch-test results.

13 balsam of Peru (Myroxylon Pereirae) patch-test-positive subjects are re-tested with 25% balsam of Peru in petrolatum and with serial doses printed on polyester squares. All substances are applied with tape strips for 3, 6, 24 (1 day [D]), 48 (2D), 72 (3D) and 96 h (4D) on each subject and for 96 h (4D) with plastic foils. Tests are followed visually and with perfusion assessments from 3 h to 9 days. Results show that pigment remnants following detachment of patches affect perfusion assessments. Such effect due to pigment is supported by readings of patch tests through the petrolatum test substance while applied with transparent foils. For most reactions, good agreement is observed between the assessment techniques when peak assessment values of reactions are compared. There is inter-individual variation in perfusion with identical tests. With the petrolatum test substance, increased visible reactivity was observed when the application time was extended up to 24 h (1D), while extension of application time increased perfusion in most cases except for an extension from 24 (2D) to 48 h (4D) where decreased perfusion resulted in most cases. Dose and application time did not affect the timing of highest reactivity of reactions in most cases.

Adult↗

PubMed2000

Assessment of balsam of Peru patch tests.

To find an ideal test technique for as low a dose of balsam of Peru (Myroxylon Pereirae) as possible, subjects testing positive to balsam of Peru are re-tested with a 25% concentration of balsam of Peru in petrolatum. Applications are with Finn Chambers for 6 different application times, and directly by foils for 96 h (4 days (D)). The goals are to confirm which subjects are positive and which are not, and, using that information, to see if it is possible to distinguish between these 2 groups, tested concomitantly at much lower serial dose levels, in terms of perfusion or by visual assessments. 5 different serial doses are applied with strips for 3-96 h (4D) and with foils for 96 h (4D). The Finn Chamber tests allow a distinction between visually positive and negative subjects supported by perfusion assessments. With the foils, a 24x lower serial dose level than with the 25% test substance is sufficient to distinguish between positive and negative subjects in terms of perfusion values. This approach requires readings up to 9 days. With this test, the visual approach yields only 3 of 10 positive subjects. This study demonstrates that a lower test dose is possible with perfusion assessments compared to visual ones.

Adult↗

PubMed2000

Skin irritation from air-oxidized ethoxylated surfactants.

Surfactants are known to be skin irritants, but change in their irritant potential due to change in composition during handling and storage has not previously been investigated. The aim of this study was to investigate the influence of oxidation products on the irritant potential of a non-ionic ethoxylated alcohol, C12E5. Pure and oxidized C12E5 were tested, using 2 different patch test procedures; 1 with a single 24 h exposure and 1 with repeated exposures. 18 healthy volunteers participated in each of these studies. Evaluations were made by visual scoring and by measurement of transepidermal water loss and skin blood flow. In the single exposure study, no significant difference in skin irritation was observed between pure C12E5 and a sample of oxidized C12E5 at the concentrations tested (1, 3, 9 and 27%). After repeated exposures, however, the oxidized C12E5 was significantly more irritant than pure C12E5 at the concentrations 9% and 27% (p<0.05). Non-ionic ethoxylated surfactants are known for their weak skin irritant effect and are, due to this, often included in products with prolonged contact with the skin, i.e., skin care products. An increased irritant potential after oxidation might be of importance due to the conditions of use.

Adult↗

PubMed2000

Dental erosion in Cuban children associated with excessive consumption of oranges.

Marked erosion at the mesial edges of upper front teeth was observed during an examination of Cuban children. The preferential erosion of mesial edges produced characteristic V-shaped defects on upper central incisors, and the aim of the present study, carried out on 12-yr-old children (N = 1010) in 10 communities in the Province of Havana was to establish the frequency of dental erosion and explain its occurrence. The symmetrical erosion of teeth 11 and 21 (excluding crown injuries and attrition) were clinically classified into four grades: 0.5 = objectionable; 1 = abnormal mesial shortening of incisal edges; 2 = V-shaped defect of cutting edges; 3 = exposure of dentine and extension of the erosive defect to the lateral incisors. In four of the communities, children did not show or rarely showed incisal erosion. In the other six communities, the frequency was surprisingly high (16.6-40.9%). Overall, 17.4% of children exhibited erosion, and the occurrence was significantly higher in girls (20.7%) than in boys (15.0%). The typical V-shaped pattern of erosion seems to be a consequence of the manner in which citrus fruits are eaten. There was also a positive correlation between the frequency of dental erosion and the proximity of citrus plantations, which presumably related to the extent of (daily) orange consumption.

Adolescent↗

PubMed2000

T helper 1-type cytokine transcription in peripheral blood mononuclear cells of pseudorabies virus (Suid herpesvirus 1)-primed swine indicates efficient immunization.

