The irritable bowel syndrome: in your dreams?
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Colonic Diseases, Functional↗
Biomedical subjects
W C Orr
Publications and source records attributed to W C Orr.
Relationship between antioxidants, prooxidants, and the aging process.
It is argued that reduced oxygen species may be one of the causal factors underlying the aging process. Experimental studies strongly support the view that the rate of metabolism is inversely associated with the rate of aging. It is pointed out that Pearl's rate of living theory is widely misunderstood, because of the mistaken belief that it advocates a fixed metabolic potential for different species or genotypes within a species. The in vivo level of oxidative stress tends to increase with age in insects and mammals as indicated by increased exhalation of alkanes. A search for the causes of this increase revealed that an age-associated decline in antioxidant defenses is neither widespread nor very impressive in magnitude. A comparison of antioxidant defenses (activities of SOD, catalase, and glutathione) in six different mammalian species did not suggest a clear association between these defenses and maximum life span potential of the species. In contrast, mitochondrial rates of O2- and H2O2 were found to increase with age in insects and mammals, and the MLSP of six mammals was found to be inversely correlated with liver mitochondrial rates of O2- and H2O2 generation. It seems that the age-related increase in oxidative stress is mainly due to the enhanced rate of O2- and H2O2 generation. It is hypothesized that variations in the rates of aging in different species, that are otherwise closely related phylogenetically, may be in part due to differences in rates of O2- and H2O2 production. Overall, the rates of oxidant generation are a better correlate of the rates of aging than are the levels of antioxidant defenses.
Aging↗
The effects of catalase gene overexpression on life span and resistance to oxidative stress in transgenic Drosophila melanogaster.
Oxygen free radicals and hydroperoxides have been postulated to play a causal role in the aging process, implying that antioxidant enzymes may act as longevity determinants. Catalase (H2O2:H2O2 oxidoreductase; EC1.11.1.6) is the sole enzyme involved in the elimination of H2O2 in Drosophila melanogaster; glutathione peroxidase being absent. A genomic fragment containing the Drosophila catalase gene was used to construct transgenic Drosophila lines by means of P element-mediated transformation. Enhanced levels of catalase (up to 80%) did not prolong the life span of flies, nor did they provide improved protection against oxidative stress induced by hyperoxia or paraquat treatment. However, enhanced resistance to hydrogen peroxide was observed in the overexpressors.
Animals↗
Broad-complex function during oogenesis in Drosophila melanogaster.
The Broad-Complex (BR-C) appears to encode factors that mediate ecdysone effects during the larva-adult transition. The main goal of this study was to gain insight into what roles the BR-C might play during oogenesis. The main findings are as follows. First, as determined by heteroallele studies and clonal analysis, de12 is a somatic line mutation that appears to fall into the broad domain of the BR-C. Second, the de12 mutation is associated with the insertion of the gypsy transposon at position 169.5 (Chao and Guild, Embo J, 1986, 5:143-150) in the BR-C domain. In its new context this gypsy element exhibits ovarian-specific activation. Both this gypsy activation and the de12 phenotype are partially suppressible by su(f) and su(Hw). Third, we have identified a set of transcripts that cross-hybridize with BR-C sequence spanning the gypsy insertion site (166-179). There are significant differences in these cross-hybridizing species, both in size and relative abundance, between de12 and its parent strain. Finally we have determined that in de12 there is a premature arrest of chorion gene amplification in the late stages of oogenesis.
Animals↗
Relationship between catalase activity, life span and some parameters associated with antioxidant defenses in Drosophila melanogaster.
This study was conducted on Drosophila melanogaster mutants with different levels of catalase activity in order to assess the role of antioxidant defenses in the aging process. We present here the analysis of two mutant strains: the catn1/catn4 heterozygote which exhibits no detectable catalase activity and the catn2 homozygote which exhibits approximately 14% that of the parent reference strain. Since insects lack glutathione peroxidase activity, catalase activity provides the sole enzymatic mechanism for the removal of H2O2. Average and maximum life spans of flies were unaffected by the absence or low levels of catalase activity. The mutants however exhibited adaptive responses in their metabolic rate or glutathione content. The metabolic rate of flies was significantly lowered in the null mutants. Glutathione concentration tended to increase in flies with the hypomorphic catalase allele (exhibiting 14% of the normal catalase activity). Gamma-glutamylcysteine synthetase activity was significantly higher in the null flies. Activities of superoxide dismutase and glutathione reductase were unaffected. Results of this study indicate that 14% of the normal level of catalase activity allows flies to achieve both a normal life span and a normal metabolic potential. Small decreases in certain antioxidant defenses, frequently observed during aging, may be functionally not very consequential.
Aging↗
Esophageal function and gastroesophageal reflux during sleep and waking in patients with chronic obstructive pulmonary disease.
