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Biomedical subjects

L Foster

Publications and source records attributed to L Foster.

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

Accumulation of large very low density lipoprotein in plasma during intravenous infusion of a chylomicron-like triglyceride emulsion reflects competition for a common lipolytic pathway.

Very low density lipoproteins (VLDL) are produced in the liver and contain apolipoprotein (apo) B-100 and endogenous lipids. By contrast, ingestion of fat leads to formation of chylomicrons containing apoB-48 secreted from the intestine. In this study, a 60-min intravenous infusion of a chylomicron-like triglyceride emulsion was given to healthy young men to examine whether competition between chylomicrons and VLDL for the same lipolytic pathway explains the increase in VLDL seen after meals. The responses of two major VLDL subfractions were determined by measuring the concentrations of apoB-100 in fractions of triglyceride-rich lipoproteins with Svedberg flotation rates of 60-400 (large VLDL) and 20-60 (small VLDL) that were separated from plasma by density gradient ultracentrifugation. A threefold elevation in plasma triglycerides was observed during the infusion together with a consistent linear increase of large VLDL. The rate at which large VLDL accumulated in plasma differed markedly among individuals and was not enhanced by doubling of the infusion rate. The response of small VLDL was more heterogeneous; however, a decrease was seen in most subjects. The combined pattern for the two VLDL species is what would be expected if large VLDL particles are the precursors of smaller VLDL species and if lipolysis of large VLDL is inhibited through competition from the triglyceride emulsion. The extent to which the triglyceride emulsion inhibited the lipolysis of VLDL and/or influenced the synthesis rate of large VLDL was estimated from simultaneous stable isotope studies. The emulsion caused a 75-90% block of the conversion of large VLDL apoB to small VLDL apoB and there was no sign of enhanced synthesis of large VLDL after infusion of the triglyceride emulsion. The corollary of these findings is that chylomicrons and their remnants impede the normal lipolytic degradation of VLDL and could thereby be indirectly implicated in the generation of atherogenic remnant lipoproteins.

Adult↗
PubMed1995

Analysis of the stoichiometry of Rab protein prenylation.

Rab5 is a Ras-related GTP-binding protein that is post-translationally prenylated with the 20-carbon isoprenoid geranylgeranyl. We have developed a method to determine the stoichiometry of prenylation of Rab5, and Rab family members in general, based on the cell-free translation of these peptides in the presence or the absence of appropriate isoprenoids. Modification of cell-free synthesized Rab5 can be monitored by following the conversion of 35S-labeled peptide to a greater mobility isoform on urea-gradient sodium dodecyl sulfate-polyacrylamide gels. The mobility-shifted isoform also incorporates radiolabel in the presence of [3H]mevalonate or [3H]geranylgeranyl pyrophosphate, confirming post-translational modification with geranylgeranyl. A quantitative assessment of the conversion of mobility-shifted Rab5, promoted by prenylation, and the amount of incorporated radiolabel from [3H]geranylgeranyl pyrophosphate was achieved by excising gel slices containing radiolabeled isoforms and measuring the covalently associated radioactivity. Using this approach, we have established that 2 moles of geranylgeranyl is attached per mole of Rab5 peptide. A 2:1 molar ratio of geranylgeranyl:peptide is observed for both Rab5wt and a truncation mutant, Rab5(1-213), containing C-terminal motifs CCXX and XXCC, respectively. When Rab proteins ending in CXC are synthesized and processed in vitro, they also incorporate geranylgeranyl at a 2:1 stoichiometry, although extended times of incubation are required for full modification. Finally, a C-terminal Rab5 truncation mutant retaining only one cysteine also becomes modified, although only a minor fraction is fully processed. This method offers a novel, quantitative approach to investigate the stoichiometry of post-translational processing of cell-free synthesized peptides without the need to purify the native molecules.

Animals↗
PubMed1995

Immunogenicity of the recombinant serine rich Entamoeba histolytica protein (SREHP) amebiasis vaccine in the African green monkey.

We report the first study in non-human primates of the safety and immunogenicity of a recombinant vaccine designed to prevent amebic liver abscess. In a pilot study, a recombinant vaccine containing the serine rich Entamoeba histolytica protein (SREHP) attached to a maltose binding protein (SREHP/MBP), which has been shown to be effective in preventing amebic liver abscess in rodent models of infection, was used to immunize two African Green Monkeys. Vaccination with SREHP/MBP resulted in no systemic side-effects. The monkeys receiving the SREHP/MBP protein developed antibodies that recognized the recombinant SREHP/MBP molecule, the native SREHP protein, and the surface of amebic trophozoites. Antiserum from SREHP/MBP-vaccinated monkeys could block the adhesion of E. histolytica trophozoites to mammalian cells, a feature that may correlate with vaccine efficacy. Attempts to produce amebic liver abscess in naive African Green Monkeys by direct hepatic inoculation with virulent E. histolytica trophozoites was not successful, suggesting this species is probably not suitable for vaccine efficacy studies.

