Biomedical subjects

T Fischer

Publications and source records attributed to T Fischer.

At least 55 records · Page 3Linked to original sources

PubMed2001

Surface contamination to UV-curable acrylates in the furniture and parquet industry.

Surface contamination to ultraviolet radiation curable coatings (UV coatings), used increasingly in the parquet and furniture industry, is a matter of concern as a source for skin contamination. UV coatings contain chemically and biologically reactive acrylates, well known as skin contact irritants and sensitizers. Surface contamination may spread secondarily to equipment and other unexpected areas even outside the workplace. Yet, studies concerning this type of contamination are lacking due to lack of suitable sampling methods. Surface contamination of the work environment with risk for skin exposure to UV coating was measured employing a quantitative adhesive tape sampling method developed for this purpose. A pilot study was first performed at three workplaces to evaluate the contamination. In the main study, we wanted to locate and identify in detail the surface contamination of areas where problems exist, and to determine the extent of the problem. Measurements were performed at seven workplaces on two separate workdays (round 1 and 2) within a six-month period. Samples were collected from the workplaces based on the video monitoring of skin contact frequency with the surfaces and categorized into three groups to analyze risk. The pilot study indicated that surface contamination to TPGDA containing UV coatings was common, found in 76 percent of the surfaces, and varied with a maximum of 909 microg TPGDA 10 cm(-2) sampling area. In the main study TPGDA was found in 153 out of 196 collected samples (78.1%); for round one 78.1 percent (82 out of 105 samples) and for round two 78.0 percent (71 out of 91 samples). The average TPGDA mass on positive surface samples was on the first round 2,247 +/- 7,462 microg, and on the second round 2,960 +/- 4,590 microg. We conclude that surface contamination to uncured UV coatings at UV-curing lines is common and this involves a risk for harmful, unintentional skin exposure to acrylates.

Acrylates↗

PubMed2001

Anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II and renal impairment using heparin and the platelet glycoprotein IIb-IIIa antagonist tirofiban.

BACKGROUND: Patients with heparin-induced thrombocytopenia type II require an alternative to standard heparin anticoagulation. However, in patients with renal impairment, anticoagulation during cardiopulmonary bypass with agents such as danaparoid sodium or r-hirudin are associated with hemorrhage. Anticoagulation with unfractionated heparins combined with prostacyclin, a potent platelet aggregation inhibitor, is associated with severe hypotension. The authors investigated a new concept using unfractionated heparins after platelet inhibition with the short-acting platelet glycoprotein IIb-IIIa antagonist tirofiban. METHODS: Ten patients with heparin-induced thrombocytopenia type II and renal impairment were enrolled in the investigation. All had heparin-induced thrombocytopenia type II antibodies present as proved by the heparin-induced platelet aggregation assay, the heparin-platelet factor 4 enzyme-linked immunosorbent assay, or both. In all patients, preoperative anticoagulation to an activated partial thromboplastin time of 40-60 s was performed with r-hirudin. Anticoagulation during cardiopulmonary bypass was achieved with a bolus of 400 IU/kg unfractionated heparins after a bolus of tirofiban 10 microg/kg followed by an infusion of tirofiban at a rate of 0.15 microg x kg(-1) x min(-1) until 1 h before conclusion of cardiopulmonary bypass. Additional unfractionated heparins were only administered if activated clotting time decreased below 480 s. Coagulation was monitored by a abciximab-modified TEG and the adenosine diphosphate-stimulated (20 microm) platelet aggregometry. D-dimer concentrations, as a marker of venous thromboembolism, were measured before and 12, 24, and 48 h after surgery. Postoperative antithrombotic therapy was started immediately with r-hirudin to anticoagulation to an activated partial thromboplastin time of 40-60 s. RESULTS: The postoperative blood loss ranged from 110 to 520 ml. No patient needed reexploration. In no patient was there clinical evidence of thrombosis or embolism in the postoperative period or of a critical increase of the D-dimer concentrations, suggesting venous thromboembolism. Transfusion of platelets was necessary in only two patients. CONCLUSIONS: The protocol is easy to perform and no increased postoperative bleeding and no thromboembolic complications occurred. The combination of unfractionated heparins and tirofiban may be an alternative to other anticoagulation strategies in patients with heparin-induced thrombocytopenia.

