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Biomedical subjects

S Moore

Publications and source records attributed to S Moore.

At least 145 records · Page 8Linked to original sources
PubMed1994

Metastatic prostate cancer pulmonary nodules: beneficial effects of combination therapy and subsequent withdrawal of flutamide.

A case is presented of a middle-aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed.

Acid Phosphatase↗
PubMed1994

Approaches to maximizing stable expression of alpha 1-antitrypsin in transformed CHO cells.

A variety of approaches to maximizing the production of recombinant human alpha 1-antitrypsin (AAT) in Chinese hamster ovary (CHO) cells have been investigated. The highly active and inducible human cytomegalovirus immediate early (IE) promoter/enhancer was used to drive transcription of a recombinant AAT gene in transiently transfected and stably transformed CHO cells. The AAT gene was modified to incorporate highly efficient 3'RNA processing signals from the herpes simplex virus type 2 IE gene 5, and optimal translational initiation signals were created by site-directed mutagenesis. The effect of flanking the recombinant gene with matrix attachment regions was investigated. Combinations of these modifications allowed secretion of up to 44 micrograms AAT/ml per day by cell lines growing in serum-rich medium. This could be increased to up to 100 micrograms AAT/ml per day upon chemical induction of expression by propionate, butyrate or hexamethylene bisacetamide. Cell lines adapted to grow in protein-free medium produced less AAT but still responded to chemical induction to secrete up to 14 micrograms/ml per day of readily purified AAT.

Animals↗
PubMed1994

Research integration.

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Academic Medical Centers↗
PubMed1994

Atypical antipsychotics, clozapine and sulpiride do not antagonise amphetamine-induced stereotyped locomotion.

An automated tracking system which converted an animal's path between quadrants of a circular open field into a series of trips was used to analyse stereotyped locomotion in amphetamine treated rats. Amphetamine (3.5 mg/kg) increased the horizontal distance moved and the number and proportion of thigmotaxic trips around the perimeter of the apparatus (length 4 trips). To investigate the hypothesis that classic antipsychotics, but not atypical antipsychotics, would antagonise the repetitive boundary patrolling associated with amphetamine-induced hyperactivity, animals were pretreated with haloperidol (0.01, 0.025, 0.05, 0.075 mg/kg), clozapine (5, 10, 20 mg/kg) or (+/-)sulpiride (10, 20, 50 mg/kg) 30 min before 3.5 mg/kg amphetamine. The results showed that the classic antipsychotic haloperidol antagonised both hyperactivity and the increased proportion of length 4 trips. In marked contrast, the atypical antipsychotics clozapine and sulpiride antagonised hyperactivity but did not reduce the proportion of length 4 trips. The inability of atypical antipsychotics to reduce the repetitive boundary patrolling associated with amphetamine-induced hyperactivity is consistent with the action of these drugs on other forms of amphetamine-induced stereotyped behaviour, and indicates that locomotor routes under amphetamine are stereotyped. The measurement of trip lengths provides a sensitive tool for examining drug action on the spatial distribution of open field locomotion.

Amphetamine↗
PubMed1994

Lipoprotein-proteoglycan complexes from injured rabbit aortas accelerate lipoprotein uptake by arterial smooth muscle cells.

Lipoprotein-proteoglycan (LP-PG) complexes are taken up more avidly by macrophages and smooth muscle cells (SMCs) than native lipoproteins (LPs). The enhanced uptake may contribute to lipid accumulation and foam cell formation during atherogenesis. Endothelial injury is known to alter proteoglycan (PG) synthesis and distribution in the neointima developed in response to injury. The present study examines the uptake and degradation of LP-PG complexes, derived from PG of injured aortas by arterial SMCs. Rabbit apo-B lipoprotein (LP), including VLDL, IDL and LDL was isolated by ultracentrifugation and coupled with PG extracted from normal aortas (NPG) or with PG from injured aortas (IPG). Rabbit aortic SMCs were cultured from intima-media explants, incubated with 125I-LP, 125I-LP-NPG or 125I-LP-IPG for 20 h at 37 degrees C. LP binding, internalization and degradation were markedly increased (P < 0.001) for LP-NPG and LP-IPG over native LP. Competition experiments indicated that more than 50% of the LP-PG complexes were taken up by the apo-B/E receptor pathway. Phagocytosis was the second important route of uptake of these complexes, whereas the scavenger receptor played a minor part in the uptake and degradation of LP-PG complexes. Data from this study indicate that LP-PG complexes accelerate LP uptake and degradation by SMC more than native LP. Therefore, these complexes may contribute to lipid accumulation by SMC, thus generating foam cells. Furthermore, LP-PG complexes prepared from PG of injured aortas are more effective in lipid accumulation than LP-PG complexes from PG of normal aortas.

Animals↗
PubMed1994

Platyhelminth FMRFamide-related peptides (FaRPs) contract Schistosoma mansoni (Trematoda: Digenea) muscle fibres in vitro.

