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S Lindsey

Publications and source records attributed to S Lindsey.

At least 19 recordsLinked to original sources
PubMed2005

The use of pine bark and natural zeolite as biofilter media to remove animal rendering process odours.

Studies of odour-control pilot-scale biofilters at a rendering plant were conducted for five years. The biofilters contained different sizes of crushed pine bark or a mixture of zeolite and crushed bark, and treated the exhaust gases from direct-fired meal dryers. The exhaust gases were odorous and contained significant smoke. The odour concentration of the rendering process air ranged between 50,000 and 307,200 OU m(-3). Odour-removal performance measurements of the biofilters were undertaken on five occasions using forced-choice dynamic-dilution olfactometry. Biofilter odour-removal efficiencies of between 80% and 99% were measured at various influent odour concentrations and air loading rates. There was no obvious deterioration in performance of these biofilters between various sampling times in the five year study period. The biofilters also reduced the "offensiveness" of the odour. The fine crushed bark biofilter generally reduced odour concentration more efficiently than the coarse bark biofilter. The additions of zeolite to the bark medium in the biofilter had little effect on the odour-removal performance. An increase in air loading rate produced only a very small decrease in odour-removal performance. The pilot-scale biofilters had smoke removal efficiencies between 71% and 100%. Finely crushed bark removed smoke more effectively than coarsely crushed bark. Drainage from the biofilters contained significant concentrations of pollutants, suggesting that controlled leaching has potential to remove accumulated substances in biofilter media from rendering gas emissions and increase the longevity of a biofilter system.

Abattoirs↗
PubMed2000

Medicine. Communicating statistical information.

Most people, experts included, have difficulties understanding and combining statistical information effectively. Hoffrage et al. demonstrate that these difficulties can be considerably reduced by communicating the information in terms of natural frequencies rather than in terms of probabilities. Several applications in medicine, legal decision-making, and education are discussed.

DNA Fingerprinting↗
PubMed2000

A model of dual attitudes.

When an attitude changes from A1 to A2, what happens to A1? Most theories assume, at least implicitly, that the new attitude replaces the former one. The authors argue that a new attitude can override, but not replace, the old one, resulting in dual attitudes. Dual attitudes are defined as different evaluations of the same attitude object: an automatic, implicit attitude and an explicit attitude. The attitude that people endorse depends on whether they have the cognitive capacity to retrieve the explicit attitude and whether this overrides their implicit attitude. A number of literatures consistent with these hypotheses are reviewed, and the implications of the dual-attitude model for attitude theory and measurement are discussed. For example, by including only explicit measures, previous studies may have exaggerated the ease with which people change their attitudes. Even if an explicit attitude changes, an implicit attitude can remain the same.

Affect↗
PubMed1999

Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice.

The pro-inflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), plays a fundamental role in monocyte recruitment and has been implicated as a contributing factor to atherosclerosis. The predominant cell types within the vessel wall--endothelial cells, smooth muscle cells, and macrophages--all contribute to overexpression of MCP-1 in atherosclerotic tissue. In this report we assess the role of MCP-1 expression by leukocytes on lesion progression in a murine model susceptible to atherosclerosis. Bone marrow cells from mice overexpressing a murine MCP-1 transgene on a background of apoE-deficiency or from control mice were transplanted into irradiated apoE-knockout mice. After repopulation of apoE-knockout mice with bone marrow containing the MCP-1 transgene, macrophages expressing the MCP-1 transgene were found in several tissues, including the aorta. Qualitative assessment of atherosclerosis in these mice revealed increased lipid staining, a 3-fold (P<0.001) increase in the amount of oxidized lipid, and increased immunostaining for macrophage cell surface markers with anti-F4/80 and anti-CD11b antibodies. There were no differences in plasma lipids, plasma lipoprotein profiles, or body weight between the 2 groups. These results provide the first direct evidence that MCP-1 expression by leukocytes, predominately macrophages, increases the progression of atherosclerosis by increasing both macrophage numbers and oxidized lipid accumulation.

Animals↗
PubMed1999

HMG-CoA reductase regulation: use of structurally diverse first half-reaction squalene synthetase inhibitors to characterize the site of mevalonate-derived nonsterol regulator production in cultured IM-9 cells.