Adult↗

PubMed2001

Experience in upper eyelid reconstruction with the Cutler-Beard technique.

Reconstruction of full-thickness upper eyelid defects has to supply a movable lid with perfect corneal protection, good aesthetic quality, and acceptable sequelae at the donor site. The Cutler-Beard procedure, a full-thickness cutaneoconjunctival inferior eyelid advancement flap, is a reliable method for reconstruction of total or partial upper eyelid defects. Especially in older individuals, the skin of the donor site is loose and provides sufficient tissue to stretch. Color and texture of the donor matches the recipient site perfectly. Destabilization or ectropion of the donor site, the lower lid, and retraction or entropion of the recipient site, the upper lid, are the main complications. Therefore, a modification of the classic technique should be considered by implantation of an enforcing inlay in the reconstructed lid (eye bank sclera, fascia lata, ear cartilage), especially in reconstruction of extended defects of the upper lid.

Aged↗

PubMed2001

Recessive epidermolysis bullosa dystrophicans (Hallopeau-Siemens)--improvement of wound healing by autologous epidermal grafts on an esterified hyaluronic acid membrane.

Epidermolysis bullosa dystropicans of the Hallopeau-Siemens type (HS-EBD) is an autosomal-recessive blistering disease. Skin fragility due to mutations in structural proteins is responsible for further development of chronic and painful wounds, skin infections and sepsis. There is no causative treatment available. We present a case report with HS-EBD and longstanding painful wounds treated with autologous keratinocytes on an esterified hyaluronic acid membrane. Two out of three wounds treated showed a complete take of the graft. They improved markedly with a stable result over 12 months until now. Even autologous keratinocyte grafting may have a beneficial effect on chronic wounds in HS-EBD despite the fact that the genetic defects are unchanged.

Adjuvants, Immunologic↗

PubMed2001

Anaerobic initial reaction of n-alkanes in a denitrifying bacterium: evidence for (1-methylpentyl)succinate as initial product and for involvement of an organic radical in n-hexane metabolism.

A novel type of denitrifying bacterium (strain HxN1) with the capacity to oxidize n-alkanes anaerobically with nitrate as the electron acceptor to CO(2) formed (1-methylpentyl)succinate (MPS) during growth on n-hexane as the only organic substrate under strict exclusion of air. Identification of MPS by gas chromatography-mass spectrometry was based on comparison with a synthetic standard. MPS was not formed during anaerobic growth on n-hexanoate. Anaerobic growth with [1-(13)C]n-hexane or d(14)-n-hexane led to a 1-methylpentyl side chain in MPS with one (13)C atom or 13 deuterium atoms, respectively. This indicates that the 1-methylpentyl side chain originates directly from n-hexane. Electron paramagnetic resonance spectroscopy revealed the presence of an organic radical in n-hexane-grown cells but not in n-hexanoate-grown cells. Results point at a mechanistic similarity between the anaerobic initial reaction of n-hexane and that of toluene, even though n-hexane is much less reactive; the described initial reaction of toluene in anaerobic bacteria is an addition to fumarate via a radical mechanism yielding benzylsuccinate. We conclude that n-hexane is activated at its second carbon atom by a radical reaction and presumably added to fumarate as a cosubstrate, yielding MPS as the first stable product. When 2,3-d(2)-fumarate was added to cultures growing on unlabeled n-hexane, 3-d(1)-MPS rather than 2,3-d(2)-MPS was detected, indicating loss of one deuterium atom by an as yet unknown mechanism.

Alkanes↗

PubMed2001

Interferon-alpha combined with cytarabine in chronic myelogenous leukemia - clinical benefits.

