5-methoxy-N, N-dimethyltryptamine, a possible endogenous psychotoxin.
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Biomedical subjects
Publications and source records attributed to L C Clark.
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Oxygen-sensitive F-19 magnetic resonance imaging of perfluorocarbon compounds requires that fluorocarbon T1 changes correlate with the local PO2 and not with the composition of the surrounding aqueous phase. The influence of various bioconstituents and paramagnetic ions within the aqueous phase on the F-19 fluorocarbon phase T1 for PFC emulsions was evaluated at 0.14 and 0.66 T. T1 was measured for FC-43, perflubron, and a fluorinated surfactant. Controlled variables introduced in the aqueous phase included annex solution constituents, blood, pH changes, and Gd-DTPA. For a constant PO2, the F-19 T1s were independent of the emulsion constituents, blood concentration, and pH. For FC-43 and perflubron, F-19 T1 was independent of the Gd-DTPA concentration, while the aqueous phase T1 decreased by more than an order of magnitude. XMO-10 (smallest emulsion particle size) showed a slight decrease in F-19 T1 with increasing Gd-DTPA concentration at 0.66 T.
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The potential protective effect of selenium status on the risk of developing cancer has been examined in animal and epidemiologic studies. This ecological study investigated the association between U.S. county forage selenium status and site- and sex-specific county cancer mortality rates (1950-1969) using weighted least squares regression. Consistent, significant (p less than .01) inverse associations were observed for cancers of the lung, rectum, bladder, esophagus, and cervix in a model limited to rural counties and for cancers of the lung, breast, rectum, bladder, esophagus, and corpus uteri in a model of all counties. No consistent significant positive associations were observed in the rural county models. This remarkable degree of consistency for the inverse associations strengthens the likelihood of a causal relationship between low selenium status and an increased risk of cancer mortality.
Certain perfluorocarbon (PFC) compounds, commonly used as the oxygen transport components of "blood substitutes," may be breathed as neat liquids with survival because of their chemical inertness and their high solubility for oxygen and carbon dioxide. In addition, the paramagnetism of oxygen reduces the fluorine T1 value according to an inverse relationship allowing a potential method of monitoring PO2 gradients in vivo. This article presents the results of magnetic resonance (MR) imaging of the lungs of mice and rats following breathing of four PFC liquids (FC-43, FC-75, PFOB, APF-215). The images presented were obtained at two magnetic field strengths (0.66 and 0.14 T) under conditions of breathing either ambient air or pure oxygen. Spin-lattice relaxation times (T1) for the PFCs are measured both in vitro and in vivo (in the lungs) as a function of the state of oxygenation. A MR image signal strength enhancement of up to 90% is demonstrated in vivo under conditions of pure oxygen breathing.
Nuclear magnetic resonance (NMR) imaging of perfluorocarbon (PFC) emulsions and neat liquids has shown potential for in vivo oxygen imaging in blood and organ tissue. PFC compounds exhibit complicated NMR spectra caused by chemical shifts and spin-spin couplings which can lead to artifacts and degraded spatial resolution of resulting NMR images. To correct for the chemical shift artifacts, the technique of spectral deconvolution has been applied to NMR imaging of PFC compounds. The temporal filter for this process can be directly applied to raw free induction decay data in projection reconstruction or to spin-echo data in two-dimensional Fourier transform imaging techniques. The effect of chemical shift artifacts was demonstrated through the NMR imaging of two PFC compounds (F-tributylamine and F-decalin) in phantoms. Methods are presented and demonstrated which allow the chemical shift artifacts to be removed and true images of the spatial distribution of the PFC's to be recovered.
