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Biomedical subjects

R Day

Publications and source records attributed to R Day.

At least 55 records · Page 3Linked to original sources
PubMed2000

Creatine supplementation alters the response to a graded cycle ergometer test.

To determine the effects of creatine supplementation on cardiorespiratory responses during a graded exercise test (GXT) 36 trained adults (20 male, 16 female; 21-27 years old) performed two maximal GXTs on a cycle ergometer. The first GXT was done in a nonsupplemented condition, and the second GXT was done following 7 days of ingesting either 5 g creatine monohydrate, encased in gelatin capsules, four times daily (CS, 13 male, 6 female), or the same number of glucose capsules (PL, 7 male, 10 female). CS significantly (P<0.05) improved total test time [pre-CS = 1217 (240) s, mean (std. dev.) versus post-CS = 1289 (215) s], while PL administration had no effect (P>0.05) on total test time [pre-PL= 1037 (181) s. versus post-PL= 1047 (172) s]. In addition, both oxygen consumption (VO2) and heart rate at the end of each of the first five GXT stages were significantly lower after CS, but were unchanged after PL. Moreover, the ventilatory threshold occurred at a significantly greater VO2 for CS [pre-CS = 2.2 (0.4) l x min(-1) or 66% of peak VO2 versus post-CS = 2.6 (0.5) l x min(-1) or 78% of peak Vo2; pre-PL = 2.6 (0.9) l x min(-1) or 70% peak VO2 versus post-PL = 2.6 (1.1) l x min(-1) or 68% of peak Vo2]. Neither CS nor PL had an effect on peak Vo2 [pre-CS = 3.4 (0.7) l x min(-1) versus post-CS = 3.3 (0.7) l x min(-1); pre-PL = 3.7 (1.1) l x min(-1) versus post-PL = 3.7 (1.1) l x min(-1)]. Apparently, CS can alter the contributions of the different metabolic systems during the initial stages of a GXT. Thus, the body is able to perform the sub-maximal workloads at a lower oxygen cost with a concomitant reduction in the work performed by the cardiovascular system.

Adult↗
PubMed2000

Reduced heparan sulfate accumulation in enterocytes contributes to protein-losing enteropathy in a congenital disorder of glycosylation.

Intestinal biopsy in a boy with gastroenteritis-induced protein-losing enteropathy (PLE) showed loss of heparan sulfate (HS) and syndecan-1 core protein from the basolateral surface of the enterocytes, which improved after PLE subsided. Isoelectric focusing analysis of serum transferrin indicated a congenital disorder of glycosylation (CDG) and subsequent analysis showed three point mutations in the ALG6 gene encoding an alpha1,3-glucosyltransferase needed for the addition of the first glucose to the dolichol-linked oligosaccharide. The maternal mutation, C998T, causing an A333V substitution, has been shown to cause CDG-Ic, whereas the two paternal mutations, T391C (Y131H) and C924A (S308R) have not previously been reported. The mutations were tested for their ability to rescue faulty N:-linked glycosylation of carboxypeptidase Y in an ALG6-deficient Saccharomyces cerevisiae strain. Normal human ALG6 rescues glycosylation and A333V partially rescues, whereas the combined paternal mutations (Y131H and S308R) are ineffective. Underglycosylation resulting from each of these mutations is much more severe in rapidly dividing yeast. Similarly, incomplete protein glycosylation in the patient is most severe in rapidly dividing enterocytes during gastroenteritis-induced stress. Incomplete N:-linked glycosylation of an HS core protein and/or other biosynthetic enzymes may explain the selective localized loss of HS and PLE.

Biopsy↗
PubMed2000

Crosstalk between nervous and immune systems through the animal kingdom: focus on opioids.

During the course of evolution invertebrates and vertebrates have maintained common signaling molecules, such as neuropeptides. For example, complete hormonal-enzymatic systems for the biosynthesis of opioid peptides have been found in both the CNS and immune systems of these animals. These signaling molecules have been found in the blood circulation and act as immunomodulators. In vertebrates, release of the signaling molecules occurs during stress (cognitive or pathogens), which triggers the hypothalamo-hypophysial-adrenal axis. Similarly, these neuropeptides are used as messengers to initiate and stimulate the innate immune response in invertebrates. Thus, the crosstalk between nervous and immune systems has an ancient evolutionary origin and the messengers used have been conserved during the course of evolution reflecting their vital importance.

