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Biomedical subjects

J Rudnick

Publications and source records attributed to J Rudnick.

At least 19 recordsLinked to original sources

Constraints, histones, and the 30-nm spiral.

We investigate the mechanical stability of a segment of DNA wrapped around a histone in the nucleosome configuration, under the assumption that the proper model for this packaging arrangement is that of an elastic rod that is free to twist and that writhes subject to mechanical constraints. We find that the number of constraints required to stabilize the nuclesome configuration is determined by the length of the segment, the number of times the DNA wraps around the histone spool, and the specific constraints utilized. While it can be shown that four constraints suffice, in principle, to insure stability of the nucleosome, a proper choice must be made to guarantee the effectiveness of this minimal number. The optimal choice of constraints appears to bear a relation to the existence of a spiral ridge on the surface of the histone octamer. The particular configuration that we investigate is related to the 30-nm spiral, a higher-order organization of DNA in chromatin.

Biophysical Phenomena↗

Crossover behavior in the isothermal susceptibility near the 3He critical point.

We present high-resolution measurements of the isothermal susceptibility of pure 3He near the liquid-gas critical point. PVT measurements were performed in the single-phase region over the reduced temperature range 3 x 10(-5)<T/Tc-1<1.5 x 10(-1). The crossover behavior of the susceptibility along the critical isochore was analyzed using a field-theoretical renormalization-group calculation based on the phi4 model. A similar crossover analysis was performed on previously obtained Xe susceptibility measurements. A comparison of the rescaled susceptibility for 3He and Xe shows theoretically predicted universal crossover behavior.

Journal Article↗

Fluctuation-facilitated charge migration along DNA.

We propose a model Hamiltonian for charge transfer along the DNA double helix with temperature-driven fluctuations in the base pair positions acting as the rate limiting factor for charge transfer between neighboring base pairs. We compare the predictions of the model with the recent work of Barton and Zewail on the unusual two-stage charge transfer of DNA.

DNA↗

Numerical studies of domains and bubbles of langmuir monolayers

A numerical algorithm based on the finite element method has been developed to accurately determine the shape of the boundary of a domain containing "boojum" textures, which are order-parameter distributions that resemble the structure of the orbital angular momentum in a superfluid 3He droplet [N.D. Mermin, in Quantum Fluids and Solids, edited by S.B. Trickey, E. Adams, and J.Duffy (Plenum, New York, 1997)]. Within the context of the simple model we adopt, the effects of both bulk elastic anisotropy and line-tension anisotropy on the domain boundary can be examined. It is found that line-tension anisotropy must be present in order to account for domains with protruding features. Both elastic anisotropy and anisotropic line tension can result in domains with indentations. The numerical algorithm has been extended to investigate the problem of a bubble in an extended region ordered phase.

Journal Article↗

The homeodomain-containing gene Xdbx inhibits neuronal differentiation in the developing embryo.

The development of the vertebrate nervous system depends upon striking a balance between differentiating neurons and neural progenitors in the early embryo. Our findings suggest that the homeodomain-containing gene Xdbx regulates this balance by maintaining neural progenitor populations within specific regions of the neuroectoderm. In posterior regions of the Xenopus embryo, Xdbx is expressed in a bilaterally symmetric stripe that lies at the middle of the mediolateral axis of the neural plate. This stripe of Xdbx expression overlaps the expression domain of the proneural basic/helix-loop-helix-containing gene, Xash3, and is juxtaposed to the expression domains of Xenopus Neurogenin related 1 and N-tubulin, markers of early neurogenesis in the embryo. Xdbx overexpression inhibits neuronal differentiation in the embryo and when co-injected with Xash3, Xdbx inhibits the ability of Xash3 to induce ectopic neurogenesis. One role of Xdbx during normal development may therefore be to restrict spatially neuronal differentiation within the neural plate, possibly by altering the neuronal differentiation function of Xash3.

Amino Acid Sequence↗

DNA-protein cooperative binding through variable-range elastic coupling.

Cooperativity plays an important role in the action of proteins bound to DNA. A simple mechanism for cooperativity, in the form of a tension-mediated interaction between proteins bound to DNA at two different locations, is proposed. These proteins are not in direct physical contact. DNA segments intercalating bound proteins are modeled as a worm-like chain, which is free to deform in two dimensions. The tension-controlled protein-protein interaction is the consequence of two effects produced by the protein binding. The first is the introduction of a bend in the host DNA and the second is the modification of the bending modulus of the DNA in the immediate vicinity of the bound protein. The interaction between two bound proteins may be either attractive or repulsive, depending on their relative orientation on the DNA. Applied tension controls both the strength and the range of protein-protein interactions in this model. Properties of the cooperative interaction are discussed, along with experimental implications.

