Genes of human immunodeficiency virus, type I (HIV-I), their expression in Escherichia coli, and their utility in diagnosis of virus infection.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Biomedical subjects
R G Allen
Publications and source records attributed to R G Allen.
Correlates of longevity in two strains of the housefly, Musca domestica.
The general objective of this study was to identify biochemical correlates of longevity in the housefly by comparing two strains of flies that have different longevities. The average and the maximum life spans of the longer-lived "Cambridge" strain flies were 46% and 23%, respectively, greater than the shorter-lived "Thuron" strain flies. The hypothesis that longer-lived organisms have relatively more efficient mechanisms to minimize oxidative stress and maintain a relatively more reduced redox potential was tested. All measurements were made on 8-day-old male flies maintained under identical conditions. Flies of the longer-lived strain had a lower metabolic rate and contained lesser amounts of H2O2 and thiobarbituric acid-reactants than the flies of the shorter-lived strain. Reduced glutathione concentration and activities of catalase, glutathione reductase and thioltransferase were higher in the longer-lived strain indicating that longer-lived flies manifest lower levels of oxidative stress and greater ability to maintain a relatively more reducing environment than the shorter-lived flies. Superoxide dismutase (SOD) activity was similar in the two strains, but the SOD/metabolic rate ratio was higher in the longer-lived strain. Total activity of glutathione S-transferases was comparable in the two strains suggesting that differences in detoxification ability are not correlated with longevity. Only S-glutamylcysteine synthetase activity was greater in the shorter-lived strain suggesting that variation in longevity is not due to reduction in the ability to synthesize GSH. Overall, the results support the view that parameters associated with oxidative stress play a role in the aging process of the houseflies.
Animals↗
Superoxide dismutase activity and glutathione concentration during the calcium-induced differentiation of Physarum polycephalum microplasmodia.
Microplasmodia of Physarum polycephalum differentiate into spherules when the CaCl2 concentration of their nutrient medium is increased to 54mM (high-calcium). The salts starvation medium routinely used to induce differentiation contains 8mM CaCl2. This medium will not induce spherulation in the absence of a calcium salt; no other metal is essential. High-calcium also induces the spherulation of a strain of Physarum that had not been previously observed to spherulate. The striking increase in superoxide dismutase activity (SOD) and the decrease in glutathione concentration (GSH) that are characteristic of salts-induced spherulation do not occur in salts media containing high-calcium. In the absence of calcium, no significant change in SOD is observed and very little change in GSH occurs. The immediate effect of the oxidative stress associated with spherulation may be the release of calcium stores into the cytosol. The parameters modulating this stress are, in turn, sensitive to exogenous calcium concentrations.
Calcium↗
Relationship between life expectancy, endogenous antioxidants and products of oxygen free radical reactions in the housefly, Musca domestica.
The general objective of this study was to identify biochemical correlates of life expectancy in the adult male housefly. All houseflies lose flying ability prior to death, whereby, in an aging population, shorter-lived flies can be identified as flightless 'crawlers' from their longer-lived cohorts, the 'fliers'; the average lifespan of crawlers is about one-third shorter than the fliers. Neither crawlers nor fliers exhibited any physical damage to their chemoreceptive tarsi, thereby ruling out starvation as a probable cause of death. Levels of antioxidant defenses (superoxide dismutase, catalase and glutathione) and products of oxygen free radical reactions (inorganic peroxides and thiobarbituric acid [TBA]-reactants) were compared between crawlers and fliers. The fliers showed higher superoxide dismutase and catalase activities and glutathione concentration than crawlers, whereas, the amount of inorganic peroxides (H2O2) and TBA-reactants was higher in the crawlers than in fliers. Results of this study demonstrate, for the first time, that longer life expectancy of organisms belonging to the same cohort group is associated with relatively higher levels of antioxidants and lower concentrations of products of oxygen free radical reactions.
Animals↗
Oxygen free radicals play a role in cellular differentiation: an hypothesis.
Evidence from a variety of sources supports the view that oxygen free radicals play a role in cellular differentiation. It is postulated that cellular differentiation is accompanied by changes in the redox state of cells. Differentiated cells have a relatively more prooxidizing or less reducing intracellular environment than the undifferentiated or dedifferentiated cells. Changes in the redox balance during differentiation appear to be due to an increase in the rate of O2- generation. Differentiated cells, in general, exhibit higher rates of cyanide-resistant respiration, cyanide-insensitive SOD activity, and peroxide concentration and lower levels of GSH as compared to undifferentiated cells. The effects of free radicals on cellular differentiation may be mediated by the consequent changes in ionic composition.
Animals↗
Mechanisms of biologic aging.
