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Biomedical subjects

K Schaffner

Publications and source records attributed to K Schaffner.

35 records · Page 2Linked to original sources
PubMed1994

Expression of phytochrome apoprotein from Avena sativa in Escherichia coli and formation of photoactive chromoproteins by assembly with phycocyanobilin.

Phytochrome DNAs from oat (Avena sativa L.) encoding the full-length 124-kDa polypeptide, a 118-kDa fragment lacking the first 65 amino acids, and two N-terminal fragments of 65 kDa and 45 kDa were subcloned and expressed in Escherichia coli. Reducing the temperature to 25 degrees C during cell growth and the coexpression of chaperones improved the folding into a functional conformation for most of the polypeptides, and in one case the yield of polypeptides was also enhanced. A maximum yield of reconstitutable apoprotein was obtained by expressing the 65-kDa fragment consisting of 595 amino acids. The apoproteins could be assembled in the dark with phycocyanobilin into photoreversible chromoproteins. The yield of photoreversible pigment could be further increased by far-red/red irradiation cycles, indicating that the presence of the chromophore promotes the correct folding of the binding site. The chromoproteins with an intact N-terminal domain exhibit Pr and Pfr absorption bands, which are blue-shifted relative to the corresponding bands of native phytochrome due to the particular phycocyanobilin structure. The 118-kDa fragment, only lacking the 6-kDa N-terminus, exhibits a strong Pr band, but only a weak Pfr absorbance. This indicates an essential role of the front 6-kDa region of the protein in the formation of the far-red absorbing chromophore-protein complex. Otherwise, the C-terminal region seems to be less important for photoreversibility as indicated by the function of the shorter fragments.

Base Sequence↗
PubMed1993

Effects of bound monoclonal antibodies on the decay of the phototransformation intermediates I700(1,2) from native Avena phytochrome.

The kinetics of the microsecond phototransformation intermediates of 124 kDa Avena phytochrome (I700(1,2) were studied in the presence of bound monoclonal antibodies at various temperatures. A global analysis was applied to the decays at all wavelengths at each temperature in order to derive the rate constants and the decay-associated spectra of the three decay components. Monoclonal antibodies bound to specific epitopes altered the Arrhenius parameters of both I700(1,2) decay components. The strongest influence on these parameters was observed with OAT 8 (epitope between residues 624 and 686), which decreased by more than 50% the activation parameters of both components. This decrease is interpreted to result from an increased flexibility induced by this antibody in the ground state or in the transition state of bonds changing during the decay of both I700 transients. Thus, the OAT 8 epitope appears to be functionally important during the decay of the I700(1,2) intermediates. For the case of I700(1), bound OAT 23 and OAT 25 (epitopes between residues 1 and 66) reduced even further the relatively small flexibility of these bonds in the red light-absorbing form of phytochrome (Pr) without antibodies, as reflected by the high preexponential factors for its decay. This resulted also in higher activation energies for this decay in the presence of the antibodies. Thus, the amino-terminus should act as a rigid spacer of the chromophore cavity without affecting it during the microsecond transformation, because the Arrhenius parameters for these decays are similar to those for small phytochrome. The possible implications of the influence of the various antibodies on the bleaching remaining after the decay of I700(1,2) are discussed.

Antibodies, Monoclonal↗
PubMed1993

Drug testing.

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Journal Article↗
PubMed1993

Philosophical aspects of defining efficiency for biological systems--an introductory overview.

This article introduces six themes that are in active discussion in contemporary philosophy of science. The first theme deals with definitions in general and their role in cardiology in particular. The second theme is on the structure of theory in cardiology. Third, the relationship between theory and experiment is examined, and then, fourthly, the nature of reduction and the relationship between concepts of lower levels and the concepts of higher levels in cardiology is considered. A closely related fifth theme deals with "co-evolution", where progress in cardiology is traced at mutually interactive levels of organization. Finally, I discuss the relationship of evolution and the optimization of cardiac function.

Biological Evolution↗
PubMed1992

Fourier transform resonance Raman spectroscopy of phytochrome.

The Pr and Pfr forms of phytochrome in H2O and D2O have been studied by Fourier transform resonance Raman spectroscopy with near-infrared excitation (1064 nm). It is demonstrated that this technique is a powerful method for analyzing the chromophore structures of photosensitive pigments. The high spectral quality allows discussion of vibrational assignments based on an empirical approach using previously published data obtained from model compounds. The reduction in intensity of a high-frequency band assigned to the ring-C/D methine bridge vibration is an indication for the non-coplanarity of the ring D in Pfr. The high intensity of a C-H out-of-plane vibration also supports this hypothesis. In Pr, a broad peak at approximately 1100 cm-1 is assigned to an out-of-plane vibration of a strongly hydrogen-bonded pyrrole C=NH+ group. It is missing in Pfr, suggesting deprotonation of the corresponding ring during the transformation from Pr to Pfr.