Animals↗
PubMed2000

Practice and policy of measuring quality of life and health economics in cancer clinical trials: a survey among co-operative trial groups.

BACKGROUND: Co-operative groups have played an important role in the advance of health-related quality of life (HRQL) research. However, definitions of the concept, criteria for selection of existing instruments and methods for data collection and interpretation remain poorly defined in the literature. A survey was conducted amongst the major cancer co-operative groups in order to gain a better understanding of their current policy and processes to ensure optimal HRQL data collection within cancer clinical trials. The topic of health economics was similarly addressed. METHODS: A written questionnaire was addressed to 16 major European and North American cancer co-operative groups. Eleven groups responded (response rate: 69%). however, one group could not provide information for the survey, thus ten questionnaires were available for analysis. RESULTS: The results from this survey among co-operative groups show that HRQL (more than health economics) is recognized as an important, although usually secondary, outcome measure in oncology trials. On the whole, co-operative groups have a rather flexible policy towards the inclusion of HRQL (and HE) into their clinical trials, and practice is very much on a case-by-case basis, but use standard practice guidelines and internal procedures is to ensure well-defined study protocols and enhance good quality studies.

Attitude↗
PubMed2000

Efficacy of uvulopalatopharyngoplasty in unselected patients with mild obstructive sleep apnea.

OBJECTIVES: Uvulopalatopharyngoplasty (UPPP) is widely used as a first-step procedure for the surgical management of obstructive sleep apnea (OSA) syndrome but best manages obstruction occurring at the level of the oropharynx alone and not the hypopharynx. Previous publications have noted mediocre results with use of this procedure in unselected patients with OSA, but less clear is the effectiveness of this procedure in the unselected patient with mild OSA (respiratory event index [REI] 5-25). Using objective and subjective criteria, we retrospectively analyzed the results of UPPP in patients with mild OSA. METHODS: We examined 37 patients with mild OSA (REI 13.5 +/- 5.1, range 5.6-23.1) who had been operated on during 1996 with UPPP with or without tonsillectomy and/or septoplasty. Follow-up polysomnography was obtained in 25 (68%) an average of 40.5 weeks after surgery and compared with findings before surgery. Subjective assessment of sleepiness was performed with the Sleep-Wake Activity Inventory. RESULTS: Ten patients (40%) had a postoperative reduction in the REI of more than 50%, comparable with the improvements reported in those with more severe apnea. Those who did not have a reduction in REI after surgery actually saw an increase in average REI from 16.6 +/- 5 to 26.7 +/- 18.4. Similarly, subjective assessment of sleepiness with the Sleep-Wake Activity Inventory showed no statistically significant improvement after surgery. CONCLUSION: Overall, these results indicate that UPPP alone in the unselected patient provides little benefit in the management of mild OSA, similar to findings for more severe OSA. Surgeons must use great care in discerning the level of obstruction in the patient with mild OSA to tailor the appropriate retropalatal and/or retrolingual procedures and thereby achieve excellent surgical outcomes.

Adult↗
PubMed2000

Orofacial prosthesis design and fabrication using stereolithography.

The use of stereolithography for the manufacture of implantable prostheses is relatively new. Until now, its use with regard to mandibular resection has been to produce pre-operative models that allow more sophisticated planning of the contour and better preparation of the metallic framework to be implanted. This framework rejoins the sections of the mandible, returning some function, but providing no soft tissue support. Hence, the aesthetic results are not optimal. The aim of this study was to investigate the accuracy with which a stereolithographic model could be made to completely reunite both surfaces of the resected mandible and restore full contour. The design and fabrication of a mandibular prosthesis utilizing CAD/CAM technology and stereolithography is still in the early stages, but initial results indicate that with further research and better tools this could provide a new approach to mandibular resections, providing better aesthetic results.

Computer-Aided Design↗
PubMed2000

Neuroinvasion by human respiratory coronaviruses.

