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Biomedical subjects

J Moore

Publications and source records attributed to J Moore.

At least 289 records · Page 16Linked to original sources
PubMed1996

Stability of vitamins A, C, and E, carotenoids, lipids, and testosterone in whole blood stored at 4 degrees C for 6 and 24 hours before separation of serum and plasma.

To investigate whether overnight storage causes significant changes in whole blood, we measured serum and plasma concentrations of vitamins A, C, and E, carotenoids, lipids, and testosterone in whole blood samples stored in a refrigerator at 4 degrees C for 6 and 24 h before centrifugation, aliquoting and freezing them at -70 degrees C or below. In comparison with baseline samples prepared within 2 h, the mean percentage changes at 24 h were: -3.0% to +1.0% for retinol, alpha-tocopherol, and gamma-tocopherol in plasma; -8.7% to -0.1% for carotenoids in plasma; -7.2% for vitamin C in plasma and -1.8% for vitamin C in serum; -2.7% to +2.4% for lipids in serum; and +0.4% to +6.2% for testosterone in serum and plasma from men and women. Spearman's rank correlation coefficients between measurements made in the baseline samples and those made after storage for 24 h were greater than 0.9 for 11 analytes, between 0.8 and 0.9 for 7 analytes, and less than 0.8 for only 1 analyte (vitamin C in serum). The ratio of between-subject to within-subject coefficients of variation was greater than 3.0 for all analytes except lutein (ratio, 1.6), alpha-cryptoxanthin (ratio, 2.4) and vitamin C (ratio in serum, 3.0; ratio in plasma, 2.2). We conclude that storage of whole blood at 4 degrees C for 24 h before freezing does not cause important changes in the analytes studied and that this delay in processing may be incorporated in the design of large prospective studies.

Ascorbic Acid↗
PubMed1995

The relationship between mRNA half-life and gene function in the yeast Saccharomyces cerevisiae.

Saccharomyces cerevisiae (Sc) mRNAs have been described as falling into two major classes with respect to mRNA half-life [Santiago et al., Nucleic Acids Res. 14 (1986) 8347-8360]. We have used DNA sequence analysis to address the functional roles of eleven of the thirteen cDNAs upon which Santiago et al. based their conclusions. Eight had been described as copies of short half-life and five as copies of long-half-life mRNAs. We show here that five members of the short-half-life class encode known Sc cytosolic ribosomal proteins (rp). One further short-half-life cDNA appears to encode a new Sc rp related to higher eukaryotic rp S12. Among the long-half-life cDNAs, one encodes the glucose-inducible glycolytic enzyme enolase, while another is related to the mouse housekeeping gene MER5.

Animals↗
PubMed1995

A cDNA encoding ribosomal protein L3 from the parasitic nematode Toxocara canis.

A cDNA encoding the ribosomal (r) protein L3 of the parasitic nematode Toxocara canis was isolated from a library constructed from mRNA of the infective larval stage. The encoded protein has a high degree of similarity to r-protein L3 from other organisms, including mammals, yeast, plants and bacteria. The mRNA encoding r-protein L3 is derived from a single-copy gene, and experimental evidence would suggest that it contains the pan-nematode splice leader sequence at its 5' end and that the gene is interrupted by at least three introns.

Amino Acid Sequence↗
PubMed1995

A role for CD95 ligand in preventing graft rejection.

Testis is a remarkable immune-privileged site, long known for its ability to support allogeneic and xenogeneic tissue transplants. Here we have investigated the molecular basis for testis immune privilege. Testis grafts derived from mice that can express functional CD95 (Fas or Apo-1) ligand survived indefinitely when transplanted under the kidney capsule of allogeneic animals, whereas testis grafts derived from mutant gld mice, which express non-functional ligand, were rejected. Further analysis of testis showed that CD95 ligand messenger RNA is constitutively expressed by testicular Sertoli cells, and that Sertoli cells from normal mice, but not gld mice, were accepted when transplanted into allogeneic recipients. CD95 ligand expression in the testis probably acts by inducing apoptotic cell death of CD95-expressing, recipient T cells activated in response to graft antigens. These findings indicate that CD95 ligand could be used to create immune-privileged tissue for a variety of transplant uses.

Animals↗
PubMed1995

Characterisation of Saccharomyces cerevisiae genes encoding ribosomal protein YL6.

We have characterised a Saccharomyces cerevisiae cDNA (cDNA13), originally isolated on the basis of the short half-life of the corresponding mRNA. We show here that its sequence is closely related to that of the genes encoding ribosomal proteins K37, KD4 and K5 of Schizosaccharomyces pombe. 'mRNA13' also behaves like other mRNAs encoding ribosomal proteins, in that its abundance increases sharply when glucose is added to cells grown on ethanol (nutrient-upshift), and declines when cells are subjected to a mild heat-shock. Unspliced mRNA13 accumulates when cells bearing a temperature-sensitive splicing mutation are grown at the restrictive temperature. The gene(s) corresponding to cDNA13, like other ribosomal protein genes of S. cerevisiae, thus contain an intron. Southern blot analysis indicates the presence of two separate loci related to cDNA13 in the S. cerevisiae genome. From the sequence of one of these, a complete polypeptide sequence was deduced. The first 40 amino acids are identical to those of YL6, a S. cerevisiae ribosomal protein characterised only by N-terminal protein sequence analysis. There is clear evidence within the genomic sequence for the predicted intron, and for elements similar to those that regulate expression of other S. cerevisiae ribosomal protein genes.

Amino Acid Sequence↗
PubMed1995

The phenotypic changes in tumour infiltrating lymphocytes and tumour cells following intra-arterial infusion of interleukin-2 in patients with squamous cell carcinoma.

This study evaluates the morphological and phenotypic changes that occur in squamous cell carcinoma of the head and neck when local infusions of interleukin-2 (IL-2) are given. Twelve patients were treated with a range of doses of IL-2 (3 x 10(3) to 3 x 10(6) international units/day) by continuous intra-arterial infusion for 10 days. Biopsies of the tumour were taken pre- and 48 h post-therapy, snap-frozen, cut, and examined histologically and immunocytochemically. Local infusions of IL-2 increase the numbers of antigen-presenting Langerhans cells (CD1a-positive) and infiltrating lymphocytes, predominantly of the CD3 and CD4 (T-helper) phenotypes. Locally infused IL-2 results in the expression of MHC (major histocompatibility complex) class II antigens on the surface of the tumour cells, capillary and post-capillary endothelial cells, and peri-tumoural macrophages. Intratumoural NK (natural killer) cells and CD8-positive (T-cytotoxic) infiltrating lymphocytes were not increased by this therapy and CD25 (IL-2 receptor) was only increased in those patients treated at the lower dose levels. The system of intra-arterial cytokine infusion into head and neck tumours developed in this study is a useful model to examine the biological effects of cytokines, since in vivo they are mainly produced and act locally. Furthermore, the infused tumours are easily accessible to biopsy. The results from studies such as this may influence the design of tumour-targeted cytokine gene therapy programmes.

Adult↗
PubMed1995

The X-linked methylated DNA binding protein, Mecp2, is subject to X inactivation in the mouse.

DNA methylation at the promoter region of X-linked genes is associated with the maintenance of X inactivation in mammals. One of the methylated DNA binding proteins, MECP2, that binds to methylated bases in DNA is encoded by a gene (Mecp2) located on the mouse X Chromosome (Chr). To determine whether this gene was expressed from the inactive X Chr, and X-autosome translocation (T(X;16)16H) system in which expression from the Mecp2 allele on the inactive X Chr could be assayed was used. Results from these experiments indicate that Mecp2 is subject to X inactivation in mouse.

Animals↗
PubMed1995

Extensive diversity in repeat unit sequences of the cDNA encoding the polyprotein antigen/allergen from the bovine lungworm Dictyocaulus viviparus.

The complete sequence of the cDNA encoding the nematode polyprotein allergen/antigen (NPA) of the bovine lungworm Dictyocaulus viviparus was obtained by immunoscreening of cDNA expression libraries and by 5' RACE (rapid amplification of cDNA ends). The encoded polypeptide is similar in sequence to the ABA-1 allergen of Ascaris, the gp15/400 'ladder' protein of Brugia malayi, Brugia pahangi and Wuchereria bancrofti, and a 15-kDa antigen of Dirofilaria immitis. As with these, the predicted amino-acid sequence comprises a head-to-tail array of similar polypeptides with regularly spaced consensus proteinase cleavage sites. The D. viviparus protein was designated DvA-1 (D. viviparus antigen-1) and the gene dva-1. The deduced amino-acid sequence of DvA-1 showed features not observed before in other NPAs: (i) a hydrophobic leader peptide is present, (ii) none of the 12 units in the array are identical and the sequences diverge to a degree hitherto unseen in the NPAs of other nematode parasites, (iii) the predicted proteinase cleavage sites are also diverse in sequence and, in two instances, no consensus cleavage site was identifiable at the expected position, (iv) a short repeat unit is present, which is the only one containing a consensus N-glycosylation site and (v) a C-terminal extension peptide is encoded which shows no similarity to that from A. suum ABA-1. Comparison of independent cDNAs revealed slight variations in the sequence of the gene within the parasite population. Antisera to recombinant DvA-1 polypeptide identified 14-15-kDa antigens in both parasite somatic and excretory-secretory material. DvA-1 is the only NPA for which the complete coding sequence is available and the new principles which it illustrates may lie unsuspected in the NPA-encoding genes of all nematode parasites.

Amino Acid Sequence↗
PubMed1995

Pharmacokinetics and bioavailability of rhIGF-I/IGFBP-3 in the rat and monkey.

Circulating IGF-I exists primarily as part of a ternary 150 kDa complex comprising equimolar amounts of IGF-I, IGFBP-3 and acid labile subunit (ALS). It is also known that in contrast to IGF-I and IGFBP-3 there exists a substantial quantity of unbound ALS in the circulation. As part of our preclinical development program, we have investigated the pharmacokinetic properties of a complex of human recombinant IGF-I and IGFBP-3. Systematic administration of rhIGF-I/IGFBP-3 results in binding of this binary complex to endogenous free ALS and thus leads to increased circulating levels of 150 kD ternary complex (IGF-I/IGFBP-3/ALS). In contrast to the administration of free IGF-I, IGF-I/IGFBP-3 dosing leads to increased systemic IGF-I exposure (i.e. increased area under the time vs. serum concentration curve or AUC) and decreased clearance (CL). Upon administration of equimolar doses of IGF-I/IGFBP-3 to the rat and monkey, it was found that in the monkey AUC was increased and CL decreased when compared to the rat. In addition, the pharmacokinetic profile suggests that saturation of excess ALS occurs at considerably lower doses of rhIGF-I/IGFBP-3 in the monkey than in the rat. Finally, the bioavailability of rhIGF-I/IGFBP-3 was assessed in the rat and found to be approximately 85% and 50% after intramuscular and sub-cutaneous administration, respectively. It was concluded that the formation of the 150 kD ternary complex had a significant impact on increasing the systemic exposure to rhIGF-I when administered as the binary complex (rhIGF-I/IGFBP-3). In addition, IGFBP-3 increases the therapeutic index of rhIGF-I even at doses that significantly exceed the saturation of ALS.

Animals↗
PubMed1995

DNA index and ploidy distinguish normal human parathyroids from parathyroid adenomas and primary hyperplastic parathyroids.

BACKGROUND: The goal of this study was to identify factors that might aid in diagnosis and intraoperative management of hyperparathyroidism. METHODS: We analyzed biopsy specimens of 242 parathyroids from 159 patients by use of flow cytometry and image cytometry (ICM) for DNA index (DI), defined as the content of nuclear DNA compared with that expected for a DNA diploid standard, for proliferative index (PI), and for ploidy (diploid versus aneuploid or tetraploid). RESULTS: True normal and normal parathyroids from patients with solitary adenomas were uniformly diploid. Abnormal ploidy (aneuploidy or tetraploidy) was identified frequently in adenomas and occasionally in hyperplasias with the exception that multiple endocrine neoplasia (MEN) biopsy specimens were uniformly diploid. DI for adenomas was similar to that for hyperplasias, and DI of both was higher than for normal glands. ICM-DI correlated positively with flow cytometry-DI and patient age and inversely with serum parathyroid hormone. PI was relatively low in all groups but was higher for hyperplasias versus normal parathyroids from patients with solitary adenomas and MEN versus non-MEN. PI correlated inversely with patient age. CONCLUSIONS: DI by ICM differentiates normal from abnormal parathyroids. DI might influence extent of resection in two- and three-gland hyperplasia and selection of the most appropriate gland for autografting and cryopreservation in patients with four-gland hyperplasia.

Adenoma↗
PubMed1995

Increased soluble interleukin-2 receptor concentration in plasma predicts a decreased cellular response to IL-2.

Interleukin 2 (IL-2) immunotherapy has met with limited success in the treatment of renal cell carcinoma (RCC) and malignant melanoma (MM). However, non-responders still account for up to 80% of those patients receiving IL-2. A high concentration of soluble IL-2 receptor (sIL-2R) is commonly found in the blood of such patients. We investigated the possibility that high sIL-2R concentration pretreatment may interfere with the bioavailability of IL-2. The mean concentration of sIL-2R in plasma from patients with MM, RCC and head and neck cancer was 3378 U ml-1, 8778 U ml-1 and 764 U ml-1 respectively, compared with 1315 U ml-1 in plasma from healthy volunteers. Inclusion of plasma from patients with RCC and MM patient plasma in cytotoxic T-lymphocyte leukaemic (CTLL) cell/IL-2 assays inhibited the ability of CTLL cells to respond to IL-2, and an inverse correlation was found between the concentration of sIL-2R and the growth response of CTLL cell to IL-2 (r = -0.86, P = 0.003). Plasma with soluble IL-2R concentrations greater than 3000 U ml-1 produced a reduction in cell growth of more than 50% when included in CTLL IL-2 assays. The addition of increasing concentrations of IL-2 to cultures containing suppressive plasma failed to restore CTLL cell growth response to normal. Failure to saturate sIL-2R by exogenous IL-2 addition therefore suggests that another factor, initially present at a concentration similar to the sIL-2R concentration, is responsible for the observed effect. Determination of the suppressive effect of patient plasma as presented here may allow more effective IL-2 dosing schedules.

Animals↗
PubMed1995

Factors associated with Hispanic women's HIV-related communication and condom use with male partners.

To determine factors influencing Hispanic women's HIV-related communication and condom use with their primary male partner, 189 Dominican, Puerto Rican, and Mexican women were interviewed regarding sexual behaviour and condom use, relationship characteristics, perceived risk for HIV, and HIV-related communication with the primary male partner. Level of HIV-related communication with the primary male partner was associated with the woman's perceived risk for HIV and her rating of the openness with which she could communicate with her primary partner. Mexican women were less likely than Puerto Rican or Dominican women and women with multiple partners were less likely than those with one partner to communicate about HIV-related issues with their primary partner. Women reporting more condom use with their primary partner were younger, had discussed HIV-related issues more with the primary partner, and were less likely to expect negative reactions to requests for condom use than those reporting less condom use. These results suggest that prevention programmes that increase both general and HIV-specific communication between members of a couple may facilitate safer sex practices by the couple. Prevention programmes that encourage women to insist on condom use should consider the woman's expectations about her partner's reaction as a potential barrier to the initiation of safer sex practices.

Acculturation↗
PubMed1995

Uptake of halothane and isoflurane by mother and baby during caesarean section.

Twenty-three patients undergoing Caesarean section received either 0.5% halothane or 0.8% isoflurane to supplement nitrous oxide-oxygen anaesthesia. We studied the rate of uptake of the agents by the mother and fetus by measuring partial pressures in maternal arterial (Pa) and fetal umbilical venous (Puv) blood. Mean induction-delivery interval did not differ between the halothane (10.8 min) and isoflurane (11.7 min) groups. There were no differences in maternal heart rate, arterial pressure, pH and blood-gas tensions and fetal pH, blood-gas tensions or Apgar scores between the two groups. Isoflurane uptake by the mother was more rapid than halothane; at delivery, mean Pa of isoflurane as a fraction of the inspired partial pressure (Pl) was 0.44 compared with 0.35 for halothane (P < 0.05). Mean Puv as a fraction of maternal Pa at delivery was 0.71 for both agents; thus placental transfer was the same for both agents. Consequently mean Puv/Pl was greater for isoflurane (0.32) than halothane (0.26) (P < 0.05). We conclude that both halothane and isoflurane are suitable agents for general anaesthesia for Caesarean section. The rate of uptake of isoflurane by the mother during Caesarean section was more rapid than halothane. The rate of uptake by the fetus from the mother was the same for halothane and isoflurane, so that fetal partial pressure as a fraction of the inspired partial pressure was greater for isoflurane than halothane.

Adult↗