Biophysical Phenomena↗

Prostaglandin E1 long-term self-injection programme for treatment of erectile dysfunction--a follow-up of at least 5 years.

Prostaglandin E1 (PGE1) is currently the vasoactive drug of choice for intracavernous self-injection therapy in the treatment of erectile dysfunction. PGE1 is often said to have a low incidence of side-effects. However, real long-term follow-up reports are rare. Here, a report is presented on 32 patients who joined a long-term self-injection programme in which they used PGE1 for a minimum of 5 years under standardized protocol conditions. All these patients had an organic aetiology of erectile dysfunction, and their mean age was 58.7 +/- 8.6 years. The period of observation was on average 75.4 +/- 16.9 months, and the PGE1 dosage 13.5 +/- 5.9 micrograms. A total of 6799 injections were registered. The average number of injections was 213 +/- 127 per patient, which is 2.8 injections per month and patient. As regards side-effects, haematomas were registered in 1.9% of the patients and five cases of prolonged erection (0.07%) caused by unauthorized redosing were noted. Three patients developed reversible penile nodules. In 10 patients, the initial dosage had to be increased. Five patients dropped out after 5 years, none of them due to treatment complications. It is concluded that PGE1 self-injection therapy is a simple and reliable method for long-term use with hardly any side-effects. The patients do not stop treatment because of complications.

Aged↗

Elasticity theory of the B-DNA to S-DNA transition.

We propose in this note a simple model--the two-state Worm Like Chain--to describe the elasticity of the recently discovered stress-induced transformation from B-DNA to S-DNA. The model reduces for low tractions to the well-known Worm Like chain theory, which is used to describe the elastic properties of B-DNA, while in the limit of high chain-bending moduli it reduces to the two-state Ising model proposed by Cluzel et al. for the B-S transition [Cluzel, P., A. Lebrun, C. Heller, R. Lavery, J-L. Viovy, D. Chatenay, and F. Caron. 1996. DNA: an extensible molecule. Science. 271:792-794]. Our model can be treated analytically to produce an explicit form of the force-extension relationship which agrees reasonably with the observations. We use the model to show that conformational fluctuations of the chain play a role also for the B to S transformation.

DNA↗

Present state of diagnostic management in veno-occlusive dysfunction.

Pharmacocavernosometry and pharmacocavernosography are essential for the diagnosis of veno-occlusive dysfunction. Pressure fading obtained by cavernosometry correlates excellently with results of intracavernosal pharmacon testing. Venous drainage as visualized by pharmacocavernosography is essential for localization of the venous channels especially if venocorrective surgery is planned.

Erectile Dysfunction↗

Venous surgery in veno-occlusive dysfunction: long-time results after deep dorsal vein resection.

Follow-up of patients 1 year after deep dorsal vein resection gives evidence of an approximate 50-60% success rate. A careful selection of only this small percentage of patients, in whom abnormal drainage through the penile dorsum is obvious, is mandatory. Men with an arterial cofactor have to be excluded or to be subsequently treated by intracavernosal autoinjection of vasoactive substances. Late results from our study demonstrate a further loss of sufficient erection, also in men considered as persistent success by us, in the subjective view of the patient and/or his sexual partner.

Adult↗

Significance of the intracavernosal pharmacological injection test, pharmacocavernosography, artificial erection and cavernosometry in the diagnosis of venous leakage.

149 men suffering from erectile failure underwent a standardized combined procedure including intracavernosal pharmacological injection test (P test) artificial erection, pharmacocavernosography and cavernosometry with analysis of intracavernosal erection pressure and pressure drop. Patients with negative P test were considered to be suffering from 'venous leakage'; data of cavernosography and cavernosometry were analyzed in relation to the results of the P test. 99 men (66.4%) were P-test-negative. 98 of these patients (99%) had pathological cavernous drainage of the plexus santorinii during cavernosography. Flow rates for induction and maintenance of erection of the P-test-negative men were increased and intracavernosal erection pressure decreased significantly compared to the P-test-positive patients. The very diversified range of values made any individual statement impossible. In contrast to these findings, duration of pressure drop was significantly shorter among men with suspicion of venous leakage and without any overlapping compared to P-test-positive men. The findings provide evidence for the necessity, besides pharmacocavernosography, to include an estimation of intracavernosal pressure drop time in the diagnostic procedure of venous leakage in all men with confirmed negative P test.

Adult↗