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Biomedical subjects

M S Brown

Publications and source records attributed to M S Brown.

At least 19 recordsLinked to original sources
PubMed2006

Adaptation of beef cattle to high-concentrate diets: performance and ruminal metabolism.

The diet adaptation period is widely considered a critical period of time in which nutritional management practices can promote or impair subsequent performance and health. Performance studies indicate that adapting feedlot cattle with incremental increases in dietary concentrate, from approximately 55 to 90% of diet DM, in 14 d or less, while allowing ad libitum access to the diet, generally results in reduced performance during adaptation or over the entire feeding period. However, the number of cattle involved in these studies does not allow insight into the frequencies of metabolic disorders associated with the management practices tested. Adapting cattle by restricting the quantity of higher-concentrate diets offered shows promise for improving production efficiency, but further development is needed for application in commercial feedlots. Evidence suggests considerable diversity in the ability of animals to cope with ingested cereal grain, and indicates that diet adaptation procedures should affect the frequency of health-impaired or low-performing cattle in a pen. Individuals that seem to effectively regulate voluntary feed intake during adaptation generally display a steady increase in DMI as dietary concentrate is increased. These data also highlight a seemingly counterproductive, repeating cycle of overconsumption, followed by a pronounced reduction in ruminal pH, by cattle that appear to cope less favorably with grain adaptation. At least a portion of this diversity may relate to the maintenance of protozoal populations. Increases in amylolytic bacteria seemed to follow the increment of additional concentrate. Protozoa were most numerous when the diet contained approximately 60% concentrate, and lactate-utilizing bacteria increased more markedly when the diet contained more than approximately 70% concentrate. Available in vivo data suggest that the number of lactate-utilizing bacteria may reach a plateau for a given diet composition after 2 to 7 d, but thorough assessments of the time course of events using modern techniques are lacking. Further research is needed to characterize how the quantity and frequency of increases in cereal grain consumption, reflective of industry practices, impact microbial dynamics, and to identify the biological features that allow certain animals to adapt more readily to high-concentrate diets.

Adaptation, Physiological↗
PubMed2006

Effects of phase feeding of protein on performance, blood urea nitrogen concentration, manure nitrogen:phosphorus ratio, and carcass characteristics of feedlot cattle.

Two experiments with a randomized complete block design were conducted to determine the effects of phase feeding of CP on performance, blood urea nitrogen (BUN), manure N:P ratio, and carcass characteristics of steers fed in a feedlot. In Exp. 1, 45 crossbred steers (initial BW = 423 +/- 3.3 kg) were individually fed a diet formulated to contain 13.0% CP (DM basis) for 62 d. On d 63, the dietary CP was maintained at 13.0% or formulated to contain 11.5 or 10.0% CP until slaughter. Actual CP values were 12.8, 11.8, and 9.9%, respectively. Reducing the CP concentration of the diet did not affect ADG of steers from d 62 to 109 (P = 0.54) or over the 109-d feeding period (1.45, 1.50, and 1.49 kg/d for 13.0, 11.5, and 10.0% CP, respectively; P = 0.85). No differences (P > 0.12) among treatments were detected for BUN concentrations on d 0, 62, or 109. Gain:feed, DMI, and carcass characteristics did not differ among treatments (P > 0.10). In Exp. 2, 2 trials were conducted using 184 (initial BW = 406 +/- 2.6 kg) and 162 (initial BW = 342 +/- 1.9 kg) crossbred steers. Data from the 2 trials were pooled for statistical analysis, and trial effect was added to the statistical model. Steers were fed a diet formulated to contain 13.0% CP until reaching approximately 477 kg. When the average BW of the pen was 477 kg, diets were maintained at 13.0% CP or reduced to contain 11.5 or 10.0% CP. Actual CP values were 12.4, 11.5, and 9.3% CP for treatments 13.0, 11.5, and 10.0% CP, respectively. Reducing the CP content of the diet did not affect ADG after the diet changed (P = 0.16) or throughout the finishing period (P = 0.14). Immediately before slaughter, steers fed the 13.0% CP diet had greater (P < 0.001) BUN concentrations than steers fed the 11.5 and 10.0% CP diets. Carcasses from cattle fed the 11.5% CP diet had greater (P = 0.02) fat thickness than the 13.0 and 10.0% CP treatments, whereas carcasses from cattle fed 13.0% CP had greater (P = 0.004) marbling scores than steers fed the 11.5 or 10.0% CP diets. Other carcass characteristics, DMI, and G:F did not differ (P > 0.10) among treatments. The N:P ratio was increased with the 10.0% CP diet (P = 0.02) compared with the 11.5 or 13.5% CP treatments; however, manure composition did not differ (P > 0.10) among treatments. These results indicate that reduced CP concentration during the finishing period does not affect feedlot performance but can improve the N and P relationship in the manure.

