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Biomedical subjects

S J Brown

Publications and source records attributed to S J Brown.

At least 19 recordsLinked to original sources
PubMed1999

RAPD-based genetic linkage maps of Tribolium castaneum.

A genetic map of the red flour beetle (Tribolium castaneum) integrating molecular with morphological markers was constructed using a backcross population of 147 siblings. The map defines 10 linkage groups (LGs), presumably corresponding to the 10 chromosomes, and consists of 122 randomly amplified polymorphic DNA (RAPD) markers, six molecular markers representing identified genes, and five morphological markers. The total map length is 570 cM, giving an average marker resolution of 4.3 cM. The average physical distance per genetic distance was estimated at 350 kb/cM. A cluster of loci showing distorted segregation was detected on LG9. The process of converting RAPD markers to sequence-tagged site markers was initiated: 18 RAPD markers were cloned and sequenced, and single-strand conformational polymorphisms were identified for 4 of the 18. The map positions of all 4 coincided with those of the parent RAPD markers.

Alleles↗
PubMed1999

Patient-centered communication.

The term patient-centered communication (PCC) has been used to describe a group of communication strategies and behaviors that promote mutuality, shared understandings, and shared decision making in health care encounters. There is evidence to suggest that advanced practice nurse and patients use these strategies to co-produce highly individualized clinical discourse. Although the communication behaviors associated with PCC have been studied separately, their impact as an integrated communications strategy has not been studied. Suggestions for developing PCC as a mid-range theory of health care communication encompassing other more specific communication concepts are offered.

Communication↗
PubMed1998

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

AIDS Dementia Complex↗
PubMed1998

Electromyogram activity and mean power frequency in exercise-damaged human muscle.

Eight volunteers performed two bouts of 50 voluntary maximal eccentric contractions of the knee extensors of one leg 3 weeks apart. During maximal voluntary isometric contractions performed at intervals after each bout, electromyogram (EMG) mean power frequency declined after bout one (P < 0.01 Duncan's test), whereas integrated EMG did not change after either bout. These results suggest that unaccustomed eccentric contractions produce a temporary reduction in mean muscle activation frequency during subsequent maximal isometric contractions.

Adult↗
PubMed1998

Expression and ligand binding assays of soluble cytokine receptor-immunoglobulin fusion proteins.

We have developed a cloning vector for the expression of type I cytokine receptor, NO, extracellular domain (ECD)-mouse IgG1 Fc fusion proteins. The vector has a versatile polylinker that allows in-frame cloning of the receptor ECD with the mouse IgG1 sequence to encode a receptor ECD-IgG1 fusion construct. The receptor-IgG1 fusion proteins are transiently expressed in useful amounts following transfection of the expression vector into COS7 cells and G418 selection. The mouse IgG1 portion of the fusion protein provides a universal handle for purification on an affinity matrix and detection by anti-mouse IgG antibodies in ELISA or Western blot formats. The expressed receptor ECD-IgG1 fusion proteins bind their cognate ligands. In order to demonstrate that the fusion proteins have similar ligand binding affinities as the native receptors, the affinity constants (Kd) for EPOR, TNFR, IL-4R, and IL-6R-IgG1 fusion proteins were measured by surface plasmon resonance and shown to be in good agreement with published values. The TNFR-IgG1 fusion protein was employed in a demonstration of a novel ELISA format for detecting cytokine receptor binding to cytokine.

Amino Acid Sequence↗
PubMed1998

Molecular characterization of the Tribolium abdominal-A ortholog and implications for the products of the Drosophila gene.

The Drosophila homeotic selector gene abdominal-A is important for determinative decisions in the anterior abdomen. Insects vary considerably with respect to abdominal morphology, and changes in the function of homeotic selector genes and/or downstream genes under their control presumably have been important to the evolution of these differences. Mutations in Abdominal, the Tribolium ortholog of abdominal-A, have been described, and have more posterior homeotic transformations than do Drosophila variants. Here we present the organization of the Abdominal gene and the sequences of its predicted proteins, the first such report for a non-Drosophilid insect. Two predicted proteins share N-terminal sequences with those proposed to be synthesized by the Drosophila ortholog. In addition, we describe the distribution of Abdominal transcripts during embryogenesis. The Tribolium expression pattern closely resembles that of Drosophila, and does not account for the differences in mutant phenotypes.

Amino Acid Sequence↗
PubMed1998

Angiographic progression in patients with angina pectoris and normal or near normal coronary angiograms who are restudied due to unstable symptoms.