The induction of porcine cytokines, which are believed to be important for the regulation of T helper (Th)1- and Th2-specific immune responses of pigs, was analysed after in vitro restimulation with a herpesvirus, Suid herpes 1 (pseudorabies virus [PRV]), in peripheral blood mononuclear cells (PBMC). To this end, quantitative, competitive reverse transcription-polymerase chain reaction (RT-qcPCR) was established using constructed heterologous DNA MIMICS, which contain cytokine- or glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-specific primer-binding sites. This is a simple method that allows reliable determination of the differing regulation of cytokine mRNAs specific for porcine interleukin (IL)-2, -4 and -10, interferon gamma (IFN-gamma) and the housekeeping gene, GAPDH, as an endogenous control. PBMC derived from naive (innate response) and PRV-primed (memory response) outbred swine were analysed comparatively. The results demonstrated that restimulation with PRV significantly enhanced the transcription of Th1-type cytokines (IL-2 and IFN-gamma) but not of Th2-type cytokines (IL-4 and IL-10). This virus-specific cytokine response was only found with PBMC from swine protected against lethal PRV challenge infection, but not with naive PBMC or with PBMC from pigs immunized with plasmid DNA encoding PRV glycoprotein gC. Notably, PBMC derived from immune and naive pigs constitutively produced relatively high amounts of IL-10-specific mRNA, exceeding that of GAPDH mRNA, independently of the addition of viral antigen or the mitogen concanavalin A (Con A). The results of this work should help to provide a better understanding of the effector cell/cytokine network response to infection with, or vaccination against, PRV. Additionally, the simple, reliable and sensitive RT-qcPCR, when used to determine the porcine cytokine pattern, might be of prognostic value for the induction of protective immunity.

Animals↗

PubMed2000

Vascular reactivity in patients with preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome.

OBJECTIVE: Early structural and functional changes in the systemic vasculature have been proposed to play a major pathogenetic role in preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. The aim of the study was to determine vascular reactivity in patients with preeclampsia with and without HELLP syndrome with respect to those in healthy pregnant control subjects. STUDY DESIGN: Forearm blood flow was measured by strain gauge plethysmography with the venous occlusion technique in 12 hypertensive patients with HELLP syndrome, in 8 patients with preeclampsia without HELLP syndrome, and in 8 healthy normotensive pregnant control subjects. To determine vascular reactivity the forearm blood flow was measured at baseline and after forearm occlusion for a period of 5 minutes (reactive hyperemia). The investigations were repeated 4 to 6 months post partum. Forearm vascular resistance was calculated as the ratio of mean arterial pressure to forearm blood flow. RESULTS: Mean arterial pressure at rest was elevated in patients with preeclampsia (116 +/- 20 mm Hg) and in patients with HELLP syndrome (110 +/- 16 mm Hg) with respect to healthy pregnant control subjects (86 +/- 10 mm Hg; P <.05). Forearm blood flow at rest was not statistically different in patients with preeclampsia (5.1 +/- 2.6 mL/min per 100 mL) and with HELLP syndrome (4.7 +/- 1.5 mL/min per 100 mL) with respect to pregnant control subjects (5.9 +/- 3.1 mL/min per 100 mL); however, forearm vascular resistance at rest was elevated in patients with preeclampsia (25.9 +/- 9.5 units; P <.05) and in patients with HELLP syndrome(24.6 +/- 6.9 units; P <.05) with respect to healthy control subjects (17.0 +/- 6.1 units). During reactive hyperemia the peak forearm blood flow, which is an indicator of maximal vasodilatory capacity, was impaired in patients with preeclampsia (21.9 +/- 8.2 mL/min per 100 mL; P <.05) but not in patients with HELLP syndrome (37.4 +/- 17.5 mL/min per 100 mL) and healthy control subjects (44.9 +/- 15.0 mL/min per 100 mL). Consequently, minimum forearm vascular resistance was higher in women with preeclampsia (6.1 +/- 1.9 units) than in both women with HELLP syndrome (3.5 +/- 1.6 units) and the control subjects (2.8 +/- 2.4 units). CONCLUSION: Despite similarly elevated forearm vascular resistances at rest in patients with HELLP syndrome and in patients with preeclampsia, forearm vascular resistance during reactive hyperemia did not differ significantly from that in healthy control subjects in the women with HELLP syndrome but was increased in women with preeclampsia. Vasodilatory reactivity thus is reduced in preeclampsia but not in HELLP syndrome, which suggests different alterations of the vasculature.

Adult↗

PubMed2000

Metabolic activity of fresh and cryopreserved cynomolgus monkey (Macaca fascicularis) hepatocytes.