During the last decade, several studies have evaluated the treatment of chronic phase chronic myeloid leukemia (CML) with a combination of interferon (IFN)-alpha and low- dose cytarabine (Ara-C). This combination therapy has been shown to be superior compared to monotherapy with IFN-alpha in randomized studies with regard to hematologic and cytogenetic remissions. However, the survival benefit is small, and the toxicity of the combination therapy is high. This paper reviews the published studies on IFN-alpha/low-dose Ara-C for the treatment of chronic phase CML and discusses the value of the combination therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

[Exhalation of I-131 after radioiodine therapy (RIT): time dependence and chemical form].

AIM: The change of both amount and chemical forms of radioiodine exhaled in the air of rooms with patients on the therapy ward should be investigated depending on radioactivity applied, time after application, and kind of thyroid disease. METHODS: The air of ward-rooms of 62 patients with thyroid carcinoma, Graves' Disease, and autonomy which received different therapy doses, was investigated with an portable constant air flow sampler. Different chemical iodine species (organic, elemental, aerosol bound) were collected during 8 hr in various filters until 3 days after application of the radioiodine capsule, according to their chemical form. The radioactivity in the filters was measured with a well counter on defined time points after application. RESULTS: The radioactivity exhaled was between 0.008 and 0.03% related to activity of radioiodine applied. The percentage of radioiodine exhaled related to the activity applied, differed significantly depending on disease and changed as follows: Grave's Disease > autonomy > carcinoma. The exhalation of radioiodine became stronger with increasing applied activities and showed an exponential decrease with time. The most part of radioiodine was present in organic bound form. This organic portion decreased with time in favour of the other iodine species. CONCLUSION: The degree of accumulation of radioiodine orally applied within thyroid seems to be in direct proportion to the extend of its exhalation. Further measurements directly in the breathing air of RIT-patients are necessary, in order to clarify the relationship between degree of thyroid uptake and quantity as well as chemical form of radioiodine exhaled.

Air Pollutants, Radioactive↗

PubMed2001

Evaluation of post-cardiopulmonary bypass coagulation disorders by differential diagnosis with a multichannel modified thromboelastogram: a pilot investigation.

We assessed a modified multichannel thromboelastogram for differentiation of the causes of coagulopathy after cardiopulmonary bypass and its suitability as a therapy guide. Thirty adult patients undergoing surgery with cardiopulmonary bypass, who revealed a coagulopathy as observed by a prolonged activated clotting time of >150 sec after the application of protamine, were enrolled. Therapy was based on the results obtained by the computerized four-channel thromboelastogram with baseline, heparinase (2 IU/mL), heparinase/abciximab (5 microg/mL), and heparinase/fresh frozen plasma (25%) channels. The mean activated clotting time before therapy was 162.2+/-7.8 sec. Based on differential diagnosis with the modified multichannel thromboelastogram, two patients received protamine (30 mg), five desmopressin (0.4 microg/kg), 19 patients three units of fresh frozen plasma, two patients platelet transfusions, and two patients both protamine (30 mg) and three units of fresh frozen plasma. After therapy, there was a significant (p < .01) decrease of the activated clotting time to a mean value of 127+/-8.3 sec. Therapy based on the synoptic modified multichannel thromboelastogram analysis provides a guide for effective therapy of coagulopathy. However, elaboration is desirable, and larger clinical trials are necessary for a final evaluation of the protocol.

Adult↗

PubMed2001

Assessment of the resonance thromboelastograph CS-3 for differentiation of coagulation disorders: a pilot in vitro investigation of simulated post-cardiopulmonary bypass coagulopathies.

