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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 73 records · Page 4Linked to original sources

Milk and milk components reduce the motility of Ostertagia circumcincta larvae in vitro.

AIM: To examine the effects in vitro of bovine milk and milk products and soymilk on the motility of sheathed and exsheathed L3 Ostertagia circumcincta (also known as Teladorsagia circumcincta) as a measure of larval viability and infectivity. METHODS: L3 were exsheathed in 0.2% sodium hypochlorite, resuspended in Hank's Balanced Salt Solution (HBSS) pH 7.4 and incubated with test solutions at 37 degrees C for up to 48 h. The motility of 50 larvae from each incubate was assessed at selected times using a McMaster slide. Larvae were considered immotile only if straight and not moving. Fresh bovine milk, homogenised milk (3.3% fat), low-fat milk (0.2% fat) and lamb milk replacer were diluted with HBSS pH 7.4 to concentrations from 1.6-100%, and incubated with exsheathed L3 for 1, 24 or 48 h. Bovine whey protein was tested in concentrations of 5-15% at pH 2.5-6.5, casein at 5 or 7.5%, and skim milk powder from 5-15% at pH 5.5 or 6.5, all for 2, 4 or 24 h. Soymilk was tested in concentrations of 1.6-100% for 1, 2, 24 or 48 h. HBSS was used as the control solution. Sheathed L3 were incubated in HBSS pH 7.4, 50% homogenised milk in HBSS, or 50% soymilk in HBSS. Each solution was incubated for 1,2, 24 or 48 h. RESULTS: The motility of exsheathed L3 was reduced by fresh bovine milk, homogenised milk, low-fat milk, lamb milk replacer, whey, casein and skim milk solutions, but not by soymilk. The mean percentage (and SE) immotile at 48 h were: fresh milk 38% (SE 20); homogenised milk 65% (SE 7); low-fat milk 57% (SE 5); lamb milk replacer 43% (SE 7); and soymilk 7% (SE 0.5). Larval immotility increased in whey protein solutions from 5-15%, from pH 2.5-6.5 and from 2 to 24 h (all p<0.001); in skim milk from 5-15% (p<0.001), and was greater at pH 6.5 than at pH 5.5 (p<0.001); in casein from 5-7.5% (p<0.001), but was no different at pH 5.5 and 6.5. The motility of sheathed L3 was reduced at 24 h (p=0.009) and 48 h (p<0.001) by 50% homogenised milk, but not by 50% soymilk or HBSS. CONCLUSIONS: Bovine milk proteins, or components associated with the proteins, reduced the motility of both sheathed and exsheathed L3 O. circumcincta. Soymilk had no effect on nematode motility. Lower larval motility may reduce worm establishment and be a contributing factor to the smaller burdens of gastrointestinal nematodes in milk-fed animals compared with animals after weaning.

Journal Article↗

Quality control limits for fluconazole disk susceptibility tests on Mueller-Hinton agar with glucose and methylene blue.

An international collaborative study was performed in order to propose quality control limits for fluconazole disk diffusion susceptibility tests on Mueller-Hinton agar with 2% glucose and 0.5 micro g of methylene blue per ml. The supplements may be added before autoclaving the agar, or Mueller-Hinton agar plates may be flooded with a glucose-methylene blue solution. Replicate tests on both types of agar plates generated data to propose zone size limits for tests of Candida parapsilosis ATCC 22019 (22 to 33 mm), C. tropicalis ATCC 750 (26 to 37 mm), and C. albicans ATCC 90028 (28 to 39 mm). C. krusei ATCC 6258 was not useful for this purpose.

Agar↗

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

Bacterial Proteins↗

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗

Early postnatal discharge from hospital for healthy mothers and term infants.