1. The effect of cryopreservation on the metabolic capacity of monkey hepatocytes over 4 h in suspension and 24 h in culture was determined. Hepatocytes were diluted in a buffer containing 10% DMSO and frozen in a computer-controlled chamber. 2. Initial ethoxyresorufin and ethoxycoumarin O-deethylase (ECOD) activities were the same in fresh and cryopreserved (CP) hepatocytes. ECOD activity in suspensions declined over 4 h but was the same in fresh and CP hepatocytes. 3. The formation of testosterone hydroxy (OHT) metabolites (namely 6beta-OHT, 2beta-OHT, 16beta-OHT, 16alpha-OHT, 15beta-OHT, 2alpha-OHT and 6beta-OHT) was unaffected by cryopreservation. The loss of OHT activities over 4 h in CP and fresh whole cell suspensions was attributed to a loss of cofactor. CP hepatocyte cultures had equivalent OHT activities to freshly isolated hepatocytes. 4. Initial UDP-glucuronyltransferase (UGT) activities, using the substrates 4-methylumbelliferone, ethoxycoumarin and hydroxycoumarin, were equivalent in fresh and CP whole hepatocytes. At later times, UGT activity was lower in CP than fresh hepatocytes but this was due to a loss of UDPGA. Initial sulphotransferase (SULT) activities, using the substrates 2-naphthol, ethoxycoumarin and hydroxycoumarin, were equivalent in fresh and CP hepatocytes. SULT activities were less stable than UGT activities but were the same in fresh and CP hepatocytes throughout the 4-h incubation. 5. Initial glutathione S-transferase activities (using 1-chloro-2,4-dinitrobenzene) were the same in fresh and CP hepatocytes and both did not decrease over 4 h. 6. CP monkey hepatocytes are a useful model for metabolic and cytotoxicity studies. These cells can be can be used either in suspension or in culture.

Animals↗

PubMed2000

Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction.

The use of primary hepatocytes is now well established for both studies of drug metabolism and enzyme induction. Cryopreservation of primary hepatocytes decreases the need for fresh liver tissue. This is especially important for research with human hepatocytes because availability of human liver tissue is limited. In this review, we summarize our research on optimization and validation of cryopreservation techniques. The critical elements for successful cryopreservation of hepatocytes are (1) the freezing protocol, (2) the concentration of the cryoprotectant [10% dimethyl-sulfoxide (DMSO)], (3) slow addition and removal of DMSO, (4) carbogen equilibration during isolation of hepatocytes and before cryopreservation, and (5) removal of unvital hepatocytes by Percoll centrifugation after thawing. Hepatocytes of human, monkey, dog, rat, and mouse isolated and cryopreserved by our standard procedure have a viability > or = 80%. Metabolic capacity of cryopreserved hepatocytes determined by testosterone hydroxylation, 7-ethoxyresorufin-O-de-ethylase (EROD), 7-ethoxycoumarin-O-deethylase (ECOD), glutathione S-transferase, UDP-glucuronosyl transferase, sulfotransferase, and epoxide hydrolase activities is > or = 60% of freshly isolated cells. Cryopreserved hepatocytes in suspension were successfully applied in short-term metabolism studies and as a metabolizing system in mutagenicity investigations. For instance, the complex pattern of benzo[a]pyrene metabolites including phase II metabolites formed by freshly isolated and cryopreserved hepatocytes was almost identical. For the study of enzyme induction, a longer time period and therefore cryopreserved hepatocyte cultures are required. We present a technique with cryopreserved hepatocytes that allows the induction of testosterone metabolism with similar induction factors as for fresh cultures. However, enzyme activities of induced hepatocytes and solvent controls were smaller in the cryopreserved cells. In conclusion, cryopreserved hepatocytes held in suspension can be recommended for short-term metabolism or toxicity studies. Systems with cryopreserved hepatocyte cultures that could be applied for studies of enzyme induction are already in a state allowing practical application, but may be further optimized.

Animals↗

PubMed2000

Hepatic granuloma due to Propionibacterium acnes in a patient with acute myelogenous leukemia.

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Adult↗

PubMed2000

Persistent Legionella infection in a patient after bone marrow transplantation.

We report on a patient who developed Legionella pneumonia after bone marrow transplantation. Despite appropriate antibiotic treatment, disease progressed. The patient developed a lung abscess from which Legionella and Prevotella were isolated. Cure was achieved by surgical resection. The resected material was sterile, but 16S ribosomal DNA analysis revealed Legionella DNA.

Bone Marrow Transplantation↗

PubMed2000

Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis- cellularity correlates with the degree of enhancement detected by magnetic resonance imaging.