Resonance thromboelastography (RTG), a further development of the thromboelastogram (TEG), has been designed for improved differentiation of the effect of the plasmatic coagulation factors (increasing F-leg) and platelets (decreasing P-leg) on clot formation. It is based on the effect of clot elasticity on the resonance of a swinging wire. We assessed the RTG for its ability to differentiate coagulation disorders that frequently occur after cardiac surgery. The RTG was performed with a CS-3 Analyzer. Samples from 10 healthy volunteers were investigated after the following preparations: (1) baseline values, (2) dilution to a hematocrit of 30% and 20% with either hydroxyl ethyl starch (HES) 10% or plasma; (3) addition of 0.25, 0.5, and 1.0 IU/mL porcine heparin with and without heparinase; and (4) addition of 1.0, 3.0, 4.0, and 5.0 microg/mL of the antiplatelet agent abciximab (ReoPro). Increasing concentrations of abciximab led to a slower decrease or in the case of higher concentrations, to a persistent elevation of the platelet leg of the RTG. Dilution of the hematocrit with plasma had no effect on the fibrin and platelet leg; whereas, dilution with HES 10% led to an inhibition of the fibrin and platelet leg. Dilution of the plasmatic coagulation factors resulted in an inhibition of both the fibrin and the platelet leg. The addition of 0.25 and 0.5 IU/mL of heparin led to an increased coagulation time and inhibition of the fibrin and platelet legs. These effects were eliminated by the addition of heparinase. The RTG enables the evaluation of platelet function under the condition of a nonimpaired plasma coagulation system. Depletion of plasma coagulation factors and the administration of small amounts of heparin do not enable the distinction between residual effects of an anticoagulant, coagulation factor deficiency, or impaired platelet function. However, the heparin effects can be eliminated by the addition of heparinase. Further improvement may be achieved using a modified RTG by adding plasma coagulation factors in one channel for an improved evaluation of platelet function, even under the condition of a loss of procoagulants.

Abciximab↗

PubMed2000

Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha i subunits.

Activator of G protein signaling 3 (AGS3) is a newly identified protein shown to act at the level of the G protein itself. AGS3 belongs to the GoLoco family of proteins, sharing the 19-aa GoLoco motif that is a Galpha(i/o) binding motif. AGS3 interacts only with members of the Galpha(i/o) subfamily. By surface plasmon resonance, we found that AGS3 binds exclusively to the GDP-bound form of Galpha(i3). In GTPgammaS binding assays, AGS3 behaves as a guanine dissociation inhibitor (GDI), inhibiting the rate of exchange of GDP for GTP by Galpha(i3). AGS3 interacts with both Galpha(i3) and Galpha(o) subunits, but has GDI activity only on Galpha(i3), not on Galpha(o). The fourth GoLoco motif of AGS3 is a major contributor to this activity. AGS3 stabilizes Galpha(i3) in its GDP-bound form, as it inhibits the increase in tryptophan fluorescence of the Galpha(i3)-GDP subunit stimulated by AlF(4)(-). AGS3 is widely expressed as it is detected by immunoblotting in brain, testis, liver, kidney, heart, pancreas, and in PC-12 cells. Several different sizes of the protein are detected. By Northern blotting, AGS3 shows 2.3-kb and 3.5-kb mRNAs in heart and brain, respectively, suggesting tissue-specific alternative splicing. Taken together, our results demonstrate that AGS3 is a GDI. To the best of our knowledge, no other GDI has been described for heterotrimeric G proteins. Inhibition of the Galpha subunit and stimulation of heterotrimeric G protein signaling, presumably by stimulating Gbetagamma, extend the possibilities for modulating signal transduction through heterotrimeric G proteins.

Aluminum Compounds↗

PubMed2000

Interactions of metarhodopsin II. Arrestin peptides compete with arrestin and transducin.

Arrestin blocks the interaction of rhodopsin with the G protein transducin (G(t)). To characterize the sites of arrestin that interact with rhodopsin, we have utilized a spectrophotometric peptide competition assay. It is based on the stabilization of the active intermediates metarhodopsin II (MII) and phosphorylated MII by G(t) and arrestin, respectively (extra MII monitor). The protocol involves native disc membranes and three sets of peptides 10-30 amino acids in length spanning the arrestin sequence. In the absence of arrestin, not one of the peptides by itself had an effect on the amount of MII formed. However, inhibition of arrestin-dependent extra MII was found for the peptides at residues 11-30 and 51-70 (IC(50) < 100 microm) and residues 231-260 (IC(50) < 200 microm). A similar pattern of inhibition by arrestin peptides was seen when arrestin was replaced by G(t) or the farnesylated G(t)gamma C-terminal peptide. Only arrestin-(11-30) inhibited MII.G(t) less (IC(50) = 300 microm) than phosphorylated MII.arrestin. We interpreted the data by competition of the arrestin peptides for interaction sites at rhodopsin, exposed in the MII conformation and specific for both arrestin and G(t). The arrestin sites are located in both the C- and N-terminal domains of the arrestin structure.

