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Biomedical subjects

S Moore

Publications and source records attributed to S Moore.

At least 37 records · Page 2Linked to original sources

Associations of IgA and IgA-rheumatoid factor with disease features in patients with rheumatoid arthritis.

In previous studies we have shown that levels of IgM-rheumatoid factor (RF) in plasma and peripheral blood mononuclear cell supernatants are correlated with disease activity and response to second-line therapy in patients with rheumatoid arthritis (RA). The present studies were designed to examine whether IgA-RF levels are also correlated with clinical features of this disease. Two groups of RA patients were studied. Group I consisted of 87 patients in whom extensive clinical data had been collected. Group II included nine patients beginning treatment with gold or methotrexate who were studied during the first year of therapy. Measurement of IgM, IgA, IgM-RF and IgA-RF in culture supernatants and plasma was done by an ELISA method. These data were examined for correlations with clinical and laboratory features. Levels of IgA-RF in supernatants and plasma were found not to be correlated with disease features in the cross-sectional analysis of Group I patients, while IgM-RF and total IgA levels did show significant clinical correlation. Treatment of Group II patients with gold or methotrexate was associated with significant decreases in plasma levels of total IgA and IgM-RF as well as a small but statistically significant decrease in plasma IgA-RF. Plasma levels of total IgM were not altered during therapy. These findings suggest that production of IgA but not IgA-RF is correlated with disease status in patients with RA.

Arthritis, Rheumatoid

Novel germline mutation of the p53 tumor suppressor gene in a child with incidentally discovered adrenal cortical carcinoma.

PURPOSE: We report a case of adrenal cortical carcinoma in an infant, which was incidentally discovered by renal sonography after a urinary tract infection. The previous death of a sibling after rhabdomyosarcoma in infancy prompted a search for a heritable p53 tumor suppressor gene mutation in this family. PATIENTS AND METHODS: Starting with frozen adrenal carcinoma tissue, polymerase chain reaction (PCR) amplification followed by direct sequencing of exons 4-8 of p53 was used to search for a mutation. When a mutation was identified in exon 6 of the tumor p53 sequence, PCR amplification and direct sequencing of exon 6 alone was then performed on DNA from peripheral blood lymphocytes (PBLs) of all immediate family members to determine whether a germline mutation was present. A different set of primers was used by a second laboratory at our institution to independently confirm the presence of the mutation in the adrenal carcinoma and in paraffin-embedded rhabdomyosarcoma tissue of the deceased sibling. RESULTS: A C-to-T transition was identified at a CpG site in codon 196 resulting in a change from arginine to a stop codon (CGA to TGA). The identical mutation, present as the sole p53 allele in the tumor DNA samples and in the heterozygous state with wild type p53 allele in DNA from PBLs (germline), was found in the adrenal carcinoma, the rhabdomyosarcoma, and the PBLs of the tumor-bearing child and her healthy father and 5-year-old brother. This nonsense mutation of p53 has never before been reported in the germline. The extended pedigree showed only one known additional cancer. CONCLUSIONS: A novel germline p53 mutation was identified by investigation of a sibling pair with cancers associated with the Li-Fraumeni syndrome in a family with an otherwise negative history for cancer. The implications of this case for identification of carriers of p53 germline mutations and their clinical management are discussed.

Adrenal Cortex Neoplasms

The proliferation of neointimal smooth muscle cells cultured from rabbit aortic explants 15 weeks after de-endothelialization by a balloon catheter.

Endothelial denudation of rabbit aorta induces smooth muscle cell (SMC) migration and proliferation, resulting in a thickened neointima, showing features in common with atherosclerotic lesions. The SMC proliferation has been reported as a transient healing process, which regresses when the neointima is covered by regenerated endothelium. In this study, we examined the cellular proliferation of neointimal SMC, derived from denuded and from re-endothelialized areas of aortic explants. The results show that the neointimal SMC retain a higher rate of proliferation, even 15 weeks after a single endothelial injury by a balloon catheter. Neointimal SMC release more PDGF-AB and TGF-beta 1, which may play a mitogenic role for SMC proliferation. The data demonstrating that injury-induced stimulation of neointimal SMC proliferation is a persistent process, emphasize the importance of injury mechanisms of atherogenesis.