Animals↗
PubMed1995

The simian virus 40 large T antigen does not inhibit translation of the 14-kDa myelin basic protein mRNA in reticulocyte lysates or in transfected cells.

Viral T antigens are transcription factors that have been suspected of inhibiting expression of the myelin basic protein (MBP) mRNA at the translational level in vitro and in vivo. The effect of simian virus 40 (SV40) large T antigen (T-ag) was examined on the translation of the 14-kDa MBP mRNA in reticulocyte lysates and on MBP expression after transfection into cells that express SV40 T-ag. SV40 T-ag did not inhibit translation of 14-kDa MBP cRNAs in cell-free translations even at 30 microM (approximately 600 micrograms/ml) T-ag. Permanent transfection of COS-1 cells (which endogenously express SV40 T-ag) with the 14-kDa MBP cDNA resulted in the expression of the 14-kDa MBP as determined by western blot analysis. Permanent transfection of N20.1 cells, an oligodendrocyte line immortalized with a temperature-sensitive SV40 T-ag, with the 14-kDa MBP cDNA construct also resulted in the expression of the 14-kDa MBP under conditions in which the cells expressed functional SV40 T-ag. These results indicate that SV40 T-ag does not prevent expression of the MBP gene at the translational level and that in those immortalized oligodendrocyte lines that express MBP mRNA, but not MBP protein, some factor other than the SV40 large T-ag is responsible for the posttranscriptional regulation.

Animals↗
PubMed1995

Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women.

VLDL1, VLDL2, IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were quantified in 304 normolipemic subjects together with postheparin plasma lipase activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of VLDL1 and VLDL2 rose as plasma triglycerides (TGs) increased across the normal range, but the association of plasma TGs with VLDL1 showed a steeper slope than that of VLDL2 (P < .001). Plasma TG level was the most important determination of LDL subfraction distribution. The least dense species, LDL-I, decreased as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a positive association with plasma TG level in the range 0.5 to 1.3 mmol/L, increasing from about 100 to 200 mg/dL. In contrast, within this TG range the LDL-III concentration was low (approximately equal to 30 mg/dL) and changed little. As plasma TGs rose from 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentration in men (r = .45, P < .001) but not in women (r = .1, NS). Conversely, above the TG threshold of 1.3 mmol/L there was a steeper rise in LDL-III concentrations in men than in women (P < .001); 42% of the men had and LDL-III in the range associated with high risk of heart disease ( > 100 mg lipoprotein/dL plasma) compared with only 17% of the women. Other influences on the LDL subfraction profile were the activities of lipases and parameters indicative of the presence of insulin resistance. Men on average had twice the hepatic lipase activity of women. This enzyme was not strongly associated with variation in the LDL subfraction profile in men, but in women it was correlated with LDL-III (r = 39, P = .001) and remained a significant predictor in multivariate analysis. Increased waist/hip ratio, fasting insulin, and glucose were correlated negatively with LDL-I and positively with LDL-III, primarily, at least in the case of LDL-III, through raising plasma TGs. On the basis of these cross-sectional observations we postulate the following model for the generation of LDL-III. Subjects develop elevated levels of large TG-rich VLDL1 for a number of reasons, including failure of insulin action. The increase in the concentration of VLDL1 expands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein (which facilitates neutral lipid exchange between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the major LDL species.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Antibodies to the serine rich Entamoeba histolytica protein (SREHP) prevent amoebic liver abscess in severe combined immunodeficient (SCID) mice.

Amoebic liver abscess caused by Entamoeba histolytica is a major cause of morbidity and mortality worldwide. We used mice with severe combined immunodeficiency (SCID mice) to study the role of antibody in protection from amoebic liver abscess, and to identify protective antigens of E. histolytica. Antisera to recombinant versions of two major surface antigens of E. histolytica, the serine rich E. histolytica protein (SREHP) and the 170 kDa adhesin were used in this study. We found that 100% of SCID mice passively immunized with antiserum to the recombinant SREHP molecule were protected from developing amoebic liver abscess after intrahepatic challenge with virulent E. histolytica trophozoites. In contrast, preimmune serum, antiserum to a portion of the 170 kDa adhesin, and antiserum to the trpE fusion partner of SREHP did not protect SCID mice from amoebic liver abscess. Our study demonstrates that antibodies to a recombinant version of the amoebic SREHP molecule can protect against amoebic liver abscess, and suggest the recombinant SREHP molecule should be considered as a possible vaccine candidate to prevent amoebic liver abscess.

Animals↗
PubMed1994

It's what we do.

Explore the source record for details and available documents.

Critical Care↗
PubMed1993

Lead poisoning among low-income children in Orange County, California. A need for regionally differentiated policy.

OBJECTIVE: To estimate the prevalence of elevated lead levels among children in Orange County, California, and to evaluate the appropriateness of a universal pediatric blood lead screening policy in this community. DESIGN: Venous blood lead testing was conducted and results were analyzed according to seven blood lead strata ranging from less than 0.50 mumol/L (10 micrograms/dL) to 3.35 mumol/L (70 micrograms/dL) or higher. A cost analysis of the lead-testing program in Orange County was conducted. SETTING: Children meeting poverty eligibility criteria and attending the Child Health and Disability Prevention Program, the state's implementation of the federal Early and Periodic Screening, Diagnosis and Treatment (EPSDT) services program. PARTICIPANTS: A total of 5115 Orange County children between 12 and 72 months of age using EPSDT services from March through December 1992. MAIN OUTCOME MEASURES: Blood lead levels and associated costs of the testing program stratified by level of blood lead elevation. RESULTS: Blood lead levels of 0.50 mumol/L (10 micrograms/dL) or higher were found in 371 children (7.25%; 95% confidence interval, 6.66% to 7.85%), but only six children (0.12%; 95% confidence interval, 0.04% to 0.20%) had elevations greater than 1.20 mumol/L (25 micrograms/dL). Five children (83.3%) had histories of lead consumption unrelated to ingestion of lead-containing paint but related to the use of lead-containing folk remedies and cooking utensils. Costs for detection of children with blood levels elevated to 0.50 mumol/L (10 micrograms/dL) or higher was $310 per child and for levels of 1.20 mumol/L (25 micrograms/dL) or higher was $19,139 per child. CONCLUSIONS: These data suggest that lead poisoning is not a major public health problem among Orange County children and detection of infrequent cases would involve a high cost per child. In jurisdictions with newer housing, initial screening for a history of possible lead exposure alone may offer reasonable efficacy that is cost-effective. The scope of lead-testing programs should be determined according to local needs and conditions.

California↗
PubMed1993

Self-management of osteoarthritis.

Osteoarthritis is the most prevalent activity-limiting condition among older persons. In addition to, or instead of, taking nonsteroidal anti-inflammatory drugs, people use a variety of activities to manage their osteoarthritis. This study describes the self-management methods reported by 61 participants aged 60 years or older assessed on two occasions 8 months apart. A questionnaire was developed to assess levels of use of 10 self-management methods including low-impact activity, rest, range-of-motion exercises, relaxation, heat (or cold), taking medication, joint protection, massage, splints, and any other activity. On a typical day, participants used about four of these activities to manage osteoarthritis symptoms, and significantly more on a day that their arthritis was worse than usual. Three self-management scales were formed from groups of activities suggested by factor analysis (medication taking, typical management, and worse-day passive management) that demonstrated adequate internal consistency and stability across the two assessments. The findings are discussed in terms of the importance of developing a brief measure of osteoarthritis self-management, and the substantial individual variation in subsets of methods used.

Activities of Daily Living↗
PubMed1992

Molecular analysis of carbohydrate antigen-induced monoclonal IgM anti-IgG antibodies (rheumatoid factors).

Light and heavy chain variable regions of 11 monoclonal rheumatoid factors (MRF) produced after carbohydrate antigen immunization, and one MRF produced after protein immunization have been sequenced. Most carbohydrate antigen induced MRF utilized light chains that were homologous to light chains of MRF obtained from protein immune or LPS stimulated mice, and MRF derived from the autoimmune MRL/lpr mouse strain. VH gene usage was diverse for carbohydrate antigen induced MRF that bound all four isotypes of IgG, or that bound only the IgG3 isotype. In contrast VH gene use among our panel of MRF that bound the IgG1 isotype appeared restricted. Four of the five IgG1 binders used VH genes that were highly homologous to the VH nucleotide sequence of a gene encoding an NP binding monoclonal antibody. Our study confirms the use of a particular group of light chain genes among murine MRF, confirms that there is diversity in the heavy chain genes utilized among MRF, and suggests that a gene(s) homologous to the VH NP 23 J558 gene may be preferentially associated with murine MRF specificity for the IgG1 isotype.

Amino Acid Sequence↗
PubMed1991

Purification and characterization of 3-hydroxymethylglutaryl-coenzyme A reductase of Schistosoma mansoni: regulation of parasite enzyme activity differs from mammalian host.

The enzyme 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase plays a critical role in regulating the production of cholesterol, dolichols, and ubiquinones in mammals. The inhibition of this enzyme in Schistosoma mansoni is accompanied by a cessation of egg production by the female parasite and a reduced ability of the parasite to properly glycoslyate their proteins. Furthermore, we recently demonstrated that mevinolin, if given continuously over a period of 10-14 days, is a potent antischistosomal drug. In this paper, we describe the properties of purified HMG-CoA reductase from S. mansoni. Using affinity chromatography, we were able to obtain a 417-fold purification of the enzyme which had Km values similar to the rat enzyme for HMG-CoA and NADPH. The Ki value for mevinolin, a potent and selective inhibitor of the rat reductase (Ki = 0.6 nM), was significantly higher (Ki = 46 nM) for the schistosome enzyme. SDS-PAGE and HPLC of the purified enzyme resulted in the appearance of a single protein, which had a molecular weight (66,000) in the range reported for the rat enzyme. Parasite reductase activity, unlike that of its host, did not display a circadian rhythm. Furthermore, agents which elevate (cholestyramine) or decrease (cholesterol) mammalian reductase activity had no effect on the parasite enzyme. Our results suggest that the mechanism which regulates production of the parasite's enzyme may differ from its mammalian host.

Acyl Coenzyme A↗
PubMed1991

The influence of some factors on local control of early glottic cancer.

A total of 135 patients with T1N0M0 and T2N0M0 carcinoma of the vocal cord were treated during a 20-year period at St Mary's Hospital in Portsmouth by local radiotherapy. A total of 122 patients were available for local control analysis. The local control of T1 tumours was 80.5%, and for T2, 51.1%, total T1 + T2 local control was 69.7% (P less than 0.001). The only other factor in univariate analysis, which influenced the results was the overall treatment time. In the group of patients treated by an overall time of 45 days or less, the local control was 83.7%. For longer time it was 62% (P less than 0.02). Multivariate analysis confirmed these findings but brought out the importance of vocal cord mobility as the best discriminating factor between local control and failure, followed by overall treatment time.

Adult↗
PubMed1991

Chemical and enzymatic degradation of ganciclovir prodrugs: enhanced stability of the diadamantoate prodrug under acid conditions.

We report the chemical and enzymatic hydrolysis of two hydrophobic prodrugs of ganciclovir (3 = dipropionate ester; 4 = diadamantoate ester). Both prodrugs undergo hydrolysis showing a pH dependence of kobs = kH+aH+ + ko + kHO-aHO- and a pH of maximum stability near pH 5. Only 4 exhibited a shelf life (t90) greater than 2 years. Compound 4 reacts significantly slower than ganciclovir in acidic media, even though the adamantyl esters provide additional reaction sites (which would be expected to increase the rate of degradation) that are distally removed from the guanine ring system, offering negligible steric or electronic substituent effects. Both 3 and 4 hydrolyzed in tissue homogenate, where kobs followed liver greater than intestine much greater than skin. Based on these findings of chemical stability, lipophilicity, and acceptable rate of enzymatic cleavage by skin esterases, 4 meets several of the criteria required for the topical sustained delivery of ganciclovir.

Animals↗
PubMed1990

Assembly of MHC class I molecules analyzed in vitro.

Recent evidence suggests that peptide ligands take part in the assembly of class I molecules in living cells. We now describe a simple system for studying class I assembly in vitro. Detergent extracts of the mutant cells RMA-S and .174, in which class I assembly does not occur spontaneously, will support assembly in vitro when specific peptides are added. Peptides stabilize a conformational change in the class I heavy chain and association with beta 2-microglobulin, at concentrations approximately 100-fold lower than required in "peptide feeding" experiments with whole cells. We show that peptides bind class I molecules during assembly and demonstrate that the conformational change induced in the heavy chain is influenced by the concentrations of both peptide and beta 2-microglobulin.

Amino Acid Sequence↗