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Biomedical subjects

J L Nelson

Publications and source records attributed to J L Nelson.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Peroxidase: a novel pathway for chemical oxidation in human term placenta.

Hydrogen peroxide-dependent oxidation of xenobiotics in a crude fraction of human term placental membranes (nuclei, mitochondria and microsomes) was investigated. Guaiacol was employed as a model substrate. The rate of its oxidation was found to be dependent on the concentration of protein, H2O2 and the substrate as well as the pH of the buffer. Several other classical substrates for peroxidases from different sources viz. pyrogallol, benzidine, p-PDA, DMBD, ABTS, TMPD and TMBD and endogenous chemicals such as bilirubin and epinephrine were also found to undergo oxidation. The xenobiotic oxidizing capacity of the membranes was retained by CaCl2 (0.5 M) extract as well as by the partially purified enzyme obtained by affinity (Con A) chromatography. The H2O2-dependent chemical oxidation by the partially purified peroxidase was inhibited by NaN3 and KCN (IC50 values 41 and 23 microM respectively). These results suggest that peroxidase may be a major enzyme in human term placenta capable of oxidation of endogenous chemicals and xenobiotics.

Bilirubin↗
PubMedDate not supplied

HLA relationships of pregnancy, microchimerism and autoimmune disease.

Recent studies have established that there is bi-directional cell traffic between mother and fetus during pregnancy. Suprisingly, fetal cells have been found to persist in the maternal circulation for years after pregnancy. Maternal cells can also persist into adult life in her progeny. When cells from one individual are present in the body of another the term chimerism is used and a low level of non-host cells is referred to as microchimerism. Chronic graft-versus-host disease often occurs after stem cell transplantation, is a known condition of chimerism, and resembles spontaneously occurring autoimmune diseases including systemic sclerosis, Sjögren's syndrome, primary biliary cirrhosis and sometimes myositis and systemic lupus. Of central importance to the development of chronic graft-versus-host disease is the HLA relationship of host and donor cells. Considering this constellation of observations together led to the hypothesis that microchimerism and HLA-relationships are involved in the pathogenesis of some autoimmune diseases. Although much additional work is needed, results of initial studies provide support to the concept that non-host cells could participate in the pathogenesis of some autoimmune diseases.

Autoimmune Diseases↗
PubMedDate not supplied

Remission of rheumatoid arthritis during pregnancy and maternal-fetal class II alloantigen disparity.

Rheumatoid arthritis (RA) is an autoimmune disorder known to be associated with specific class II genes. Although it has been known since 1938 that the majority of women with RA experience disease improvement or remission during pregnancy, the reasons remain unknown. Pregnancy represents an immunologic challenge and maternal immune recognition of the semi-allogeneic fetus occurs as part of normal pregnancy. We hypothesized that maternal immune response to fetal HLA antigens might be associated with the effect of pregnancy on arthritis activity. To test this hypothesis, we studied HLA antigens in mother-child pairs comparing maternal-fetal HLA antigen sharing for pregnancies where arthritis improved with those where disease was active. No significant difference was observed in the two groups for class I HLA antigens. Fetal-maternal disparity for HLA-DR and HLA-DQ antigens was observed significantly more frequently in pregnancies with remission or improvement compared with those in which disease was active. These observations suggest that maternal immune response to fetal paternally-inherited class II HLA antigens may be important in RA remission observed during pregnancy.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Metabolic and immune effect of vitamin E supplementation after burn.

The effect of dietary vitamin E supplementation was studied in burned guinea pigs. Forty-four guinea pigs bearing a catheter gastrostomy received a 30% total body surface area full thickness flame burn and were given identical enteral diets (175 kcal/kg/day) except for the amount of vitamin E. Groups 1, 2, 3, and 4 received 0, 4 mg/kg/day (approximately equivalent to guinea pig's RDA) 20 or 100 mg/kg/day of vitamin E respectively. After 14 days of enteral feeding, there were no significant differences between groups in the body weights and the weights of carcass, gastrocnemius muscle, liver, and spleen. Resting metabolic expenditure on PBD 3, 6, 9, and 12 was similar in all groups. No statistical differences were seen in ear-thickness response to 2,4-dinitrofluorobenzene and lymphocytic proliferative responses to phytohemagglutinin. However, mucosal weight and protein content in group 1 were significantly less compared to groups 2 and 4 (p less than 0.05). Anemia was also significantly greater in group 1. Histologic examination of the intestinal wall, however, did not yield any physical differences associated with the addition of vitamin E to the diet. This study suggests that vitamin E supplementation in diets of burned animals may have a beneficial effect on maintenance of intestinal mucosa and erythrocyte counts over a wide-dose range.

Animals↗
PubMedDate not supplied

Gamma/delta T cells in placenta and skin: their different functions may support the paradigm of microchimerism in systemic sclerosis.