Animals

Identification and regional localization of a human IMP dehydrogenase-like locus (IMPDHL1) at 16p13.13.

Sequence-tagged sites (STSs) are versatile chromosomal markers for a variety of genome mapping efforts. In this report, we describe a randomly generated STS (323F4) from human chromosome 16 genomic DNA that has 90.0% sequence identity to the type I human inosine-5'-monophosphate dehydrogenase (IMPDH1) gene and 72% identity to the type II human inosine-5'-monophosphate dehydrogenase (IMPDH2) gene. Additional sequencing by primer walking has provided a total of 1380 bp of the human chromosome 16 sequence. The IMPDH-like sequence 323F4 was regionally localized by PCR analysis of a panel of somatic cell hybrids containing different portions of human chromosome 16 to 16p13.3-13.12, between the breakpoints found in hybrids CY196/CY197 and CY198. This regional mapping assignment was further refined to subband 16p13.13 by high-resolution fluorescence in situ hybridization using cosmid 323F4 as a probe. We conclude that a third, previously undescribed IMPDH locus, termed IMPDHL1, exists at human chromosome 16p13.13.

Animals

Use of magnetic resonance imaging to analyze the performance of hollow-fiber bioreactors.

Preliminary experiments were described that demonstrate that MRI is an effective tool for the noninvasive study of hollow-fiber bioreactors. Flow-compensated velocity-encoding pulse sequences were successively applied to analyze the velocity patterns in a module operated without cells, with an artificially induced flow field perturbation. Diffusion damping pulse sequences were also used to spatially resolve regions of cell growth in a bioreactor. These experiments provide the necessary basis from which future flow and spectroscopic studies can be conducted.

Animals

Sulfated proteoglycans of rabbit aorta: selective extraction and alternative method for glycosaminoglycan moiety analysis.

Three different solutions containing urea, guanidine hydrochloride, or a detergent mixture were used to extract proteoglycan molecules (PG) metabolically labeled with 35S from normal rabbit aortic tissue. The size distribution of whole sulfated PG and the glycosaminoglycan (GAG) compositions in the three extracts were compared and found to be characteristically determined by the type of solution used for extraction. The spectrum of sulfated PG isolated by each solution was maintained at consecutive extractions of the tissue, even if this was used after another type of solution. The extracts obtained by using the urea- or guanidine-containing solutions contained similar, rather balanced populations of large and small PG, while the detergent-containing buffer was found to preferentially extract smaller, heparan sulfate-rich aortic PG. The selectivity of various extracting solutions could be exploited to obtain preparations enriched in certain types of sulfated PG. On the other hand, one could obtain a larger variety of 35S-labeled PG from the tissue by consecutively using two solutions with different capacities of extraction. The distribution of GAG moieties among PG populations, separated by size chromatography, was investigated by one of the commonly used methods and by a new method. The standard method is based on comparison of the chromatographic profiles of the extract before and after enzymatic digestions, requiring several chromatographic runs for a sample. In the alternative method proposed, the fractions obtained after a single chromatographic separation are adsorbed onto a support membrane. Processing of the whole membrane by GAG-specific, enzymatic treatments allows simultaneous assessment of GAG types in each fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Neuropeptide F-immunoreactivity in the monogenean parasite Diclidophora merlangi.

The localisation and distribution of neuropeptide F (NPF)-immunoreactivity (IR) in the monogenean fish-gill parasite, Diclidophora merlangi, have been investigated by whole-mount immunocytochemistry interfaced with confocal scanning laser microscopy and, at the ultrastructural level, by indirect immunogold labeling. Using antisera directed to intact synthetic NPF (Moniezia expansa, residues 1-39) or to the C-terminal decapeptide (residues 30-39) of synthetic NPF (M. expansa), immunostaining was found throughout the central (CNS) and peripheral nervous systems (PNS), including the innervation of the reproductive system. Immunoreactivity was found to be more intense using the antiserum to the C-terminal decapeptide fragment of NPF. At the subcellular level, gold labeling of NPF-IR was found exclusively over the contents of dense-cored vesicles that occupied nerve axons of both the CNS and the PNS. The distribution pattern of immunostaining for NPF mirrored exactly that previously documented for the vertebrate pancreatic polypeptide (PP) family of peptides and for FMRFamide. This finding and the results of preabsorption experiments strongly suggest that NPF is the predominant native neuropeptide in D. merlangi and that it accounts for most of the immunostaining previously obtained with PP and FMRFamide antisera.

