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Biomedical subjects

J Woodward

Publications and source records attributed to J Woodward.

At least 19 recordsLinked to original sources
PubMed2006

Parenteral administration of glutamine modulates acute phase response in postparturient dairy cows.

The objective of this study was to investigate whether administration of L-Gln would affect mediators of acute phase response in postparturient dairy cows. Twenty-four multiparous Holstein cows were blocked by the expected day of calving and randomly assigned to 1 of the 3 treatment groups (n = 8/group): 1) i.v. infusion of 10 L of 0.85% NaCl (control), 2) i.v. infusion of 106, or 3) 212 g/d of L-Gln mixed with 10 L of 0.85% NaCl solution; each treatment was given 8 h/d for each of 7 consecutive days starting on d 1 after calving. Blood samples were collected 1 wk before the expected day of parturition as well as on d 0, 7, 14, and 21 after parturition; plasma concentrations of serum amyloid A (SAA), haptoglobin, and lipopolysaccharide-binding protein were measured by ELISA, and alpha(1)-acid glycoprotein was assessed by radial immunodiffusion. Concentrations of SAA, haptoglobin, and alpha(1)-acid glycoprotein increased in control cows after parturition, reaching peak values on d 0 or 7 postpartum (60, 1,093, and 963 microg/mL, respectively). Cows infused with 106 g/d of L-Gln had greater concentrations of SAA in plasma on d 14 and 21 compared with controls (62.8 vs. 30.2 and 71.1 vs. 34.5 microg/mL, respectively). Cows infused with 212 g/d of L-Gln had greater concentrations of SAA on d 7 (82.5 vs. 53.9 microg/mL) and lower concentrations of haptoglobin on d 14 and 21 postpartum compared with controls (264 vs. 621 and 175 vs. 587 microg/mL, respectively). Cows treated with 106 and 212 g/d of L-Gln had greater plasma lipopolysaccharide-binding protein concentrations on d 7 compared with control group (50.0 and 35.6 vs. 10.8 microg/mL, respectively). There were no treatment differences with respect to milk yield and DM intake during the experimental period. In conclusion, our data indicate that i.v. administration of L-Gln modulated acute phase mediators in dairy cows after parturition and warrants further research into the mechanisms behind these effects.

Acute-Phase Proteins↗
PubMed2005

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗
PubMed2003

Patients' experiences and opinions of home blood pressure measurement.

Regular measurement of the blood pressure (BP) is necessary to monitor the treatment of hypertension, and self-measurement is one technique of obtaining such measurements. The aim of this study was to investigate the experiences of individuals who have carried out home BP measurement. A qualitative method using semistructured interviews was used with 13 subjects. These were adults with hypertension who had previous experience of measuring their own BP, and were recruited to the study from one UK general medical practice. Interviews were recorded and transcribed, and data from the interviews have been analysed using phenomenological principles and identifying 'meaning units.' The findings suggest that participants were willing to carry out home measurements and several were pleased to have been asked to be more involved in their own management. All found the technique straightforward. Most noted marked variability in the day-to-day BP measurements. Several exhibited the 'white coat' phenomenon (spuriously raised BP in certain settings only). Some participants showed considerable know-ledge of hypertension and its consequences. They reported being aware of their own BP level and whether this was within acceptable limits. They also reported being willing to take further measurements, and to consider adjusting their treatment in the light of these measurements. Other participants showed less knowledge and enthusiasm, and considered the management of hypertension to be the doctor's job. The findings suggest that for some individuals home BP measurement is acceptable. They also help to explain why, for some individuals, it is not. Using the findings, a number of changes to current practice could be made, which might make home measurements more acceptable and easier to perform. As a result, a new proforma for use in everyday practice has been designed. The study shows that there is considerable scope for sharing BP measurement and management decisions in hypertension with patients themselves.

Aged↗
PubMed2003

Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes.