The advent of electrochemical sensors for intermittent sampling of blood gases and hydrogen ions in the clinic, intensive care, and surgical units has revolutionized diagnostic and critical care medical technics. The use of electrochemical sensors for continuous transcutaneous monitoring of blood gases is further enhancing the medical surveillance of patients. The more recent introduction of glucose and other electroenzymatic sensors has stimulated broad research in the development of metabolic monitoring. For the present research, the glucose sensor widely used for the rapid specific micro-analysis of whole blood and plasma is explored for possible use as an in vivo intravascular or tissue-implanted sensor. This sensor is based on the polarographic measurement of hydrogen peroxide generated by glucose oxidase (EC 1.1.3.4) held between two membranes. The first membrane allows the diffusion of glucose, ions, and many other small molecules, while the second membrane allows the diffusion of the glucose-generated hydrogen peroxide to the platinum surface, but excludes ascorbic acid, bilirubin, and uric acid. Such sensors respond rapidly and specifically when acutely implanted subcutaneously in cats and dogs. They function well as glucose-sensor-tipped venous catheters. One sensor was repeatedly used for in vitro polarograms, subcutaneous and blood glucose monitoring, over a period of ten months, with storage in the cold between uses, with the complete retention of its response characteristics.
Oxygen tension in the peritoneum has been continuously measured with a Silastic tonometer having an integral oxygen electrode and inlet and outlet tubes for gasequilibrated electrolyte solution. Remote kinetic calibration of the system is periodically performed. Tonometers were implanted in six rabbits. Peritoneal oxygen tension was measured in awake and anesthetized rabbits under various oxygen breathing conditions.
Protection of the enzyme layer of glutaraldehyde vapor-stabilized glucose oxidase-based glucose sensors from attack by proteolytic enzymes and peritoneal macrophages can be accomplished by covering with a regenerated cellulose (viscose) membrane, as commonly used for laboratory dialysis. These implanted sensors are not externally polarized, but continuously consume oxygen and glucose and generate gluconic acid and hydrogen peroxide. On the average (sensors in 45 mice) the activity declines with time, almost vanishing by 600 days. However, the fact that some sensors retain nearly all of their activity for over 500 days indicates that glucose sensors can be made with a life span compatible with the requirements for an artificial pancreas (glucose sensor/insulin pump). Limited observation with similar implanted lactate sensors indicates their life span to be shorter.
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It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group. In addition, proteolytic activity levels in the buccal cells were increased nearly 3-fold in patients with oral trauma (P < 0.01) or diabetes (P < 0.02), as well as pregnant women (P < 0.04). Excluding these subgroups of patients in epidemiological studies increase the differences in levels of proteolytic activities between both the nonsmoking comparison group and smokers and between the comparison group and patients with oral leukoplakia or erythroplakia. Evaluation of prerandomization levels of proteolytic activities of patients in cancer chemoprevention trials will increase the statistical power by allowing stratified randomization based on levels of proteolytic activities. The observed increases in levels of proteolytic activities in tissues at higher than normal risk of cancer development suggest that levels of proteolytic activities should be used as immediate marker endpoints in human cancer prevention trials using protease inhibitors as potential anticarcinogenic agents.
The objective of this cross-sectional study was to determine whether plasma selenium concentration predicts the prevalence of adenomatous polyps of the colon and rectum. The source population for the study was 101 patients undergoing sequential colonoscopies at the Veterans Affairs Medical Center, Tucson, AZ. The study population was then limited to the 48 patients (all male) undergoing their initial colonoscopy who did not have a diagnosis of colorectal cancer. For each of these patients, a prediagnostic fasting plasma selenium concentration was determined. The data from this study suggest that fasting plasma selenium concentrations may be an important risk factor for colorectal adenomas. Patients with fasting plasma selenium concentrations below the median (< 128 mcg/liter) were significantly more likely to have one or more adenomatous polyps (prevalence odds ratio 4.2) and more adenomatous polyps (3.5 times) per patient. There was also a suggestion of a more proximal distribution of adenomatous polyps in the patients with a lower level of selenium. These associations were not confounded by age or smoking. The results of this study are consistent with the experimental animal studies, geographic mortality studies, and prospective cohort studies of selenium and colorectal cancer.