OBJECTIVE: Sacroiliitis is a hallmark of the spondyloarthropathies (SpA). The degree of inflammation can be quantified by magnetic resonance imaging (MRI). The aim of this study was to further elucidate the pathogenesis of SpA by quantitative cellular analysis of immunostained sacroiliac biopsy specimens and to compare these findings with the degree of enhancement in the sacroiliac joints (SJ) as detected by dynamic MRI. METHODS: The degree of acute sacroiliitis detected by MRI after intravenous administration of gadolinium-DTPA was quantitatively assessed by calculating the enhancement observed in the SJ and chronic changes were graded as described in 32 patients with ankylosing spondylitis (n=18), undifferentiated SpA (n=12) and psoriatic arthritis (n=2). Back pain was graded on a visual analogue scale (VAS, 0-10) and disease duration (DD) was assessed. Shortly after MRI, SJ of patients with VAS > 5 were biopsied guided by computed tomography. Immunohistological examination was performed using the APAAP technique; only whole sections > 3 mm were counted. RESULTS: By MRI, chronic changes </= grade II were detected in nine patients (group I, DD 2.5 (SD 2.9) years) and > II in 13 patients (group II, DD 7.3 (SD 4.8) years), while enhancement < 70% was found in eight (group A, DD 5.6 (SD 3.3) years) and > 70% in 12 patients (group B, DD 4.7 (SD 5.8) years). The relative percentage of cartilage (78-93%), bone (7-18%) and proliferating connective tissue (1-4%) was comparable between the groups (range). There were more inflammatory cells in group I compared with group II (mean (SD) 26.7(20.1) versus 5.3 (5. 2), p=0.04) and group A compared with B (21.8 (17.3) versus 6.0 (5. 6), p=0.05) cells/10 mm(2)), T cells (10.9 (8.5)) being slightly more frequent than macrophages (9.6 (16.8/10 mm(2))). Clusters of proliferating fibroblasts were seen in three and new vessel formation in seven cases. CONCLUSION: This study shows that T cells and macrophages are the most frequent cells in early and active sacroiliitis in SpA. The correlation of cellularity and MRI enhancement provides further evidence for the role of dynamic MRI to detect early sacroiliitis.

Acute Disease↗

PubMed2000

The regulator of G protein signaling family.

Regulator of G protein signaling (RGS) proteins are responsible for the rapid turnoff of G protein-coupled receptor signaling pathways. The major mechanism whereby RGS proteins negatively regulate G proteins is via the GTPase activating protein activity of their RGS domain. Structural and mutational analyses have characterized the RGS/G alpha interaction in detail, explaining the molecular mechanisms of the GTPase activating protein activity of RGS proteins. More than 20 RGS proteins have been isolated, and there are indications that specific RGS proteins regulate specific G protein-coupled receptor pathways. This specificity is probably created by a combination of cell type-specific expression, tissue distribution, intracellular localization, posttranslational modifications, and domains other than the RGS domain that link them to other signaling pathways. In this review we discuss what has been learned so far about the role of RGS proteins in regulating G protein-coupled receptor signaling and point out areas that may be fruitful for future research.

Amino Acid Sequence↗

PubMed2000

Angiotensin II receptor subtypes determine induced NO production in rat glomerular mesangial cells.

Angiotensin II (ANG II) and nitric oxide (NO) have contrasting vascular effects, yet both sustain inflammatory responses. We investigated the impact of ANG II on lipopolysaccharide (LPS)/interferon-gamma (IFN)-induced NO production in cultured rat mesangial cells (MCs). LPS/IFN-induced nitrite production, the inducible form of nitric oxide synthase (NOS-2) mRNA, and protein expression were dose dependently inhibited by ANG II on coincubation, which was abolished on ANG II type 2 (AT(2)) receptor blockade by PD-123319. Homology-based RT-PCR verified the presence of AT(1A), AT(1B), and AT(2) receptors. To shift the AT receptor expression toward the type 1 receptor, two sets of experiments were performed: LPS/IFN preincubation for 24 h was followed by 8-h coincubation with ANG II; or during 24-h coincubation of LPS/IFN and ANG II, dexamethasone was added for the last 6-h period. Both led to an amplified overall expression of NOS-2 protein and NO production that was inhibitable by actinomycin D in the first setup. Induced NO production was enhanced via the AT(1) receptor; however, it was diminished via the AT(2) receptor. In conclusion, induced NO production is negatively controlled by the AT(2), whereas AT(1) receptor stimulation enhanced NO synthesis in MCs. The overall NO availability depended on the onset of the inflammatory stimuli with respect to ANG II exposure and the available AT receptors.

Angiotensin II↗