Search PubMed⌕ Search

Biomedical subjects

D Currie

Publications and source records attributed to D Currie.

44 records · Page 3Linked to original sources

Muscle glycogen repletion after exercise in trained normal and diabetic rats.

We hypothesize that training results in a faster and greater repletion of glycogen in skeletal muscles of normal and diabetic rats. Normal male Sprague-Dawley rats (100-140 g) were divided into two groups--one to train by treadmill running for 10 wk and the other to remain sedentary. Forty-eight hours after the last training session the rats of both groups were exercised to exhaustion. One subgroup of each was fed oral glucose (3 g/kg) at exhaustion and killed 60 min later. The other was killed at exhaustion. The glycogen concentration of soleus, plantaris, and red and white gastrocnemius was determined in all rats. The trained group had higher glycogen levels after glucose feeding in all muscles (P less than 0.002) and repleted their muscle glycogen more rapidly (P less than 0.05). However, in diabetic rats (45 mg streptozotocin/kg body wt) the trained and sedentary rats have similar glycogen levels and glycogen repletion rates in all muscles. Compared with the normal trained rats, the diabetic trained rats had slower glycogen repletion rates (P less than 0.05).

Animals↗

Analysis of the involvement of cells from donor and recipient mice in adoptive transfer of antitumor immunity.

In this study, we attempted to analyze the effector cells for adoptive transfer of protective immunity directed against a P815Ys tumor. The spleen, lymph node, and peritoneal exudate cells obtained from immune mice at Day 7 to Day 10 after last challenge were tested for their in vitro cell-mediated cytotoxicity against P815Ys cells, using a 4-hr 51Cr release assay. The immune spleen lymphocytes (ISL) showed no cytotoxicity, whereas the peritoneal exudate cells exhibited marked cytotoxicity. Unexpectedly, when ISL or peritoneal exudate cells were adoptively transferred i.v. into mice bearing the P815Ys tumor, it was the ISL but not the peritoneal exudate cells that provided the hosts with significant protection. Using alloantibodies for negative depletion of cells in ISL, it was found that, after treatments with anti-Thy 1.2 or anti-Lyt 1 antiserum plus complement but not with anti-Lyt 2 or complement alone, the protective capacity of ISL can be abolished, indicating that the effector cells for conferring protective immunity to the host are Lyt 1-bearing T-cells. Moreover, culture supernatants of ISL with or without mitomycin C-treated P815Ys contain helper factor, interferon, and interleukin 2, which enhanced the in vitro generation of cell-mediated cytotoxicity against P815Ys. Taken together, these results strongly suggest that the donor helper T-cells are the effector cells responsible for adoptive transfer of protective immunity. We next examined the contribution of host cells. Syngeneic mice were made to become either T-cell (with thymectomy and irradiation)- or macrophage (with the administration of silica) depleted and were then subjected to adoptive transfer experiments. Both the thymectomized and the silica-treated mice, after receiving the ISL, showed significantly better survival times than did normal mice. Thus, the data suggest that the elimination of T-cells or inactivation of macrophages, presumably with immunosuppressive activity in the recipients, will allow further improvement of their battle for survival against tumor.

Animals↗

Inhibition of beta-adrenergic response in cultured epidermal cells by phorbol myristate acetate.

Treatment of cultured epidermal cells with the tumor promoter, phorbol myristate acetate (PMA), results in a 75% inhibition of the normal isoproterenol stimulated 7-fold increase in cAMP accumulation. Maximum inhibition occurred 3 h after PMA treatment. The effect of phorbol ester on the beta-adrenergic system in mouse epidermis thus appears to be due to its action on the epidermal cell membrane and does not require mediation by macrophages.

Animals↗

Contamination of animal feedingstuffs with undeclared antimicrobial additives.

A study was carried out on 397 feedingstuffs and 11 premixes on which 161 (39.5%) were declared free of medication and 247 (60.5%) were medicated. These were subjected to analysis for the presence of antibiotics. Of the 247 medicated feeds 87 (35.2%) contained undeclared antimicrobials of which 59 (23.9%) were at a concentration sufficient to allow quantification by HPLC. Of the 161 unmedicated feeds 71 (44.1%) were shown to contain detectable antimicrobials of which 42 (26.1%) contained concentrations which could be quantified by HPLC. The most frequently identified contaminating antimicrobials were chlortetracycline (CTC) (15.2%), sulphonamides (6.9%), penicillin (3.4%) and ionophores (3.4%). Four samples (ionophores--3, sulphadimidine--1) contained therapeutic concentrations and one sample a supra-therapeutic concentration (monensin). The remainder were sub-therapeutic. All the contaminating concentrations of sulphadimidine detected were sufficient to cause violative tissue residues if fed to animals immediately prior to slaughter.

