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Biomedical subjects

K Scott

Publications and source records attributed to K Scott.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lipase-catalyzed fractionation of conjugated linoleic acid isomers.

The abilities of lipases produced by the fungus Geotrichum candidum to selectively fractionate mixtures of conjugated linoleic acid (CLA) isomers during esterification of mixed CLA free fatty acids and during hydrolysis of mixed CLA methyl esters were examined. The enzymes were highly selective for cis-9,trans-11-18:2. A commercial CLA methyl ester preparation, containing at least 12 species representing four positional CLA isomers, was incubated in aqueous solution with either a commercial G. candidum lipase preparation (Amano GC-4) or lipase produced from a cloned high-selectivity G. candidum lipase B gene. In both instances selective hydrolysis of the cis-9,trans-11-18:2 methyl ester occurred, with negligible hydrolysis of other CLA isomers. The content of cis-9, trans-11-18:2 in the resulting free fatty acid fraction was between 94 (lipase B reaction) and 77% (GC-4 reaction). The commercial CLA mixture contained only trace amounts of trans-9,cis-11-18:2, and there was no evidence that this isomer was hydrolyzed by the enzyme. Analogous results were obtained with these enzymes in the esterification in organic solvent of a commercial preparation of CLA free fatty acids containing at least 12 CLA isomers. In this case, G. candidum lipase B generated a methyl ester fraction that contained >98% cis-9,trans-11-18:2. Geotrichum candidum lipases B and GC-4 also demonstrated high selectivity in the esterification of CLA with ethanol, generating ethyl ester fractions containing 96 and 80%, respectively, of the cis-9,trans-11 isomer. In a second set of experiments, CLA synthesized from pure linoleic acid, composed essentially of two isomers, cis-9,trans-11 and trans-10,cis-12, was utilized. This was subjected to esterification with octanol in an aqueous reaction system using Amano GC-4 lipase as catalyst. The resulting ester fraction contained up to 97% of the cis-9,trans-11 isomer. After adjustment of the reaction conditions, a concentration of 85% trans-10,cis-12-18:2 could be obtained in the unreacted free fatty acid fraction. These lipase-catalyzed reactions provide a means for the preparative-scale production of high-purity cis-9,trans-11-18:2, and a corresponding CLA fraction depleted of this isomer.

Chemical Fractionation↗
PubMed1999

Effect of material deprivation on Epstein-Barr virus infection in Hodgkin's disease in the West Midlands.

We have used Townsend scores from postcode data to compare levels of material deprivation and Epstein-Barr virus (EBV)-positivity for 223 patients diagnosed with Hodgkin's disease (HD) in the period 1981-1997. The presence of EBV in HD tumours was determined using in situ hybridization to target the abundantly expressed EBV early RNAs. EBV was detected in the malignant Hodgkin and Reed-Sternberg cells in 47/223 HD cases (21%). There was found to be a tendency for higher Townsend scores (indicative of higher levels of material deprivation) in EBV-positive HD patients, but this association was not statistically significant. When various subgroups of patients from the study were examined separately the indication of higher Townsend scores in EBV-positive patients was found to be more marked for patients with mixed cellularity disease (P = 0.09) and for females (P = 0.03). The results of this study suggest that differences in the level of material deprivation are important in determining the likelihood of EBV-positive HD in the UK, particularly for certain subgroups of patients. It is not known what specific socioeconomic factors are responsible for these differences, although alterations in the timing or rate of primary EBV infection, or decline in the level of EBV-specific immunity, may be important.

Adolescent↗
PubMed1999

Cross-education of muscle strength is greater with stimulated than voluntary contractions.

Cross-education enhances the performance of muscles not directly involved in the chronic conditioning of the muscles in a remote limb. Substantial cross-education occurs after training with eccentric contractions or with contractions evoked by electromyostimulation (EMS). Since during EMS and eccentric contractions, skin and muscle afferents are activated that have excitatory effects on contralateral homologous muscles, it was hypothesized that exercise training with stimulated vs. voluntary eccentric contractions would lead to greater cross-education. Thirty-two women were randomly assigned to a voluntary (Vol), an EMS, or remote EMS (rEMS) exercise group and performed 840 voluntary or stimulated eccentric contractions over 6 weeks. All subjects, including nonexercising controls (Con), were tested pre- and posttraining for maximal voluntary and stimulated isometric and eccentric quadriceps strength. Ipsilateral voluntary and stimulated forces increased in all groups. Changes in EMG activity paralleled those in voluntary force in each limb. No changes occurred in grip strength. The great contra- and ipsilateral strength gains after EMS training were most likely related to an additive effect of EMS and muscle lengthening.

