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Biomedical subjects

T J Nelson

Publications and source records attributed to T J Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1988

Irradiating with a prosthesis or metal pin in the radiation treatment field.

This is a case study of a patient who had a liposarcoma of the tibia and also had a titanium pin directly in the treatment field. A total midline dose of 63 Gy was prescribed. The effects of the pin in the treated area was examined. Four different methods were used to examine and verify the delivered dose: (1) Treatment planning computerized isodose curves, (2) A parallel plate ion chamber and polystyrene phantom, (3) TLD, and (4) Film dosimetry. The results from all four methods of dose examination are compiled and are used to make a decision on what to do about the dose non-uniformity due to the dense titanium pin. If a prosthesis or metal pin is in the treatment area, one must determine the composition of the pin. Then one should verify or examine the results of the dose perturbations produced. One may or may not want to change the original dose prescription but the dose throughout the irradiated volume will be changed due to the metal pin. It is important to evaluate these effects, as discussed in this article, to accurately deliver a prescribed dose.

Bone Nails↗
PubMed1988

Prolonged RNA changes in the Hermissenda eye induced by classical conditioning.

The incorporation of 32P into mRNA and the total amount of mRNA were increased 3- to 4-fold in eyes isolated from Hermissenda crassicornis trained to associate light with rotation on a turntable compared with animals trained with equal numbers of light and rotation events presented randomly and with naive animals. Incorporation of 32P into poly(A)- RNA was reduced by as much as 60%. The RNA changes were strongly correlated with the degree of learning and could not be accounted for by changes in [32P]ATP content. The RNA changes were maximal at 24 hr and were still detectable after 4 days, indicating that associative conditioning produces a period of increased DNA transcription that could be an intermediate step in memory consolidation. The RNA changes may in part account for recently observed conditioning-specific changes in the synthesis rates of specific proteins.

Analysis of Variance↗
PubMed1987

In vivo metabolism of the cardiovascular toxin, allylamine.

Previous evidence from this laboratory demonstrated that allylamine, a known cardiovascular toxin, is metabolized in vitro to acrolein, which has been hypothesized to act as a distal toxin. In this study, 3-hydroxypropylmercapturic acid was isolated and identified by MS, NMR, and 2D-NMR spectroscopy as the sole urinary metabolite of allylamine metabolism in vivo. Parallel experiments showed reduced glutathione (GSH) depletion in several organs (most marked in aorta, blood, and lung), which is consistent with GSH conjugation of the proposed acrolein intermediate. These findings indicate that allylamine was metabolized in vivo to a highly reactive aldehyde which was converted to a mercapturic acid through a GSH conjugation pathway; the exact mechanisms of cellular damage remain unclear.

Acetylcysteine↗
PubMed1987

Activation of rat caudate tyrosine hydroxylase phosphatase by tetrahydropterins.

Tyrosine hydroxylase phosphatase activity in rat caudate nucleus was separated into three peaks by chromatography on DEAE-cellulose. [32P]Tyrosine hydroxylase phosphorylated by cyclic AMP-dependent protein kinase was dephosphorylated only by the major peak eluting at 0.3 M NaCl, while tyrosine hydroxylase phosphorylated by Ca2+-calmodulin-dependent protein kinase was also dephosphorylated by two calcium-inhibited phosphatases. The Vmax of the enzyme in the major DEAE peak was increased by 10 microM tetrahydrobiopterin (BH4) from 0.78 to 5.0 fmol min-1 mg-1 while the Km was only slightly affected, increasing from 45 to 62 pM. The activation could not be reversed by dilution. On Sephadex G-200, the enzyme was found to consist of two major forms with molecular masses of 420 and 100 kDa. In contrast to the activation of liver phosphatases by freezing with beta-mercaptoethanol, activation by tetrahydrobiopterin was not associated with a shift in the molecular weight of the phosphatase to lower molecular weight forms. Other reduced pterins, including tetrahydroneopterin, 6-methyltetrahydropterin, and 5-methyltetrahydrofolate, also activated the enzyme, while oxidized pterins had no effect. GTP, the metabolic precursor of tetrahydrobiopterin, was a potent inhibitor of the phosphatase reaction, inhibiting by 65% at a concentration of 1 microM. These findings suggest a close regulatory interrelationship between the tetrahydrobiopterin synthetic pathway and catecholamine biosynthesis.

Animals↗
PubMed1987

Interaction of tyrosine hydroxylase with ribonucleic acid and purification with DNA-cellulose or poly(A)-sepharose affinity chromatography.

