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Biomedical subjects

J L Nelson

Publications and source records attributed to J L Nelson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Partial purification and characterization of a peroxidase activity from human placenta.

Peroxidases can metabolize a variety of xenobiotics to reactive intermediates capable of binding to protein or DNA. The potential role of these enzymes in fetotoxicity has not been explored. In this study, the presence of peroxidase activity was observed in human term and pre-term placenta. Human term placental peroxidase activity (HTPP) was partially purified by concanavalin A affinity chromatography from CaCl2 extracts of the particulate fraction. HTPP appears to be a membrane-bound glycoprotein. Arachidonic acid-dependent oxidation of guaiacol was not observed, suggesting that the peroxidase activity was not due to prostaglandin synthase. Moreover, HTPP preparations were devoid of catalase and spectrally dissimilar from human haemoglobin, cytochrome P-450, eosinophil peroxidase and myloperoxidase, suggesting an endogenous origin. An Mr of approx. 119,000 was determined for HTPP by gel filtration. Cathodic slab-PAGE of cetyltrialkylammonium bromide-solubilized HTPP yielded two peroxidase-staining bands.

Chromatography, Affinity↗
PubMed1990

Evaluation of the 1987 revised criteria for rheumatoid arthritis in a cohort of newly diagnosed female patients.

The revised criteria for the diagnosis of rheumatoid arthritis (RA) were presented in 1987. We tested these criteria on 135 women from a population-based study of patients with newly diagnosed RA. None of the 19 women with probable RA and 100 of the 116 women with definite RA met the 1987 criteria. The 1987 criteria appear to be less sensitive or more specific than the criteria formulated in 1956.

Adult↗
PubMed1990

Tyrosine loading increases dopamine metabolite concentrations in the brain.

Administration of haloperidol (1.5 mg/kg) to rats increased concentrations of dopamine metabolites in the corpus striatum, nucleus accumbens, hypothalamus and amygdala. Treatment of similar rats with various doses (25, 100 or 400 mg/kg) of tyrosine methyl ester in combination with the haloperidol led to additional elevations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the corpus striatum and hypothalamus at the lowest dose tested. Therefore, it is concluded that during periods of increased neuronal activity, as induced by haloperidol, tyrosine availability may become a rate-limiting factor in dopamine metabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Effect of vitamin A in enteral formulae for burned guinea-pigs.

A burned guinea-pig model (30 per cent body surface area) was used to study the effects of dietary vitamin A. Sixty-five female guinea-pigs were infused enterally via gastrostomy feeding tubes with identical formulate (175 kcal/kg/day, 20 per cent of calories as protein) containing varying amounts of vitamin A. Groups I, II, III and IV received formulae containing 0, 10,000 iu (approximately equivalent to the guinea-pigs' RDA), 50,000 iu (5 x RDA) and 250,000 iu (25 x RDA) of vitamin A per litre, respectively. After 14 days of tube feeding, the animals were killed. Group I animals had evidence of vitamin A deficiency including low haemoglobin levels, lower red blood cell counts and lower caecal mucosal weight. Findings of hypervitaminosis A were observed only in animals given the highest dose of vitamin A (25 x RDA). These were elevated serum alkaline phosphatase and complement C3 levels and enlarged adrenal glands. Group IV also showed defective cell-mediated immunity as reflected by reduced delayed cutaneous response to dinitrofluorobenzene. In a second experiment groups I, II, III and IV were given formulas containing 0, 1 x RDA, 5 x RDA, and 10 x RDA of vitamin A respectively for 14 days. Through postburn days 12 to 14 they were injected subcutaneously with 3 x 10(8) of Staphylococcus aureus once daily. On postburn day 15 the animals were killed and the numbers of viable bacteria at each injection site were counted. No significant differences were observed in viable bacterial numbers between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Avoidable claims in the liability experience of Virginia FPs insured by the reciprocal.

In response to the threat of litigation, physicians practice defensive medicine. A more effective means of reducing malpractice liability and improving the quality of patient care is to practice defensible medicine, i.e., those practice patterns that reduce the potential for claims and increase the likelihood that when claims do arise, they can be successfully defended. Unlike hospital-based specialists, family physicians can directly influence a significant portion of their risk of suit. By focusing management time and attention on the factors in their office practices that are linked to malpractice claims activity, family physicians can reduce the likelihood of being involved in claims.

Adult↗
PubMed1989

Possible role of ammonia in experimental cancer anorexia.

