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Biomedical subjects

R A Floyd

Publications and source records attributed to R A Floyd.

178 records · Page 10Linked to original sources
PubMed1971

Investigation of respiratory and ion transport properties of aging bean stem slices.

Ion and oxygen uptake were studied on aging bean stem slices. Oxygen uptake was high immediately after slicing, decreased to a minimum at 100 minutes, and then increased again. Ion uptake per unit of O(2) uptake data suggested that metabolic energy was utilized almost exclusively for sodium transport in fresh tissue but was diverted to potassium transport as the slices aged. Oxygen and ion uptake in fresh slices was less sensitive to 2,4-dinitrophenol as compared to the aged slices, indicating major metabolic and physiological changes occurred during aging. This was further substantiated by the tissue response to cyanide and antimycin A. Oxygen uptake was decreased by cyanide (22% by 1 mm) and antimycin A (14% by 1 microgram per milliliter) in fresh slices but not in aged slices. Potassium uptake that developed during aging was sensitive to cyanide and antimycin A. The results are pertinent to understanding the role of the stem in regulating ion transport in plants.

Journal Article↗
PubMed1970

Influence of calcium on sodium and potassium absorption by fresh and aged bean stem slices.

The influence of Ca on the aging processes of bean stem (Phaseolus vulgaris) slices and on the absorption of K and Na by fresh and aged slices was investigated. In the presence of Ca, fresh tissue showed a preferential Na uptake. The preference for Na over K resulted from a differential depressive effect of Ca on absorption of these two ions. In aged tissue Na uptake was also depressed, but K absorption was accelerated, with a net result of a much greater absorption of K than Na.The presence of Ca in the aging medium promoted the development of K-absorbing capacity as well as an increase in the rate of respiration but did not influence the loss of capacity to absorb Na as tissue aged. This, along with the demonstration that protein synthesis is involved in the development of K-absorbing capacity by aging tissue, suggests that Ca may have an effect on basic physiological processes concerned with development of ion absorption by aging tissue. The influences that Ca may have on the physical and physiological aspects of ion transport are discussed.

Journal Article↗
PubMedDate not supplied

ESR spin trapping studies on the OH* free radical reactions of idebenone.

Experiments have been performed using oxidized (ID-O) and reduced (ID-H) idebenone in various spin trapping systems. The following results were obtained. (1) ID-O does not have any detectable scavenger effect on the OH* free radicals when they are generated by means of Fenton reaction and trapped using DMPO, PBN or 4-POBN. (2) ID-H represents a serious competition for all spin traps used in capturing OH* free radicals. The mechanism of this competition is, however, not a direct reaction, but it is based on the rather quick autoxidation of the dissolved ID-H generating O2(-*) radicals. They interact with the OH* radicals (or with the OH-spin adducts) by means of electron donation to them. This statement has been proven by showing (i) that O2* radicals generated during the autoxidation of ID-H can directly be trapped on DMPO; (ii) the effect of ID-H on the OH* free radicals is abolished if SOD is added to the system; (iii) the O2(-*) radicals generated by ID-H autoxidation reduce directly the OH-spin adducts on various kinds of nitroxide type spin traps (e.g. TEMPO, TMPN). (3) The rate of autoxidation of ID-H in solution is about an order of magnitude faster than that of ubiquinone. Similar differences could be observed in the rate of reduction of the oxidized forms of both compounds by Na-borohydride. The results fully explain the in vitro protective effect of ID-H against lipid peroxidation of artificial membranes.

Journal Article↗
PubMedDate not supplied

Age influence on oxidative events during brain ischemia/reperfusion.

Brain readily undergoes oxidative damage if it is organizationally disrupted. Iron plays a catalytic role in mediating oxidative damage in brain homogenate. Utilizing several methods to assess oxidative events, including salicylate trapping of hydroxyl free radicals, spin-trapping of free radicals and quantitation of protein oxidation, we have clearly demonstrated that oxidative events do occur in the ischemia/ reperfusion lesioned Mongolian gerbil brain. In the gerbil model, ischemia/reperfusion insult (IRI) mediated protein oxidative damage is accompanied by a concomitant loss of glutamine synthetase activity. The loss of glutamine synthetase activity may possibly lead to the build-up of glutamate, an excitotoxic amino acid which has been strongly implicated in the neuronal death observed in hippocampus following an IRI. The brain homogenate from an IRI-lesioned animal is more susceptible to peroxidation than comparable sham-operated control animals. We have discovered that an IRI causes lethality in older gerbils more readily than in younger gerbils. We have also found that the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) protects gerbils from an IRI. Data are presented which implicate that an IRI may seriously impair the energy production capacity of older gerbils more than comparable oxidative stresses in younger animals. We hypothesize that energy production capacity and its utilization for the synthesis of new gene products may be key events which help mediate survival from an IRI. In addition we hypothesize that higher brain functions, including memory and learning are inversely correlated with oxidative damage in the brain. The elucidation of the mechanisms involved in this fascinating area of research and the design of new protective agents to prevent oxidative damage in brain is a most exciting challenge.