Tyrosine hydroxylase in bovine adrenal medulla was activated up to fourfold by incubation with low concentrations (15 micrograms/ml) of ribonucleic acids. At higher RNA concentrations, enzyme activity was inhibited. This interaction with RNA was exploited with the use of poly(A)-Sepharose and DNA-cellulose to effect a rapid purification of stable tyrosine hydroxylase from rat brain and bovine adrenal medulla in high yield (up to 58%). With the purified rat brain enzyme, RNA acted as an uncompetitive inhibitor, a concentration of 15 micrograms/ml lowering the Vmax of tyrosine hydroxylase from 1050 to 569 nmol min-1 mg-1 and lowering the Km for tyrosine from 6.1 to 3.6 microM. With the natural cofactor, tetrahydrobiopterin (BH4), two Km values were obtained, indicating the presence of two forms of the enzyme. Both Km values were decreased only slightly by RNA. The purified brain and adrenal enzymes both contained about 0.07 mol of phosphate/63,000-Da subunit; in both cases, cyclic AMP-dependent protein kinase catalyzed the incorporation of an additional 0.8 mol of phosphate/subunit. The purified enzyme also contains ribonucleic acid, which comprises about 10% of the total mass and appears to be important for full activity.

Animals↗
PubMed1987

Two enzymatic methods for determination of the phosphate content of phosphoproteins.

Two new enzymatic methods are described for the determination of the amount of inorganic phosphate covalently bound to macromolecules. In the first method, the inorganic matter obtained after ashing is incubated with [1-14C] pyruvate in the presence of pyruvate oxidase and the enzymatically formed 14CO2 is collected. The other method uses glycogenolytic enzymes to generate NADH which is then measured fluorometrically. The use of these two phosphate-dependent enzymes allows the measurement of phosphate at up to 1000 times greater sensitivity than is obtainable with the phosphomolybdic acid method, thus permitting phosphate analyses to be performed on microgram quantities of proteins.

Molybdenum↗
PubMed1987

In vivo-like drug responses of human tumors growing in three-dimensional gel-supported primary culture.

An in vitro test of cell sensitivity to drugs that indicates in vivo response is an important need in cancer therapy and cancer drug development. Toward this end, we previously developed a collagen gel-supported culture system for growth of human tumors. This three-dimensional culture system is general and grows tumors at high frequency directly from surgery or biopsy that maintain important in vivo properties in vitro, including tissue architecture. We report here that with autoradiographic techniques measuring cellular DNA synthesis the drug responses of individual cells within the tissue structure of in vitro-grown tumors can be determined. Twenty tumor classes, including all the major ones, have been measured in toto at greater than 50% frequency. Quantitative and qualitative results show increasing cell kill with rising cytotoxic drug concentration, differential drug sensitivities of multiple cell types within individual cultured tumors, differential sensitivities of a series of tumors of the same histopathological classification to a single drug, differential sensitivities of individual tumors to a series of drugs, and sensitivity patterns of various tumor types similar to the sensitivities found in vivo. Therefore, the results indicate that potentially important therapeutic data can be obtained from tumor specimens growing in vitro for the individual cancer patient as well as for rational and relevant screening for new agents active against human solid tumors.

Antineoplastic Agents↗
PubMed1983

A neural network model for cognitive activity.

A consideration of the storage of information as an energized neuronal state leads to the development of a new type of neural network model which is capable of pattern recognition, concept formation and recognition of patterns of events in time. The network consists of several layers of cells, each cell representing by connections from the lower levels some combination of features or concepts. Information travels toward higher layers by such connections during an association phase, and then reverses during a recognition phase, where higher-order concepts can redirect the flow to more appropriate elements, revising the perception of the environment. This permits a more efficient method of distinguishing closely-related patterns and also permits the formation of negative associations, which is a likely requirement for formation of "abstract" concepts.

Association Learning↗
PubMed1982

Allylamine cardiotoxicity--IV. Metabolism to acrolein by cardiovascular tissues.

Acrolein was detected in homogenates of rat aorta, lung, skeletal muscle, and heart incubated with allylamine. Semicarbazide and hydralazine, which protect against allylamine-induced myocardial injury in vivo in the rat, inhibited acrolein formation. Hydrogen peroxide, a product of oxidative deamination, was generated during allylamine oxidation. Acrolein was also produced from allylamine by bovine plasma amine oxidase and porcine kidney diamine oxidase but not by rat liver or brain homogenates. Allylamine competitively inhibited benzylamine oxidation in rat aorta, but pargyline-sensitive monoamine oxidase was not involved in acrolein production. The high activity in aorta, the competition with benzylamine, and the sensitivity to benzylamine oxidase inhibitors indicate that benzylamine oxidase is the active enzyme in oxidizing allylamine. The formation of acrolein may be the basis of the cardiotoxic action of allylamine.

Acrolein↗
PubMed1980

Allylamine cardiotoxicity: II. Histopathology and histochemistry.

