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Biomedical subjects

T Kraft

Publications and source records attributed to T Kraft.

At least 19 recordsLinked to original sources

Parallel inhibition of active force and relaxed fiber stiffness by caldesmon fragments at physiological ionic strength and temperature conditions: additional evidence that weak cross-bridge binding to actin is an essential intermediate for force generation.

Previously we showed that stiffness of relaxed fibers and active force generated in single skinned fibers of rabbit psoas muscle are inhibited in parallel by actin-binding fragments of caldesmon, an actin-associated protein of smooth muscle, under conditions in which a large fraction of cross-bridges is weakly attached to actin (ionic strength of 50 mM and temperature of 5 degrees C). These results suggested that weak cross-bridge attachment to actin is essential for force generation. The present study provides evidence that this is also true for physiological ionic strength (170 mM) at temperatures up to 30 degrees C, suggesting that weak cross-bridge binding to actin is generally required for force generation. In addition, we show that the inhibition of active force is not a result of changes in cross-bridge cycling kinetics but apparently results from selective inhibition of weak cross-bridge binding to actin. Together with our previous biochemical, mechanical, and structural studies, these findings support the proposal that weak cross-bridge attachment to actin is an essential intermediate on the path to force generation and are consistent with the concept that isometric force mainly results from an increase in strain of the attached cross-bridge as a result of a structural change associated with the transition from a weakly bound to a strongly bound actomyosin complex. This mechanism is different from the processes responsible for quick tension recovery that were proposed by Huxley and Simmons (Proposed mechanism of force generation in striated muscle. Nature. 233:533-538.) to represent the elementary mechanism of force generation.

Actins

Effect of Ca2+ on weak cross-bridge interaction with actin in the presence of adenosine 5'-[gamma-thio]triphosphate).

In the presence of the nucleotide analog adenosine 5'-[gamma-thio]triphosphate (ATP[gamma S]), effects of Ca2+ on stiffness and equatorial x-ray diffraction patterns of single skinned fibers of the rabbit psoas muscle were studied. It is shown that cross-bridges in the presence of ATP[gamma S] have properties of the weak-binding states of the ATP hydrolysis cycle. Raising the Ca2+ concentration up to pCa 4.5 has little effect on actin affinity of cross-bridges in the presence of ATP[gamma S]. However, the rate constants for cross-bridge dissociation and reassociation from and to actin are reduced by about 2 orders of magnitude. In addition, nucleotide affinity of the cross-bridge is much smaller at high Ca2+ concentrations. Implications for interpretation of fiber stiffness recorded during isotonic shortening and the rising phase of a tetanus are discussed.

Actins

Storage of chemotherapy drugs for use in the human tumor stem cell assay.

Tumor chemosensitivity assays require the frequent in vitro use of antineoplastic drugs. Economy and convenience are greatly enhanced if these drugs are stored in aliquots for use as needed. This study investigated the stability of eight common antineoplastic agents at -60 degrees C. Activity was measured as inhibition of colony formation in a commonly used soft agar culture system using an experimentally induced murine sarcoma. Our results indicate no loss of activity with these drugs under the specified storage conditions.

Animals

Intraretinal distribution of cone pigments in certain teleost fishes.

Microspectrophotometric investigations of visual pigments in the teleost family Cichlidae determined that morphological "twin cones" need not be "pigment twins" as well. In each species there were two pigments that could be found in these cells; a "longwave" and a "shortwave" type whose precise spectral location varies for each species, making the terms red and green inadequate to describe them. Studies of the receptor mosaic with the nitro-blue tetrazolium chloride reduction technique permitted the sampling of larger receptor populations and confirmed that twin cones in several cichlid species could be either longwave-longwave, longwave-shortwave, or shortwave-shortwave pairs, and that the relative proportions of these twin cone types vary in different parts of the retinas. Nonuniform distribution of pigment types was also evident in the eyes of several other species from a variety of piscine taxa.

Animals

In vivo desensitization of a phobic shop steward.

Techniques used in behaviour therapy effectively counteract the symptoms presented by the patient. The question arises as to the precise nature of such intervention, and whether this form of treatment is in fact a superficial one which deals only with symptom removal, or whether this is really a much more fundamental form of therapy, in which the patient alters as a whole. The case reported here is of interest in that, during a course of in vivo desensitization, in which the therapist accompanied the patient on journeys through London, it was shown that, as the symptoms were alleviated, there were concomitant changes in his whole personality structure. He no longer needed to be a militant shop steward and developed an amicable relationship with his employers, and yet he was still able to negotiate a pay rise for the men. This suggests that the treatment had an effect on his hostility level, so that he could deal effectively with his superiors without the need to fight them. This has important theoretical and ethnical implications.

Adult