Journal Article↗
PubMedDate not supplied

The effects of the molecular environment on the kinetics of catalase reaction and its relevance to cell aging.

Catalase-mediated oxygen evolution from H(2)O(2) was measured with a Clark electrode in a closed, buffered aqueous medium in a properly designed experimental model. Addition of various molecules (bovine serum albumin, egg albumin, dextrane, starch and PEG-8000) in increasing concentrations up to greater than 20% by volume decreased the rate of oxygen evolution in a linear fashion, although there were some quantitative differences between the effects of various components. The rotational correlation time of the spin label TMPN in BSA and egg albumin increased considerably in both protein solutions indicating a very significant increase of the microviscosity of these media. The results are interpreted in terms of the molecular enzyme kinetic model (MEKM) predicting that apart from microviscosity, the average mass distribution and the distance of the nearest two lattice points formed by components of the medium are also inversely proportional to both the forward and backward rate constants of the formation of the enzyme-substrate complex. These observations, on one hand, lend further experimental support to the MEKM and on the other one, are consistent with the membrane hypothesis of aging which explains the loss of cell functions by an age-dependent increase of intracellular density.

Journal Article↗
PubMedDate not supplied

Age effect on brain pH during ischemia/reperfusion and pH influence on peroxidation.

Older gerbils are more sensitive to ischemia/reperfusion injury (IRI) than younger ones. Utilizing 31P-NMR to monitor in vivo pH and high energy phosphates of brain cortex undergoing an IRI showed that cortical intracellular pH decreased to 6.35 after ischemia and then increased with reperfusion, but older gerbils required significantly more time to recover than younger animals. Brain high energy phosphates dropped during ischemia but rebounded within 20 min reperfusion in younger gerbil brain but remained significantly lower in older gerbil brain for 50 min. These data suggest that IRI-induced brain acidification may enhance oxidative damage. In an in vitro system it was shown in both young and old brain homogenate that peroxidation rate increased when the pH of the incubation medium was decreased from 7.4 to 6.4. This was true in the presence or absence of an ADP/Fe/Ascorbate system in both young and old brain homogenate. Enhancement of peroxidation rate by ADP/Fe/Ascorbate addition was much more pronounced at pH 7.4 (30- to 40-fold increase) as compared to pH 6.4 (7.8- to 9.5-fold increase). This data can be interpreted to indicate that the lower pH makes endogenous Fe more available to catalyze oxidative damage. The fact that brain pH and high energy phosphates remain lower in older gerbil brains during IRI suggests that brain mitochondria from older animals are less capable of responding to a large oxidative stress brought on by an IRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMedDate not supplied

Factors influencing collagen-induced autoimmune ear disease.

In 1981, the authors described a type II collagen-induced autoimmune ear disease (CIAED) model. The purpose of this study was to gather further evidence that this is a sound animal model to use in evaluating inner ear diseases. The temporal bone lesions of CIAED in Lewis and Wistar rats were characterized by the presence of sensorineural hearing loss with mild atrophy of the organ of Corti and spiral ganglion degeneration, vestibular dysfunction with vacuolar degeneration of the crista ampullaris, otospongiosis-like lesions in the tympanic annules, cochlear vasculitis, and eustachian tube disease. Both cellular and humoral immune responses to type II collagen were demonstrated. The induction of ear lesions depends on many factors. In general, animals immunized with antigens in complete Freund's adjuvant showed relatively more severe lesions than animals immunized with antigens in incomplete Freund's adjuvant, but the duration of the immunization seems to be a more important factor in reproducing severe lesions. The strain and the source of the animals are also important factors in autoimmune inner ear diseases, as is the condition of the host animals. Subclinical or clinical mycoplasma infection in the rat markedly reduced the incidence and severity of lesions in type II collagen-induced arthritis. Many researchers did not consider sialoductal adenovirus, widely present among laboratory rats, a lesion-producing factor in rats. Although many factors influence the induction and severity of CIAED, these animal models provide an excellent new avenue of inner ear research.