Amino Acid Sequence↗

PubMed2000

A novel site on the Galpha -protein that recognizes heptahelical receptors.

Specific domains of the G-protein alpha subunit have been shown to control coupling to heptahelical receptors. The extreme N and C termini and a region between alpha4 and alpha5 helices of the G-protein alpha subunit are known to determine selective interaction with the receptors. The metabotropic glutamate receptor 2 activated both mouse Galpha(15) and its human homologue Galpha(16), whereas metabotropic glutamate receptor 8 activated Galpha(15) only. The extreme C-terminal 20 amino acid residues are identical between the Galpha(15) and Galpha(16) and are therefore unlikely to be involved in coupling selectivity. Our data reveal two regions on Galpha(16) that inhibit its coupling to metabotropic glutamate receptor 8. On a three-dimensional model, both regions are found in a close proximity to the extreme C terminus of Galpha(16). One module comprises alpha4 helix, alpha4-beta6 loop (L9 Loop), beta6 sheet, and alpha5 helix. The other, not described previously, is located within the loop that links the N-terminal alpha helix to the beta1 strand of the Ras-like domain of the alpha subunit. Coupling of Galpha(16) protein to the metabotropic glutamate receptor 8 is partially modulated by each module alone, whereas both modules are needed to eliminate the coupling fully.

Antibodies↗

PubMed2000

Observation of cavity-mediated long-range light forces between strongly coupled atoms

We report on the observation of long-range forces between ultracold rubidium atoms that are mutually coupled by the field of a driven high-finesse optical cavity. Even for much less than one photon in the cavity on average, the forces strongly influence the spatial distribution of the atoms. This manifests itself as an asymmetric normal-mode spectrum of the strongly coupled atoms-cavity system. Expressions are given for the dipole force and the diffusion coefficient for the atoms in the presence of the other atoms. The data agree well with calculated spectra, which include the full motional dynamics of the many-atom system.

Journal Article↗

PubMed2000

Membrane-associated GAIP is a phosphoprotein and can be phosphorylated by clathrin-coated vesicles.

GAIP (G alpha interacting protein) is a member of the RGS (regulators of G protein signaling) family and accelerates the turnover of GTP bound to Galphai, Galphaq, and Galpha13. There are two pools of GAIP-a soluble and a membrane-anchored pool. The membrane-anchored pool is found on clathrin-coated vesicles (CCVs) and pits in rat liver and AtT-20 pituitary cells. By treatment of a GAIP-enriched rat liver fraction with alkaline phosphatase, we found that membrane-bound GAIP is phosphorylated. By immunoprecipitation carried out on [(32)P]orthophosphate-labeled AtT-20 pituitary cells stably expressing GAIP, (32)P-labeling was associated exclusively with the membrane pool of GAIP. Phosphoamino acid analysis revealed that phosphorylation of GAIP occurred largely on serine residues. Recombinant GAIP could be phosphorylated at its N terminus with purified casein kinase 2 (CK2). It could also be phosphorylated by isolated CCVs in vitro. Phosphorylation was Mn(2+)-dependent, using both purified CK2 and CCVs. Ser-24 was identified as one of the phosphorylation sites. Our results establish that GAIP is phosphorylated and that only the membrane pool is phosphorylated, suggesting that GAIP can be regulated by phosphorylation events taking place at the level of clathrin-coated pits and vesicles.

Animals↗

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↗