BACKGROUND: Syndrome X patients commonly remain symptomatic during follow-up and may be readmitted with unstable anginal symptoms. Angiographic disease progression must be considered as a possible mechanism for instability, particularly where multiple coronary risk factors are present and an interval of several years has elapsed since previous angiography. METHODS AND RESULTS: We reviewed data from 139 consecutive patients with chest pain and normal or near normal coronary angiograms (101 patients with completely normal angiograms and 38 patients with minimal lumenal irregularities). During a 5-year period, 24 patients (19 women, median age 56 years) underwent repeat angiography due to primary unstable angina (median interval between angiograms 58 months (range 8-130 months)). This group included three patients with minimal lumenal irregularities and four patients with left bundle branch block. Only two patients had progression to significant angiographic stenosis (> 30% diameter reduction); both were male patients with minimal irregularities at baseline angiography, left bundle branch block and multiple coronary risk factors. However, overall only two of 18 (11%) patients with one or more conventional coronary risk factors had angiographic progression. CONCLUSIONS: Unstable symptoms in patients with chest pain and previously normal or near normal coronary arteriograms are rarely due to angiographic disease progression. However, the presence of minimal lumenal irregularities at baseline angiography and LBBB may identify a sub-group at increased risk.

Adult↗
PubMed1998

Manipulation of knee extensor force using percutaneous electrical myostimulation during eccentric actions: effects on indices of muscle damage in humans.

Percutaneous electrical myostimulation (PES) was used to manipulate the force produced by the knee extensor muscles during eccentric exercise, thereby providing a model to investigate the role of force in muscle damage. Two eccentric exercise bouts of equal work were performed by nine subjects, using fixed voltage PES at 20 Hz (to produce moderate muscle forces) and 100 Hz (to produce high muscle forces). Muscle contractility, serum creatine kinase activity (CK) and muscle soreness (MS) were evaluated before, and up to 14 days after exercise. Data are presented as means+/-SEM, and were analysed using repeated measures analysis of variance (ANOVA), t-tests and Wilcoxon tests. Peak forces were higher during the 100 Hz bout than the 20 Hz bout for repetitions 1 (472+/-60 vs 237+/-23 Newtons), 10 (381+/-26 vs 233+/-26 Newtons), 20 (310+/-24 vs 218+/-24 Newtons), all p < 0.01, t-test and 30 (297+/-27 vs 204+/-21 Newtons), p < 0.05, t-test. Following the 100 Hz bout, maximum voluntary contractile force (MVC) was lower (p<0.01, ANOVA), and CK was higher (p<0.0001, ANOVA) than after the 20 Hz bout. Subjects also reported greater MS on days 2 to 6 (p<0.05, Wilcoxon test) following the 100 Hz bout. Despite a decline in the stimulated 20:100 Hz tetanic force ratio after each bout (p<0.01, ANOVA) there was no difference between bouts (p>0.05, ANOVA). The higher rise in CK and MS after the 100 Hz bout, together with the greater deficit in MVC, suggest that in humans, muscle force is a contributing factor to muscle injury during eccentric actions.

Adolescent↗
PubMed1998

Isolation of erythropoietin receptor agonist peptides using evolved phage libraries.

Cyclic peptides capable of activating the erythropoietin receptor (EPOR) were isolated from phage display libraries by screening with a novel EPOR-IgG fusion protein reagent. A parental clone ERB1 (EPO Receptor Binder 1) was first isolated from a phage display library displaying 38 random amino acids as an N-terminal fusion with the M13 minor capsid protein, pill. An evolved library was then produced from the parental sequence using an oligonucleotide saturation mutagenesis strategy which yielded EPOR binding sequences with 20 times the relative affinity of ERB1. Two synthetic peptides were constructed from these sequences both of which bind the EPO receptor in specific ELISA, and act as full agonists in EPO dependent cell proliferation assays. These peptides are 18 amino acids in length, disulfide-bonded, and have a minimum consensus sequence of CXXGWVGXCXXW, where X represents positions tolerant of several amino acids.

Amino Acid Sequence↗
PubMed1997

Serum endothelin levels and pain perception in patients with cardiac syndrome X and in healthy controls.

The possible algogenic effects of elevated serum endothelin levels in cardiac syndrome X were investigated in a case-control study that examined somatic pain perception in the forearm during submaximal effort tourniquet and cold immersion tests. Pain threshold to both ischemic and cold stimulation of the forearm was demonstrated to be significantly lower in patients with syndrome X than in matched healthy controls, and a negative correlation between ischemic pain threshold and endothelin levels was demonstrated.