The activity of HMG-CoA reductase (HMGR) is tightly regulated, in part through post-transcriptional mechanisms that are mediated by nonsterol products of mevalonate metabolism. Previous reports have suggested that these mediators are derived from farnesyl pyrophosphate (FPP). Recent studies have implicated FPP hydrolysis products (e.g., farnesol), the squalene synthetase (SQS) reaction products presqualene pyrophosphate (PSQPP) and squalene, or their metabolites. To distinguish among these possible mediators, we evaluated the ability of HMGR and SQS inhibitors to induce compensatory increases in HMGR activity in cultured IM-9 cells. Mevinolin (HMGR inhibitor) produced predicted increases in HMGR activity that were related to the degree of cholesterolgenesis inhibition (e.g., 4-fold, 9-fold, and 17-fold increases relative to 50%, 76%, and 90% inhibition, respectively). By contrast, a variety of structurally distinct reversible, competitive, first half-reaction SQS inhibitors all reduced cholesterolgenesis by up to 90% with no appreciable increases in HMGR activity. These observations strongly suggest that nonsterol-mediated post-transcriptional mechanisms regulating HMGR activity remain intact after SQS first half-reaction inhibition, indicating that nonsterol regulator production is independent of SQS action and ruling out PSQPP, squalene and their metabolites as possible mediators. Unexpectedly, the SQS mechanism-based irreversible inactivator, zaragozic acid A (ZGA) exhibited the greatest degree of HMGR modulation, producing 5-fold, 11-fold, and 40-fold increases in HMGR activity at concentrations that produced 25%, 50%, and 75% cholesterolgenesis inhibition, respectively. The markedly greater magnitude of HMGR stimulation by ZGA versus mevinolin at similar levels of cholesterolgenesis inhibition suggests that ZGA may directly interfere with the production or action of the nonsterol regulator.

Alkyl and Aryl Transferases↗
PubMed1997

3-(4-chlorophenyl)-2-(4-diethylaminoethoxyphenyl)-A-pentenonitrile monohydrogen citrate and related analogs. Reversible, competitive, first half-reaction squalene synthetase inhibitors.

Squalene synthetase (SQS) catalyzes the head-to-head condensation of two molecules of farnesyl pyrophosphate (FPP) to form squalene. The reaction is unique when compared with those of other FPP-utilizing enzymes, and proceeds in two distinct steps, both of which involve carbocationic reaction intermediates. In this report, we describe the mechanism of action of, and structure-activity relationships within, a series of substituted diethylaminoethoxystilbenes that mimic these reaction intermediates, through characterization of the biochemical properties of 3-(4-chlorophenyl)-2-(4-diethylaminoethoxyphenyl)-A- pentenonitrile monohydrogen citrate (P-3622) and related analogs. As a representative member of this series, P-3622 inhibited SQS reversibly and competitively with respect to FPP (Ki = 0.7 microM), inhibited the enzymatic first half-reaction to the same extent as the overall reaction, exhibited a 300-fold specificity for SQS inhibition relative to protein farnesyltransferase inhibition, inhibited cholesterol synthesis in rat primary hepatocytes (IC50 = 0.8 microM), in cultured human cells (Hep-G2, CaCo-2, and IM-9; IC50 = 0.2, 1.2, and 1.0 microM), and in chow-fed hamsters (62% at 100 mg/kg) without accumulation of post-squalene sterol precursors, and reduced plasma cholesterol in experimental animals. Structure-activity relationships among 72 related analogs suggest that the phenyl residues and central trans-olefin of the stilbene moiety serve as mimics of the three isoprene units of the donor FPP, that substitutions across the central olefin and para-substitutions on the terminal phenyl residue mimic the branching methyl groups of the donor FPP, and that the diethylaminoethoxy moiety of these molecules mimics the various carbocations that develop in the C1-C3 region of the acceptor FPP during reaction. Members of this series of reversible, competitive, first half-reaction SQS inhibitors that show a high degree of specificity for SQS inhibition relative to inhibition of other FPP-utilizing enzymes and other cholesterol synthesis pathway enzymes may serve as useful tools for probing the unique catalytic mechanisms of this important enzyme.

Animals↗
PubMed1997

Electron tomography of large, multicomponent biological structures.

Electron tomography is an extremely useful method for deriving three-dimensional structure from electron microscope images. The application of this technique to the reconstruction of large, complex structures such as mitochondria is described in conjunction with several tools for segmentation, measurement, classification, and visualization. In addition, the use of massively parallel computers to perform the tomographic reconstruction efficiently using R-weighted backprojection or iterative techniques is described.

Algorithms↗
PubMed1997

CP-225,917 and CP-263,114, novel Ras farnesylation inhibitors from an unidentified fungus. I. Taxonomy, fermentation, isolation, and biochemical properties.