Animal Feed↗

Evaluation of a modified EC Four Plate Method to detect antimicrobial drugs.

This paper describes a modification of the EC Four Plate Method based on microbial growth inhibition of Bacillus subtilis on agar medium at pH 6.0, 7.2 and 8.0 and Micrococcus luteus at pH 8.0 developed to cope with large numbers of samples. The method's performance was evaluated by determining the Minimum Inhibitory Concentrations of 66 commonly used drugs and determining the between-assay variation of antimicrobial control standards. The modified method proved particularly sensitive for beta-lactams, tetracyclines, quinolones, marcrolides and lincosamides and least sensitive for anticoccidials and nitrofurans. The pH 6.0 and 7.2 plates were more sensitive for 39 of the 66 antimicrobials (59%) whereas the two pH 8.0 plates (B. subtilis, M. luteus) were the most sensitive for 27 (41%). Muscle samples were taken from 1830 routine meat inspection investigations between 1994 and 1996. Of the 38 (2%) positive meat inspection carcasses, the following antimicrobials were confirmed above the MRL: penicillin G (10), oxytetracycline (16), sulphadimidine and sulphadiazine in combination (4) and chlortetracycline (1). The method as described is technically simple, cost effective, robust, suitable for large sample throughput and for frozen, thawed or fresh tissues. When all four plates are used the pattern of inhibition can reduce unnecessary confirmatory assays by indicating the antimicrobial group most likely to be present.

Animals↗

Expression of the CYP1A1 gene in peripheral lymphocytes as a marker of exposure to creosote in railroad workers.

We have conducted a pilot study to assess levels of cytochrome CYP1A1 gene expression in human peripheral lymphocytes as a molecular biomarker assay for polycyclic hydrocarbon exposure. Basal and 3-methylcholanthrene-induced levels of gene expression were measured by standard slot-blot mRNA analyses in mitogen-stimulated cultures of peripheral blood lymphocytes from creosote-exposed railroad workers and unexposed control subjects. Dermal and inhalation exposure of workers to creosote may vary substantially as a function of working conditions related to temperature. Therefore, blood specimens were collected from separate groups during the winter, fall, and summer. Basal and induced CYP1A1 gene expression levels were not elevated in workers from any of the three seasonal studies. However, induced/basal (inducibility) CYP1A1 mRNA ratios from workers sampled in the summer (when actual exposures were greatest) were significantly higher when compared to those of controls (P < 0.01). These studies demonstrate the potential usefulness of specific gene expression assays in human peripheral lymphocytes for the assessment of carcinogen exposure in human populations.

Adult↗

Racial differences in restriction fragment length polymorphisms and messenger RNA inducibility of the human CYP1A1 gene.

Recent studies have examined the relationship between genetic polymorphisms of the human cytochrome P-4501A1 (CYP1A1) gene and lung cancer susceptibility. We have quantified genotypic frequencies and measured gene expression in the CYP1A1 gene within racially diverse groups in order to determine the relationship between genotype and transcriptional regulation of the CYP1A1 gene. Lymphocytes were obtained from 68 individuals of European-American, African-American, and Asian descent, and CYP1A1 gene inducibility was measured in mitogen-stimulated cells. CYP1A1 gene inducibility was significantly lower in African-Americans than in European-Americans or Asians, while several other population parameters were found to have no effect on gene expression levels. Restriction fragment length polymorphism analysis of lymphocyte DNA following MspI restriction enzyme digestion revealed a significant difference in the frequencies of CYP1A1 genotypes between European-Americans and Asians. The only homozygous variants detected were of Asian descent. The frequencies of CYP1A1 genotypes in all races conformed to Hardy-Weinberg genotypic equilibrium. When CYP1A1 gene inducibility was compared to CYP1A1 genotype, no significant correlations were found. These studies, along with our previous survey of CYP1A1 gene expression in creosote-exposed workers, add further support to the use of CYP1A1 gene inducibility as a potential marker of polycyclic aromatic hydrocarbon exposure in human populations.

Adult↗