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Biomedical subjects

C Parker

Publications and source records attributed to C Parker.

At least 55 records · Page 3Linked to original sources
PubMed2001

Recovery from hip and knee arthroplasty: Patients' perspective on pain, function, quality of life, and well-being up to 6 months postoperatively.

OBJECTIVE: To provide a more detailed description from patients' perspectives than is yet available of recovery from hip and knee arthroplasty and to use this information to test 2 assumptions about recovery from these procedures: that recovery from knee arthroplasty, as assessed by patients, routinely reaches the level achieved by hip arthroplasty; and that fatigue is prolonged after major orthopedic surgery. DESIGN: A cohort study. SETTING: University teaching hospitals. PARTICIPANTS: Consecutive patients undergoing hip (n = 107) or knee (n = 53) arthroplasty. INTERVENTIONS: Unilateral hip or knee arthroplasty. MAIN OUTCOME MEASURES: Standardized self-rated measurements of pain, function, quality of life, and well-being from preoperatively to 6 months follow-up. RESULTS: Pain and function improved significantly less after knee arthroplasty than after hip arthroplasty, but the 2 procedures led to similar improvements in life evaluation, mood, and subjective health. Fatigue was only transiently increased. CONCLUSION: The findings were inconsistent with both assumptions. Nevertheless, despite poorer recovery in pain and function, patients receiving knee arthroplasty felt that life had improved as much as did patients with hip arthroplasty. Detailed information about how major joint arthroplasty in routine practice affects patients' lives can be used to advise patients and clinicians and can invalidate influential, but inaccurate, assumptions.

Activities of Daily Living↗
PubMed2001

First Person Account: landing a Mars lander.

The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Account series. We hope that mental health professionals--the Bulletin's primary audience--will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex-patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized, and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients with experiences they believe should be shared might encourage these patients to submit their articles to Schizophrenia Bulletin, First Person Accounts, EEI Communications, 66 Canal Center Plaza, Suite 200, Alexandria, VA 22314.--The Editors.

Autobiographies as Topic↗
PubMed2001

The use of a whole body index with bone scintigraphy to monitor the response to therapy in Paget's disease.

Bone scintigraphy has long been used to assess Paget's disease and investigate the response to therapy. Objective visual assessment is, however, difficult. The aim of this study was to derive, from a bone scintigram, an index which objectively measured the extent and severity of Paget's disease in the entire skeleton. This whole body index would provide a single numerical value which could be used to monitor the response to therapy in both monostotic and polyostotic disease. Comparison with other methods of assessing the condition, such as biochemical markers and pain scores, would also be possible. The whole body index was developed and used to retrospectively analyse 80 bone scintigrams on 40 patients. The majority of patients (36) received treatment with a bisphosphonate between the two scintigrams. Whole body index was compared with serum alkaline phosphatase measured at the same time; a significant correlation was found (before treatment P=0.001, after treatment P<0.001). The change in whole body index and alkaline phosphatase following treatment with various bisphosphonates was also investigated and a significant correlation found (P<0.001). Whilst performing the analysis it was also noted that the increase in uptake of the radiopharmaceutical was significantly greater in the cortical long bones than in the trabecular axial skeleton. This study suggests that a whole body index may be a suitable tool for assessing the response to treatment in Paget's disease.

Aged↗
PubMed2000

Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.