Animals

Enhanced incorporation of [14C]glucosamine into glycosaminoglycans of aortic neointima of balloon-injured and cholesterol-fed rabbits in vitro.

Glycosaminoglycans (GAG), which form the elementary constituent of extracellular matrix proteoglycans (PG), are implicated in the pathogenesis of atherosclerosis, mainly due to their lipoprotein binding capability and their abundance in a developing lesion during atherogenesis. However, the reasons for the increment of GAG content are poorly understood. In the present study, the influence of two well known atherogenic factors on arterial GAG synthesis were examined by estimating the incorporation of [14C]glucosamine into aortic GAG in an in vitro incubation system. Radioactivity associated with GAG was taken to represent their synthesis. GAG synthesis by neointimal tissue of rabbit aortas, 12 weeks following balloon catheter deendothelialization was measured and compared in rabbits fed a normal or 0.25% cholesterol supplemented diet for the preceding 6 weeks. In normolipaemic rabbits synthesis was found to be 12,438 +/- 173, 17,884 +/- 1390 and 15,960 +/- 1355 dpm/mg dry defatted tissue from uninjured (control), deendothelialized (DEA) and reendothelialized (REA) areas of rabbit aortas, respectively. This incorporation of radioactivity was significantly greater in hypercholesterolaemic rabbits corresponding to 13,426 +/- 239, 32,670 +/- 3077 and 27,496 +/- 3287 in the control, DEA and REA, respectively. The results demonstrated a synergistic effect of cholesterol feeding and arterial endothelial denudation in stimulating GAG synthesis. Although GAG synthesis was found to be stimulated by either cholesterol feeding or arterial injury, the stimulation by cholesterol feeding alone was only marginal. Further, results show a much higher retention of newly synthesized GAG by the tissue from REA. This study provided a possible explanation for increased GAG content in a developing proliferative lesion.

Animals

The social context of adolescent sexuality: safe sex implications.

This study was an examination of the sexual worlds of 153 adolescents aged 15 to 18 years through the content analysis of interviews on the topics of love, romance, relationships between the sexes, sexual values and sexual behaviors. The aim was to develop more detailed descriptions of the dimension of adolescent sexuality and relate these dimensions to sexual risk, that is, the tendency to engage in unprotected intercourse, an activity which increases vulnerability to AIDS and other sexually transmitted diseases. To this end, seven themes were isolated from the interview scripts, these being permissiveness, double standards, belief about sexual control (the Id Factor), romance, regrets about permissiveness, sexual aggression, and questioning. Measures of four of these themes were constructed, and sex and sub-group differences explored, as were the relationships between themes and sexual risk. The implications of different "pathways" to sexual risk-taking were discussed.

Acquired Immunodeficiency Syndrome

Neuropeptide F (Moniezia expansa): localization and characterization using specific antisera.

Immunocytochemical techniques used in conjunction with confocal scanning laser microscopy (CSLM) and electron microscopy have been used to demonstrate, for the first time, the distribution of the parasitic platyhelminth neuropeptide, neuropeptide F (NPF) in the cestode, Moniezia expansa. Antisera were raised to intact NPF(1-39) and to the C-terminal decapeptide of NPF(30-39). These antisera were characterized and validated for use in both immunocytochemistry and radioimmunoassay (RIA). NPF immunoreactivity (IR) was detected using both antisera throughout all of the major components of the central and peripheral nervous systems of the worm. The pattern of NPF-IR was found to mirror the IR obtained using a C-terminally directed pancreatic polypeptide (PP) antiserum and FMRFamide antisera; blocking studies using these antisera revealed that FMRFamide and PP antisera cross-react with NPF(M. expansa). RIA of acid-alcohol extracts of the worm measured 114 ng/g using the C-terminal NPF antiserum and 56 ng/g using the whole-molecule-directed antiserum. While the C-terminally-directed NPF antiserum cross-reacts with NPF-related peptides from other invertebrates, the whole-molecule-directed NPF antiserum is specific for NPF(M. expansa). The C-terminal NPF antiserum has potential for use in the identification and purification of NPF analogues from other platyhelminth parasites.

