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Biomedical subjects

D Weaver

Publications and source records attributed to D Weaver.

At least 37 records · Page 2Linked to original sources
PubMed1998

Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation.

Congo red (CR) has been shown to inhibit the accumulation in scrapie-infected cells of prion protein (PrP) in the abnormal protease-resistant form (PrP-res). However, it was not clear if this effect was due to a direct interaction of CR with either PrP-res or its protease-sensitive precursor (PrP-sen) or to a less direct effect on living cells. Here we show that CR inhibits PrP-res formation in a simple cell-free reaction composed predominantly of purified PrP-res and PrP-sen. Structurally modified CR analogues were also compared in both the cell-free conversion reaction and scrapie-infected neuroblastoma cells. Methylation of the central phenyl groups at the 2,2' positions diminished the inhibitory potency by > or = 10-fold. In contrast, there was little effect of 3,3' methylation of the phenyls, deletion of one phenyl, or addition of an amido group between the phenyls. The relative activities of these compounds were well correlated in both cellular and acellular systems. Molecular modeling indicated that CR and 3,3'-methyl-CR have little rotational restriction about the biphenyl bond and can readily adopt a planar conformation, as can phenyl-CR and amido-CR. In contrast, 2,2'-methyl-CR is restricted to a nonplanar conformation of the biphenyl group. Thus, planarity and/or torsional mobility of the central phenyl rings of CR and its analogues is probably important for inhibition of PrP-res formation. On the other hand, variations in the intersulfonate distance in these molecules had little effect on PrP-res inhibition. These results indicated a high degree of structural specificity in the inhibition of PrP-res formation by CR and related compounds.

Animals↗
PubMed1998

Inactivation of DNA-dependent protein kinase by protein kinase Cdelta: implications for apoptosis.

Protein kinase Cdelta (PKCdelta) is proteolytically cleaved and activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. A role for PKCdelta in apoptosis is supported by the finding that overexpression of the catalytic fragment of PKCdelta (PKCdelta CF) in cells is associated with the appearance of certain characteristics of apoptosis. However, the functional relationship between PKCdelta cleavage and induction of apoptosis is unknown. The present studies demonstrate that PKCdelta associates constitutively with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The results show that PKCdelta CF phosphorylates DNA-PKcs in vitro. Interaction of DNA-PKcs with PKCdelta CF inhibits the function of DNA-PKcs to form complexes with DNA and to phosphorylate its downstream target, p53. The results also demonstrate that cells deficient in DNA-PK are resistant to apoptosis induced by overexpressing PKCdelta CF. These findings support the hypothesis that functional interactions between PKCdelta and DNA-PK contribute to DNA damage-induced apoptosis.

Apoptosis↗
PubMed1998

Building a nursing management analysis capacity in a teaching hospital.

The authors describe one institution's efforts to create the capacity to use standard hospital information systems to address clinical and operational nursing questions. This work involved not only technical aspects of information management system creation but also building the human currency to make the information available and useful. Because the information available to nursing comes from the same data sources that feed operational management and finance departments, nursing can now speak in the same language at the policy tables.

Budgets↗
PubMed1997

Functional interaction between DNA-PK and c-Abl in response to DNA damage.

How DNA damage is converted into intracellular signals that can control cell behaviour is unknown. The c-Abl protein tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents, whereas the DNA-dependent protein kinase (DNA-PK), consisting of a serine/threonine kinase and Ku DNA-binding subunits, requires DNA double-strand breaks or other DNA lesions for activation. Here we demonstrate that c-Abl interacts constitutively with DNA-PK. Ionizing radiation stimulates binding of c-Abl to DNA-PK and induces an association of c-Abl with Ku antigen. We show that DNA-PK phosphorylates and activates c-Abl in vitro. Cells deficient in DNA-PK are defective in c-Abl activation induced by ionizing radiation. In a potential feedback mechanism, c-Abl phosphorylates DNA-PK, but not Ku, in vitro. Phosphorylation of DNA-PK by c-Abl inhibits the ability of DNA-PK to form a complex with DNA. We also show that treatment of cells with ionizing radiation results in phosphorylation of DNA-PK that is dependent on c-Abl. Our results support the hypothesis that there are functional interactions between c-Abl and DNA-PK in the response to DNA damage.

Animals↗
PubMed1997

Association of BRCA1 with Rad51 in mitotic and meiotic cells.

BRCA1 immunostaining reveals discrete, nuclear foci during S phase of the cell cycle. Human Rad51, a homolog of bacterial RecA, behaves similarly. The two proteins were found to colocalize in vivo and to coimmunoprecipitate. BRCA1 residues 758-1064 alone formed Rad51-containing complexes in vitro. Rad51 is also specifically associated with developing synaptonemal complexes in meiotic cells, and BRCA1 and Rad51 were both detected on asynapsed (axial) elements of human synaptonemal complexes. These findings suggest a functional interaction between BRCA1 and Rad51 in the meiotic and mitotic cell cycles, which, in turn, suggests a role for BRCA1 in the control of recombination and of genome integrity.