BACKGROUND: Length of postnatal hospital stay has declined dramatically in the past thirty years. There is ongoing controversy concerning whether or not staying less time in hospital is harmful or beneficial. OBJECTIVES: The objective of this review was to assess the safety, impact and effectiveness of a policy of early discharge for healthy mothers and term infants, with respect to the health and well-being of mothers and babies, satisfaction with postnatal care, overall costs of health care and broader impacts on families. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (April 2002), the Effective Practice and Organisation of Care Review Group specialised register of clinical trials, the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966 to 2001), CINAHL (1982 to 2001), EMBASE (1988 to 1993) and reference lists of articles. SELECTION CRITERIA: Randomized trials comparing early discharge from hospital of healthy mothers and term infants, of greater than or equal to 2500 grams, with standard care in the settings in which trials were conducted. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were abstracted independently by all five reviewers. MAIN RESULTS: Eight trials were identified involving 3600 women. There was substantial variation in the definition of 'early discharge', and the extent of antenatal preparation and midwife home care following discharge offered to women in intervention and control groups. Five trials recruited and randomized women in pregnancy, three randomized women following childbirth. Post randomization exclusions were high. Protocol violations occurred in both directions. No statistically significant differences in infant or maternal readmissions were found in six trials reporting data on these outcomes. Three trials had mixed results showing either no significant difference or results favouring early discharge for the outcome of maternal depression although none used a well-validated standardised instrument. The results of six trials showed that early discharge had no impact on breastfeeding although significant heterogeneity was present between studies. REVIEWER'S CONCLUSIONS: The findings are inconclusive. There is no evidence of adverse outcomes associated with policies of early postnatal discharge, but methodological limitations of included studies mean that adverse outcomes cannot be ruled out. It remains unclear how important midwifery support at home is to the safety and acceptability of early discharge. Large well-designed trials of early discharge programs incorporating process evaluation to assess the uptake of co-interventions, and using standardised approaches to outcome assessment are needed.

Female↗

Humic acid enhanced remediation of an emplaced diesel source in groundwater. 1. Laboratory-based pilot scale test.

The enhanced solubility of petroleum-derived compounds in humic acid solutions is the basis for a new groundwater remediation technology. In this unique pilot-scale test, a stationary contaminant source consisting of diesel fuel was placed below the water table in a model sand aquifer (1.2 x 5.5 x 1.8-m deep) and flushed with water at a flow rate of 2 cm/h over 5 years. At 51 days, laboratory grade humic acid was added to the water and maintained at a level of approximately 0.8 g/l. The addition of humic acid had only a small impact on the aqueous transport of the BTEX components, which were rapidly dissolved from the diesel, but had a large effect on the flushing of PAHs, including methylated naphthalenes (MNs). Binding to aqueous humic acid enhanced the solubilization of MNs two- to tenfold. During aqueous transport, biodegradation of the BTEX and PAHs occurred, limiting the lateral and longitudinal extent of the diesel contaminant plume in the model aquifer. It appears that through enhanced solubilization, the overall biodegradation rate of the MNs was increased. As the various MNs were depleted from the diesel source, the MN plume shrank and then disappeared.

Biodegradation, Environmental↗

Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease).

There are at least eight genetic entities known as the ceroid-lipofuscinoses in humans which share clinical and pathological features that have caused them to be grouped together under the eponym of Batten disease. They present pathologically as lysosomal storage diseases but are also characterised by severe neurodegeneration. Although the biochemical defects appear primarily centred on lysosomes and defects in proteolysis, the link between this and pathogenesis of neuronal death is poorly understood. The pathogenesis of neurodegeneration has been studied particularly in two animal models these being the English setter dog and the New Zealand Southhampshire sheep (OCL6). In these, and some of the human entities, there is evidence of mitochondrial dysfunction. This includes the accumulation of subunit c of ATP synthase as a component of storage material in at least six of eight genetic forms of the disease; structural abnormalities of mitochondria and selective loss of neurons in areas of the brain that are particularly metabolically active. Direct evidence of dysfunction comes from mitochondrial function tests in fibroblasts and, in animal models, isolated liver mitochondria. Supporting evidence of mitochondrial dysfunction was shown by disturbances in proportions of energy-rich phosphates in fibroblasts in some of these diseases. If these various defects were reflected in neurons, then it would support the hypothesis that neuron death was associated with energy-linked excitotoxicity.

Animals↗

Gastric emptying of two whey-based formulas of different energy density and its clinical implication in children with volume intolerance.

OBJECTIVE: Whey-based formulas have faster gastric emptying than casein-based formulas. Isoenergetic, isovolumic, whey-based formulas of different osmolarity and fat content empty in a similar manner. Will the gastric emptying of high and low energy density whey-based formulas be similar? DESIGN: We studied the gastric emptying rate of equal volumes of two whey-based formulas of different energy density (4.18 kJ/ml and 6.27 kJ/ml) and osmolality (270 and 450 mOsm/kg, respectively) in 10 children (4.5-12 y) with volume intolerance and resultant inability to gain weight. RESULTS: The two formulas had comparable gastric emptying rates at 30, 60, 90 and 120 min. Over a one month clinical trial, substitution of the lower energy density whey-based formula (no weight gain over 2 months) with an equal volume of the high energy density formula produced a mean weight gain of 1.17+/-0.5 kg per patient without change in tolerance. CONCLUSION: The higher density whey-based formula can safely substitute an equal volume of a lower energy density formula to produce weight gain without affecting tolerance. IMPLICATION: This provides an important intervention for increasing energy intake in children with volume intolerance or fluid restriction.