Amino Acid Sequence

Anaesthetic modification of regional myocardial functional adjustments during myocardial ischaemia: halothane vs fentanyl.

During myocardial ischaemia, functional compensation occurs by non-ischaemic regions of the left ventricle (LV). Anaesthetics may affect compensation by altering contractility, metabolism and perfusion. This was studied in dogs anaesthetized with fentanyl (150 micrograms kg-1 loading dose and 100 micrograms kg-1 h-1) or 0.75% and 1.5% halothane and subjected to left anterior descending artery (LAD) occlusion. After 15 min of anterior wall ischaemia, cardiac output, mean arterial pressure and LV maximum dP/dt were diminished in the 1.5% halothane but not in the 0.75% halothane or fentanyl groups. In all groups, stroke volume decreased, LV end-diastolic pressure increased and anterior wall function deteriorated (measured as systolic shortening, peak systolic intramyocardial pressure (IMP), regional wall stroke work (RSW) and slope of preload recruitable stroke work curve (Mw)) with ischaemia. Functional changes in the lateral (non-ischaemic) wall were different between groups. Regional function during occlusion in this area improved with fentanyl (mean (SEM) IMP, RSW and Mw increased by 23 (2)%, 37 (3)% and 69 (7)%, respectively), was relatively well maintained with 0.75% halothane and diminished with 1.5% halothane.

Anesthesia, Inhalation

Investigation of evidence for anticipatory postural adjustments in seated subjects who performed a reaching task.

The paradigm for study of anticipatory postural adjustments permits investigation of the coordination of postural and voluntary components of functional movement. The purpose of this study was to investigate whether there were anticipatory postural adjustments for voluntary movement in seated subjects under clinically relevant conditions. Eight neurologically normal subjects performed a reaching task to a target placed at shoulder height, 45 degrees to the right of midline. Onsets and magnitudes of lateral and fore-aft reactive forces associated with the movement and of electromyographic (EMG) activity of the ipsilateral deltoid and external abdominal oblique and contralateral paraspinal muscles were monitored. Conditions of trunk support, reach speed, and distance reached were manipulated. Onsets of deltoid muscle EMG activity preceded onsets of postural muscle (external oblique and paraspinal) EMG activity in 70% of all trials for seated subjects in contrast to reports of EMG activity onset in the postural muscles in advance of the prime mover in standing subjects who performed a similar task. The role of the trunk musculature and the significance of reactive forces in advance of hand movement were equivocal. This study has implications for evaluation of postural instability in persons unable to stand for testing.

Adult

In situ ultrastructural characterization of chondroitin sulfate proteoglycans in normal rabbit aorta.

We used a monoclonal antibody recognizing chondroitin sulfate (CS) to investigate by immunocytochemistry the characteristics displayed in situ by aortic proteoglycans (PG) containing CS side chains. The antibody specifically precipitated metabolically labeled PG from aortic extracts. Anti-CS specificity was also tested directly on tissue sections and was confirmed by the virtual abolition of immunolabeling on those previously digested with CS-specific enzymes. The overall CS-PG distribution assessed by light microscopy after embedding in Lowicryl KM4 by silver-enhanced immunogold recapitulated that obtained on frozen sections with immunoperoxidase. Extracellular concentrations of CS-PG were very high in the innermost regions of aorta and decreased in the media. The reaction was weak and diffuse in the adventitia. By electron microscopy, the detailed labeling of CS-PG discriminated patterns of organization at both the regional and the molecular level and enabled morphometric estimations. In relation to other components of the extracellular matrix, we found that CS-PG and elastin mutually excluded each other, while two types of CS-PG were differently associated with collagen within media or adventitia. The use of high-resolution immunodetection for the in situ characterization of aortic CS-PG could add specific information relevant to many biological processes in which these molecules have been implicated.

Animals