This study was conducted to assess esophageal function and pulmonary resistance changes with esophageal acidification in patients with COPD. Twelve patients with COPD and a mean age of 55.6 years were studied. Each patient underwent standard esophageal manometry, 24-h ambulatory pH testing, esophageal acid clearance evaluation during sleep, and an assessment of pulmonary resistance with and without esophageal acid perfusion. Neither airway resistance nor conductance was altered by the esophageal acid infusion; LES pressures were normal and esophageal contractile pressures were mildly decreased. Acid exposure in the upright and supine positions was within normal limits. Acid clearance during sleep was similar to that in normal subjects; however, acid clearance during waking appeared to be somewhat prolonged in the COPD patients. We conclude that patients with COPD do not have a bronchoconstrictive reflex to distal esophageal acidification, and esophageal function in these patients appears to be relatively normal.
Adult↗
Chest pain and the esophagus: is it more obvious in the CCU?
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Chest Pain↗
Genetic markers in familial narcolepsy.
We studied three patients in a single family (father and two sons), all with long histories of overwhelming daytime sleepiness, hypnagogic hallucinations and sleep paralysis. Two of the three had a clear history of cataplexy. Multiple sleep latency tests revealed extremely short sleep onset latencies and at least two sleep onset rapid eye movement periods in each patient. Histocompatibility studies were remarkable for negative HLA-DR2 antigens in all three.
Adolescent↗
Effects of ranitidine, given t.d.s., on intragastric and oesophageal pH in patients with gastrooesophageal reflux.
The purpose of this study was to determine the effects of 150 mg ranitidine, 300 mg ranitidine or placebo, administered every 8 h, on gastro-oesophageal pH and heartburn parameters in reflux patients. Twelve symptomatic reflux patients received each of the three treatments in a randomized, double-blind, crossover fashion. Intragastric and oesophageal pH were monitored continuously for a 24 h period. Meals were standardized, consumed at set times and patients were allowed to recline and sleep from 23.00 hours until 06.00 hours only. The gastric record was analysed for the percentage of time that the pH was greater than or equal to 4. The oesophageal record was analysed for acid contact time (percentage time (%) pH less than or equal to 4.0) and reflux episode frequency. Finally, patients recorded each new episode of heartburn and graded daytime heartburn severity at the end of each hour. Ranitidine increased the median (%) time that the intragastric pH remained at or above 4, from 4.5 (placebo) to 33.9% (150 mg dose) and 33.3% (300 mg dose). Ranitidine dose-dependently reduced the median 24-hour oesophageal acid contact time from 13.3% (placebo) to 6.8% (150 mg dose) and 2.5% (300 mg dose). The 300 mg dose significantly reduced daytime heartburn episode frequency and severity while the 150 mg dose reduced heartburn severity only. We conclude that 150 and 300 mg doses of ranitidine administered every 8 h have major, sometimes dose-dependent effects on the objective parameters and symptoms of gastro-oesophageal reflux.
Adult↗
The effect of esophageal acid volume on arousals from sleep and acid clearance.
To assess the effect of different volumes of acid infused into the esophagus, seven normal volunteers were studied in the waking and sleep state. All subjects were studied for three nights in the sleep laboratory, which included complete polysomnographic monitoring and esophageal pH recording. Multiple infusions of either 5, 15, or 25 ml of 0.1 N HCL were administered each night. Similar infusions were also accomplished in the waking state. The results showed a significant (p less than 0.05) decrease in the arousal from sleep with 25-ml vs 5-ml infusions. During sleep, the latency to the first swallow was significantly (p less than .05) shorter with the 25-ml infusion when compared with that of the 5-ml infusion. While awake, the infusion volume did not affect the latency to the first swallow. The acid clearance times were not significantly altered by the different volumes infused. It is concluded that the larger volumes of acid in the esophagus create an afferent "warning" signal to the central nervous system to produce a rapid arousal from sleep along with a shortened interval to the first swallow. These responses rapidly empty the larger acid volumes from the esophagus.
Arousal↗
Noncardiac chest pain: conundrum of cause and effect.
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Chest Pain↗
cDNA and deduced amino acid sequence of Drosophila catalase.
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Amino Acid Sequence↗
Effect of age on superoxide dismutase, catalase, glutathione reductase, inorganic peroxides, TBA-reactive material, GSH/GSSG, NADPH/NADP+ and NADH/NAD+ in Drosophila melanogaster.
The objective of this study was to investigate the possible role of oxygen free radicals in the aging process by studying the pattern of age-related changes in a broad spectrum of antioxidant defenses and indicators of oxidative stress in adult male Drosophila melanogaster. There were selective, but not universal, changes in the antioxidant defenses and indicators of oxidative stress. Activities of catalase and glutathione reductase and concentration of reduced glutathione decreased during the latter part of life. Superoxide dismutase activity tended to increase with age whereas glutathione peroxidase activity was undetectable. The ratios of reduced/oxidized glutathione and NADPH/NADP+, which are widely regarded as indicators of oxidative stress, decreased in the terminal phase of life. NADH/NAD+ ratio increased in the latter part of life. Concentration of inorganic peroxides increased during the first trimester of life and remained unchanged thereafter while that of thiobarbituric acid-reactants tended to decrease during aging. The main conclusion of this study is that age-related changes in antioxidant defenses and in levels of oxygen free radical reaction products are selective in nature and are quite variable in different species and tissues; however, the level of oxidative stress tends to increase during aging.