The progression of cardiac lesions induced in the rat by allylamine administration (0.1% in drinking water) was studied histopathologically and histochemically. Early changes (4-8 days) consisted of piecemeal acute apical and subendocardial myocardial necrosis with morphologic features of coagulation necrosis and myocytolysis. These early lesions progressed and coalesced; resolution of the subendocardial necrosis was associated with remarkably proliferative fibroblastic tissus. Late lesions (21 days to 3 months) consisted of extensive dense fibrous tissue with adjacent continuing focal necrosis and organization. Although vascular alterations were not present during the early course of injury, after 21 days an exuberant proliferation of cells, predominantly within the intima of intramyocardial smaller arteries and not associated with total occlusion or thrombosis, became evident. Other late lesions included rare intraventricular mural thrombi and cartilagenous metaplasia of trabeculae carnae. Early histochemical alterations (3 days) included focal myocardial cell "calcification," demonstrated by the alizarin red S stain, and increased monoamine oxidase (MAO) staining in apical subendocardium and periarterial myocytes. As necrosis continued and fibrosis developed (7-21 days) MAO dramatically increased in pericicatricial and periarterial cells. Biochemical measurement of myocardial MAO showed an initial drop in activity, followed by a steady rise to high activity (21 days), especially toward a Type "B" MAO substrate. Although there are many similarities between allylamine-induced myocardial necrosis and ischemic or catecholamine-induced myocardial damage, other unusual findings-especially the early histochemical and chemical MAO alterations and the proliferative late vascular and cicatricial lesions-suggest that the primary pathophysiologic effect of allylamine, mediated through the MAO system, is on the medial smooth muscle of intramyocardial arteries.

Allylamine↗
PubMedDate not supplied

Specific protein changes during memory acquisition and storage.

Changes in several distinct types of neuronal proteins are now known to be associated with learning. In this review, we will summarize the properties of these proteins and relate these properties to prominent theories of the biochemical basis of memory.

Animals↗
PubMedDate not supplied

How protective are respirator assigned protection factors: an uncertainty analysis.

This investigation evaluated the risk of overexposure for a selected assigned protection factor by performing Monte Carlo simulations. A model was constructed to assess respirator performance by calculating the concentration inside the respirator. Estimates of the factors that affect respirator performance were described as distributions. The distributions used a worst case estimate for concentration in the workplace, the worst case for respirator performance (the fifth percentile person), and the worst case for exhalation valve leakage. A Monte Carlo analysis then provided estimates of the percentage of time that concentration inside the respirator exceeded the occupational exposure limit (OEL). For a half-facepiece respirator with an APF of 10, the calculations indicated a low risk of being exposed above an OEL, with mean exposures being controlled well below an OEL.

Humans↗
PubMedDate not supplied

Workplace protection factors--supplied air hood.

Several organizations list assigned protection factors. For supplied air hoods, the value of the assigned protection factors varies from <10 to 2,000 depending on the organization. Workplace protection factors (WPFs) of a supplied air hood were measured during aircraft sanding and painting operations on several types of aircraft to evaluate whether the American National Standard Z88.2 (1992) assigned protection factor of 1,000 was realistic. The primary contaminant during these activities is strontium chromate. Samples collected inside the hood show that employees during sanding and painting operations were not exposed to strontium. The respirator performed adequately. This study is consistent with other simulated and WPF studies in that the ANSI Z88.2 WPF of 1,000 is supported.

Aircraft↗
PubMedDate not supplied

The effect of inhalation resistance on facepiece leakage.

Air purifying respirators use filters to remove particulate air contaminants. Resistance to airflow generally increases as the filter loads and a "filter cake" is formed. It has been recommended by ANSI and the Occupational Safety and Health Administration that filters should be replaced when the wearer notices they are hard to breathe through. Repeated faceseal leak rate measurements were made during respiratory wear over a range of simulated breathing resistances from 5.6 to 19.6 mm (0.22 to 0.77 inches) of water. The measured faceseal leak rates increased as the breathing resistance increased and varied depending on the initial leak rate at the 5.6 mm pressure. The increase in faceseal leak rate from 5.6 to 19.6 mm breathing resistance was as high as a factor of 4. Theoretically, a person with an initial respirator penetration of 2.5% could have that value increase to 10% as filter loading increased breathing resistance by 14 mm. Some research has shown that breathing resistances between 60 and 140 mm of water would be "noticeable but well tolerated." It is not known if workers would be able to detect an increase in breathing resistance that would lead to a significant increase in faceseal leakage. These data suggest a need to establish a replacement schedule for all filters used in the workplace. How often a filter should be replaced is difficult to determine. Breathing resistance would vary depending on the individual filter and aerosol loading characteristics, the concentration of the aerosol in the workplace, and breathing rates.

Air Pollutants, Occupational↗