Animal Feed↗
PubMed2003

Digital electron microscopic examination of human sural nerve biopsies.

Diabetic peripheral polyneuropathy is characterized by axonal degeneration and regeneration as well as by Schwann cell and microvascular changes. These changes have been described at both the light (LM) and the electron microscopic (EM) levels; however, EM has not been applied to large clinical trials. Our goal was to adapt the rigorous techniques used for quantifying human biopsies with LM image analysis to accommodate ultrastructural analyses. We applied digital image capture and analysis to the ultrastructural examination of axons in sural nerve biopsies from diabetic patients enrolled in a multicenter clinical trial. The selection of sural nerve biopsies was based on the quality of specimen fixation, absence of physical distortion, and nerve fascicle size (> or =100,000; < or =425,000 microm2). Thin sections were collected on formvar-coated slot grids, stabilized with carbon and scanned on a Phillips CM100 transmission electron microscope. Digital images were captured with a Kodak Megaplus 1.6 camera. A montage was constructed using software derived from aerial mapping applications, and this virtual image was viewed by EM readers. Computer-assisted analyses included identification and labeling of individual axons and axons within regenerating clusters. The average density of regenerating myelinated axon clusters per mm2 was 65.8 +/- 5.1, range of 0-412 (n = 193). These techniques increase the number of samples that may be analyzed by EM and extend the use of this technique to clinical trials using tissue biopsies as a primary endpoint.

Axons↗
PubMed2002

Regulation of SREBP processing and membrane lipid production by phospholipids in Drosophila.

Animal cells exert exquisite control over the physical and chemical properties of their membranes, but the mechanisms are obscure. We show that phosphatidylethanolamine, the major phospholipid in Drosophila, controls the release of sterol regulatory element-binding protein (SREBP) from Drosophila cell membranes, exerting feedback control on the synthesis of fatty acids and phospholipids. The finding that SREBP processing is controlled by different lipids in mammals and flies (sterols and phosphatidylethanolamine, respectively) suggests that an essential function of SREBP is to monitor cell membrane composition and to adjust lipid synthesis accordingly.

Animals↗
PubMed2002

Effects of restricted versus conventional dietary adaptation on feedlot performance, carcass characteristics, site and extent of digestion, digesta kinetics, and ruminal metabolism.