The authors outline the progression of thought on the mechanism of the aging process, giving emphasis to environmental factors that influence genetic events. Discussion is limited to those theories that explain fundamental causes of aging and have a firm thermodynamic basis. The authors propose that the cumulative result of continual oxidative stress and other thermodynamic processes (such as amino-acid racemization and nonenzymatic glycosylation), resulting in altered function and increasing the net entropy of living systems, governs the rate of the aging process.
Aging↗
Retinal hemorrhage thresholds for Q-switched neodymium-Yag laser exposures.
Thresholds for retinal vitreal and contained hemorrhages were determined for 1064 nm laser light at 30-nsec and 4-nsec pulsewidths. Rhesus monkeys received graded exposures from a neodymium-yag laser onto either the macular or extramacular region of the retina. Contained hemorrhages appeared as concentric ring structures with white punctate centers. The vitreal hemorrhage was characterized by the presence of choroidal blood in the vitreal chamber at the exposure site. The 30-nsec contained hemorrhage threshold (ED50) was 1.7 mJ on the macula and 2.1 mJ for an extramacular exposure. The 30-nsec vitreal hemorrhage macular threshold was 2.3 mJ, and the extramacular threshold was 6.6 mJ. The threshold for the 4-nsec pulsewidths to produce a hemorrhage (vitreal or contained) on the retina (macula or extramacular) was 340 microJ.
Animals↗
Iron induces oxidative stress and may alter the rate of aging in the housefly, Musca domestica.
Iron is known to play a catalytic role in the generation of oxygen free radicals in vitro. The present study was conducted in order to determine the in vivo effects of iron intake. Administration of 2 mM ferrous chloride to adult male houseflies in their drinking water significantly shortened their life span, increased the concentration of inorganic peroxides and chloroform-soluble fluorescent material, and stimulated the activity of catalase. Levels of superoxide dismutase activity, glutathione and oxygen utilization were unaffected. Overall, these results indicate that iron causes oxidative stress in vivo and may influence the rate of aging.
Aging↗
Alterations in superoxide dismutase, glutathione, and peroxides in the plasmodial slime mold Physarum polycephalum during differentiation.
Changes in the level of antioxidant defenses and the concentration of free radical by-products were examined in differentiating (M3cVII and LU897 X LU863), non-differentiating (LU887 X LU897), and heterokaryon microplasmodia of the slime mold Physarum polycephalum during spherulation in salts-only medium. As differentiation proceeded, superoxide dismutase activity increased by as much as 46 fold; glutathione concentration and the rate of oxygen consumption decreased; cyanide-resistant respiration, hydrogen peroxide, and organic peroxide concentrations increased. The non-differentiating culture failed to exhibit any of these changes. A heterokaryon obtained by the fusion of differentiating and non-differentiating strains was observed to differentiate at a very retarded rate and to exhibit the changes observed in the spherulating strains at a correspondingly slower rate. These observations suggest that a free radical mechanism may be involved in the differentiation of Physarum microplasmodia into spherules.
Cell Differentiation↗
Relationship between metabolic rate, free radicals, differentiation and aging: a unified theory.
Metabolic rate is a major factor governing the rate of aging in both homeotherms and poikilotherms and is inversely related to life span. Homeotherms exhibit stable basal metabolic rates and species-specific life spans. Conversely, in poikilotherms, both basal metabolic rate and life span vary greatly. Metabolic potential (total energy consumed/g/life span) is a species-specific characteristic in Homoetherms and poikilotherms. Length of life is dependent upon the rate at which this fixed metabolic potential is expended, that is, metabolic rate. Oxygen-free radicals produced by metabolism can cause molecular damage. Accumulation of lipofuscin granules, Schiff-base-like, fluorescent material and thiobarbituric acid-reactants, as well as increased exhalation of pentane with age are indicative of free, radical-induced molecular damage. Metabolic rate influences the rate of age-related changes. There is an overlapping compensatory balance between various components of the antioxidant defense system. The total antioxidant capacity of cells tends to decline with age. A dynamic equilibrium may exist between the rate of free radical generation and antioxidant levels. The establishment of this equilibrium is associated with differentiation. It is hypothesized that loss of the equilibrium between free radical generation and antioxidant defenses results in dysdifferentiation, aging and cancer.
Aging↗
Effects of exogenous antioxidants on the levels of endogenous antioxidants, lipid-soluble fluorescent material and life span in the housefly, Musca domestica.