The cytochrome P450-derived epoxyeicosatrienoic acids (EETs) have potent effects on renal vascular reactivity and tubular sodium and water transport; however, the role of these eicosanoids in the pathogenesis of hypertension is controversial. The current study examined the hydrolysis of the EETs to the corresponding dihydroxyeicosatrienoic acids (DHETs) as a mechanism for regulation of EET activity and blood pressure. EET hydrolysis was increased 5- to 54-fold in renal cortical S9 fractions from the spontaneously hypertensive rat (SHR) relative to the normotensive Wistar-Kyoto (WKY) rat. This increase was most significant for the 14,15-EET regioisomer, and there was a clear preference for hydrolysis of 14, 15-EET over the 8,9- and 11,12-EETs. Increased EET hydrolysis was consistent with increased expression of soluble epoxide hydrolase (sEH) in the SHR renal microsomes and cytosol relative to the WKY samples. The urinary excretion of 14,15-DHET was 2.6-fold higher in the SHR than in the WKY rat, confirming increased EET hydrolysis in the SHR in vivo. Blood pressure was decreased 22+/-4 mm Hg (P:<0.01) 6 hours after treatment of SHRs with the selective sEH inhibitor N:, N:'-dicyclohexylurea; this treatment had no effect on blood pressure in the WKY rat. These studies identify sEH as a novel therapeutic target for control of blood pressure. The identification of a potent and selective inhibitor of EET hydrolysis will be invaluable in separating the vascular effects of the EET and DHET eicosanoids.

8,11,14-Eicosatrienoic Acid↗
PubMed2000

Human complement protein C8 gamma.

Human C8 gamma is a 22 kDa subunit of complement component C8, which is one of five components (C5b, C6, C7, C8, C9) that interact to form the cytolytic membrane attack complex (MAC) of complement. C8 contains three nonidentical subunits (alpha, beta, gamma) that are products of different genes. These subunits are arranged asymmetrically to form a disulfide-linked C8 alpha-gamma dimer that is noncovalently associated with C8 beta. C8 alpha and C8 beta are homologous to C6, C7 and C9 and together these proteins comprise what is referred to as the 'MAC protein family'. By comparison, C8 gamma is distinct in that it belongs to the lipocalin family of small, secreted proteins which have the common ability to bind small hydrophobic ligands. While specific roles have been identified for C8 alpha and C8 beta in the formation and function of the MAC, a function for C8 gamma and the identity of its ligand are unknown. This review summarizes the current status of C8 gamma structure and function and the progress made from efforts to determine its role in the complement system.

Amino Acid Sequence↗
PubMed2000

Reduced gut intraepithelial lymphocytes in VLA1 null mice.

Very late antigen 1 (VLA1) is an integrin collagen receptor that is expressed by lymphocytes in several disease states. VLA1 blockade has been shown to ameliorate gut disease in experimental graft-versus-host disease. Here we show that in the VLA1 null mouse, which is generally healthy, there is a 50% reduction in gut intraepithelial lymphocytes (IELs) despite an otherwise normal lymphocyte distribution in peripheral blood and lymphoid organs. The gammadelta to alphabeta ratios of IELs are unchanged. We also find that IL2-stimulated splenocytes from VLA1 null animals show a deficiency in adhesion to fibrillar and basement membrane collagen as well as reduced proliferation in response to collagen substratum. These results suggest that some, but not all, intraepithelial lymphocytes require VLA1 to survive or proliferate within the gut epithelium or possibly to traverse the basement membrane.

Animals↗
PubMed2000

Identification, functional characterization, and regulation of a new cytochrome P450 subfamily, the CYP2Ns.

The screening of liver and heart cDNA libraries from the teleost Fundulus heteroclitus with degenerate oligonucleotide probes to conserved alpha-helical regions in mammalian P450s resulted in the identification of two cDNAs that together represent a novel P450 subfamily, the CYP2Ns. Northern analysis demonstrated that CYP2N1 transcripts are most abundant in liver and intestine, whereas CYP2N2 mRNAs are most abundant in heart and brain. CYP2N1 and CYP2N2 proteins were co-expressed with NADPH-cytochrome P450 oxidoreductase in Sf9 insect cells, and their ability to metabolize arachidonic acid and xenobiotic substrates was examined. Both CYP2N1 and CYP2N2 metabolize arachidonic acid to epoxyeicosatrienoic acids. Epoxidation is highly regio- and enantioselective with preferential formation of (8R,9S)-epoxyeicosatrienoic acid (optical purities are 91 and 90% for CYP2N1 and CYP2N2, respectively) and (11R, 12S)-epoxyeicosatrienoic acid (optical purities are 92 and 70% for CYP2N1 and CYP2N2, respectively). CYP2N1 and CYP2N2 also catalyze the formation of a variety of hydroxyeicosatetraenoic acids. Both P450s have benzphetamine N-demethylase activities but show minimal alkoxyresorufin O-dealkylase activities. To investigate factors affecting CYP2N expression in vivo, CYP2N transcripts were examined following starvation and/or treatment with 12-O-tetradecanoyl phorbol-13-acetate. Intestinal CYP2N1 mRNAs decrease in starved and/or phorbol ester-treated fish, whereas intestinal CYP2N2 transcripts decrease only following phorbol ester treatment. Interestingly, cardiac CYP2N2 expression decreases following phorbol ester treatment but increases following starvation. These results demonstrate that members of this novel P450 subfamily encode early vertebrate forms of arachidonic acid catalysts that are widely expressed and are regulated by environmental factors. Given the wealth of information on the functional role of P450-derived arachidonate metabolites in mammals, we postulate that CYP2N1 and CYP2N2 products have similar biological functions in early vertebrates. The identity of the mammalian orthologue(s) of the CYP2Ns remains unknown.