Three experiments were conducted to determine effects of restricting intake of the final finishing diet as a means of dietary adaptation compared with diets increasing in grain over a period of 20 to 22 d on overall cattle performance, carcass characteristics, digestibility, digesta kinetics, and ruminal metabolism. In Exp. 1, 84 Angus x Hereford yearling steers (initial BW = 418 +/- 29.0 kg) were fed for 70 d. Restricting intake during adaptation had no effect (P > 0.10) on overall ADG:DMI, but decreased (P < 0.05) DMI compared with ad libitum access to adaptation diets, which resulted from differences during the initial 28 d of the experiment. In Exp. 2, 150 mixed crossbred steer calves (initial BW = 289 +/- 22.9 kg) were fed for an average of 173 d. Restricting intake decreased (P < 0.01) overall daily gain (1.51 vs 1.65 kg/d) and DMI (8.68 vs 9.15 kg/d) compared with ad libitum fed steers; however, ADG:DMI was not influenced (P > 0.10) by adaptation method. Experiment three used eight ruminally and duodenally fistulated steers (initial BW = 336 +/- 20 kg) in a completely random design. Total tract digestibility, digesta kinetics and ruminal metabolism were determined. Restricting intake reduced (P < 0.10) daily DMI variation from d 1 through 7, 8 through 14, and 22 through 28 compared with ad libitum feeding of three adaptation diets. Restricted steers had reduced (adaptation method x period interaction, P < 0.05) intakes and fecal excretions of ADF and greater OM digestibilities on d 4 through 7, 11 through 14, and 18 through 21. Digesta kinetics and ruminal metabolism were generally not affected (P > 0.10) by adaptation method. Our results suggest that restricted-feeding of the final diet as a means of dietary adaptation can be used in finishing cattle with few problems from acidosis or related intake variation. In light-weight steers (Exp. 2), disruptions in intake during the adaptation period might have resulted in restriction for an extended period, which decreased (P < 0.01) hot carcass weight compared with calves fed ad libitum. Effects of limit feeding during the initial 28 d of the feeding period on site and extent of digestion, digesta kinetics, and ruminal metabolism were minimal, supporting few differences in performance across the finishing period for yearling cattle.

Adaptation, Physiological↗
PubMed2001

Decreased lipid synthesis in livers of mice with disrupted Site-1 protease gene.

Site-1 protease (S1P) cleaves membrane-bound sterol regulatory element-binding proteins (SREBPs), allowing their transcription-stimulating domains to translocate to the nucleus where they activate genes governing lipid synthesis. S1P is a potential target for lipid-lowering drugs, but the effect of S1P blockade in animals is unknown. Here, we disrupt the S1P gene in mice. Homozygous germ-line disruptions of S1P were embryonically lethal. To disrupt the gene inducibly in liver, we generated mice homozygous for a floxed S1P allele and heterozygous for a transgene encoding Cre recombinase under control of the IFN-inducible MX1 promoter. When IFN was produced, 70-90% of S1P alleles in liver were inactivated, and S1P mRNA and protein were reduced. Nuclear SREBPs declined, as did mRNAs for SREBP target genes. Cholesterol and fatty acid biosynthesis in hepatocytes declined by 75%. Low density lipoprotein (LDL) receptor mRNA declined by 50%, as did the clearance of (125)I-labeled LDL from plasma, but plasma cholesterol fell, suggesting that LDL production was reduced. These data raise the possibility that S1P inhibitors may be effective lipid-lowering agents, but they suggest that nearly complete inhibition will be required.

Animals↗
PubMed2001

Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR.

Sterol regulatory element-binding protein-1c (SREBP-1c) enhances transcription of genes encoding enzymes of unsaturated fatty acid biosynthesis in liver. SREBP-1c mRNA is known to increase when cells are treated with agonists of liver X receptor (LXR), a nuclear hormone receptor, and to decrease when cells are treated with unsaturated fatty acids, the end products of SREBP-1c action. Here we show that unsaturated fatty acids lower SREBP-1c mRNA levels in part by antagonizing the actions of LXR. In cultured rat hepatoma cells, arachidonic acid and other fatty acids competitively inhibited activation of the endogenous SREBP-1c gene by an LXR ligand. Arachidonate also blocked the activation of a synthetic LXR-dependent promoter in transfected human embryonic kidney-293 cells. In vitro, arachidonate and other unsaturated fatty acids competitively blocked activation of LXR, as reflected by a fluorescence polarization assay that measures ligand-dependent binding of LXR to a peptide derived from a coactivator. These data offer a potential mechanism that partially explains the long-known ability of dietary unsaturated fatty acids to decrease the synthesis and secretion of fatty acids and triglycerides in livers of humans and other animals.

