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Biomedical subjects

T L Miller

Publications and source records attributed to T L Miller.

124 records · Page 7Linked to original sources

Formation of hydrogen and formate by Ruminococcus albus.

Radioisotopic growth studies with specifically labeled (14)C-glucose confirmed that Ruminococcus albus, strain 7, ferments glucose mainly by the Embden-Myerhof-Parnas pathway to acetate, ethanol, formate, CO(2), H(2), and an unidentified product. Cell suspensions and extracts converted pyruvate to acetate, H(2), CO(2), and a small amount of ethanol. Formate was not produced from pyruvate and was not degraded to H(2) and CO(2), indicating that formate was not an intermediate in the production of H(2) and CO(2) from pyruvate. Cell extract and (14)C-glucose growth studies showed that the H(2)-producing pyruvate lyase reaction is the major route of H(2) and CO(2) production. An active pyruvate-(14)CO(2) exchange reaction was demonstrable with cell extracts. The (14)C-glucose growth studies indicated that formate, as well as CO(2), arises from the 3 and 4 carbon positions of glucose. A formate-producing pyruvate lyase system was not demonstrable either by pyruvate-(14)C-formate exchange or by net formate formation from pyruvate. Growth studies with unlabeled glucose and labeled (14)CO(2) or (14)C-formate suggest that formate arises from the 3 and 4 carbon positions of glucose by an irreversible reduction of CO(2). The results of the studies on the time course of formate production showed that formate production is a late function of growth, and the rate of production, as well as the total amount produced, increases as the glucose concentration available to the organism increases.

Bacteria↗

Evaluation of neutralized chemical agent identification sets (CAIS) for skin injury with an overview of the vesicant potential of agent degradation products.

Vesication and skin irritation studies were conducted in hairless guinea-pigs to determine the vesicant and skin irritation potential of chemically-neutralized Chemical Agent Identification Sets (CAIS). The CAIS are training items that contain chemical warfare-related material--sulfur mustard (HD), nitrogen mustard (HN) or lewisite (L)--and were declared obsolete in 1971. Animals were dosed topically with 'test article'--neat HD, 10% agent/chloroform solutions or product solutions (waste-streams) from neutralized CAIS--and evaluated for skin-damaging effects (gross and microscopic). Product solutions from the chemical neutralization of neat sulfur mustard resulted in microvesicle formation. All agent-dosed (HD or agent/chloroform solutions) sites manifested microblisters as well as other histopathological lesions of the skin. Waste-streams from the neutralization of agent (agent/chloroform or agent/charcoal) were devoid of vesicant activity. Cutaneous effects (erythema and edema) were consistent with the skin-injurious activity associated with the neutralizing reagent 1,3-dichloro-5,5-dimethylhydantoin (DCDMH). Chemical neutralization of CAIS was effective in eliminating/reducing the vesicant property of CAIS containing agent in chloroform or agent on charcoal but was inefficient in reducing the vesicant potential of CAIS containing neat sulfur mustard.

Animals↗

Effect of hydroxychlorodiphenyl ethers (chlorinated pre-and isopredioxins) on erythrocyte membrane adenosinetriphosphatase activity.

The effect of hydroxychlorodiphenyl ethers (HO-ClX-DPEs; chlorinated pre- and isopredibenzodioxins), contaminants of technical chlorophenol preparations, on human erythrocyte membrane-bound adenosinetriphosphatases (ATPases) has been investigated. Both 2- and 3-HO-Cl9-DPE inhibited the Na+ + K+-activated, Mg2+-dependent ATPase (Na+, K+, Mg2+-ATPase). The Mg2+-dependent ATPase (Mg2+-ATPase) was stimulated at lower concentration of these compounds, but at higher concentrations there was a gradual decrease in the extent of stimulation, 2-Hydroxy-21, 41, 41-trichlorodiphenyl ether (2-HO-Cl3-DPE; Irgasan DP-300; Triclosan) was not as effective as the nonachloro compounds at inhibiting Na+, K+, Mg2+-ATPase and was inactive at stimulating Mg2+-ATPase. Pure pentachlorophenol (PCP) caused both inhibition of Na+, K+, Mg2+-ATPase and stimulation of Mg2+-ATPase, although each effect required a higher concentration of PCP than was needed for the HO-CL9-DPEs. The possible relationship of the effects of HO-CL x-DPEs on human erythrocyte membrane ATPase activities to the potent hemolytic activity of these compounds is discussed.

Adenosine Triphosphatases↗

The acute toxicity of nonachloropredioxin and 3- and 4-hydroxynonachlorodiphenyl ether in mice.

