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Biomedical subjects

R Day

Publications and source records attributed to R Day.

At least 19 recordsLinked to original sources
PubMed2000

CPAP therapy in patients with mild OSA: implementation and treatment outcome.

Objectives: To determine continuous positive airway pressure (CPAP) treatment compliance and reversal of excessive daytime sleepiness in patients with mild OSA.Background: CPAP therapy is the most widely accepted and used intervention in patients with a diagnosis of obstructive sleep apnea (OSA). There are, however, no widely accepted protocols to help guide the rational use of CPAP therapy. Patients with mild OSA (respiratory event index (REI) >5 or </=25) represent a subset of the OSA population where CPAP implementation needs to be evaluated.Methods: This is a retrospective study of 740 consecutive patients evaluated for sleep apnea in 1996. Mild OSA was documented in 241 patients, of whom, 41 opted for CPAP therapy. Implementation of CPAP treatment included an education session and an overnight clinical polysomnography (CPSG) for titration purposes. Patients returned for follow-ups after 1 week and 1 year of CPAP use. During each appointment, compliance and response to treatment were evaluated.Results: Of the initial 41 patients nine were lost to follow-up, 16 discontinued CPAP use during the first week, and 16 were still using CPAP after 1 year. For the 16 still using CPAP after one year, hours of use the first week was correlated to hours of use the first year (r=0.81). Patients using CPAP more than 4 h/night experienced a marked improvement in daytime sleepiness after 1 year (P<0.01).Conclusions: Patients with mild OSA showed a high rate of CPAP discontinuation. Those patients who manifested good compliance during the first week of treatment continued using CPAP for the entire first year. These patients experienced improved alertness during the day. A 1 week trial on CPAP therapy is warranted to identify patients who benefit from this form of therapy.

Journal Article↗
PubMed2000

A randomized trial of the efficacy and tolerability of the COX-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Rofecoxib/Ibuprofen Comparator Study Group.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). It is not known whether a specific inhibitor of COX-2 will provide efficacy in osteoarthritis (OA) comparable with NSAIDs. Therefore, we compared the efficacy and safety of the rofecoxib, which specifically inhibits COX-2, with those of the NSAID ibuprofen in patients with OA. OBJECTIVE: To compare the clinical efficacy and tolerability of rofecoxib (12.5 and 25 mg once daily) with ibuprofen (800 mg 3 times daily). METHODS: A randomized, double-blind trial of 809 adults with OA was conducted. Patients with OA in whom the knee or hip was the primary source of pain were randomized to 1 of 4 treatment groups on demonstration of disease activity: placebo; rofecoxib, 12.5 or 25 mg once daily; or ibuprofen, 800 mg 3 times daily. Clinical efficacy and safety were monitored during a 6-week treatment period. RESULTS: Both doses of rofecoxib demonstrated efficacy clinically comparable with ibuprofen as assessed by 3 primary end points (pain walking on a flat surface [Western Ontario and McMaster Universities Osteoarthritis Index], patient global assessment of response to therapy, and investigator global assessment of disease status) according to predefined comparability criteria. Both rofecoxib doses and the ibuprofen dose provided significantly (P<.001) greater efficacy than placebo on all primary end points. Results from secondary end points were consistent with those of the primary end points. All treatments were well tolerated; the overall incidence rates of clinical adverse experiences were not significantly different (P>.05) among the treatment groups. CONCLUSION: Rofecoxib was well tolerated and provided clinical efficacy comparable with a high dose of the NSAID ibuprofen.

Aged↗
PubMed2000

Evidence that anoreceptive intercourse with ejaculate exposure is associated with rapid CD4 cell loss.

OBJECTIVE: To determine whether ejaculate exposure through anoreceptive intercourse is associated with rapid CD4 cell loss. DESIGN: Self-reported behavioral, demographic data and blood samples were gathered longitudinally at ten semiannual visits from individuals participating in the Multicenter AIDS Cohort Study (MACS). PATIENTS/PARTICIPANTS: A group of 937 HIV-seropositive men who were continuously followed for four to ten semiannual visits. OUTCOME MEASURES: A loss of 10% or more in CD4 cells between the first two of any three consecutive semiannual visits that was followed by a 10% or greater loss between the second and third visits. RESULTS: A period of rapid CD4 cell loss over three semiannual visits occurred in 389 of the 937 (42%) HIV-seropositive men studied. Men who reported one or more anoreceptive intercourse partners with whom they were exposed to ejaculate (RAI-E) during the 12 months immediately preceding their visits were more than twice as likely to show this rapid CD4 cell loss compared with men with no such partners. CONCLUSIONS: The association between RAI-E partnerships and rapid CD4 cell loss suggests factors associated with ejaculate exposure (e.g., sexually transmitted diseases) may hasten the clinical progression of HIV disease. It is suggested that infectious diseases, which are known to be associated with ejaculate exposure, may be the causal factor underlying the association between RAI-E partnerships and rapid CD4 cell loss in these men, although the presence of these diseases was not ascertained in these data. HIV-infected individuals should be cautioned against unprotected anoreceptive intercourse.