Animals↗
PubMed2001

SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation.

In liver, the synthesis of cholesterol and fatty acids increases in response to cholesterol deprivation and insulin elevation, respectively. This regulatory mechanism underlies the adaptation to cholesterol synthesis inhibitors (statins) and high calorie diets (insulin). In nonhepatic cells, lipid synthesis is controlled by sterol regulatory element-binding proteins (SREBPs), membrane-bound transcription factors whose active domains are released proteolytically to enter the nucleus and activate genes involved in the synthesis and uptake of cholesterol and fatty acids. SCAP (SREBP cleavage-activating protein) is a sterol-regulated escort protein that transports SREBPs from their site of synthesis in the endoplasmic reticulum to their site of cleavage in the Golgi. Here, we produced a conditional deficiency of SCAP in mouse liver by genomic recombination mediated by inducible Cre recombinase. SCAP-deficient mice showed an 80% reduction in basal rates of cholesterol and fatty acid synthesis in liver, owing to decreases in mRNAs encoding multiple biosynthetic enzymes. Moreover, these mRNAs failed to increase normally in response to cholesterol deprivation produced by a cholesterol synthesis inhibitor and to insulin elevation produced by a fasting-refeeding protocol. These data provide in vivo evidence that SCAP and the SREBPs are required for hepatic lipid synthesis under basal and adaptive conditions.

Animals↗
PubMed2001

Insulin inhibits transcription of IRS-2 gene in rat liver through an insulin response element (IRE) that resembles IREs of other insulin-repressed genes.

Recent data indicate that sustained elevations in plasma insulin suppress the mRNA for IRS-2, a component of the insulin signaling pathway in liver, and that this deficiency contributes to hepatic insulin resistance and inappropriate gluconeogenesis. Here, we use nuclear run-on assays to show that insulin inhibits transcription of the IRS-2 gene in the livers of intact rats. Insulin also inhibited transcription of a reporter gene driven by the human IRS-2 promoter that was transfected into freshly isolated rat hepatocytes. The human promoter contains a heptanucleotide sequence, TGTTTTG, that is identical to the insulin response element (IRE) identified previously in the promoters of insulin-repressed genes. Single base pair substitutions in this IRE decreased transcription of the IRS-2-driven reporter in the absence of insulin and abolished insulin-mediated repression. We conclude that insulin represses transcription of the IRS-2 gene by blocking the action of a positive factor that binds to the IRE. Sustained repression of IRS-2, as occurs in chronic hyperinsulinemia, contributes to hepatic insulin resistance and accelerates the development of the diabetic state.

Animals↗
PubMed2001

Expression of sterol regulatory element-binding protein 1c (SREBP-1c) mRNA in rat hepatoma cells requires endogenous LXR ligands.

The current paper describes a line of cultured rat hepatoma cells (McA-RH7777 cells) that mimics the behavior of rat liver by producing an excess of mRNA for sterol regulatory element-binding protein 1c (SREBP-1c) as opposed to SREBP-1a. These two transcripts are derived from a single gene by use of alternative promoters that are separated by many kilobases in the genome. The high level of SREBP-1c mRNA is abolished when cholesterol synthesis is blocked by compactin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase that inhibits cholesterol synthesis. Levels of SREBP-1c mRNA are restored by mevalonate, the product of the HMG CoA reductase reaction, and by ligands for the nuclear hormone receptor LXR, including 22(R)-hydroxycholesterol and T0901317. These data suggest that transcription of the SREBP-1c gene in hepatocytes requires tonic activation of LXR by an oxysterol intermediate in the cholesterol biosynthetic pathway. Reduction of this intermediate lowers SREBP-1c levels, and this in turn is predicted to lower the rates of fatty acid biosynthesis in liver.

Animals↗
PubMed2001

Supernumerary orbital muscle in congenital eyelid retraction.