Adult↗
PubMed1998

Assembly of the Drosophila phototransduction cascade into a signalling complex shapes elementary responses.

The subcellular compartmentalization of signalling molecules helps to ensure the selective activation of different signal-transduction cascades within a single cell. Although there are many examples of compartmentalized signalling molecules, there are few examples of entire signalling cascades being organized as distinct signalling complexes. In Drosophila photoreceptors, the InaD protein, which consists of five PDZ domains, functions as a multivalent adaptor that brings together several components of the phototransduction cascade into a macromolecular complex. Here we study single-photon responses in several photoreceptor mutant backgrounds, and show that the InaD macromolecular complex is the unit of signalling that underlies elementary responses. We show that the localized activity of this signalling unit promotes reliable single-photon responses as well as rapid activation and feedback regulation. Finally, we use genetic and electrophysiological tools to illustrate how the assembly of signalling molecules into a transduction complex limits signal amplification in vivo.

Animals↗
PubMed1998

GLC1A mutations point to regions of potential functional importance on the TIGR/MYOC protein.

PURPOSE: The aim of this study was to screen affected members of glaucoma families for mutations in the Trabecular Meshwork Inducible Glucocorticoid Response (TIGR) gene also known by the name myocilin (MYOC) or by combined names such as TIGR/MYOC. Our primary objectives were (1) to identify mutations responsible for glaucoma in members of three families for which we have shown linkage between chromosome 1 GLC1A-region markers and the primary open angle glaucoma (POAG) phenotype, and (2) to determine the relationship of these and other mutations to key points of predicted function and structure of the TIGR/MYOC protein. METHODS: DNA sequence determination was used to identify sequence changes in sections of the TIGR/MYOC gene that were PCR-amplified from genomic DNA from the probands of three previously-reported GLC1A juvenile-onset POAG families, UM:JG1, UM:JG3, UM:GL57, and unmapped family UM:JG5. Allele-specific oligonucleotide hybridization was used to screen for the identified mutations in PCR-amplified DNA from individual members of each pedigree and from a panel of 11 additional juvenile glaucoma family probands, 42 adult POAG family probands, and 43 normal individuals. Computerized algorithms were used to identify functional motifs and predict structures of normal and mutant forms of the protein. RESULTS: Sequence changes were found that alter amino acids in the olfactomedin-like domain near the carboxy terminal end of the TIGR protein in affected members of families UM:JG1 (Pro370Leu), UM:JG3 (Val426Phe), UM:GL57 (Glu323Lys) and UM:JG5 (Gly252Arg). Co-segregation of glaucoma and Pro370Leu, Val426Phe, and Gly252Arg in known GLC1A families suggests that these are mutations. Although the Gly252Arg substitution observed in UM:JG5 is non-conservative, it was not possible to distinguish whether it is a mutation or a polymorphism. None of the sequence changes described in these families were observed in other juvenile glaucoma cases in this study, nor in any of the POAG or phenotypically normal individuals tested here. Analysis of amino acid sequence changes resulting from mutations described in this and other works demonstrate localization of many mutations in the vicinity of predicted functional motifs in the olfactomedin-like domain. Identification of rat latrophilin (LPH1/CIRL) as a new member of the olfactomedin-like protein family to which TIGR/MYOC belongs suggests that the region of olfactomedin homology is a protein domain that can occur in different protein contexts. CONCLUSIONS: Location of mutations described in this and previous work suggests that some specific predicted protein motifs in the olfactomedin-like domain may be important to TIGR/MYOC function. In some cases, the role of TIGR/MYOC in the etiology of glaucoma may result from alteration of the sequences recognized by modifying enzymes such as casein kinase II. In other cases altered protein folding may affect access of enzymes to their target sequences on TIGR/MYOC. Although modifications and structures discussed here are predicted rather than proven, they provide a useful theoretical framework for design of subsequent experiments. Alterations to protein folding and predicted modification motifs cannot explain the pathogenic mechanisms of all of the known TIGR/MYOC glaucoma mutations.

Adult↗
PubMed1998

TRP, TRPL and trouble in photoreceptor cells.

