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Biomedical subjects

M W Davis

Publications and source records attributed to M W Davis.

At least 37 records · Page 2Linked to original sources
PubMed1997

avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans.

Ivermectin is a widely used anthelmintic drug whose nematocidal mechanism is incompletely understood. We have used Caenorhabditis elegans as a model system to understand ivermectin's effects. We found that the M3 neurons of the C.elegans pharynx form fast inhibitory glutamatergic neuromuscular synapses. avr-15, a gene that confers ivermectin sensitivity on worms, is necessary postsynaptically for a functional M3 synapse and for the hyperpolarizing effect of glutamate on pharyngeal muscle. avr-15 encodes two alternatively spliced channel subunits that share ligand binding and transmembrane domains and are members of the family of glutamate-gated chloride channel subunits. An avr-15-encoded subunit forms a homomeric channel that is ivermectin-sensitive and glutamate-gated. These results indicate that: (i) an ivermectin-sensitive chloride channel mediates fast inhibitory glutamatergic neuromuscular transmission; and (ii) a nematocidal property of ivermectin derives from its activity as an agonist of glutamate-gated chloride channels in essential excitable cells such as those of the pharynx.

Alternative Splicing↗
PubMed1996

Biology and clinical potential of stem-cell factor.

Stem-cell factor (SCF) is a hematopoietic growth factor that acts on both primitive and mature progenitor cells. Preclinical studies have shown that recombinant SCF can protect against lethal irradiation, elicit multilineage hematopoietic responses and increases in bone marrow cellularity, and increase the number of circulating peripheral blood progenitor cells (PBPCs) in a dose-dependent manner. Both preclinical and early clinical studies using recombinant methionyl human SCF plus recombinant methionyl human granulocyte colony-stimulating factor (Filgrastim) have demonstrated increased PBPC mobilization as compared with the use of either factor alone. These data suggest a clinical role for the combination.

Animals↗
PubMed1996

Toward development of an implantable tissue engineered liver.

Hepatocyte transplantation on implantable devices is a tissue engineering approach to improve the treatment of liver disease and the efficacy of ex vivo gene therapy. Diverse physiological functions and high metabolic activity of the liver represent significant challenges to engineering implantable devices that provide long-term hepatic support. Liver tissue engineering research has explored alternatives to direct hepatocyte injection that include hepatocyte attachment to microcarriers, encapsulation and transplantation on biodegradable polymer scaffolds. Successful function of hepatocytes transplanted on implantable devices in animal models has been documented by production of albumin and other liver-specific markers, and clearance of bilirubin and urea metabolites. Strategies used to achieve these successes are reviewed, with particular emphasis on biodegradable polymer scaffolds, and two areas of investigation that may improve the function of implantable tissue engineered liver devices are highlighted.

Animals↗
PubMed1995

Peptidyl alpha-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency.

A series of peptidyl alpha-ketoheterocycles were synthesized and evaluated for their in vitro inhibition of human neutrophil elastase (HNE). Several heterocycles, including oxazoline and benzoxazole, afforded extremely potent inhibitors of HNE (1p-r) with nanomolar to subnanomolar Ki values. The structure-activity relationships revealed that for compounds with a Ki < 1000 nM potency tends to be positively correlated with the sigma I value of the heterocycle. Furthermore, the results in this study support the hypothesis that, in the covalent enzyme-inhibitor adduct, the azole nitrogen atom of the inhibitor heterocycle participates in a hydrogen-bonding interaction with the active-site His-57.

Amino Acid Sequence↗
PubMed1995

Mutations in the Caenorhabditis elegans Na,K-ATPase alpha-subunit gene, eat-6, disrupt excitable cell function.

We have cloned a Na,K-ATPase alpha-subunit gene from Caenorhabditis elegans and discovered that it is identical to the gene eat-6, eat-6 mutations cause feeble contractions and slow, delayed relaxations of pharyngeal muscle. The resting membrane potential of eat-6 mutant pharynxes is consistently depolarized compared to wild-type. The action potentials are smaller, and the return to resting potential is slower. To explain these abnormalities, we propose that a reduction of Na,K-ATPase activity in eat-6 mutants leads to a reduction of the ion concentration gradients that power membrane potential changes.

Amino Acid Sequence↗
PubMed1994

Functional dissection of a predicted class-defining motif in a class II tRNA synthetase of unknown structure.

A core of eight beta-strands and three alpha-helices was recently predicted for the active site domain of Escherichia coli alanyl-tRNA synthetase, an enzyme of unknown structure [Ribas de Pouplana, L1., Buechter, D. D., Davis, M. W., & Schimmel, P. (1993) Protein Sci. 2, 2259-2262; Shi, J.-P., Musier-Forsyth, K., & Schimmel, P. (1994) Biochemistry 26, 5312-5318]. A critical part of this predicted structure is two antiparallel beta-strands and an intervening loop that make up the second of three highly degenerate sequence motifs that are characteristic of the class II aminoacyl-tRNA synthetases. We present here an in vivo and in vitro analysis of 21 rationally designed mutations in the predicted 34-amino acid motif 2 of E. coli alanyl-tRNA synthetase. Although this motif in E. coli alanyl-tRNA synthetase is of a different size than and has only two sequence identities with the analogous motif in yeast aspartyl- and Thermus thermophilus seryl-tRNA synthetases, whose structures are known, the functional consequences of the mutations are explainable in terms of those structures. In particular, the analysis demonstrates the importance of the predicted motif 2 in adenylate formation, distinguishes between two similar, but distinct, predicted models for this motif, and distinguishes between the functional importance of two adjacent phenylalanines in a way that strongly supports the predicted structure. The results suggest that similar analyses will be generally useful in testing models for active site regions of other class II aminoacyl-tRNA synthetases of unknown structure.

Acylation↗
PubMed1994

The use of light-cured composite resin on altered diagnostic casts.

Light-cured composite resin as an alternative to wax for altered diagnostic casts is demonstrated. The value of altered diagnostic casts as a diagnostic tool is addressed. The benefits in the use of composite resin versus the traditional use of wax are emphasized.

Acrylic Resins↗
PubMed1994

A model for clinical teaching as a scholarly endeavor.

The traditional ways that academia has approached documentation of scholarship are relatively narrow and best fit those disciplines whose practice is research and writing. In professional practice disciplines such as nursing, writing and research are critical, but they are not the only scholarly activities in which faculty are involved. A model resulting from work from the Carnegie Foundation for the Advancement of Teaching offers a broader view of scholarship in which clinical teaching has academic legitimacy. The components of scholarship included in the model are discovery, practice, integration, and teaching.

Clinical Competence↗
PubMed1993

A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia.

Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of > or = 1.5 x 10(9)/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events.

Adult↗
PubMed1993

Reaping the benefits of electronic medical record systems.

An electronic medical record system can provide benefits beyond the obvious functions of efficient and less labor-intensive scanning, archiving, retrieving, and printing of patient care information. The less tangible benefit of providing record access to several users simultaneously is difficult to quantify, but can enhance operations and improve the quality of patient care throughout a healthcare facility.

Abstracting and Indexing↗