Effects of exogenous antioxidant administration (0.5% and 2% ascorbate, beta-carotene and alpha-tocopherol in sucrose) on life-span, metabolic rate, activities of superoxide dismutase and catalase, levels of glutathione, inorganic peroxides and chloroform-soluble fluorescent material (lipofuscin) were examined in adult male houseflies. Administration of antioxidants at a level of 0.5% did not affect life-span, whereas, 2% ascorbate and alpha-tocopherol decreased average life-span. Metabolic rate of flies was unaffected, except by 2% ascorbate, which caused a decrease. Superoxide dismutase activity was depressed by 2% ascorbate at all ages, and by beta-carotene and alpha-tocopherol in older flies. Catalase activity was unaffected except by alpha-tocopherol at younger ages. Glutathione concentration was decreased by ascorbate and beta-carotene at both concentrations administered. Inorganic peroxides (H2O2) were increased by 2% beta-carotene and alpha-tocopherol. Only high concentrations of ascorbate and beta-carotene decreased the level of soluble fluorescent material. Results suggest that administration of exogenous antioxidants causes a compensatory depression of endogenous defenses.
Animals↗
Relationship between gamma-irradiation, life span, metabolic rate and accumulation of fluorescent age pigment in the adult male housefly, Musca domestica.
The patterns of fluorescent age pigment (FAP) accumulation in response to gamma-irradiation were examined in adult male houseflies under conditions of relatively high and low levels of physical activity. Flies were exposed to 0, 20, 40, and 66 kR and their level of physical activity was altered by permitting or restricting flight activity. Under conditions of high activity the mean life span of flies exposed to 20 kR and 40 kR was greater than in the controls. The mean life span of high activity flies exposed to 66 kR and all groups of low activity irradiated flies was less than the control life span. The force of mortality as indicated by Gompertz slope was greater in high activity controls than in unirradiated flies maintained under low activity conditions. Gompertz slope was similar in corresponding high and low activity groups exposed to radiation. Radiation decreased the rate of FAP accumulation in high activity groups, but increased the rate of FAP accumulation under low activity conditions. The low activity control and low activity flies exposed to 20 kR had a lower FAP accumulation than the corresponding high activity groups at 14 days of age. At this age, low activity groups of flies exposed to 40 kR and 66 kR had concentrations of FAP that were similar to the corresponding high activity groups. These results indicate that radiation exposure decreased longevity by causing damage rather than by increasing the rate of aging.
Aging↗
Effects of experimentally altered glutathione levels on life span, metabolic rate, superoxide dismutase, catalase and inorganic peroxides in the adult housefly, Musca domestica.
Effects of varied levels of glutathione, an intracellular redox buffer, were examined in the adult male housefly in order to study the inter-relationship between enzymic and non-enzymic antioxidant defenses. An increase of over 100% in the concentrations of glutathione was induced by the administration of 3 mM L-2-oxothiazolidine-4-carboxylate (LOC), which increases the intracellular level of cysteine. A decrease in glutathione concentration of up to 85% was achieved by the administration of L-buthionine-SR-sulfoximine (BUS), which irreversibly inhibits glutamylcysteine synthetase. Life spans of houseflies were shortened by a decrease in the glutathione concentration, but were not prolonged by augmentation of glutathione. Metabolic rate and superoxide dismutase activity were independent of glutathione concentration. H2O2 was increased by both experimental regimes, whereas catalase activity was decreased by BUS. Results suggest that catalase activity is influenced by glutathione concentration.
Animals↗
Ocular effects of pulsed Nd laser radiation: variation of threshold with pulsewidth.
This study of retinal damage thresholds in the rhesus monkey eye investigated the effects of Nd:YAG laser radiation at four pulsewidths; 4, 30, and 200 ns, and 10 microseconds. The thresholds for induction of minimal ophthalmoscopically visible lesions for the four pulsewidths were 158, 326, 170, and 425 microJ, respectively, incident at the eye in single-pulse exposures. The data are interpreted to imply a flat trend of threshold with pulsewidth over the range of pulsewidths examined, in agreement with maximum permissible exposures quoted in existing laser safety standards. This finding is in contrast with the hypothesis of an anomalous trend of increasing threshold with decreasing pulsewidth which was suggested for the nanosec-microsec pulsewidth range based on the sparse data base previously available.
Animals↗
Visual evoked potential correlates of laser flashblindness in rhesus monkeys I. Argon laser flashes.
The visual evoked potential (VEP) in four rhesus monkeys was used to assess the transient loss of visual function resulting from single 100-ms argon laser flashes (476.5 and 514.5 nm) whose energy levels did not exceed the maximum permissible exposure (MPE). VEP's were elicited by high-contrast square-wave test gratings which were phase-reversed at a frequency of 6 Hz, and were recorded using bipolar electrodes implanted in the foveal projection region of area 17. The parameters which were investigated included (1) flash size (focused vs. expanded), (2) position of the electrode's receptive field relative to the position of the flash (0, 1.5, 3.0, and 4.5-deg separation), (3) flash exposure level (50, 5.0, and 0.5% of the MPE), (4) peak wavelength of the test grating (454, 540, and 630 nm), and (5) spatial frequency of the test grating (1.0, 4.0, 6.0, and 12.0 c/deg). The results of the flash-size experiment revealed that the expanded flash, whose retinal diameter was approximately 750 microns, eliminated or severely attenuated the VEP for a longer duration than did the focused flash and also resulted in a more gradual recovery function. The combined results of the flash position and energy level experiments indicated that the effective energy of the focused flash declined rapidly beyond 1.5 deg, but still approximated 4% of its maximum value as far as 4.5 deg from its center. Few, if any, wavelength-specific effects were observed after exposure to either the 476.5- or 514.5-nm flashes, even when the energy of the flashes was reduced to a small fraction of the MPE. Finally, the flash effect was considerably longer in duration for the 12.0 c/deg grating relative to the low and intermediate frequency gratings. In general, the findings suggest that the focused and expanded argon laser flashes produce a VEP suppression whose time course and other characteristics correlate well with those associated with behaviorally observed flashblindness in humans after exposure to intense noncoherent flashes.