Increased amounts of foetal cells persisting after pregnancy could be involved in the pathogenesis of systemic sclerosis (SSc) and other autoimmune diseases. Evidence suggests a specific role for a subset of T lymphocytes showing the gamma/delta T cell receptor (TCR) at the foetal/maternal interface. gamma/delta T cells significantly increase in the early pregnancy decidua and recognize trophoblast antigens, probably a highly evolutionarily conserved molecule such as Hsp60 or Hsp60-derived peptides, and are likely to suppress the maternal anti-foetal immune response via TGFbeta production, thus contributing to pregnancy maintenance. The similarity between the presence of host gamma/delta T cells in pregnancy decidua and in SSc skin suggests that the functional activities of these cells can be differentially modulated by several mechanisms including the nature of the antigen and the involved organs. To support pregnancy, the decidual microenvironment might induce a Th2 activity of host Vdelta1 + T cells. On the contrary, either the presence of foetal cells in the skin of SSc patients or an as yet unidentified stimulus (i.e. infections), may trigger Vdelta1 + T cells toward the Th1 phenotype with the subsequent activation of cytotoxicity and modulation of the cytotoxic alpha/beta acquired T cell response. On these grounds, understanding the mechanisms which prevent the maternal immune system from rejecting a semiallogenic foetus could be helpful to understand the development of some autoimmune diseases, and potentially to develop new targeted therapeutic strategies.

Chimera↗
PubMedDate not supplied

Multi-trace-element supplementation in enteral formulas for burned guinea pigs.

A burned guinea pig model (30% total-body surface area) was used to study the effects of supplemental trace elements. The animals were fed via gastrostomy with identical formulas (175 kcal.kg-1.day-1, 20% of calories as protein) supplemented with varying amounts of the multi-trace-element preparation MTE-5. Animals in group 1 received no MTE-5, group 2 received 5 ml/L diet, group 3 received 20 ml/L diet, and group 4 received 50 ml/L diet. After 14 days of tube feeding, the animals were killed. Results indicated no significant differences in resting metabolic rate or body weight. However, animals in group 4 were found to have heavier carcass, jejunum gut, and mucosal weights compared with animals in group 1. In a second experiment, all animals received 5 ml of MTE-5/L diet. In each group, however, one of the trace elements (manganese, chromium, selenium, and copper) was elevated to the concentration found in 50 ml of MTE-5. The results shows no significant group differences when only one of the trace elements was elevated in the diet. Together, these results demonstrated that the addition of trace elements to an enteral diet increased carcass and gut mucosal weight in a standard dose-response fashion. All four of the trace elements evaluated were necessary for this response. It is suggested that the addition of larger requirements of trace elements than previously reported may be beneficial after thermal injury.

Animals↗
PubMedDate not supplied

The effect of trichloroethylene on male sexual behavior: possible opioid role.

Trichloroethylene (TCE) is a chlorinated hydrocarbon solvent which is widely used as an industrial degreasing agent. Workers exposed to TCE often exhibit symptoms similar to those symptoms produced by narcotics. The present studies evaluated the effects of TCE exposure on measures of male sexual behavior in rats. The data indicated that TCE (1000 mg/kg, PO) 4 hours before testing produced an increased ejaculation latency effect on male copulatory behavior. Naltrexone (2.0 mg/kg, IP) given 15 minutes before testing blocked this TCE-induced effect. Animals given chronic TCE administration showed tolerance to TCE's effect by the end of two weeks. Cross-tolerance to morphine was also demonstrated at this time. Quaternary naloxone failed to block any of the TCE-induced effects. These data suggest that many of TCE's effects may be mediated via the endogenous opioid system at a CNS level.

Animals↗
PubMedDate not supplied

Post injury hypermetabolic response and magnitude of translocation: prevention by early enteral nutrition.

The relationship between hypermetabolism and bacterial translocation was investigated in guinea pigs receiving a 40% burn. Animals were infused intragastrically with a complete enteral diet or Ringer's solution for 48 h, given 10(10) 14C-labeled Escherichia coli intragastrically, and killed 4 h later. Resting metabolic expenditure (RME), translocation (dpm of the 14C-labeled E. coli) to the portal blood and ileal mucosa, plasma cortisol, and urinary vanillylmandelic acid (VMA) were determined. Enterally fed animals had significantly lower RME, cortisol, VMA, and dpm, but higher mucosal and body weight than the Ringer's group. Disintegrations per minute (dpm) in the blood were positively correlated with RME (r = 0.856), cortisol (r = 0.872), VMA (r = 0.759), and dpm mucosa (r = 0.836) and inversely correlated with mucosal weight (r = -0.883). We conclude that bacterial translocation is reduced by early feeding and is an important cause of hypermetabolism and stress hormone production after burn injury.

Animals↗