Caseins↗

Successful use of recombinant factor VIIa in a patient with inhibitor secondary to severe factor XI deficiency.

Factor XI (FXI) inhibitors are a rare complication of inherited FXI deficiency. We report the successful use of recombinant factor VIIa (FVIIa) in a patient with a high-responding inhibitor undergoing cataract extraction. At the time of surgery there were limited available data on the optimal management of patients with FXI deficiency. A 62-year-old Ashkenazi Jewish woman had a lifelong history of excessive bleeding secondary to severe FXI deficiency (2 U dL-1), and received FXI concentrate (FXI:C) when she underwent a colposuspension procedure. She was subsequently diagnosed with a FXI inhibitor of 16 Bethesda units (BU) when she developed a poor response to FXI:C at the time of total hip replacement. Two months later she was admitted for cataract extraction. The FXI level was < 1 U dL-1 with an inhibitor titre of 48 BU. She received 90 microg kg-1 of FVIIa immediately preoperatively followed by continuous infusion at a rate of 20 microg kg-1 h-1 for 24 h. The cataract extraction was successful and there was no excess bleeding during surgery or in the postoperative period. Mutation analysis of the FXI gene showed that the patient was homozygous for the type II genotype [exon 5, Glu117-->Ter]. The reason for the low prevalence of inhibitor formation in patients with FXI deficiency is unclear but may reflect a number of factors including reporting bias, the rarity of absent circulating FXI:C activity, and the infrequent use of FXI replacement therapy.

Blood Loss, Surgical↗

Population genetics of wolf spiders of fragmented habitat in the wheat belt of New South Wales.

Possible effects of habitat fragmentation on the population genetics of a species of wolf spider (Lycosidae) from remnant Callitris woodland in the wheat belt of central western New South Wales in Australia are examined. Single-strand conformational analysis of mitochondrial cytochrome oxidase (subunit 1) was used to characterize the haplotypes of 295 spiders in six blocks each of four woodland sites. DNA sequences were collected from 119 of these spiders to confirm haplotype scoring, allow phylogeny estimation and permit calculation of sequence-based statistics. Intra-block tests do not suggest widespread effects of fragmentation. Genetic diversity is high in all blocks, with 25 haplotypes being identified. Nucleotide diversity is relatively low, as all of the haplotypes are closely related. One block had a significantly low value for the Ewens/Watterson test of neutrality and one block's value was nearly significantly high. Two blocks had nearly significant values of the Harpending Raggedness Index testing for recent population bottlenecks. No other intrablock tests approach significance. Interpopulation comparisons show significant nonhomogeneity of haplotype frequencies globally and in all pairwise comparisons. Relationships between woodland blocks based on haplotype frequencies are discordant with geographical proximity. Haplotype distribution patterns suggest that population structuring existed prior to fragmentation. We develop two measures of genetic distinctiveness to identify subpopulations of interest for conserving evolutionary processes in a species' regional population. One is based on the sum of pairwise FST values and one on the spatial distribution of genetic variation. High values of the measure suggest a subpopulation might have been recently perturbed and low values that it is relatively undisturbed. The two measures identify different blocks as being of particular interest.

Animals↗

The pepsinogen releasing effect of Helicobacter pylori lipopolysaccharide.

BACKGROUND: Helicobacter pylori lipopolysaccharide (LPS) affects pepsinogen release by a nontoxic mechanism. We hypothesized that this effect was characteristic of the organism and related to the clinical status of the strain. MATERIALS AND METHODS: LPS was isolated from 11 H. pylori strains whose pathogenic profile was known and four other nongastric bacteria. The effects of luminal LPS on guinea pig gastric mucosal pepsinogen release was evaluated using the Ussing chamber technique. CCK-8 (10(-9)M) was used as a positive control. RESULTS: H. pylori LPS dose-dependently stimulated pepsinogen release with a maximal stimulation at 250 microg/ml (approximately 4500; p < .001 vs. control). LPS from other Helicobacter or Campylobacter species had no effect on pepsinogen release. ANOVA demonstrated significant differences in the efficacies of pepsinogen release between the 11 clinical H. pylori strains (p < .0001) despite the fact that they were all cagA+ and 90 had the cytotoxic vacA subtype s1. Physical and chemical disruption of the LPS suggested that both the structure and the carbohydrate composition of this molecule may play a critical role in pepsinogen release. Polymyxin B partly (p < .03) inhibited and dephosphorylation completely inhibited (p = .0002) LPS-stimulated pepsinogen release. CONCLUSION: Pepsinogen release is an innate property of all cagA+H. pylori LPS. The structure of the molecule and composition of side-chains are important in this response which appears to be partially lipid A driven.