Aging↗
Persistent hypoxemia and excessive daytime sleepiness in chronic obstructive pulmonary disease (COPD).
Fourteen patients with chronic obstructive pulmonary disease (COPD) and chronic hypoxemia were studied to evaluate the relationship between hypoxemia and objective and subjective daytime sleepiness. Patients were selected with a waking PaO2 of less than 70 mm Hg and less than 50 percent predicted FEV1. Clinically, none of these patients had complaints of significant daytime sleepiness. Each patient underwent standard all-night polysomnographic evaluation followed by a multiple sleep latency test (MSLT). There was no significant correlation between the mean sleep onset latency for the MSLT and the waking PaO2, PCO2, FEV1, or spontaneous desaturations during sleep. Patients with COPD exhibited a mean MSLT that was within normal limits, despite a short total sleep time and numerous arousals from sleep. We conclude that there appears to be no relationship between chronic daytime hypoxemia and subjective reports and objective measures of daytime sleepiness.
Aged↗
Esophageal acid contact time and heartburn in acute treatment with ranitidine and metoclopramide.
Ranitidine and metoclopramide were compared for their ability to reduce esophageal acid contact time and heartburn. Twelve patients with histories of heartburn received ranitidine 150 mg bid, metoclopramide 10 mg qid, and placebo (ranitidine-matched) bid in a randomized, open-label, crossover fashion. Esophageal pH was monitored with an antimony electrode and portable recording unit for 24 h under strictly controlled laboratory conditions. Ranitidine significantly (p less than or equal to 0.05) reduced 24-h acid contact time from 11.6% to 6.4%. Reflux episode frequency was also significantly (p less than or equal to 0.05) reduced from 82 to 45 episodes per day and from 12 to 2 episodes at night. In contrast, metoclopramide did not reduce 24-h acid contact time or daytime reflux episode frequency, although nighttime episode frequency was significantly (p less than or equal to 0.05) decreased. Only ranitidine significantly reduced heartburn frequency and severity. We conclude that acute treatment with ranitidine, but not metoclopramide, significantly reduces esophageal acid contact time, reflux episode frequency, and heartburn frequency and severity in patients with gastroesophageal reflux.
Adult↗
The effect of raw onions on acid reflux and reflux symptoms.
Patients with gastroesophageal reflux often describe heartburn after "spicy meals." One ingredient common to most such meals is onion. We investigated the effects of onion on acid reflux and reflux symptoms in 16 normal subjects and 16 heartburn subjects. Subjects were studied with an esophageal pH probe for 2 h after the ingestion of a plain hamburger and a glass of ice water. The identical meal, with the addition of a slice of onion, was ingested on a counterbalanced day. Variables measured were number of reflux episodes, percentage of the time pH was less than four, heartburn episodes, and belches. Ingestion of onions did not increase any of the reflux variables measured in normals. However, onions significantly increased all measures in heartburn subjects, compared with the no-onion condition, and compared with normals under the onion condition. Onions can be a potent and long-lasting refluxogenic agent in heartburn patients.
Adult↗
A female sterile screen of the Drosophila melanogaster X chromosome using hybrid dysgenesis: identification and characterization of egg morphology mutants.
We have conducted a hybrid dysgenic screen of the X chromosome for mutations affecting female fertility, with particular attention to those causing abnormal egg and eggshell morphology. In a screen of 4017 dysgenic strains, 398 mutants derived from 168 different germ lines were isolated and assigned to eight classes according to their diverse phenotypes. One interesting class consists of mutants that block oogenesis at specific stages. Our analysis has focused on mutations affecting eggshell formation, including mutants that lay morphologically abnormal sterile eggs as well as those that lay no eggs but exhibit blocks in the late stages of oogenesis. A subset of 48 mutants was assorted into 30 allelic groups by inter se complementation and genetically localized by interval mapping. Two multiallele complementation groups, de1 (7 alleles) and ne1 (8 alleles), were identified as well as five two-allele complementation groups. A search for alleles among mutants generated in other female sterile screens was unsuccessful, pointing to the distinctive nature of the dysgenic mutant collection. The single case of allelism determined in this study was one with a lethal allele of the Broad-Complex, l(1)npr, suggesting a possible involvement of ecdysone in choriogenesis. A subset of 18 dysgenic strains was analyzed for P element hybridization and 16 of these were found to have hybridization signals in the appropriate cytogenetic interval. By examining these signals in two or more alleles of the same complementation group, we have been able to tentatively localize two mutations. Light and electron microscopy of the eggshell in 43 different strains has revealed a variety of effects. The respiratory appendages were defective in 27 of these mutants. Effects on the ultrastructure of the main body of the endochorion were not strongly correlated with the appendage defects, and could be classified as minor (14 mutants) or major (16 mutants). Although 13 mutants showed no ultrastructural chorion defects, six of these had defective respiratory appendages.
Animals↗