CD4 Lymphocyte Count↗
PubMed2000

Posttranslationally modified tubulins and microtubule organization in hemocytes of the brine shrimp, Artemia franciscana.

Crustaceans possess blood cells (hemocytes) that mediate organismal defense and are analogous to vertebrate leukocytes. In order to more fully characterize these types of cells, hemocytes of the branchiopod crustacean, Artemia franciscana, were analyzed. The data indicate that Artemia have one type of hemocyte, ranging in morphology from compact and spherical to flat and spreading when examined in vitro. Electron microscopy revealed many cytoplasmic granules in the hemocytes and only a limited number of other membrane-bound organelles. Centrioles and microtubules were also visible in thin sections of chemically fixed samples. The cytoplasm of spherical hemocytes was completely labeled by general antitubulin antibodies, but in flattened hemocytes packing of cytoskeletal elements was less tight and individual microtubules were observed. Probing of Western blots disclosed acetylated, tyrosinated, and detyrosinated tubulin isoforms in hemocyte homogenates, the first characterization of posttranslationally modified tubulins in this cell type. Acetylated tubulin was restricted to a subset of microtubules, whereas tyrosinated microtubules were displayed more abundantly. Staining obtained with antibody to detyrosinated tubulin was unusual because it was limited to the perinuclear region of hemocytes. Incubation of blood cells with a monoclonal antibody to gamma-tubulin yielded fluorescent dots sometimes in pairs, a pattern characteristic of centrosomes. The findings support the conclusion that Artemia hemocytes undergo rapid morphogenesis in vitro accompanied by extensive rearrangement of their microtubules, the latter probably indicative of cytoskeletal changes that occur during cell movement and phagocytosis. Additionally, the hemocytes contain posttranslationally modified alpha-tubulins and centrosome-associated gamma-tubulin, both with the potential to influence microtubule organization and function.

Animals↗
PubMed2000

Micellar electrokinetic chromatography separations of dynorphin peptide analogs.

Prodynorphin is a precursor that has multiple cleavage sites to release various dynorphin opioid peptides. The dynorphin analogs used in this study have 18 amino acid residues. A series of dynorphin-like peptides, differing by a single residue (alanine substitution) were assembled by Fmoc solid-phase procedures and purified by preparative high performance liquid chromatography (HPLC). Separation of the Ala-scan dynorphin analogs was investigated by micellar electrokinetic chromatography (MEKC) employing anionic, cationic and zwitterionic surfactants. The role of electrostatic and hydrophobic forces in analyte-surfactant interactions is discussed with respect to the observed elution patterns. Separation of all dynorphin analogs by MEKC using a zwitterionic surfactant shows this technique to be powerful for separating closely related peptide species. It also demonstrates the potential for using MEKC for the prescreening of peptide libraries to determine their biological activity toward specific receptors. Results from the separation of dynorphin analogs by free solution and ion-pairing capillary electrophoresis are also presented.

Amino Acid Sequence↗
PubMed2000

Comparative characterization of two forms of recombinant human SPC1 secreted from Schneider 2 cells.

SPC1 (furin/PACE), an enzyme belonging to the S8 group of serine endoproteases, is a type I integral membrane protein that catalyzes the processing of a multitude of precursor proteins. We report here the use of transfected Drosophila melanogaster Schneider 2 cells to produce milligram amounts of two forms of recombinant human SPC1. In order to investigate the role of the cysteine-rich region (CRR) of SPC1, we compared the biochemical and enzymatic properties of hSPC1/714 that has the C-terminal tail and transmembrane region of the native enzyme removed with that of hSPC1/585 which had, in addition, the CRR deleted. Two stable cell lines were established. The S2-hSPC1/714 line secreted a major form of apparent molecular weight of 83 kDa and a minor form of 80 kDa whereas the S2-hSPC1/585 line secreted a single 59-kDa protein. PNGase F treatment of the different forms demonstrated that the enzymes were glycosylated. Automated NH(2)-terminal sequencing revealed that all purified forms resulted from processing at the expected zymogen activation site. Removal of the CRR resulted in a broadening of the enzyme's pH range, a shift of K(0.5) for Ca(2+), and a shorter enzymatic half-life when compared to the longer form, which suggest that the CRR of hSPC1 may help in stabilizing the enzyme's proteolytic activity. The use of this high-level expression system will meet the demand for material necessary to perform biochemical and structural studies that are needed to further our understanding of this and other SPCs at the molecular level.

Amidohydrolases↗
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

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↗