Plasma concentrations of ammonia were elevated significantly in tumor-bearing rats prior to the onset of anorexia and continued to increase as the tumor grew and anorexia developed. Associated with this hyperammonemia were elevated levels of brain glutamine and large neutral amino acids (phenylalanine, tyrosine, tryptophan, methionine, histidine). Concentrations of the dopamine metabolites, DOPAC or HVA were elevated in the corpus striatum, nucleus accumbens, hypothalamus and amygdala of anorectic tumor-bearing rats only, while levels of the serotonin metabolite, 5-HIAA, were increased in these brain regions in both anorectic and non-anorectic tumor-bearing rats. Infusing ammonium salts into non-tumor-bearing rats elicited anorexia and alterations in brain amino acid profile and neurotransmitter metabolism that were similar to those observed in anorectic tumor-bearing rats. Therefore, we conclude that ammonia released by tumor tissue may have a direct role in the etiology of experimental cancer anorexia.

Amino Acids↗
PubMed1989

Transcriptional proofreading in Escherichia coli.

A novel transcriptional proofreading mechanism associated with the beta-subunit of wild-type RNA polymerase from Escherichia coli is suggested from the following data. The purified holoenzyme contains an NTPase activity which specifically converts noncognate NTPs to their corresponding NDP in a template-dependent manner during in vitro transcription of synthetic single- and double-stranded templates. In contrast, purified enzyme from an rpoB mutant which shows increased transcriptional error lacked template-dependent NTP hydrolytic activity. The NTP hydrolytic activity of wild-type enzyme was critically dependent on the integrity of the initiation complex, and required continued transcriptional elongation. Transcription and translation of the lacZ gene proceeded 17% faster in the mutant than in its wild-type parent. These results are discussed in terms of a proofreading model in which the rate of transcription is limited by proofreading events that involve recognition and hydrolysis of noncognate NTPs before they can be misincorporated into RNA.

DNA-Directed RNA Polymerases↗
PubMed1989

The effect of PGE in multiple experimental models. II. Effect on steady-state levels of plasma and brain amino acids and transmitters.

Elevations in prostaglandin E (PGE) have been documented in tumor and trauma patients. The physiologic significance of this elevation is not fully established. Utilizing a long-acting derivative of PGE, 16,16-dimethyl-prostaglandin E (dPGE), in a rat model, we evaluated its effects on metabolic rates, amino acid, and neurotransmitter metabolism. dPGE was not found to significantly alter resting metabolic rate. It did decrease the plasma level of three amino acids, including tyrosine. Although dPGE also decreased brain tissue levels of tyrosine, no significant alterations were observed on amine neurotransmitters or metabolites.

Amino Acids↗
PubMed1989

The relationship of burn-induced hypermetabolism to central and peripheral catecholamines.

The role of brain and circulating catecholamines as mediators of burn-induced hypermetabolism was investigated in two experiments. Following a 30% body surface area full-thickness open-flame burn, rats exhibited a short period (3 to 4 days) of anorexia followed by a more prolonged (several weeks) hyperphagic-hypermetabolic response. During this hypermetabolic period, norepinephrine concentrations were increased in the brain and circulating epinephrine levels were elevated. Depletion of brain norepinephrine using 6-hydroxydopamine led to increased body weight gain, but did not increase resting energy expenditure in burned rats. Similarly, the reduction of circulating catecholamines through removal of the adrenal medulla resulted in a decreased loss of body weight and only slight reductions in resting energy expenditure. Therefore, these results suggest that although brain norepinephrine and circulating epinephrine have a role in the full expression of hypermetabolism, these compounds do not appear to be major mediators of this response to burn trauma.

Adrenal Medulla↗
PubMed1988

Hyperammonemia in anorectic tumor-bearing rats.

Plasma ammonia concentrations were significantly elevated by 150% in anorectic rats bearing methylcholanthrene sarcomas. Assessment of ammonia levels in blood draining these sarcomas indicated nearly a 20-fold increase as compared with venous blood in control rats, suggesting the tumor mass as the source of this increase in ammonia. Infusing increasing concentrations of ammonium salts produced anorexia and alterations in brain amino acids in normal rats that were similar to those observed in anorectic tumor-bearing rats. Therefore, these results suggest that ammonia released by tumor tissue may be an important factor in the etiology of cancer anorexia.

Amino Acids↗
PubMed1988

Reduction of tumor growth following treatment with a glutamine antimetabolite.