BRCA1 Protein↗
PubMed1996

The physiological and behavioral effects of radio music on singly housed baboons.

The response of four singly caged baboons to radio music was measured using behavioral and physiological indices. Heart rate and blood pressure, measured through a tether system, as well as behavior, were recorded during a two-week period in which radio music was available in half of the samples. The behavior of the subjects, as well as their blood pressure, did not vary in relation to radio music. Heart rate was significantly lower when the radio was on.

Animals↗
PubMed1996

Application of a new technology to the design of effective anti-vibration gloves.

Gloves that attenuate vibration above approximately 25 Hz and that exceed the characteristics of standard viscoelastic gloves have been developed using an air bladder system in the palm and fingers of a glove. Testing was performed on a variety of viscoelastic gloves currently marketed to obtain the ratio of energy leaving the handle of a vibrating device and the energy entering the hand. Several simple rectangular air bladders of varying thickness were developed and tested for their vibration attenuating characteristics. A four degree-of-freedom, lumped-parameter model of the vibration response of the human and air bladder was developed using measured hand and bladder parameters. This model, along with subjective criteria, was used to design and fabricate two prototype air bladder gloves. These gloves were tested and found to exceed adopted standard requirements and the characteristics of standard viscoelastic gloves. The prototypes in this study will be further developed, adapted and marketed for practical applications.

Air↗
PubMed1994

The contributions of renin and vasopressin to the adaptation of the Australian spinifex hopping mouse (Notomys alexis) to free water deprivation.

Xeric-adaptation was studied during 28 days of total water deprivation (TWD) in Notomys alexis. Beyond 7 days, the initial reductions in body weight and increases in haematocrit, plasma renin and juxtaglomerular (JG) cell morphological activity returned to normal. Mus musculus showed similar changes at 7 days but could not be maintained thereafter. TWD decreased the blood pressure of Notomys but endogenous angiotensin and vasopressin did not support pressure to a greater extent than controls, as revealed by selective antagonists. The normal morphology of the JG apparatus in Notomys was similar to other rodents. Fluid volume and blood pressure maintenance during TWD in Notomys do not depend upon enhanced activities of the renin-angiotensin and antidiuretic hormonal systems.

Adaptation, Physiological↗
PubMed1992

Effect of an anterior wall motion abnormality on the results of single-plane and biplane left ventriculography.

Although the biplane area-length method would be optimal for all left ventriculograms, 2 contrast injections are needed in laboratories with single-plane imaging equipment. The purpose of this study was to develop practical guidelines to identify the need for biplane left ventriculography in laboratories with single-plane equipment. From a retrospective analysis of 91 consecutive biplane ventriculograms (group 1), guidelines were identified that predicted when the ejection fraction calculated by the biplane method would differ significantly from the single-plane value. These guidelines were derived from information immediately available to the operator in the laboratory at the time of the procedure. Patients in group 1 were divided into 3 subgroups: biplane exceeding single-plane ejection fraction by greater than or equal to 0.05 (n = 20); single-plane exceeding biplane ejection fraction by greater than or equal to 0.05 (n = 14); and ejection fractions within +/- 0.04 by the 2 methods (n = 57). By multivariate analysis, the only predictor of a higher ejection fraction calculated by the biplane method was an anterior wall motion abnormality. This finding was tested prospectively in a separate group of 60 patients (group 2). Left ventriculograms in group 2 patients were stratified before analysis by the presence or absence of an anterior wall motion abnormality. In patients with anterior wall motion abnormalities, the biplane ejection fraction was greater than the single-plane value by 0.05 +/- 0.04 (range -0.03 to +0.15). In contrast, this difference in patients without anterior wall motion abnormalities was -0.01 +/- 0.04 (range -0.09 to +0.06; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗
PubMed1992

Marketing nursing beyond the walls.

Nurse self-actualization and service to the community are two key concepts that nurse administrators must address in developing the vision for the future direction of the nursing department. A marketing venture at a university teaching hospital demonstrated a cost-effective mechanism to meet these goals.

Adolescent↗
PubMed1991

Phenotypic inhibition of the renin-angiotensin system, emergence of the Ren-2 gene, and adaptive radiation of mice.

The renin-angiotensin system in sub-genus Mus displays unique features including duplication of the renin gene in most strains, strong expression of the second gene in submandibular gland of males, and inhibited responses to injected renin. Our findings indicate that this inhibition results from a paucity of renin substrate and is consistent with first-order kinetics. We find substrate paucity to be a feature of both sexes and all sub-species and strains of Mus irrespective of gene duplication. Attempts to increase the level of substrate in blood by intravenous injection caused marked increases in blood pressure in Mus, suggesting that substrate paucity was a phenotypic prerequisite for successful emergence of enhanced renin expression in salivary gland. We propose that these phenomena are linked to salivary "lethal factor", possibly transferred by biting, in an evolutionary sequence that has provided a major selective advantage for Mus and influenced the ecology and evolution of rodents.

Angiotensinogen↗