Amino Acid Sequence↗
PubMed2000

Completely converting a blood service region to the use of safer plasma.

BACKGROUND: Three types of plasma are widely available for transfusion. Two plasma components, FFP donor retested (FFP-DR), and solvent/detergent-treated plasma (SDP), are now considered to be safer from infectious complications than FFP. STUDY DESIGN AND METHODS: A large regional blood center attempted to provide FFP-DR exclusively to all its 42 hospitals. Significant planning, increases in computer capabilities, and expansion of component storage areas were completed before initiation of this program. RESULTS: During the first 6 months of the FFP-DR program, the blood center was not able to supply the entire region exclusively with FFP-DR. Consequently, SDP was utilized to supplement the program and to successfully and completely convert the region's 42 hospitals to the use of safer plasma. CONCLUSION: Two new plasma components were utilized to completely convert a blood service region to the use of safer plasma.

Blood Banks↗
PubMed2000

Assessing research outcomes by postal questionnaire with telephone follow-up. TOTAL Study Group. Trial of Occupational Therapy and Leisure.

BACKGROUND: Face-to-face assessment of research outcomes is expensive and may introduce bias. Postal questionnaires offer a cheaper alternative which avoids observer bias, but non-response and incomplete response reduce the effective sample size and may be equally serious sources of bias. This study examines the extent and potential effects of missing data in the postal collection of outcomes for a large rehabilitation trial. METHODS: Questionnaires containing a number of established scales were posted to participants in a trial of occupational therapy after stroke. Response was maximized by telephone and postal reminders, and incomplete questionnaires were followed up by telephone. Scale scores obtained by imputing values to questionnaire items missing on return were compared with those achieved by telephone follow-up. FINDINGS: Response to the initial posting was 60%, rising to 85% after reminders. Participants receiving the experimental treatment were more likely to respond without a reminder. There were no significant differences on any known factors between eventual responders and non-responders. Of the questionnaires, 43% were incomplete on return: partial responders were significantly different to complete responders on baseline disability and home circumstances. Of the incomplete questionnaires, 71% were resolved by telephone follow-up. In these, the scale scores achieved by telephone were generally higher than those derived by conventional imputation. CONCLUSION: Postal outcome assessment achieved a good response rate, but considerable effort was needed to minimize non-response and incomplete response, both of which could have been serious sources of bias.

Bias↗
PubMed2000

Characterization of a discontinuous epitope of the human immunodeficiency virus (HIV) core protein p24 by epitope excision and differential chemical modification followed by mass spectrometric peptide mapping analysis.