Assessment of arterial-venous differences across transplanted methylcholanthrene-induced sarcomas in rats revealed significant decreases in plasma concentrations of glutamine, serine and glucose. Treatment with the glutamine antimetabolite, acivicin, significantly reduced tumor weights by 65% at the conclusion of the experiment 34 days after tumor induction. These results suggest that glutamine is an essential metabolic substrate for tumor growth and that blockade of glutamine utilization can inhibit the growth of these transplantable sarcomas.

Amino Acids↗
PubMed1988

Reversal of neurochemical aberrations after tumor resection in rats.

Assessment of biochemical parameters in methylcholanthrene sarcoma-bearing rats 2 days after the onset of anorexia revealed several biochemical aberrations in blood and brain. Plasma levels of glucose were decreased and lactate concentrations were increased. The plasma and brain amino acid profiles were also greatly altered in these rats, characterized by increased brain concentrations of glutamine and large neutral amino acids. Analysis of regional neurotransmitter and metabolite levels by high-performance liquid chromatography suggested increases in the neuronal activity of dopamine and serotonin in each brain region examined. Surgical removal of the tumors in another group of anorectic tumor-bearing rats was followed by the return of normal feeding within 6 days. Associated with the normalization of food intake was the reversal of these biochemical aberrations in blood and brain. It is hypothesized that the utilization of glutamine and excretion of ammonia by tumor tissue is the precursor of these alterations in brain amino acids and neurotransmitters, which may be causing anorexia.

Amino Acids↗
PubMed1988

Animals, handicapped children and the tragedy of marginal cases.

There are human beings whose psychological capacities are rivalled or exceeded by many non-human animals; such humans are often referred to as 'marginal cases'. R G Frey has argued that there is no secure, non-arbitrary way of morally distinguishing between marginal humans and non-human animals. Hence, if the benefits of vivisection justify such painful and lethal procedures being performed on animals, so is the vivisection of marginal humans justified. This is a conclusion Frey is driven to with 'great reluctance', but which he can see no way to avoid. This paper points out a feature of the condition of marginal humans unnoticed by Frey and his critics: such humans have suffered a tragic harm. It points towards an analysis of this harm, in terms of counterfactuals holding for marginal humans but not for psychologically equivalent animals. Finally, it discusses the moral implications of the harm that such humans have suffered, and argues that it serves as the basis of a defence for preferring humans to non-humans in cases of morally inescapable conflict.

Animal Experimentation↗
PubMed1987

Neurotransmitter alterations associated with feeding and satiety.

Chronically malnourished rats were sacrificed in a food-deprived state, following eating a small amount of food, or following feeding to satiation. Regional analysis of brain neurotransmitter, neurotransmitter precursor and metabolite concentrations revealed significantly elevated levels of dopamine metabolites in the corpus striatum and nucleus accumbens of the satiated rats. Food-deprived and both refed groups exhibited elevated concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid, in most brain areas examined. These results suggest increased metabolism of dopamine to be associated with satiety rather than with the act of feeding alone. Increased serotonin metabolism appears to reflect overall nutritional status rather than the onset of satiety.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Rheumatoid factors from patients with rheumatoid arthritis possess private repertoires of idiotypes.

Considerable interest has focused on idiotypic cross-reactivity among antibody molecules. Cross-reactive idiotypes (Id) on monoclonal and polyclonal rheumatoid factors (RF) have been found frequently. Sufficient attention has not been directed, however, to the proportion of RF exhibiting the cross-reactivity, leaving the impression of extensive RF cross-reactivity when, in fact, this might represent a small minority of total RF molecules in a given individual. We have examined the polyclonal RF from patients with rheumatoid arthritis (RA) for cross-reactive Id in three different assays and with different Id-anti-Id systems. First, a sensitive liquid-phase radioimmunoassay was used in which panels of sera were tested for inhibition of different, idiotypically unrelated, Id-anti-Id interactions. When compared with normal sera, some of the sera from patients with RA caused minimal inhibition of Id-anti-Id interactions. None, however, caused marked inhibition of any Id-anti-Id system. Secondly, the panels of sera were also tested in a direct binding ELISA to detect partially cross-reactive Id that may not have been identified in the inhibition radioimmunoassay without differing results. Finally, results similar to the autologous Id-anti-Id inhibition assay were also found when the panels of RA sera were tested in two nonautologous Id-anti-Id systems, in which the anti-Id reacted with other than their own Id. These studies indicate that although cross-reactivity with some RF of an individual's total RF population may be seen frequently, an individual's repertoire of RF is itself private, quite diverse, and unique to that individual.

Antibodies, Anti-Idiotypic↗