PubMed Health⌕ Search

Biomedical subjects

W C Orr

Publications and source records attributed to W C Orr.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1979

Hypersomnolent and nonhypersomnolent patients with upper airway obstruction during sleep.

When the syndrome consisting of sleep-induced apnea and hypersomnolence is due to upper airway obstruction, the hypersomnolence is believed to be the direct result of deprivation of sleep related to such obstructions. The purpose of this report is to describe a group of four asymptomatic subjects with upper airway obstruction during sleep. These subjects were matched with a group of patients with the syndrome of sleep-induced apnea and hypersomnolence. There were no significant differences between symptomatic and asymptomatic groups in terms of the absolute number of upper airway obstructions (252 vs 231), their mean duration (20.8 vs 25.9 seconds), the mean arterial carbon dioxide tension during sleep (39 vs 39 mm Hg), or the electroencephalographic patterns during sleep. The only variables that emerged as significantly different between the two groups were the weights (128 vs 90 kg; P less than 0.05), the low arterial oxygen pressure (PaO2) on waking (54 vs 80 mm Hg; P less than 0.002), and the lower PaO2 during sleep (47 vs 70 mm Hg; P less than 0.01) in the symptomatic patients. From these data, we conclude that the hypersomnolence in patients with sleep-induced apnea due to upper airway obstruction cannot be explained by deprivation of sleep, and other factors need to be carefully examined in future studies.

Adult↗
PubMed1979

Progesterone therapy in obese patients with sleep apnea.

Seven morbidly obese patients with sleep-related upper airway obstruction (UAO) were studied before and during progesterone treatment. All subjects had severe daytime somnolence, and five of the seven had congestive heart failure. All subjects were studied for one or two consecutive baseline nights in the sleep laboratory. Six of the seven subjects showed a mean of greater than 100 UAOs. Patients were treated for two to four weeks with medroxyprogesterone acetate, 20 mg three times daily. At the end of the treatment period, the sleep studies were repeated. There was no significant difference in the incidence, mean duration, or rate per minute of apneic episodes occurring before and with progesterone treatment. Severe hypoxemia during sleep persisted with treatment, as did the occurrence of cardiac arrhythmias. There was a significant improvement in the waking Pao2 with progesterone treatment.

Adult↗
PubMed1979

Nocturnal levels of growth hormone in hyperactive children of small stature.

Growth disturbances have been demonstrated in hyperactive children treated with stimulant medication. This study examines sleep related growth hormone secretion in patients with hyperactive syndrome and relative short stature. Five such patients were compared with 9 age matched controls. There were no differences in sleep patterns, and growth hormone levels for the hyperactive children were within normal limits. This study suggests that hyperactive children with short stature have normal sleep patterns and normal sleep related growth hormone secretion.

Body Height↗
PubMed1978

Diversity and abundance of polyadenylated RNA from Achlya ambisexualis.

The diversity, abundance, and DNA sequence representation of poly(adenylic acid) containing RNA derived from cells of Achlya ambisexualis cultured in defined and undefined media have been determined. The kinetics of hybridization of polyadenylated RNA with complementary DNA were the same for both culture conditions and revealed the presence of three frequency classes containing 29, 220, and 3000 different sequences of an average length of 1150 nucleotides. Complexity estimates derived from experiments in which polyadenylated RNA was hybridized to unique sequence DNA were in good agreement with these results. The kinetics of hybridization of complementary DNA with an excess of nuclear DNA indicate that approximately 10% of the RNA is transcribed from reiterated DNA sequences while the remainder is transcribed from single copy sequences.

Base Sequence↗