Human coronaviruses (HCoV) cause common colds but can also infect neural cell cultures. To provide definitive experimental evidence for the neurotropism and neuroinvasion of HCoV and its possible association with multiple sclerosis (MS), we have performed an extensive search and characterization of HCoV RNA in a large panel of human brain autopsy samples. Very stringent reverse transcription-PCR with two primer pairs for both viral strains (229E and OC43), combined with Southern hybridization, was performed on samples from 90 coded donors with various neurological diseases (39 with MS and 26 with other neurological diseases) or normal controls (25 patients). We report that 44% (40 of 90) of donors were positive for 229E and that 23% (21 of 90) were positive for OC43. A statistically significant higher prevalence of OC43 in MS patients (35.9%; 14 of 39) than in controls (13.7%; 7 of 51) was observed. Sequencing of nucleocapsid protein (N) gene amplicons revealed point mutations in OC43, some consistently found in three MS patient brains and one normal control but never observed in laboratory viruses. In situ hybridization confirmed the presence of viral RNA in brain parenchyma, outside blood vessels. The presence of HCoV in human brains is consistent with neuroinvasion by these respiratory pathogens. Further studies are needed to distinguish between opportunistic and disease-associated viral presence in human brains.

Brain↗
PubMed2000

High plasma growth hormone (GH) levels inhibit expression of GH secretagogue receptor messenger ribonucleic acid levels in the rat pituitary.

Synthetic GH secretagogues (GHSs) act via a receptor (GHS-R) distinct from that of GH-releasing hormone. The GHS-R has been cloned from the pituitary and is expressed not only in the pituitary but also in specific areas of the brain, including the hypothalamus. Recent studies suggest that hypothalamic GHS-R expression is regulated by GH. This study was designed to investigate whether pituitary GHS-R expression is modulated by GH. Female Wistar-Furth rats were injected sc with either saline (control) or GC tumor cells (GC) that secrete rat GH. The tumors were allowed to develop for 1-4 weeks. At weeks 1-4, control (n = 4-8) and GC rats (n = 3-8) were killed. Pituitary GHS-R messenger RNA (mRNA) was measured by a quantitative competitive PCR assay. The endogenous GHS-R mRNA levels were measured by determining the amount of competitive template RNA required to produce equimolar amounts of native and competitive template PCR products. The mean log plasma GH levels were significantly greater in the GC rat group than in the control group at weeks 2, 3, and 4. At these times, the mean log pituitary GHS-R mRNA contents were significantly lower in the GC rat group than in the control group. No relationship could be established between log estradiol levels and GHS-R levels. These data indicate that pituitary GHS-R expression is modulated by GH.

Animals↗
PubMed2000

The effect of capsaicin on the thermal and metabolic responses of men exposed to 38 degrees C for 120 minutes.

OBJECTIVE: To determine the thermoregulatory response of humans to heat following an ingestion of capsaicin. METHODS: The thermoregulatory responses of 7 men (aged 22-28 years) to a 2-hour exposure to 38 degrees C (50% relative humidity) were compared following ingestion of either placebo or capsaicin. The capsaicin dose (2 mg x kg(-1)) was ingested 1 hour prior to the heat exposure, and all subjects were encouraged to overhydrate for 48 hours prior to each trial. Core temperature, mean skin temperature, cardiac output, and oxygen consumption were measured every 30 minutes. In addition, the changes (pre-exposure vs postexposure) in body mass and plasma volume were calculated. RESULTS: As expected, core temperature, cardiac output, and oxygen consumption all increased significantly (P < .05) with exposure time. There were also significant decreases over time in body mass and plasma volume. These aforementioned changes, however, were not significantly different (P > .05) between the placebo and capsaicin trials, except for mean skin temperature. The treatment effect for mean skin temperature was significant (P = .013), with the capsaicin response (34.7 degrees C) registering lower than the placebo measurement (35.1 degrees C). CONCLUSIONS: It appears that humans respond differently than animals to capsaicin ingestion. For humans, ingesting a 2-mg x kg(-1) dose of capsaicin 1 hour prior to heat exposure does not alter a person's ability to thermoregulate in the heat.

Adult↗
PubMed2000

Subtilase-like pro-protein convertases: from molecular specificity to therapeutic applications.