Calcium influx through the TRP and TRPL light-activated channels triggers a complex regulatory hierarchy resulting in positive and negative feedback regulation of the phototransduction cascade. Recent studies have begun to elucidate the function of TRP and TRPL in vivo, and to examine their relationship to intracellular calcium changes during the light response.

Animals↗
PubMed1998

A vancomycin monitoring program at a community hospital.

BACKGROUND: Because of concern about patients' increased risk of developing resistance to vancomycin, a vancomycin monitoring program involving education, not restriction, on the prudent use of vancomycin was developed at the Barnes-Jewish Christian (BJC) North Region hospitals in St Louis. The program was spearheaded by the pharmacy department and monitored by interdisciplinary committees within the hospital. METHODS: An educational note based on a Centers for Disease Control and Prevention (CDC) guideline for prudent use of vancomycin was prepared and placed in patient charts by a designated pharmacist. This intervention was tracked along with the medical staff's response to the note. In a one-year period, the rate of appropriate use of vancomycin increased from 59% to 80% (p < 0.01), whereas the number of care interventions involving vancomycin usage decreased by approximately 75%. DISCUSSION: A community hospital can promote appropriate use of antibiotics, in this case vancomycin. The fact that the rate at which vancomycin was appropriately prescribed increased and the number of pharmacist interventions (notes) decreased suggests that the vancomycin note reminders and related educational material were successful. Although these numbers do not represent 100% compliance, treatment with vancomycin may have been clinically appropriate for some of the cases even if the situation was not listed as an appropriate use in the CDC guideline. CONCLUSION: The vancomycin monitoring program, which represents a simple means of intervening and maintaining continuous monitoring and quality improvement in a clinical area, continues at the BJC North Region hospitals.

Anti-Bacterial Agents↗
PubMed1998

Low-dose intra-articular ketorolac for pain relief following arthroscopy of the knee joint.

The systemic administration of nonsteroidal anti-inflammatory agents has been shown to improve analgesia following arthroscopy of the knee joint. Ketorolac 60 mg, when given intra-articularly, provides better postoperative analgesia than an identical dose administered systemically. We compared the postoperative analgesic effect of ketorolac 10 mg given intravenously with 5 mg intra-articularly in 60 patients undergoing arthroscopy of the knee joint under general anaesthesia. Patients were randomly allocated in a double-blind manner to receive 0.25% bupivacaine 20 ml and ketorolac 5 mg intra-articularly (n = 27) or intravenous ketorolac 10 mg followed by 0.25% bupivicaine 20 ml (n = 30) at the end of surgery. There were no differences between the groups in terms of their physical characteristics or in the nature of procedure performed. There was no statistical difference between the two groups in time to first analgesia or postoperative visual analogue pain scores at 1, 2 and 4 h (p = 0.6). The median consumption of a standard analgesic was reduced in the intra-articular group in the second 24-h period but this did not achieve statistical significance (p = 0.08). Only five patients in total needed postoperative morphine. A reduced amount of locally applied ketorolac (5 mg) provides similar analgesia to a higher systemic dose (10 mg) following knee arthroscopy.

Adolescent↗
PubMed1998

Incomplete muscle activation after training with electromyostimulation.

Training with voluntary or electromyostimulation (EMS)-evoked eccentric contractions should produce complete muscle activation, since EMS and eccentric contractions preferentially recruit large motor units. Subjects (22 women ages 18-40) were randomly assigned to a voluntary (VOL; n = 8), EMS (n = 8), or control group. VOL and EMS groups trained the quadriceps at the same, increasing force levels 4 times/week for 6 weeks using voluntary or EMS-evoked eccentric contractions. VOL improved voluntary more than EMS-evoked eccentric strength. EMS improved EMS-evoked strength more than voluntary. EMS training improved EMS-evoked eccentric strength more than VOL training improved voluntary eccentric strength. EMS-evoked to voluntary force ratio increased from 0.57 (+/- 0.11) to 1.20 (+/- 0.35) in EMS and did not change in VOL (all changes p < .05). Six of eight EMS subjects produced greater EMS-evoked force posttraining, suggesting incomplete muscle activation after EMS training.

Adolescent↗
PubMed1998

A hirudin-sensitive, growth-related proteinase from human fibroblasts.

We have identified a hirudin-sensitive proteinase from human fibroblasts. Inhibition of this enzyme results in partial inhibition of cell growth in culture. The enzyme has a molecular weight of about 38000, and can be isolated by affinity chromatography with a hirudin-agarose matrix. The enzyme is apparently not closely related to thrombin, but does show a high level of amino acid sequence homology with fragments of a protein isolated from the synovial fluid of rheumatoid arthritis patients, which acts as a mitogen for human T lymphocytes.