PURPOSE: Although several reports of supernumerary orbital muscles related to the levator palpebrae superioris have been published, no case has been associated with congenital eyelid retraction. This report describes an apparent causal relationship between an accessory levator muscle slip and congenital eyelid retraction. METHODS: Case report and literature review. RESULTS: Release of the anomalous muscle's attachment from the superior tarsal border alone resulted in resolution of the eyelid retraction. CONCLUSIONS: Eyelid muscle anomalies may be a cause of congenital eyelid retraction. Ophthalmologists who treat eyelid disorders should be aware of this possibility when evaluating and operating on patients with congenital eyelid retraction.

Child, Preschool↗
PubMed2001

Patient-specific models for lung nodule detection and surveillance in CT images.

The purpose of this work is to develop patient-specific models for automatically detecting lung nodules in computed tomography (CT) images. It is motivated by significant developments in CT scanner technology and the burden that lung cancer screening and surveillance imposes on radiologists. We propose a new method that uses a patient's baseline image data to assist in the segmentation of subsequent images so that changes in size and/or shape of nodules can be measured automatically. The system uses a generic, a priori model to detect candidate nodules on the baseline scan of a previously unseen patient. A user then confirms or rejects nodule candidates to establish baseline results. For analysis of follow-up scans of that particular patient, a patient-specific model is derived from these baseline results. This model describes expected features (location, volume and shape) of previously segmented nodules so that the system can relocalize them automatically on follow-up. On the baseline scans of 17 subjects, a radiologist identified a total of 36 nodules, of which 31 (86%) were detected automatically by the system with an average of 11 false positives (FPs) per case. In follow-up scans 27 of the 31 nodules were still present and, using patient-specific models, 22 (81%) were correctly relocalized by the system. The system automatically detected 16 out of a possible 20 (80%) of new nodules on follow-up scans with ten FPs per case.

Automation↗
PubMed2001

Spiral versus electron-beam CT for coronary artery calcium scoring.

PURPOSE: To determine differences in coronary artery calcium detection, quantification, and reproducibility, as measured at electron-beam computed tomography (CT) and subsecond spiral CT with retrospective electrocardiogram gating in an asymptomatic adult population. MATERIALS AND METHODS: Seventy subjects asymptomatic for coronary heart disease underwent both electron-beam CT and subsecond spiral CT. In all subjects, two images each were obtained with both scanners. Two experienced readers using three different algorithms scored each of the four scans: one score for the electron-beam CT images and two scores for the spiral CT images. RESULTS: With a 130-HU threshold for the quantification of calcium, there were no significant differences in interscan and interobserver variation in calcium scores between the electron-beam CT and spiral CT images. There was greater interobserver (P <.001) and interscan (P <.03) variation in scores when a 90-HU threshold was used for spiral CT images. With a 130-HU threshold, when calcium scores were used for clinical risk stratification, there was a significant difference between the results obtained with electron-beam CT and those obtained with spiral CT (P <.05). CONCLUSION: Spiral CT has not yet proved to be a feasible alternative to electron-beam CT for coronary artery calcium quantification. There are systematic differences between calcium scores obtained with single-detector array subsecond spiral CT and those obtained with electron-beam CT.

Adult↗
PubMed2001

Semantic processing in visual word recognition: activation blocking and domain specificity.

Lexical decision to a target is typically facilitated when a related prime is simply read, but is typically eliminated if subjects carry out a letter search on the prime when probe and prime appear simultaneously. Three experiments involving the addition of a task-irrelevant word to this prime search paradigm address (1) Stolz and Besner's (1996, 1998) account in which semantic priming is eliminated because letter search on the prime instantiates an activation block between lexical and semantic levels of representation, (2) Chiappe, Smith, and Besner's (1996) account that activation blocking is domain specific, and (3) Neely and Kahan's (2001) claim that semantic activation is context independent and capacity free. The results are (1) consistent with the account that activation blocking is general to a level, rather than item specific, (2) consistent with the account that activation blocking is domain specific, and (3) inconsistent with the claim that semantic activation is context independent and capacity free.

Association↗