Limited proteolysis of most large protein precursors is carried out in vivo by the subtilisin-like pro-protein convertases. Many important biological processes such as peptide hormone synthesis, viral protein processing and receptor maturation involve proteolytic processing by these enzymes, making them potential targets for the development of novel therapeutic agents. However, the efficient development of such molecules requires a better understanding of the molecular mechanisms of proteolytic protein processing. Herein, we review the most recent findings on the molecular aspects of subtilisin-like convertase activity, such as the structural analysis of the proteases, the mechanisms of enzyme/substrate specificity, their interaction with other proteins such as 7B2, and the comparative tissue and cellular distribution of the enzymes and their substrates. These data are then used as a background for the review of the known biological functions of subtilisin-like pro-protein convertases, the reported clinical cases involving proteolytic processing defects and, finally, the ongoing development of new therapeutic inhibitor molecules based on this knowledge.

Animals↗
PubMed1999

Heparin, cell adhesion, and pathogenesis of inflammatory bowel disease.

Tissue repair involves a close interplay between growth factors and cell adhesion molecules. The normal healing process may be disrupted by pathophysiological states such as inflammation, due to loss of growth factors, cell adhesion molecules, or both, which results in a reduced rate of healing. Such events may occur in inflammatory bowel disease during mucosal restitution. We postulate that the beneficial response to heparin observed in inflammatory bowel disease may result from mechanisms in addition to anticoagulation. These include the restoration of high-affinity receptor binding by antiulcerogenic growth factors, such as basic fibroblast growth factor, that normally rely on the presence of heparan sulphate proteoglycans, such as syndecan-1, as co-receptors. Loss of syndecan-1 has been observed in the ulcerated mucosa of patients with inflammatory bowel disease. This loss may lead to impaired binding of basic fibroblast growth factor and a reduced rate of ulcer healing. We suggest that heparin restores high-affinity receptor binding of basic fibroblast growth, and so increases the rate of mucosal recovery.

Anticoagulants↗
PubMed1999

The detection of brief daytime sleep episodes.

INTRODUCTION: In the present study we evaluated the characteristics of sleep-onset detection (during daytime nap opportunities) as a function of differing sleep lengths among healthy, asymptomatic subjects. METHODS: Twenty subjects were randomized into a Latin square design in which each subject received 1, 5, 10, and 20 minutes of sleep during an MSLT. Subjects were asked after each nap if they fell asleep. The rate of sleep detection was analyzed as a function of sleep duration. RESULTS: Three subjects detected sleep onset after 1 minute of sleep, 7 subjects after 5 minutes of sleep, 10 subjects after 10 minutes of sleep, and 14 after 20 minutes of sleep (chi 2 = 9.63, p < .05). CONCLUSIONS: The present data indicate the importance of sleep duration in an individual's ability to detect the occurrence of sleep. Importantly, only three subjects detected sleep after 1 minute of sleep, emphasizing the dangerous nature of brief sleep episodes in the context of public safety.

Adult↗
PubMed1999

Carboxypeptidase D is a potential candidate to carry out redundant processing functions of carboxypeptidase E based on comparative distribution studies in the rat central nervous system.

Post-translational processing is essential for the biological activation of many proteins and peptides. After precursor cleavage at specific single residues or pairs of basic residues by the proprotein convertases, the C-terminal basic residues are removed. Carboxypeptidase E was thought to be the only enzyme responsible. Recent studies with carboxypeptidase E-deficient mice, Cpe(fat)/Cpe(fat), indicated the existence of carboxypeptidase E-like carboxypeptidases, such as carboxypeptidase D. In order to define potential redundant functions in vivo, we compared the distributions of both carboxypeptidases in the rat central nervous system and selected endocrine tissues. Carboxypeptidase D messenger RNA was abundantly expressed in glial cells in the gray and white matter, while neurons in several brain regions, such as the piriform cortex, basolateral amygdala and hippocampus, also expressed high levels of carboxypeptidase D messenger RNA. Co-localization of carboxypeptidases E and D messenger RNAs was observed in many brain regions, the spinal cord and endocrine tissues. Immunohistochemistry showed the intracellular distribution of carboxypeptidase D with a perinuclear pattern. The extensive distribution of carboxypeptidase D in both glial and neuronal cells indicates the important role of carboxypeptidase D in peptide processing, possibly working together with furin, a ubiquitously expressed proprotein convertase. The co-localization of carboxypeptidases D and E suggests that carboxypeptidase D may, at least partially, compensate for carboxypeptidase E processing functions in Cpe(fat)/Cpe(fat) mice.