Aged↗
PubMed1997

Indices of skeletal muscle damage and connective tissue breakdown following eccentric muscle contractions.

Indirect indices of exercise-induced human skeletal muscle damage and connective tissue breakdown were studied following a single bout of voluntary eccentric muscle contractions. Subjects (six female, two male), mean (SD) age 22 (2) years performed a bout of 50 maximum voluntary eccentric contractions of the knee extensors of a single leg. The eccentric exercise protocol induced muscle soreness (P < 0.05 Wilcoxon test), chronic force loss, and a decline in the 20:100 Hz percutaneous electrical myostimulation force ratio [P < 0.01, repeated measures analysis of variance (ANOVA)]. Serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities were elevated (P < 0.01, repeated measures ANOVA) following the bout. The mean (SD) CK and LDH levels recorded 3 days post-exercise were 2815 (4144) IU.l-1 and 375 (198) IU.l-1, respectively. Serum alkaline phosphatase activity showed no changes throughout the study, and a non-significant increase (P = 0.058, repeated measures ANOVA) in pyridinoline was recorded following the bout. Urinary hydroxyproline (HP) and hydroxylysine (HL) excretion, expressed in terms of creatinine (Cr) concentration, increased after exercise (P < 0.05 and P < 0.01, respectively, repeated measures ANOVA). An increased HP:Cr was recorded 2 days post-exercise and HL:Cr was increased above baseline on days 2, 5, and 9 post-exercise. This indirect evidence of exercise-induced muscle damage suggests that myofibre disruption was caused by the eccentric muscle contractions. Elevated urine concentrations of indirect indices of collagen breakdown following eccentric muscle contractions suggests an increased breakdown of connective tissue, possibly due to a localised inflammatory response.

Adult↗
PubMed1997

An abnormal distribution of melatonin receptors in the newborn rat with inherited prenatal hydrocephalus.

Melatonin binding in the brain of hydrocephalic H-Tx rats was examined by autoradiography. At the time of birth, hydrocephalic animals showed an abnormality in the distribution of high-affinity melatonin receptors dorsal to the cerebral aqueduct when compared to controls. Whereas newborn rats of the H-Tx strain that were unaffected by hydrocephalus had melatonin receptors in a tectal midsagittal strip overlying the aqueduct and spanning the anterior half of the tectum, hydrocephalic rats lacked melatonin receptors in the most anterior part of this region. In these animals, the length of the aqueduct over which receptors were missing was compressed and was additionally occluded by dystrophic ependyma. The first signs of ventricular expansion characteristic of hydrocephalus were evident.

Animals↗
PubMed1997

Effect of surface photorefractive keratectomy and laser in situ keratomileusis on the corneal endothelium.

PURPOSE: To investigate endothelial cell loss in pairs of fresh human autopsy globes following high-diopter myopic photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK). SETTING: Center for Research on Ocular Therapeutics and Biodevices and Magill Laser Center for Vision Correction, Storm Eye Institute, Charleston, South Carolina, USA. METHODS: In the first part of the study, 12 globes had either -10 diopters (D) multizone surface PRK or -10 D single-zone LASIK. In the second part, three groups of 5 globes each had -15 D, -20 D, or -25 D multizone-blend LASIK procedures. Fellow globes in both groups were used as untreated controls. Corneoscleral buttons were excised from all globes. Following 7 days in corneal organ culture, the endothelial surface was stained with two vital dyes: calcein-AM and ethidium homodimer. Fluorescence microscopy was used to obtain endothelial cell counts. RESULTS: The mean dead cells per square millimeter (cells/mm2) were 0.94 in the -10 D PRK treated corneas compared with 0.91 in the fellow untreated eyes (P = 0.06(. The mean dead cells/mm2 in the -10 D single-zone LASIK-treated corneas and in the fellow untreated eyes were 0.61 (P = 0.88). The mean dead cells/mm2 in the -15 D, -20 D, and -25 D multizone-blend LASIK-treated corneas were 3.08, 2.33, and 5.55, respectively, compared with 3.49, 1.92, and 5.01 in the fellow untreated eyes (P = 0.276, P = 0.339, and P = 0.427, respectively). Dead cell counts for treated and control paired corneas were highly correlated in all treatment groups. CONCLUSIONS: No significant endothelial cell loss occurred after -10 D PRK or LASIK corrections up to -25 D. Although this study has limitations that prevent direct extrapolation to the clinical situation, it does afford a comparable clinical correlate for endothelial cell toxicity following a typical excimer laser ablations.