Astrocytes may be infected with the human immunodeficiency virus type 1 (HIV-1) or exposed to the HIV protein gp120, yet their role in the pathogenesis of HIV dementia is largely unknown. To characterize the effects of HIV on astrocytic transcription, microarray analysis and ribonuclease protection assays (RPA) were performed. Infection of astrocytes by HIV or treatment with gp120 had differential and profound effects on gene transcription. Of the 1153 oligonucleotides on the immune-based array, the expression of 108 genes (53 up; 55 down) and 82 genes (32 up; 50 down) were significantly modulated by gp120 and HIV infection respectively. Of the 1153 oligonucleotides on the neuro-based array, 58 genes (25 up; 33 down) and 47 genes (17 up; 30 down) were significantly modulated by gp120 and HIV infection respectively. Chemokine and cytokine induction occurred predominantly by HIV infection, whereas gp120 had no significant effect. These results were confirmed by RPA. The authors conclude that profound alterations of astrocytic function occur in response to HIV infection or interaction with viral proteins, suggesting that astrocytes may play an important role in the pathogenesis of HIV dementia.

AIDS Dementia Complex↗
PubMed2002

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

Calcium-dependent protection from complement lysis in Naegleria fowleri amebae.

Pathogenic Naegleria fowleri amebae are resistant to the lytic effects of serum complement. The presence of surface glycoproteins or removal of the membrane attack complex (MAC) of complement from the cell surface by vesiculation serve to protect the amebae from complement lysis. The specific mediators important in stimulating complement resistance are not defined. These studies were undertaken to examine the effect of Ca(2+) ions in initiating complement resistance of N. fowleri in contrast to non-pathogenic complement-sensitive N. gruberi. Chelation of extracellular calcium with ethylene glycol tetraacetic acid (EGTA) or chelation of intracellular calcium with 1,2-bis-(O-Aminophenoxy) ethane-N,N,N,N tetraacetic acid tetra (acetoxymethyl) ester (BAPTA-AM) increased complement lysis of N. fowleri. Chelation of calcium ions did not affect complement sensitivity of N. gruberi. Increased lysis of ionomycin-treated N. fowleri was detected after exposure to serum complement, suggesting that a threshold level of Ca(2+) mediates complement resistance before survival mechanisms are overwhelmed and lysis occurs. A differential influx of Ca(2+) ions occurred in fura-2 labeled N. fowleri after deposition of complement component C9 to form the MAC complex on the cell surface in comparison to N. gruberi. These studies suggest that Ca(2+) ions influence complement resistance in N. fowleri but do not play a role in altering the sensitivity of N. gruberi to complement.

Animals↗
PubMed2001

Identification and characterization of lymphoid precursors in the murine intestinal epithelium.

Although in vivo evidence supports a role for the murine intestinal epithelium in the extrathymic generation of certain intraepithelial T lymphocytes (IEL), no intraepithelial cells with in vitro lymphoid progenitor potential have yet been demonstrated. Using reaggregate fetal thymic organ culture techniques, we show that a subset of CD3(-) cells isolated from the intestinal epithelium of young mice is capable of generating T cells (alpha beta and gamma delta) and NK1.1(+) cells in vitro. A novel IEL subset bearing a low level of CD45 was identified and found to comprise cells expressing highly immature lymphoid markers including CD34, c-kit, CD122, CD127 and high levels of CD16 and CD44. This subset represents 20-30% of intraepithelial CD45(+) cells from 4-week-old wild-type and nude mouse strains and contains cells with in vitro T cell differentiation capacity. The identification of such an early pluripotent precursor phenotype within the intestinal epithelium implies that the potential for T cell generation exists at this site, and suggests that extrathymic T cell generation may occur within the epithelium itself.

Animals↗
PubMed2000

Activation of mitogen-activated protein kinases is required for alpha1-adrenergic agonist-induced cell scattering in transfected HepG2 cells.

Activation of alpha1B-adrenergic receptors ((alpha1B)AR) by phenylephrine (PE) induces scattering of HepG2 cells stably transfected with the (alpha1B)AR (TFG2 cells). Scattering was also observed after stimulation of TFG2 cells with phorbol myristate acetate (PMA) but not with hepatocyte growth factor/scatter factor, epidermal growth factor, or insulin. PMA but not phenylephrine rapidly activated PKCalpha in TFG2 cells, and the highly selective PKC inhibitor bisindolylmaleimide (GFX) completely abolished PMA-induced but not PE-induced scattering. PE rapidly activated p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK, c-Jun N-terminal kinase (JNK), and AP1 (c-fos/c-jun). Selective blockade of p42/44 MAPK activity by PD98059 or by transfection of a MEK1 dominant negative adenovirus significantly inhibited the PE-induced scattering of TFG2 cells. