Search PubMed⌕ Search

Biomedical subjects

J Moore

Publications and source records attributed to J Moore.

At least 37 records · Page 2Linked to original sources
PubMed1996

Oxybenzone oxidation following solar irradiation of skin: photoprotection versus antioxidant inactivation.

We used noninvasive Fourier transform (FT) Raman spectroscopy to follow the fate of the broadly used ultraviolet UVA sun blocker, oxybenzone, after topical application to the skin. Our results showed that oxybenzone is rapidly photo-oxidized, yielding oxybenzone semiquinone, a potent electrophile, which reacts with thiol groups on important anti-oxidant enzymes and substrates, such as thioredoxin reductase and reduced glutathione, respectively. Although oxybenzone is an excellent broad spectrum UVA filter, its rapid oxidation followed by the inactivation of important antioxidant systems indicates that this substance may be rather harmful to the homeostasis of the epidermis. Furthermore, these results demonstrate that FT-Raman spectroscopy is a useful method for studying the transport and metabolism of active ingredients in topical preparations.

Administration, Topical↗
PubMed1996

Three dimensional analysis of the retinal vasculature using immunofluorescent staining and confocal laser scanning microscopy.

AIM: To undertake a qualitative and quantitative analysis in three dimensions of the human retinal vasculature. METHOD: Fixed and excised whole retinas were permeabilised and subjected to immunofluorescent staining for blood vessel components followed by confocal laser scanning microscopy. Single projection and stereoimages were constructed using computer software. XZ sections through the retina were constructed and the vasculature analysed using appropriate software. RESULTS: Immunofluorescent staining with no discontinuities was present in vessels of all sizes, the confocal images of the capillary network being free of out of focus blur at all depths. Quantitative analysis of XZ sections confirmed the qualitative impression of sharp delineation of the deep retinal capillary plexus, an absence of laminar arrangement of capillaries within the inner retina, and a truncated cone of capillaries around the foveal avascular zone (FAZ) wherein the superficial capillaries approached the FAZ more closely than those in the deeper retina. CONCLUSION: Immunofluorescent staining of the retina and confocal laser scanning microscopy were shown to be useful in analysing accurate three dimensional reconstructions of the normal retinal vasculature without affecting overall tissue architecture.

Adult↗
PubMed1996

Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.

PURPOSE: Breast cancer frequently overexpresses the product of the HER2 proto-oncogene, a 185-kd growth factor receptor (p185HER2). The recombinant humanized monoclonal antibody (rhuMAb) HER2 has high affinity for p185HER2 and inhibits the growth of breast cancer cells that overexpress HER2. We evaluated the efficacy and toxicity of weekly intravenous administration of rhuMAb HER2 in patients with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS: We treated 46 patients with metastatic breast carcinomas that overexpressed HER2. Patients received a loading dose of 250 mg of intravenous rhuMAb HER2, then 10 weekly doses of 100 mg each. Patients with no disease progression at the completion of this treatment period were offered a maintenance phase of 100 mg/wk. RESULTS: Study patients had extensive metastatic disease, and most had received extensive prior anticancer therapy. Adequate pharmacokinetic levels of rhuMAb HER2 were obtained in 90% of the patients. Toxicity was minimal and no antibodies against rhuMAb HER2 were detected in any patients. Objective responses were seen in five of 43 assessable patients, and included one complete remission and four partial remissions (overall response rate, 11.6%; 95% confidence interval, 4.36 to 25.9). Responses were observed in liver, mediastinum, lymph nodes, and chest wall lesions. Minor responses, seen in two patients, and stable disease, which occurred in 14 patients, lasted for a median of 5.1 months. CONCLUSION: rhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy. This is evidence that targeting growth factor receptors can cause regression of human cancer and justifies further evaluation of this agent.

Adult↗
PubMed1996

Recombinant human growth hormone (GH)-binding protein enhances the growth-promoting activity of human GH in the rat.

To address the role of the GH-binding protein (GHBP) in GH physiology, two forms of recombinant human GHBP (rhGHBP) were given alone or in combination with rhGH to hypophysectomized rats or GH-deficient dwarf rats. Hypophysectomized rats were given daily sc injections of excipient, hGH, rhGHBP, or rhGH plus rhGHBP (produced in Escherichia coli) for 7 days. Injections of rhGH induced dose-related body weight gain and bone growth that were increased by the coadministration of rhGHBP with rhGH; rhGHBP alone had no effect. Serum insulin-like growth factor increased 24 h later when rhGH was given together with rhGHBP (P < 0.01), but not when rhGH was given alone. E. coli-derived rhGHBP also enhanced the bioactivity of coadministered rhGH in the GH-deficient dwarf rat. In contrast, the glycosylated rhGHBP, made in human A293 cells, inhibited the growth-promoting activity of coadministered rhGH. The opposite effects of these two forms of rhGHBP could be explained by clearance studies that showed radiolabeled rhGH bound to A293 cell-derived rhGHBP to be cleared more rapidly from the blood than free rhGH. Natural rabbit GHBP and E. coli-derived rhGHBP both prolonged the presence of rhGH in blood. It is proposed that by slowing the clearance of GH, GHBP increased the bioactivity of GH. In summary, codelivery of rhGHBP and rhGH caused a dose-dependent enhancement of the activity of rhGH in two rat models of GH deficiency. This suggests that endogenous circulating GHBP may increase the activity of blood-borne GH in a similar manner.

Animals↗
PubMed1996

Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

Animals↗
PubMed1996

Safety and immunogenicity of Staphylococcus aureus type 5 capsular polysaccharide-Pseudomonas aeruginosa recombinant exoprotein A conjugate vaccine in patients on hemodialysis.

Seventeen volunteers with ESRD on hemodialysis, negative for infection with HIV or hepatitis B and C and not receiving immunosuppressive therapy, were injected two times 6 wk apart with 25 micrograms of Staphylococcus aureus Type 5 capsular polysaccharide-Pseudomonas aeruginosa exoprotein A (rEPA) conjugate. Controls were healthy adults, 18 to 44 yr old, injected previously with the same vaccine. None of the patients had fever or significant elevations in their SGOT or SGPT attributable to the vaccine. Two vaccinees had transient induration > 1 cm in diameter at the injection site. The preimmunization geometric mean (GM) Type 5 antibody levels of the ESRD patients and controls were similar. Type 5 antibody levels of the three major immunoglobulin (lg) classes rose at 2 and 6 wk after immunization (P < 0.001 for lgG, P < 0.005 for lgM, and P = 0.0001 for lgA). Reimmunization at 6 wk did not elicit a booster response. At 6 months, the GM lgG level of the patients was approximately 50% of that of the healthy volunteers and 14 of 17 had a more than fourfold higher antibody level than the preimmune value. The GM lgM level, in contrast, declined to the preimmunization value. Vaccine-induced Type 5 antibodies had opsonophagocytic activity. There was a slight increase of lgG antibodies to the heterologous S. aureus Type 8 polysaccharide (P < 0.01) that was sustained at 6 months. The S. aureus Type 5-rEPA vaccine is safe and immunogenic in ESRD patients, and evaluation of its effectiveness against S. aureus bacteremia in this at-risk group is planned.

ADP Ribose Transferases↗
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↗