Aged↗
PubMed1997

Molecular characterization and embryonic expression of the even-skipped ortholog of Tribolium castaneum.

In short germ insects, the procephalon and presumptive anterior segments comprise most of the embryonic rudiment which lengthens as posterior segments are added during development (Sander, K. (1976) Adv. Insect Physiol. 12, 125-238). The expression pattern of a grasshopper ortholog of the primary pair-rule gene even-skipped (eve) suggests that it is not relevant to segmentation in this short germ insect (Patel, N.H., Ball, E.E. and Goodman, C.S. (1992) Nature 357, 339-342). However in Drosophila, a long germ insect that forms all segments simultaneously, eve plays a vital role in segment formation (Nüsslein-Volhard, C., Wieschaus, E. and Klüding, H. (1984) Roux's Arch. Dev. Biol. 193, 267-282). We have characterized the eve ortholog of the beetle Tribolium castaneum. The homeodomain sequence is highly conserved between beetle, fly, and grasshopper eve orthologs. Tc eve is expressed in stripes during segmentation, but in a pattern differing in some details from that of the fly gene. This pattern is coincident with that detected with a cross-reacting antibody (Patel, N.H., Condron, B.G. and Zinn, K. (1994) Nature 367, 429-434). Thus, an ancestral even-skipped gene appears to have evolved a role in segmentation in a common ancestor of flies and beetles. Unlike vertebrate orthologs but similar to eve, Tc eve is not linked to the homeotic complex.

Amino Acid Sequence↗
PubMed1997

Exercise-induced skeletal muscle damage and adaptation following repeated bouts of eccentric muscle contractions.

Repeated bouts of eccentric muscle contractions were used to examine indirect indices of exercise-induced muscle damage and adaptation in human skeletal muscle. Twenty-four subjects (18 females, 6 males) aged 20.0 +/- 1.4 years (mean +/- S.D.) performed an initial bout of either 10 (n = 7), 30 (n = 9) or 50 (n = 8) maximum voluntary eccentric contractions of the knee extensors, followed by a second bout of 50 contractions 3 weeks later using the same leg. Muscle soreness was elevated after all bouts (P < 0.05, Wilcoxon test), although the initial bout reduced the soreness associated with the second bout. Force loss and a decline in the 20:100 Hz percutaneous electrical myostimulation force ratio were observed after all exercise bouts (P < 0.01). Serum creatine kinase activity was elevated following the initial bouts of 30 and 50 repetitions (P < 0.01), but there was no increase following 10 repetitions. No increase in serum creatine kinase activity was observed in any group following the second bout of contractions (P > 0.05). We conclude that skeletal muscle adaptation can be brought about by a single bout of relatively few eccentric muscle contractions. Increasing the number of eccentric muscle repetitions did not result in an increased prophylactic effect on skeletal muscle.

Adaptation, Physiological↗
PubMed1996

Changes in human skeletal muscle contractile function following stimulated eccentric exercise.

Indices of human skeletal muscle contractile function were examined in nine subjects for up to 9 days following a single bout of stimulated eccentric exercise. Eccentric muscle actions of the knee extensor muscles were evoked by percutaneous electrical myostimulation (PES). Delayed onset muscle soreness (DOMS), elevated serum creatine kinase activity, chronic force loss, and a decline in the 20:100 Hz force ratio were observed in the days postexercise. The exercised knee extensor muscles demonstrated an impaired ability to respond to PES. This was evident by an increased time delay between the start of 100 Hz PES and the onset of contraction immediately postexercise [22.3 (SD 15.9)%, P < 0.01] and 3 days postexercise [14.9 (SD 18.1)%, P < 0.05]. Muscle relaxation rates appeared unaffected by the eccentric exercise protocol, where the muscles showed no differences in the time between the end of PES and the onset of relaxation (P > 0.05). During the days following the exercise, no significant differences were observed in the time between the start of contraction and attainment of 70% of the mean tetanic force following a single 1-s pulse of PES. Similarly, no significant differences were observed in the time between the start of relaxation and attainment of 70% of the total relaxation during the same time. The increased delay in excitation-contraction coupling observed immediately postexercise and 3 days after the exercise, may reflect a damage-induced delay in action potential propagation. Muscle relaxation rates postexercise remained unchanged, which would seem to indicate normal functioning of the sarcoplasmic reticulum, suggesting this was not the site of failure in excitation-contraction coupling.

Adult↗