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Biomedical subjects

Keith Williams

Publications and source records attributed to Keith Williams.

25 records · Page 2Linked to original sources
PubMed2003

Measuring continuity of care for clients of public mental health systems.

OBJECTIVES: The aims of this research were to generate a set of time-variant measures of continuity of outpatient care using administrative data, and to evaluate the validity of these measures for persons in the community with serious mental illness (SMI) who use public mental health services. DATA SOURCES: Individuals with SMI were identified using multistage random sampling from shelters, streets, and public mental health clinics in Houston, Texas. STUDY DESIGN: The study design was observational, cross-sectional, and retrospective. Based on a review of the literature, five distinct conceptual dimensions of continuity of care were defined: timeliness, intensity, comprehensiveness, stability, and coordination. Repeated measures of continuity were generated for each day of the year. Construct validity was assessed by comparing continuity for housed persons and homeless persons based on the assumption that homelessness is a risk factor for low continuity of outpatient care. DATA COLLECTION: Subjects were interviewed to collect sociodemographic and clinical information. Service use was retrospectively tracked through the administrative records of multiple public sector agencies. PRINCIPAL FINDINGS: All five continuity measures demonstrated good construct validity by the fact that homelessness was significantly (p < 0.001) and substantially associated with lower continuity of care. DISCUSSION: The five continuity-of-care measures are relatively easy and inexpensive to generate using administrative data. The five continuity-of-care measures may be useful for identifying individuals at risk for poor outcomes and for evaluating the ability of public service systems to keep clients engaged in care over time.

Adult↗
PubMed2003

Molecular determinants of proton-sensitive N-methyl-D-aspartate receptor gating.

Extracellular protons inhibit N-methyl-D-aspartate (NMDA) receptors with an IC50 value in the physiological pH range. To identify the molecular determinants of proton sensitivity, we used scanning mutagenesis of the NR1 subunit to search for residues that control proton inhibition of NMDA receptors. Homology modeling of the extracellular domains suggested that residues at which mutations perturbed pH sensitivity were localized in discrete regions. The majority of mutations that strongly affected proton sensitivity were clustered in the extracellular end of the second transmembrane domain (M3) and adjacent linker leading to the S2 portion of the glycine-binding domain of NR1. Mutations in NR2A confirmed that the analogous region controls the pH sensitivity of this subunit and also identified the linker region between the third transmembrane domain (M4) and the S2 portion of the NR2 glutamate binding domain as an additional determinant of proton sensitivity. One mutant receptor, NR1(A649C)/NR2A(A651T), showed a 145-fold reduction in the IC50 for protons (IC50, 17.3 microM corresponding to pH 4.9). The M3-S2 linker region has been suggested to control NMDA receptor gating, leading to the hypothesis that the proton sensor and receptor gate may be structurally and functionally integrated.

Amino Acid Sequence↗
PubMed2003

The impact of father absence on adolescent separation-individuation.

The authors compared separation-individuation and psychological separation from fathers of 25 adolescent boys who were living with both biological parents with that of 25 boys who were living with their biological mothers in homes in which the fathers did not reside. The results showed that the boys in the 2 groups did not differ on measures of separation-individuation and that the quality of the mother-son relationship mediated several of the assessed separation-individuation manifestations. The authors' initial data analysis with regard to psychological separation showed that boys who lived in homes in which the father was a nonresident were more separated on 2 of the 4 dimensions assessed; however, when controlled for quality of mother-son and father-son relationship, these differences were not significant. The frequency of father contact in homes in which the father did not reside was positively correlated with healthy separation but negatively correlated with functional, attitudinal, and emotional independence from the father. The results of the study support the importance of the quality of a child's relationship with his or her mother and father as a mediator of several dimensions of the separation-individuation process.

Adolescent↗
PubMed2002

Hormonally regulated alpha(4)beta(2)delta GABA(A) receptors are a target for alcohol.

Here we report that low concentrations of alcohol (1-3 mM) increased Cl(-) currents gated by a recombinant GABA(A) receptor, alpha(4)beta(2)delta, by 40-50% in Xenopus laevis oocytes. We also found greater hippocampal expression of receptors containing alpha(4) and delta subunits, using a rat model of premenstrual syndrome (PMS) in which 1-3 mM alcohol preferentially enhanced GABA-gated currents, and low doses of alcohol attenuated anxiety and behavioral reactivity. The alcohol sensitivity of delta-containing receptors may underlie the reinforcing effects of alcohol during PMS, when eye saccade responses to low doses of alcohol are increased.

Animals↗
PubMed2002

Channel blockers acting at N-methyl-D-aspartate receptors: differential effects of mutations in the vestibule and ion channel pore.

A large number of structurally diverse compounds act as open-channel blockers of NMDA receptors. They may share discrete or overlapping binding sites within the channel. In this study, the effects of mutations in and around the membrane-spanning and pore-forming regions of NMDA receptor subunits were studied with three blockers, MK-801, memantine, and TB-3-4, using recombinant NMDA receptors expressed in Xenopus laevis oocytes. Mutations at the critical asparagine residues in the M2 loop of NR1 and NR2B and at a tryptophan residue in M2 of NR2B reduced block by MK-801, memantine, and TB-3-4. Mutations at residues in the pre-M1, M1, M3, post-M3, and post-M4 regions had differential effects on the three blockers. Many mutations in these regions reduced block by MK-801 and TB-3-4 but had no effect on block by memantine. The differential effects on block by memantine and MK-801 are unlikely to be caused by differences in the size of these blockers. Benzyl rings in MK-801 and TB-3-4 may make hydrophobic interactions with aromatic and hydrophobic amino acid residues in the pore. Some mutations in the pre-M1 and M3 regions generated constitutively open channels, characterized by large holding currents. The effects of the various mutants are discussed in the context of models based on the known structure of the pore of the KcsA potassium channel and on previous studies dealing with solvent accessible residues in NMDA receptor subunits as determined by modification after cysteine mutagenesis.

Amino Acid Sequence↗
PubMedDate not supplied

Carbamylation of proteins in 2-D electrophoresis--myth or reality?

Carbamylation is widely quoted as being a problem in 2-D gel analysis and the associated sample preparation steps. This modification occurs when iso-cyanate, a urea break-down product, covalently modifies lysine residues, thus inducing a change in isoelectric point. Urea is used at up to 9 M concentrations in sample preparation and 2-D gels because of its ability to disrupt protein structure and effect denaturation without the need for ionic surfactants such as SDS. We have studied carbamylation using 7 M urea and 2 M thiourea, under a range of experimental temperatures to establish when, and if, it occurs and what can be done to minimize the modification. The actual time required for protein extraction from a tissue is usually short compared to the time required for procedures such as reduction and alkylation and IPG rehydration and focusing. Therefore, it is the temperature during these post-extraction procedures that is the most critical factor. Our experiments have shown that carbamylation does not occur during electrophoresis in the presence of urea, even with prolonged run-times. However, under poorly controlled sample preparation and storage conditions, it can become a major event.

Alkylation↗