Animals↗
Visual evoked potential correlates of laser flashblindness in rhesus monkeys. II. Doubled-neodymium laser flashes.
The effects of Q-switched (20-ns) doubled-neodymium (Nd-2) laser flashes upon the visual evoked potential (VEP) of two rhesus monkeys were studied and compared with the effects of 100-ms argon laser flashes described previously. VEP's were recorded under barbiturate anesthesia using bipolar electrodes chronically implanted in foveal striate cortex, and were elicited by 6-Hz phase-reversing gratings. The parameters which were investigated included the retinal area and energy level of the flash, and the wavelength, spatial frequency, and contrast of the test grating. The effects produced by the Q-switched pulses at 50% of the maximum permissible exposure (MPE) were smaller in magnitude than those produced by the longer duration argon flashes. The reduced effects of the Nd-2 pulses were attributed to the lower energy contained in these flashes, as dictated by the MPE standards. In other respects, the Nd-2 flash effects closely paralleled the argon effects. The results of the various experiments suggest that VEP decrements produced by long and short flashes are similar at equal energy levels, despite the fact that the shorter flashes are believed to produce considerably less pigment bleaching.
Animals↗
Effects of the free radical generator paraquat on differentiation, superoxide dismutase, glutathione and inorganic peroxides in microplasmodia of Physarum polycephalum.
The herbicide paraquat was used to investigate the effects of oxidative stress on the spherulation of Physarum polycephalum microplasmodia. The responses of a white non-differentiating strain of Physarum were compared with those of a common yellow strain that readily spherulates in salts-only starvation medium. The addition of paraquat to the salts medium increased the specific activity of superoxide dismutase in both strains; it also induced an increase in the intracellular inorganic peroxide concentration in both strains. Glutathione concentration was higher in the paraquat-treated yellow strain than in the controls. Paraquat had no effect on glutathione concentration in white microplasmodia. Paraquat accelerated spherulation in yellow microplasmodia. The white microplasmodia responded to the herbicide by cleaving into structures similar to immature spherules; however, these structures were not viable. The results of this study support the hypothesis that free radicals are involved in cell state transitions.
Free Radicals↗
Biosynthesis and processing of pro-opiomelanocortin-derived peptides during fetal pituitary development.
We have investigated the molecular weight forms of pro-opiomelanocortin (POMC)-derived peptides present in rat pituitaries during fetal and early postnatal development (embryonic Day 14 to 3 day neonate). At all early ages examined, the major immunoreactive form of corticotropin (ACTH) was POMC. Only during late fetal and early postnatal stages did progressively larger amounts of 4.5K ACTH, a major POMC processing end product, appear. This form was found almost exclusively in isolated anterior lobes. In contrast, 3.5K size endorphin(s), another POMC derivative, were present in whole glands even at early stages (Day 14), and were the major POMC derivative(s) found in isolated intermediate-posterior lobes of older fetuses. Despite the early appearance of 3.5K endorphin(s), alpha-MSH did not appear until Day 19 and was detected only in isolated intermediate-posterior lobes. We have also cultured dispersed fetal pituitary cells in the presence of radioactive amino acids. After immunoprecipitation using affinity-purified antisera, followed by fractionation of the radiolabeled products, we found that POMC biosynthesis does occur in cultures of Day 14 embryonic pituitary cells, and that the major POMC-derived end product produced is 3.5K size endorphin(s). These findings demonstrate that POMC is synthesized at least by Day 14 of rat pituitary development and that lobe-specific processing characteristic of the corresponding adult lobe is apparent at the earliest stages that the lobes can be separated. The presence of 3.5K-sized endorphins at early ages is consistent with the possibility that POMC synthesis first occurs in the intermediate lobe. The noncoordinate appearance of alpha-MSH, 1-39 ACTH, and endorphins implies that the activities of certain cleavage enzymes and acetylation enzymes responsible for lobe-specific post-translational POMC processing may be expressed at different times during development.
Adrenocorticotropic Hormone↗