During the course of our screening for squalene synthase inhibitors and Ras farnesylation inhibitors, a novel fungal culture was discovered to produce two structurally unique compounds, CP-225,917 and CP-263,114, as well as zaragozic acid A (squalestatin I). The two compounds are characterized by a bicyclo[4.3.1]dec-1,6-diene core plus two extended alkyl chains. CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 microM and 20 microM, respectively. CP-225,917 inhibits squalene synthase with an IC50 value of 43 microM and CP-263,114 with an IC50 of 160 microM. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phoma species.

Alkyl and Aryl Transferases↗
PubMed1996

Homeobox genes and male reproductive development.

PURPOSE: Homeobox genes encode transcription factors that dictate developmental events in philogenetically diverse organisms. In comparison to what is known about their role in embryogenesis, we know very little concerning homeobox gene function in neonates or adults. In this communication, we review studies that address the possible role of homeobox genes in male reproductive development, a system active in neonate and adult animals. METHODS: Studies have shown that many homeobox genes are expressed in germ cells of the testis, while less is known about the identity of homeobox genes expressed in somatic cells of the testis or epididymis. Hox homeobox genes display a pattern of expression in testis that is dependent on their paralogous and orthologous position within the Hox gene chromosome clusters. Other homeobox genes are expressed in the male reproductive system, including many POU and Prd/Pax homeobox gene family members. More recently, it has been shown that the orphan homeobox gene, Pem, originally isolated by subtraction hybridization on the basis of its differential expression in tumor cell lines, is selectively expressed in reproductive tissue. Alternatively spliced Pem transcripts accumulate in testis and epididymis that differ from those expressed in tumors and placenta. Pem transcripts accumulate postnatally in the epididymis in a developmentally regulated manner. CONCLUSIONS: The highly regulated pattern of expression exhibited by many homeobox genes in the male reproductive system suggests that homeobox transcription factors may dictate developmental events in this system. However, future studies are needed to determine the specific functional roles homeobox genes in male reproductive development and spermatogenesis.

Adult↗
PubMed1995

Inhibition of mammalian squalene synthetase activity by zaragozic acid A is a result of competitive inhibition followed by mechanism-based irreversible inactivation.

Squalene synthetase (SQS, EC 2.5.1.21) catalyzes the first committed step in the formation of cholesterol and thus represents an ideal site for selectively inhibiting sterol formation. Previous studies have demonstrated that the fungal metabolite, zaragozic acid A (ZGA-A), inhibits SQS activity by mimicking the substrate farnesyl pyrophosphate, the reaction intermediate presqualene pyrophosphate, or both, through a process that confers increased apparent potency in the presence of reduced enzyme concentrations, an observation consistent with either tight binding reversible competitive inhibition or mechanism-based irreversible inactivation. The studies outlined in this report provide multiple lines of evidence indicating that ZGA-A acts as a mechanism-based irreversible inactivator of SQS. 1) Inhibition of SQS by ZGA-A is dependent on the [SQS] present in the incubation reaction, and this inhibition is time-dependent and follows pseudo-first order reaction kinetics, exhibiting kobs values that range between 2 x 10(-4)/s and 23 x 10(-4)/s for [ZGA-A] within the log-linear range of the inhibition curve, and a bimolecular rate constant of 2.3 x 10(5) M-1s-1.2) SQS activity is titratable by ZGA-A, such that for each [ZGA-A] evaluated, inactivation exhibits a threshold [SQS] whereby enzyme activity at lower [SQS] is totally inhibited. 3) Time-dependent inactivation exhibits saturation kinetics with a Km for the process of 2.5 nM, which is approximately equal to the IC50 for SQS inhibition under these conditions, suggesting that inactivation results from selective modification of a functional group of the enzyme active center rather than from a nonspecific bimolecular reaction mechanism and that most, if not all of the inhibition results from irreversible inactivation. 4) Saturable, time-dependent inactivation occurs with similar inactivation kinetics for both the microsomal and trypsin-solubilized forms of the enzyme, indicating that irreversible inactivation by ZGA-A is not a consequence of membrane modification but is a direct effect of the inhibitor on the enzyme. 5) Inactivation is biphasic, exhibiting a rapid ("burst") phase followed by a second, pseudo-first order phase, similar to that previously noted for irreversible inactivators in other enzyme systems, and occurs even in the presence of 5 mM concentrations of the nucleophylic scavenger dithiothreitol, suggesting that the reaction between ZGA-A and SQS occurs at or near the active center prior to diffusion of reactive species out of the catalytic cleft. 6) Inactivation can be prevented through competition with the substrate, farnesyl pyrophosphate, further identifying the active center as the site of modification.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

The hostel outreach program: assertive case management for homeless mentally ill persons.

OBJECTIVE: This study measured the impact of an assertive case management program for psychiatrically disabled homeless persons in metropolitan Toronto. It was hypothesized that the program would improve residential stability, reduce psychiatric symptoms, improve social functioning, improve social networks, and increase use of appropriate services. METHOD: For 59 clients admitted to the program, assessments for the nine-month period before program entry were completed and were repeated nine months later. The Brief Psychiatric Rating Scale and a version of the Scale for Level of Functioning were the main measures of outcome. RESULTS: At follow-up significant improvements in residential stability and reductions in psychopathology were demonstrated. Improvements in social functioning and increases in social network size were significant. Although no baseline data about service use were collected, clients used basic support services during their first nine months in the program. CONCLUSIONS: The success of the program demonstrates that a difficult-to-treat patient population can be helped in a humane fashion if trained personnel are available.

Activities of Daily Living↗
PubMed1992

The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis.

OBJECTIVE: To develop and validate revised criteria for global functional status in rheumatoid arthritis (RA). METHODS: Revised criteria were formulated and tested for criterion and discriminant validity in 325 patients with RA. RESULTS: The revised criteria developed are as follows: class I = able to perform usual activities of daily living (self-care, vocational, and avocational); class II = able to perform usual self-care and vocational activities, but limited in avocational activities; class III = able to perform usual self-care activities but limited in vocational and avocational activities; class IV = limited in ability to perform usual self-care, vocational, and avocational activities. Usual self-care activities include dressing, feeding, bathing, grooming, and toileting; vocational and avocational activities are both patient-desired and age-, and sex-specific. The distribution properties of this classification schema were superior to those of the original Steinbrocker criteria. Mean Health Assessment Questionnaire scores were significantly (P less than 0.0001) different between, and increased across, the 4 classes. CONCLUSION: Although there are limitations inherent in the use of global ordinal scales, the American College of Rheumatology revised criteria will be useful in describing the functional consequences of RA. A more detailed quantitative measure of physical disability should be used, however, for optimal monitoring of patients' clinical status in office practice and clinical research.

Activities of Daily Living↗
PubMed1992

Low density lipoprotein from humans supplemented with n-3 fatty acids depresses both LDL receptor activity and LDLr mRNA abundance in HepG2 cells.

Fish oil supplementation in humans is often associated with an expanded low density lipoprotein (LDL) pool that is not thought to reflect increased production. Since data on clearance of LDL after fish oil supplementation (FO-LDL) are equivocal, normal volunteers (four men and three women) received ten capsules containing 3.6 g eicosapentaenoic acid and 2.9 g docosahexaenoic acid (approximately 2.5% total calories as methyl esters) for 2 weeks. Total plasma cholesterol was unchanged, but triglycerides decreased 30%. Low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were unchanged. Analysis of the LDL particles revealed that increased esterified cholesterol caused the FO-LDL core/surface ratio to be greater than baseline LDL (BL-LDL), resulting in a shift in mean LDL density from 1.060 to 1.056. N-3 fatty acids in FO-LDL were also increased greater than 40% at the expense of n-6 and n-9 fatty acids. Human hepatoma HepG2 cells were used to study the effects of FO-LDL on LDL receptor activity and mRNA abundance for the LDL receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and various apolipoproteins associated with cholesterol metabolism. In this system FO-LDL reduced LDL receptor activity compared to BL-LDL. Scatchard analysis revealed that LDL receptor number (Bmax) was reduced to one-third normal (P less than 0.001) whereas particle binding affinity was unchanged. The mRNA abundance for the LDL receptor and apoA-I were also depressed, even by low concentrations (10 micrograms/ml and 20 micrograms/ml LDL protein) of FO-LDL as compared to BL-LDL. HepG2 cells incubated with FO-LDL had decreased cellular free cholesterol but increased cholesteryl esters. Thus, moderate supplementation with fish oil n-3 fatty acids in normal humans enriches their LDL particles in cholesteryl esters and n-3 fatty acids. These particles depress both LDL receptor activity and LDL receptor mRNA abundance in HepG2 cells.

Apolipoproteins↗
PubMed1991

Dietary saturated fatty acids (12:0, 14:0, 16:0) differ in their impact on plasma cholesterol and lipoproteins in nonhuman primates.

Three species of monkey (rhesus, cebus, and squirrel) were rotated through five purified diets containing 31% energy as various fat blends (P:S between 0.1 and 1.0) for 12-wk periods to compare the impact of specific dietary fatty acids on plasma lipids and lipoproteins. As 12:0 + 14:0 was replaced by 16:0, a significant decrease occurred in total and LDL cholesterol, whereas slight increases in total cholesterol and the LDL-HDL ratio occurred when 16:0 replaced 18:2. Hegsted and Keys regression equations provided a good fit for the observed data, but the predicted total cholesterol response was perfect (r = 0.995) for both equations when 16:0 was considered neutral. Thus, under these conditions 16:0 was less cholesterolemic than 12:0 + 14:0 and only slightly cholesterolemic compared with 18:2.

Animals↗
PubMed1990

Dietary palmitic acid (16:0) enhances high density lipoprotein cholesterol and low density lipoprotein receptor mRNA abundance in hamsters.

In order to examine the qualitative effect of different fats and specific fatty acids on plasma lipids and lipoprotein metabolism, six low fat, cholesterol-free diets were fed to young male hamsters (10/group) for a 4-week period. Fat blends were formulated with coconut oil, palm oil, soybean oil, high oleic acid safflower oil, butter, corn oil, and canola oil. Diets contained 13% energy as fat and dietary polyunsaturate/saturate ratios ranged from 0.12 to 1.04, one of which incorporated the American Heart Association-recommended concentrations of saturates, monoenes, and polyenes and another reflected the current American Fat Blend. In three diets the polyunsaturate/monounsaturate/saturate ratio was held constant while only the 12:0, 14:0, and 16:0 were varied. Plasma lipoproteins and apoproteins were assessed in conjunction with the abundance of specific hepatic and intestinal mRNA for the low density lipoproteins (LDL) receptor and various apolipoproteins associated with cholesterol metabolism. The plasma cholesterol response was lowest with the American Heart Association blend and equally elevated by the more saturated, low polyene diets (polyunsaturate/saturate, 0.12-0.38). Replacing 12:0 plus 14:0 from coconut oil with 16:0 as palm oil induced a significant increase in high density lipoprotein (HDL) cholesterol with a trend toward decreased LDL. These shifts in lipoprotein cholesterol were corroborated by measures of the LDL/HDL ratio, the plasma apolipoprotein B/apolipoprotein A1 ratio, and differences in the synthesis of apolipoproteins and the LDL receptor based on estimates of the mRNA for these proteins in the liver and gut, using specific cDNA probes for apolipoprotein A1, apolipoprotein B, apolipoprotein E, and the LDL receptor. Although it has been suggested that dietary polyenes lower total plasma cholesterol, including HDL, and that saturated fat increases both these pools of cholesterol, the current data represents the first evidence that a specific saturated fatty acid, i.e., palmitic acid, may enhance HDL production.

Animals↗
PubMed1989

Lactose protects against estrogen-induced pigment gallstones in hamsters fed nutritionally adequate purified diets.

To evaluate the impact of dietary factors on gallstone induction in hamsters, male Syrian hamsters were fed for 2-8 wk purified diets that varied in type and amount of simple sugar (glucose vs. lactose, 17.5-72%), fat (2-5%), fiber (0-15%) and estrogen (0 or 300 micrograms/kg diet). Plasma and liver cholesterol and plasma triglycerides were measured, daily weight gain was determined, cecal weights were obtained, and gallbladder bile was scored by light microscopy and analyzed chemically for its lithogenicity and gallstone incidence. Lactose reduced plasma lipids, especially triglycerides, and hepatic cholesterol accumulation, and maintained a lower biliary cholesterol concentration. When fed at 30% or more, lactose reduced weight gain, increased cecal volume 2- to 4-fold and prevented gallstone formation. Diarrhea and death from 'wet tail' was associated with gallstones and was frequent in hamsters fed glucose without fiber, but its incidence was essentially eliminated by rice flour plus fiber or lactose. Under these experimental conditions of time and diet, estrogen supplementation was required for the formation of gallstones. These appeared to be pigment stones containing a minimal amount of cholesterol. In summary, pigment gallstones were induced in less than 8 wk in hamsters fed estrogen-supplemented purified diets. Lactose feeding improved lipid metabolism and reduced gallstone formation, apparently through its impact on large bowel metabolism.

Animals↗
PubMed1989

Retinal pigment epithelium possesses both LDL and scavenger receptor activity.

The lipid metabolism of photoreceptors depends in part on the retinal pigment epithelium (RPE). One aspect of cholesterol homeostasis in cultured bovine RPE was evaluated by measuring low-density lipoprotein (LDL) and scavenger receptor activity with [125I]-LDL and [125I]Ac-LDL, respectively. Incubation of RPE cells in the presence of increasing concentrations of LDL or Ac-LDL resulted in down-regulation of the LDL receptor but not the scavenger receptor, patterns consistent with the presence of both receptors on these cells. This receptor profile distinguishes the RPE cell from fibroblasts and indicates its similarity to macrophages and arterial endothelial cells.

Animals↗