Adrenal Glands↗
PubMed1999

Repeated nocturnal sleep latencies in narcoleptic, sleepy and alert subjects.

OBJECTIVES: The purpose of this study was to assess nocturnal sleep latencies among narcoleptics. METHODS: Thirteen narcoleptics and matched sleepy and alert controls participated in this study. Subjects were awakened three times on each of two experimental nights. The latencies to sleep and rapid eye movement sleep were evaluated at the beginning of the night and following each experimental awakening. RESULTS: The alert group (AG) had a significantly longer mean nocturnal sleep latency than the narcoleptic (NG) and sleepy groups (SG). The sleep latencies at 23:00 and 01:10 h were significantly longer than the latencies at 03:10 and 05:10 h. The interaction between group and time of night demonstrated longer latencies at 23:00 and 03:10 h for the AG when compared to the SG and the NG. At 01:10 and 05:10 h all groups had comparable latencies. The number of subjects in the NG who had multiple sleep onset REM periods (SOREMPs) was significantly higher than in either the AG or the SG. CONCLUSIONS: Narcoleptics were found to have a heightened propensity to fall asleep and increased number of SOREMPs during nocturnal sleep opportunities. These characteristics are consistent with the daytime polysomnographic findings known in this patient population.

Adult↗
PubMed1999

Expression of syndecan-1 in inflammatory bowel disease and a possible mechanism of heparin therapy.

Heparin apparently aids healing in ulcerative colitis although its mechanism of action is unknown. The purpose of this study was to investigate the hypothesis that heparin functions as a coreceptor molecule for basic fibroblast growth factor, a role usually performed by heparan sulfate chains on syndecan-1. A marked reduction of syndecan-1 immunostaining was found in reparative epithelium from inflammatory bowel disease patients. Removal of heparan sulfate on gastrointestinal epithelial cells in vitro reduced the proliferative response to basic fibroblast growth factor. The response to basic fibroblast growth factor was completely restored by the addition of heparin. Loss of syndecan-1 expression occurs in the regenerative mucosa in inflammatory bowel disease. Although this may facilitate tissue motility, its loss probably adversely affects the ability of cells to bind basic fibroblast growth factor. The present data show that heparin may substitute the loss of functional activity of syndecan-1 in the binding of basic fibroblast growth factor.

Cells, Cultured↗
PubMed1999

Assessment of combined movements of the lumbar spine in asymptomatic and low back pain subjects using a three-dimensional electromagnetic tracking system.

Combined movement examination (CME) is used by physiotherapists to assess and treat patients with low back pain (LBP). However, this method has not been subjected to quantitative assessment. The purpose of this study was to discover if CME of the lumbar spine could be measured with acceptable intra-examiner reliability and to make a preliminary investigation of the effect of LBP on the results of CME. Combined movement examination of the human thoracolumbar spine was measured using a three-dimensional electromagnetic goniometer (3SPACE Fastrak Polhemus, Colchester, Vermont, USA). 1. Intra-examiner reliability of CME was evaluated using a test-retest design; examination was repeated in 23 subjects without LBP and 16 with LBP. 2. A sample of 31 subjects without LBP and 23 subjects with LBP underwent CME, which involved measuring right and left sideflexion in the flexed, neutral and extended position. Pearson's r and the intraclass correlation coefficient for all variables ranged from 0.79 to 0.93 (P < 0.05). A MANOVA test (P < 0.05), comparing the combined effects of the two variables for each position, was used to test for a difference between the positions attained by the subjects with LBP and those without. Generally LBP subjects showed smaller ranges of movement than those without LBP. Each position was recorded as a degree of rotation around the x-axis (flexion/extension) and around the y-axis (left and right sideflexion). CME can be carried out with acceptable intra-examiner reliability; preliminary evidence is presented concerning the effectiveness of CME in identifying reduced spinal movement in LBP subjects.

Adult↗