Chemical Phenomena↗
PubMed1990

Quantum yield of production of singlet molecular oxygen (1 delta g) in aqueous dispersions of small unilamellar lipid vesicles. A time-resolved near-IR phosphorescence study.

The quantum yield of formation and kinetic behaviour of O2(1 delta g) in D2O dispersions of small unilamellar vesicles (SUVs) of dipalmitoyl phosphatidylcholine were studied by time-resolved detection of near-IR phosphorescence. At a SUV concentration of 26 nM, O2(1 delta g) is not quenched by the vesicles. It diffuses quickly through the lipid bilayer and a partition equilibrium of O2(1 delta g) between the lipid bilayer and the buffer is attained before decay occurs. In this equilibrium situation O2(1 delta g) is mostly located in the buffer phase, which permits the determination of absolute quantum yields for O2(1 delta g) production, phi delta, by comparison of the luminescence in the dispersions with that in neat D2O. The maximal phi delta values for the sensitizers incorporated in the SUV bilayer were 0.47 +/- 0.09 for the dipyridyl complex of zinc(II) phthalocyanine (ZnPc), 0.35 +/- 0.08 for porphycene, and 0.36 +/- 0.08 for 2,7,12,17-tetra-n-propylporphycene. These values are equal to those in neat organic solvents but lower than those previously obtained in SUVs by using chemical trapping agents. The high degree of organization of the environment around the sensitizers does not influence their efficiency of producing O2(1 delta g). While no concentration dependence is observed for ZnPc (at least up to a local concentration of 20 mM in the bilayer), phi delta for both porphycenes significantly decreases above a local concentration of 4 mM in the bilayer. This result is expected in view of previous observations on the concentration dependence of other photophysical parameters of the porphycenes in such microheterogeneous media.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1989

Tetra-n-propylporphycene as a tumour localizer: pharmacokinetic and phototherapeutic studies in mice.

The porphin isomer tetra-n-propyl-porphycene (TPP) was incorporated into unilamellar liposomes of dipalmitoylphosphatidylcholine and intravenously injected at a dose of 2 mg/kg to BALB/c mice bearing a MS-2 fibrosarcoma. Pharmacokinetic studies show that TPP is selectively transported by serum lipoproteins and delivered to the tumour tissue with good efficiency (approx. 1 microgram of the TPP per g of tissue at 24 h after injection) and selectivity (ratio of TPP concentration in the tumour to the peritumoural tissue 16.7 at 24 h). Large doses of TPP are also accumulated by the liver, in agreement with the elimination of the drug via the biliary route, while no TPP is recovered from the brain. Red light-irradiation (300 J/cm2) of the tumour area caused extensive necrosis, while only little cutaneous photosensitivity was observed. Since TPP has a large absorbance in the 630-640 nm region, can be synthesized with a high degree of purity and is an efficient generator of singlet oxygen, this drug represents a potential candidate as a phototherapeutic agent for tumours.

Animals↗
PubMed1989

Evolution of clinical ethics teaching at the University of Pittsburgh.

The authors explain that several years of effort, by many faculty from a variety of disciplines, were required to expand medical ethics teaching at the University of Pittsburgh School of Medicine beyond the preclinical years. Since 1986, faculty associated with the school's Center for Medical Ethics have begun a comprehensive ethics teaching program for all four years and the residency period; they also are attempting to develop an ethics consultation service. The authors describe the program, its promise and plans, and the significant difficulties involved in establishing and maintaining it, not only problems of long-term funding but of the uninformed and negative attitudes of some students and faculty toward ethics teaching, especially in the clinical setting. Also discussed are the pros and cons of using cases in ethics teaching and the program's approaches to evaluation and to training clinical faculty in clinical ethics issues.

Education, Medical↗
PubMed1985

Responsibility and compensation for tardive dyskinesia.

Lawsuits seeking compensation for the suffering caused by tardive dyskinesia are becoming more common. Although most mental health professionals view the problem in the context of malpractice litigation, tardive dyskinesia is an example of a "mass accident," for which there are a number of judicially created remedies. These remedies include placing liability on manufacturers, asking society as a whole to bear the burden, and allowing patients with tardive dyskinesia to continue to carry the costs of their injuries. In attempting to influence policy in this area, psychiatrists should be sensitive to the implications of any policy for patient care.

Antipsychotic Agents↗