Adult↗

Combined genomic and antisense analysis reveals that the transcription factor Erg is implicated in endothelial cell differentiation.

It has recently been shown that the transcription factor Erg, an Ets family member, drives constitutive expression of the intercellular adhesion molecule 2 (ICAM-2) in human umbilical vein endothelial cells (HUVECs) and that its expression is down-regulated by the pleiotropic cytokine tumor necrosis factor alpha (TNF-alpha). To identify other Erg target genes and to define its function in the endothelium, a combined approach of antisense oligonucleotides (GeneBloc) and differential gene expression was used. Treatment of HUVECs with Erg-specific GeneBloc for 24, 48, and 72 hours suppressed Erg mRNA and protein levels at all time points. Total RNA extracted from HUVECs treated with Erg-specific or control GeneBloc was analyzed for differences in gene expression using high-density, sequence-verified cDNA arrays containing 482 relevant genes. Inhibition of Erg expression resulted in decreased expression of ICAM-2, as predicted. Four more genes decreased in Erg-deficient HUVECs were the extracellular matrix proteins SPARC and thrombospondin, the adhesive glycoprotein von Willebrand factor, and the small GTPase RhoA. Each of these molecules has been directly or indirectly linked to angiogenesis because of its role in vascular remodeling, adhesion, or shape change. Therefore, the role of Erg in vascular remodeling was tested in an in vitro model, and the results showed that HUVECs treated with Erg GeneBloc had a decreased ability to form tubulelike structures when grown on Matrigel. These results suggest that Erg may be a mediator of the TNF-alpha effects on angiogenesis in vivo.

Antigens, CD↗

Identification of the first invertebrate interleukin JAK/STAT receptor, the Drosophila gene domeless.

The JAK/STAT signaling pathway plays important roles in vertebrate development and the regulation of complex cellular processes. Components of the pathway are conserved in Dictyostelium, Caenorhabditis, and Drosophila, yet the complete sequencing and annotation of the D. melanogaster and C. elegans genomes has failed to identify a receptor, raising the possibility that an alternative type of receptor exists for the invertebrate JAK/STAT pathway. Here we show that domeless (dome) codes for a transmembrane protein required for all JAK/STAT functions in the Drosophila embryo. This includes its known requirement for embryonic segmentation and a newly discovered function in trachea specification. The DOME protein has a similar extracellular structure to the vertebrate cytokine class I receptors, although its sequence has greatly diverged. Like many interleukin receptors, DOME has a cytokine binding homology module (CBM) and three extracellular fibronectin-type-III domains (FnIII). Despite its low degree of overall similarity, key amino acids required for signaling in the vertebrate cytokine class I receptors [3] are conserved in the CBM region. DOME is a signal-transducing receptor with most similarities to the IL-6 receptor family, but it also has characteristics found in the IL-3 receptor family. This suggests that the vertebrate families evolved from a single ancestral receptor that also gave rise to dome.

Amino Acid Motifs↗

Psychometric evaluation of the early/late preferences scale.

This paper examines the psychometric quality of the Early/Late Preferences Scale (PS) relative to that of the Composite Morningness Scale (CS). Questionnaires were completed by 670 undergraduate students aged 16-37 years (mean 22.5), of whom 64% were female. Both scales displayed satisfactory inter-item correlations and similar total mean scores to those reported previously, although the CS had higher variability. Principal axis factor analysis produced single-factor solutions for both scales, although loadings for Items 7 and 9 on the PS were low. Internal consistencies for both scales were good (PS = 0.86, CS = 0.90) with only a small improvement achieved by deleting Items 7 and 9 from the PS. Test-retest reliability over 11 weeks was good for both scales (PS = 0.92, CS = 0.89). Differences between morning, evening and intermediate groups in self-rated alertness at different times of day, and significant correlations with other indices of morning-evening orientation, provided evidence of validity for both scales. These results indicate that PS is psychometrically comparable with CS. In view of its simpler format and lower cultural specificity, PS may be considered a preferable measure for most applications.

Adaptation, Psychological↗