The acute intraperitoneal LD50 values of hydroxynonachlorodiphenyl ethers (HO-Cl9-DPEs) in mice have been determined. The acute toxicity of each of these compounds is compared with that of pentachlorophenol (PCP) and 2-hydroxy-2',4,4'-trichlorodiphenyl ether (2-HO-Cl3-DPE; Irgasan DP-300; Triclosan), a commonly used bactericide. The order of acute toxicity observed was: 2-HO-Cl9-DPE greater than technical PCP approximately equal to pure PCP greater than 3-HO-Cl9-DPE greater than 4-HO-Cl9-DPE greater than 2-HO-Cl3-DPE. Symptomatology following exposure to the HO-Cl9-DPEs was similar to that observed for PCP, a known uncoupler of oxidative phosphorylation. 2-HO-Cl3-DPE, however, produced clinical signs suggestive of a suppressive effect on the central nervous system. Data on time response following a lethal dose of each of these compounds was also obtained.

Animals↗

The acute toxicity of penta-, hexa-, and heptachlorohydroxydiphenyl ethers in mice.

The acute intraperitoneal LD50 values of various hydroxychlorodiphenyl ethers (HO-ClX-DPEs; X = 5-7) in mice have been determined. The acute toxicities observed were on the order of, or slightly less than, that observed previously for 2-hydroxy-2',4,4'-trichlorodiphenyl ether (2-HO-Cl3-DPE; Irgasan DP-300; Triclosan), a commonly used bactericide. However, the acute toxicities determined for these compounds were substantially less than have been observed for HO-Cl9-DPEs and pentachlorophenol. The HO-ClX-DPEs had a marked hypothermic effect, similar to that produced by 2-HO-Cl3-DPE. Symptomatology following exposure to the HO-ClX-DPEs (X = 5-7) suggested a nonspecific depressant effect on the central nervous system.

Animals↗

Effects of acute gastric distention and recovery on tendency for ventricular arrhythmia in dogs.

The gastric distention-volvulus (GDV) syndrome occurs commonly in large-breed dogs and may prove fatal in 15-68% of cases. Approximately 43% of cases with gastric distention (GD) or volvulus develop cardiac arrhythmias that can contribute to mortality. Most of these arrhythmias are ventricular in origin and ventricular fibrillation (VF) may be the cause of death. This study used an iatrogenic model of acute GD to investigate the prevalence of ventricular arrhythmias during acute GD and its recovery, if programmed electrical stimulation (PES) may uncover tendency to VF, if the Q-T interval corrected for heart rate (Q-Tc) of the electrocardiogram (ECG) predicts tendency to VF, and if hemodynamic changes predate VF. Eleven beagles, anesthetized with morphine and alpha-chloralose, and instrumented so that vascular pressures, cardiac output, and PES could be recorded, were used. Five were unperturbed, whereas acute GD to a pressure of 30 mm Hg for 1.5 hours was produced in 6 others. The results were as follows. No dogs with GD developed spontaneously occurring arrhythmias. VF was produced in no dogs by conventional PES, but occurred in all dogs (P < .05) with GD and none of the controls, using accelerated ventricular pacing. The Q-Tc interval of the ECG prolonged minimally in dogs with GD, and shortened (P < .05) in controls. Some hemodynamic changes did predate VF. In conclusion, dogs with acute GD have a tendency for VF, which may be uncovered by accelerated PES. The mechanism for the vulnerability to arrhythmia with GD is unknown.

Acute Disease↗

Interaction of hydroxychlorobiphenyls--polychlorinated biphenyl metabolites--with the human erythrocyte membrane.

Effects of hydroxychlorobiphenyls (polychlorinated biphenyl metabolites) and chlorobiphenyls on membranes have been studied with the human erythrocyte membrane as a model. Many of the hydroxychlorobiphenyls are very effective hemolytic agents, whereas the parent chlorobiphenyls are generally quite ineffective at inducing hemolysis. The hemolytic potency of the hydroxychlorobiphenyls varies with the degree of chlorination and, more importantly, with the position of the chloro- and hydroxy- substituents. At lower concentrations, the hydroxychlorobiphenyls protect the erythrocyte against hypotonic hemolysis, while they induce hemolysis at higher concentrations. In the range of concentrations of each hydroxychlorobiphenyl required for maximum protection, the erythrocytes exist in altered morphological forms as opposed to normal discocytes. The chlorobiphenyls at lower concentrations also protect the erythrocytes from hypotonic hemolysis, but they do not induce hemolysis at higher concentrations. These studies suggest that products of the metabolism of chlorobiphenyls may be more biologically active than the parent compounds themselves. Effects on membranes may thus play a role in the mammalian toxicity of the hydroxychloro- and chlorobiphenyls.

Erythrocyte Membrane↗

Complex criticism.

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Humans↗