Animals↗
PubMedDate not supplied

Enchondral cartilage rests collagen-induced autoimmunity: a possible pathogenetic mechanism of otosclerosis.

Collagen autoimmunity has been suggested as one etiologic mechanism to otosclerosis. Although substantial studies relating this disease to collagen autoimmunity have been reported, a basic understanding of the pathogenic mechanism involved is lacking. Some otosclerosis patients have a high level of antibody to type II collagen. In addition, complement and antibody were deposited in the stapes from otosclerosis patients. Furthermore, the otic capsule and stapes have been found to contain type II collagen by immunohistologic studies and biochemical analysis. Otospongiosis-like lesions have also been produced in rats by immunizing them with type II collagen. This finding led us to postulate a hypothesis of an autoimmunity to type II collagen as an etiopathogenesis of this illness. Our initial hypothesis has been updated to incorporate new findings in the field of cell biology. The role of interleukin 1, osteoclasts, osteoblasts, bone resorption, and other factors such as minor collagens, calcitonin, vitamin D, parathyroid hormone, collagenase, and prostaglandins are incorporated in this updated hypothesis.

Animals↗
PubMedDate not supplied

Reaction of chromium (VI) with hydrogen peroxide in the presence of glutathione: reactive intermediates and resulting DNA damage.

The reaction of chromium(VI) with hydrogen peroxide was studied in the presence of glutathione. In vitro, reaction of chromium(VI) with hydrogen peroxide alone led to production of hydroxyl radical as the significant reactive intermediate, while reaction of chromium(VI) with glutathione led to formation of two chromium(V)-glutathione complexes and the glutathione thiyl radical. Incubation of chromium(VI) with glutathione prior to addition of hydrogen peroxide led to formation of peroxochromium(V) species and a dramatic increase in hydroxyl radical production over that detected in the reaction of chromium(VI) with hydrogen peroxide alone. In contrast, addition of chromium(VI) to a preincubated mixture of glutathione and hydrogen peroxide led to a decrease in hydroxyl radical production over that obtained in the reaction of chromium(VI) with hydrogen peroxide. When pBR322 DNA was added to the above reactions, the extent of chromium(VI)-induced DNA strand breakage correlated with the relative amount of hydroxyl radical formed. Reaction of chromium(VI) with calf thymus DNA in the presence of a preincubated mixture of glutathione and hydrogen peroxide led to detection of the 8-hydroxydeoxyguanosine adduct, whose formation correlated with that of hydroxyl radical production. No significant chromium-DNA adduct formation was detected. The results suggest that, in the cellular metabolism of chromium(VI), preformed chromium(V)-glutathione complexes may react with hydrogen peroxide in a Fenton-type manner to produce hydroxyl radical as the DNA-damaging agent. However, if glutathione reacts with hydrogen peroxide prior to exposure to chromium(VI), the amount of hydroxyl radical generated may not be sufficient to cause significant DNA damage.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2'-Deoxyguanosine↗
PubMedDate not supplied

Serum concentrations of 5-FU, ftorafur, and a major serum metabolite following ftorafur chemotherapy.

Daily 24-hour serum levels of ftorafur (FT), 5-FU, and a major FT metabolite, dehydroftorafur (DFT), were monitored by high-performance liquid chromatography as part of a phase I study designed to evaluate FT as a radiosensitizing 5-FU pro-drug in patients with advanced gastrointestinal cancers. At a daily iv bolus FT dose of 1.0 g/m2, 5-FU was not detected in serum concentrations above the reliable assay limits of approximately 25 ng/ml; FT did not generate the extracellular (serum) 5-FU concentrations required for sensitization by 5-FU per se. DFT was present in every patient serum tested and was confirmed to be a metabolite of FT by in vitro conversion to 5-FU. Chemical ionization solid-probe mass spectrometry of the DFT metabolite indicates the dehydro FT structure proposed by other researchers. In six of eight patients monitored, a consistent relationship was noted between serum levels of FT and DFT.

Chromatography, High Pressure Liquid↗