Amino Acid Sequence↗
PubMed1998

Physician retention plans help reduce costs and optimize revenues.

Recruiting primary care physicians can cost a large practice millions of dollars in recruitment expenses and lost revenue. And competition among practices to attract physicians can cause a position to remain unfilled for a year or longer. Thus, the ability to retain physicians is critical to the financial well-being of a practice. Successful implementation of a physician retention plan can help reduce turnover, improve morale among the physicians, and foster a perception of a practice as a health services provider of choice. Penn State Geisinger Health System, Danville, Pennsylvania, developed a physician retention plan for its multispecialty group practice of nearly 1,000 physicians to reduce its costs associated with physician recruitment. The plan is organized into four phases of physician employment: recruitment, preemployment, employment, and postemployment.

Community Networks↗
PubMed1998

HealthPartners Health Plans: catching up to growth.

Leaders at HPHP, the only regional health plan in Arizona connected to local delivery systems, must control costs and manage spiraling growth to achieve the goal of becoming number one in state membership. But its status might change--owners are looking at potential capital partners or purchasers.

Aged↗
PubMed1997

Calmodulin regulation of Drosophila light-activated channels and receptor function mediates termination of the light response in vivo.

Calmodulin (CAM) participates in a variety of intracellular transduction processes by modulating signaling molecules in response to calcium changes. We report the characterization of Drosophila Cam mutants and the role of CAM in photoreceptor cell function. Contrary to current models of excitation and TRP channel function, we demonstrate that the transient phenotype of trp mutants can be explained by CAM regulation of the TRPL channel rather than by the loss of a store-operated conductance leading to depletion of the internal stores. We also analyzed light responses in a variety of mutant and transgenic backgrounds and demonstrate the importance of calmodulin in mediating calcium-dependent negative regulation of phototransduction. Our results show that CAM coordinates termination of the light response by modulating receptor and ion channel activity.

Animals↗
PubMed1997

Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration.

The NRL gene encodes an evolutionarily conserved basic motif-leucine zipper transcription factor that is implicated in regulating the expression of the photoreceptor-specific gene rhodopsin. NRL is expressed in postmitotic neuronal cells and in lens during embryonic development, but exhibits a retina-specific pattern of expression in the adult. To understand regulation of NRL expression and to investigate its possible involvement in retinopathies, we have determined the complete sequence of the human NRL gene, identified a polymorphic (CA)n repeat (identical to D14S64) within the NRL-containing cosmid, and refined its location by linkage analysis. Since a locus for autosomal recessive retinitis pigmentosa (arRP) has been linked to markers at 14q11 and since mutations in rhodopsin can lead to RP, we sequenced genomic PCR products of the NRL gene and of the rhodopsin-Nrl response element from a panel of patients representing independent families with inherited retinal degeneration. The analysis did not reveal any causative mutations in this group of patients. These investigations provide the basis for delineating the DNA sequence elements that regulate NRL expression in distinct neuronal cell types and should assist in the analysis of NRL as a candidate gene for inherited diseases/syndromes affecting visual function.

Adult↗
PubMed1997

Lights out: deactivation of the phototransduction cascade.

The phototransduction G-protein-coupled signaling cascade is an extremely rapid response to photons of light. Equally important to activation of signaling is switching the signal off. A variety of strategies, ranging from the action of kinases and phosphatases, to feedback regulation by substrates and small molecules, ensures efficient inactivation. Here, we focus on phototransduction in Drosophila as a paradigm for the study of deactivation in a complex G-protein-coupled signaling pathway in vivo.

Animals↗
PubMed1997

Sentara Health System--reinventing the organization.

This Norfolk, Va.-based system began a five-year effort to change the way it does business by streamlining governance and involving physicians in management. Now in its third year of "Reinventing Sentara," it's focusing on increasing covered lives and cutting costs while increasing quality; some 15 priority redesign projects were identified and half of those have been implemented.

Centralized Hospital Services↗
PubMed1997

Harvard Pilgrim Health Care--leading the competition and growing.

New England's largest HMO wants to be even bigger. The product of a 1995 merger, Harvard Pilgrim is seeking ways to reduce per-member-per-month costs, creating new health plans with greater choice of providers, changing physician relationships from staff-model to group practice and looking at other merger opportunities.

Cost Control↗