Molluscan FMRFamide and two recently discovered platyhelminth FMRFamide-related peptides (FaRPs), GNFFRFamide from the cestode Moniezia expansa and RYIRFamide from the terrestrial turbellarian Artioposthia triangulata, cause dose-dependent contractions of individual muscle fibres from Schistosoma mansoni in vitro. The most potent FaRP tested was the turbellarian peptide RYIRFamide, which produced a concentration-dependent effect between 10(-9) and 10(-7) M. FMRFamide and GNFFRFamide were less potent, inducing contractions between 10(-8)-10(-6) M and 10(-7)-10(-5) M respectively. The contractile effect of each of these peptides was blocked by the presence of 1 microM FMR-D-Famide. FMRF free acid did not elicit contraction of the muscle fibres. The FaRP-induced contractions did not occur if the Ca2+ was omitted and 0.5 microM EGTA was added to the extracellular medium. The FaRP-induced contractions were not blocked by the Ca2+ channel blockers nicardipine, verapamil or diltiazem, although high K+-induced contractions of these fibres were blocked by nicardipine. These data indicate the presence of FaRP receptors on schistosome muscle fibres and demonstrate their ability to mediate muscle contraction. The action of these endogenous flatworm peptides on schistosome muscle is the first demonstration of a direct excitatory effect of any putative neurotransmitter on the muscle of a flatworm, and establishes a role for FaRPs in neuromuscular transmission in trematodes. In addition, it provides the first evidence that the peptidergic nervous system is a rational target for chemotherapeutic attack in parasitic platyhelmiths.

Amino Acid Sequence↗
PubMed1994

Isolation of lipoprotein-proteoglycan complexes from balloon catheter deendothelialized aortas and the uptake of these complexes by blood monocyte-derived macrophages.

Lipoprotein-Proteoglycan (LP-PG) complexes from the neointima, developed in response to injury, were studied to examine their ability to stimulate lipid accumulation in blood monocyte-derived macrophages (BMDM). LP-PG complexes were extracted from intimal-medial tissues from normal and balloon catheter deendothelialized aortas of normocholesterolemic rabbits, in 0.16 M NaCl for 24 h at 4 degrees C. The extract was purified through an anti-apo-B affinity column. Adsorbed material dissociated with 4 M Gu-HCI buffer was analyzed for lipoproteins (LP) and glycosaminoglycans (GAG). Results demonstrated that LP-PG complexes consisted of apo-B associated with chondroitin sulfate and hyaluronic acid. BMDM were incubated with 125I-LP, 125I-LP-NPG (from normal aortas) or 125I-LP-IPG (from injured aortas) for 20 h at 37 degrees C. LP binding, internalization and degradation was markedly increased for LP-NPG and LP-IPG over native LP. Phagocytosis appeared to be the primary route of uptake of LP-PG complexes. Competition experiments indicated that about 40% of the uptake of LP-PG complexes is mediated by the apo-B/E receptor pathway. The scavenger receptor played a minor part in the uptake of LP-PG complexes. Data from this study indicate that LP-PG complexes are present in normal and injured aortas of normocholesterolemic rabbits and these complexes accelerate LP uptake by BMDM more than native LP. Therefore, LP-PG complexes may contribute to lipid accumulation by BMDM, thus generating foam cells. Furthermore, LP-PG complexes prepared from PG of injured aortas are more effective in lipid accumulation than LP-PG complexes from PG of normal aortas.

Animals↗
PubMed1994

Homeless youths: sexual and drug-related behaviour, sexual beliefs and HIV/AIDS risk.

Homeless, Anglo-Australian and Greek-Australian 16-year-olds were questioned about their sexual behaviour and sexual beliefs. Measures of sexual risk-taking included type of behaviour, condom use and number of partners. Drug risk was assessed by extent of i.v. drug use, and sharing and cleaning needles. Sexual beliefs included self-perceptions of sexual anxiety, arousal, exploration and commitment. In addition, motivations for engaging in, or avoiding, sex were elicited. The behaviour patterns of homeless adolescents placed them at considerable risk of HIV infection for both sexual and drug risk, and significantly more so than their home-based peers. Gender stereotypic self-perceptions were reported, and homeless and Anglo-Australian youths demonstrated a more masculine style in their self-perceptions than were Greek-Australians. Preferred motivations for sex differed, with homeless youths less concerned about the consequences of sex and more with self-gratification than the home-based adolescents. For homeless girls, higher levels of sexual risk were predicted by perceptions of greater arousal and by less concern about the consequences of sexual activity. Implications for targeted interventions are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Early identification and remediation of phonological-processing deficits in first-grade children at risk for reading disabilities.

The present study assessed 486 first-quarter first graders on their reading and phonological-processing skills and intelligence. Based on this assessment, and using the classification data from Hurford et al.'s (1993) study, 99 children were identified as being at risk for reading difficulties: 53 children at risk for reading disabilities (RD) and 46 children at risk for becoming "garden-variety" poor readers (GV). Half of the RD and GV groups received the phonological-processing intervention. Posttraining assessment indicated that the training procedure not only was effective in increasing the phonological-processing skills of the trained participants, but also increased their reading ability. Both of the RD and GV trained groups benefited from the training. Analyses also indicated that the initial screening device was somewhat less accurate in the present study in identifying at-risk children than in our previous studies (85% vs. approximately 98%, respectively). The results of the present study indicate that it is possible to identify children at risk for reading difficulties and to significantly improve their phonological-processing and reading abilities.

Child↗
PubMed1994

Understanding innovation in social service delivery systems.

Progress in the social services is driven by innovation. It depends on the ability of social work researchers and practitioners to find innovative solutions to the problems they face. Innovation entails the creation, adaptation, and adoption of new approaches to service delivery. The most fundamental type of innovation is the creation of a new service product. However, innovations in the way services are delivered are equally important. This paper provides a model for understanding innovation in social services.

Delivery of Health Care↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

Discrepancies in kinematic calculations of HOLZ lines.

We have found significant differences between the results of computer simulations of HOLZ line patterns. The computations in question are made in the kinematical approximation. After trivial errors are eliminated the programs fall into two groups. There is a discrepancy between the two that increases with distance from the zone axis. The difference is small but not negligible at the level of precision used in determining lattice parameters or strain. We show which of the two is correct in the kinematic approximation and that the discrepancy between the two groups is of the order of the error introduced by dynamical interaction.

Computer Simulation↗