A combination of epitope excision, epitope extraction, and differential chemical modification followed by mass spectrometric peptide mapping was used for the characterization of a discontinuous epitope that is recognized by the mouse anti-HIV-p24 monoclonal antibody 5E2.A3. In epitope excision, the protein is first bound to an immobilized antibody and then digested with proteolytic enzymes. In epitope extraction, the protein is first digested and subsequently allowed to react with the antibody. After epitope excision of the p24-5E2.A3 complex with endoproteinase Lys-C, a large fragment remained affinity bound corresponding to amino acids 1-158 of HIV-p24 (fragment 1-158). Further digestion, however, resulted in loss of affinity. Moreover, no affinity-bound fragments were observed after an epitope extraction experiment. These data from the epitope excision and extraction experiments suggest that the epitope is discontinuous. For the further characterization of the epitope, amino groups in the epitope-containing fragment were acetylated in both the affinity bound and free states followed by mass spectrometric analysis. Two successive acetylation reactions were performed: (1) the first used a low molar excess of acetic anhydride, and (2) the second, after separation from the antibody, a high molar excess of its hexadeuteroderivative. This isotopic labeling procedure, in combination with high resolution mass spectrometry, allowed the precise determination of relative reactivities of amino groups. In this study, no differences were observed in the ranking of the relative reactivities of five lysine residues. However, the N-terminal amino group was found to be part of the discontinuous epitope.

Acetylation↗
PubMed1999

The tetratricopeptide repeat domain and a C-terminal region control the activity of Ser/Thr protein phosphatase 5.

Protein Ser/Thr phosphatase 5 is a 58-kDa protein containing a catalytic domain structurally related to the catalytic subunits of protein phosphatases 1, 2A, and 2B and an extended N-terminal domain with three tetratricopeptide repeats. The activity of this enzyme is stimulated 4-14-fold in vitro by polyunsaturated fatty acids and anionic phospholipids. The structural basis for lipid activation of protein phosphatase 5 was examined by limited proteolysis and site-directed mutagenesis. Trypsinolysis removed the tetratricopeptide repeat domain and increased activity to approximately half that of lipid-stimulated, full-length enzyme. Subtilisin removed the tetratricopeptide repeat domain and 10 residues from the C terminus, creating a catalytic fragment with activity that was equal to or greater than that of lipid-stimulated, full-length enzyme. Catalytic fragments generated by proteolysis were no longer stimulated by lipid, and degradation of the tetratricopeptide repeat domain was decreased by association with lipid. A truncated mutant missing 13 C-terminal residues was also insensitive to lipid and was as active as full-length, lipid-stimulated enzyme. These results suggest that the C-terminal and N-terminal domain act in a coordinated manner to suppress the activity of protein phosphatase 5 and mediate its activation by lipid. These regions may be targets for the regulation of protein phosphatase 5 activity in vivo.

Amino Acid Sequence↗
PubMed1999

Non-specific action of methoxamine on Ito, and the cloned channels hKv 1.5 and Kv 4.2.

The alpha1-adrenoceptor agonist methoxamine acted independently of receptor activation to reduce Ito and the sustained outward current in rat ventricular myocytes, and hKv 1.5 and Kv 4.2 cloned K+ channel currents. Two hundred microM methoxamine reduced Ito by 36% in the presence of 2 microM prazosin, and by 37 and 38% after preincubation of myocytes with either N-ethylmaleimide or phenoxybenzamine (n=6). The EC50 values at +60 mV for direct reduction of Ito, hKv 1.5, and Kv 4.2 by methoxamine were 239, 276, and 363 microM, respectively, with Hill coefficients of 0.87-1.5. Methoxamine accelerated Ito and Kv 4.2 current inactivation in a concentration- and voltage-dependent manner. Apparent rate constants for methoxamine binding and unbinding gave Kd values in agreement with EC50 values measured from dose-response relations. The voltage-dependence of block supported charged methoxamine binding to a putative intracellular site that sensed approximately 20% of the transmembrane electrical field. In the presence of methoxamine, deactivating Kv 4.2 tail currents displayed a distinct rising phase, and were slowed relative to control, such that tail current crossover was observed. These observations support a dominant mechanism of open channel block, although closed channel block could not be ruled out. Single-channel data from hKv 1.5 patches revealed increased closed times with blank sweeps and decreased burst duration in the presence of drug, and a reduction of mean channel open time from 1.8 ms in control to 0.4 ms in 500 microM methoxamine. For this channel, therefore, both open and closed channel block appeared to be important mechanisms for the action of methoxamine.

Adrenergic alpha-Agonists↗