Biomedical subjects

W Bushman

Publications and source records attributed to W Bushman.

22 records · Page 2Linked to original sources

PubMed1993

Voiding dysfunction in patients with spastic paraplegia: urodynamic evaluation and response to continuous intrathecal baclofen.

Patients with hereditary spastic paraplegia (HSP), a degenerative central nervous system disorder characterized by progressive lower extremity spasticity, frequently experience symptoms of voiding dysfunction. Urodynamic evaluation of patients with HSP has not been reported, and the etiology of voiding dysfunction remains unexplained. We present our evaluation of three men (ages 42-62 years) with this rare syndrome. Urgency of urination was a uniform and dominant complaint, and two patients regularly experienced urge incontinence. Other symptoms included frequency (n = 3), nocturia (n = 3), and diminished force of stream (n = 1). Postvoid residual volumes were less than 25 ml in all patients. On urodynamic evaluation the two patients with urge incontinence displayed cystometric evidence of involuntary detrusor contractions. Pelvic floor EMG recordings suggested detrusor-sphincter dyssynergia (DSD). In addition, one patient exhibited markedly diminished bladder compliance (1.0 ml/cm H2O) and capacity (50 ml). All patients reported marked symptomatic improvement when treated with continuous intrathecal baclofen. Evaluation during baclofen treatment revealed increases in bladder compliance and capacity, with apparent resolution of DSD in one patient. Voiding symptoms in these patients most likely arise from a neurogenic etiology; however, a contributory role for chronic outlet obstruction from striated muscle spasticity may also exist.

Adult↗

PubMed1985

Control of directionality in lambda site specific recombination.

The simple relation between the substrates and products of site-specific recombination raises questions about the control of directionality often observed in this class of DNA transactions. For bacteriophage lambda, viral integration and excision proceed by discrete pathways, and DNA substrates with the intrinsic property of recombining in only one direction can be constructed. These pathways display an asymmetric reliance on a complex array of protein binding sites, and they respond differently to changes in the concentrations of the relevant proteins. The Escherichia coli protein integration host factor (IHF) differentially affects integrative and excisive recombination, thereby influencing directionality. A four- to eightfold increase in intracellular IHF coincides with the transition from exponential to stationary phase; this provides a mechanism for growth phase-dependent regulation of recombination that makes the cellular physiology an intrinsic part of the recombination reaction.

Bacterial Proteins↗

PubMed1985

Interaction of the lambda site-specific recombination protein Xis with attachment site DNA.

Nuclease protection experiments show that Xis protein of bacteriophage lambda specifically binds attachment (att) site DNA. The region of Xis binding, present in both the phage att site and the right prophage att site, extends from position -102 to position -62 in the P arm. The sequence of this region, the positions of purines protected by Xis against methylation, and the binding of Xis to a resected att site indicate the presence of two binding sites. The postulated recognition elements, contained in 13-base-pair direct repeats separated by 7 base pairs, are situated on the same face of the DNA helix. Protection experiments performed with DNase I suggest that the DNA wraps around (or along the surface of) the bound Xis protein. The Xis binding data presented here establishes that Xis, like the other two proteins involved in lambda site-specific recombination, interacts specifically with att DNA. This rules out that class of models in which the profound effects of Xis on the directionality of site-specific recombination are mediated solely through protein-protein interactions or modification of another protein. In addition, nuclease protection experiments with pairwise combinations of the proteins show that Xis and integration host factor (IHF), or Xis and Int, can bind simultaneously to either the phage or right prophage att sites, and the DNA sequences protected are the sum of those protected with each protein alone. It is therefore unlikely that the effect of Xis on the direction of recombination is exerted by directly blocking the binding of Int or IHF to one or more of their respective binding sites.

Attachment Sites, Microbiological↗

PubMed1984

Determinants of directionality in lambda site-specific recombination.

The DNA structural features governing directionality in lambda site-specific recombination are shown to reside in regions of the phage attachment site more than 70 bp to the left and more than 40 bp to the right of the cross-over region. Disposition of these sequences on the same attachment site in integration, and on different attachment sites in excision, determines the opposite effects of Xis protein upon the two reactions (stimulation of excision and inhibition of integration). The binding of Xis to two adjacent directly repeated sequences in the left phage arm is shown to occur in a highly cooperative manner, to alter the conformation of the DNA, and to produce a 32-fold stimulation of Int binding to an adjacent locus.

Bacteriophage lambda↗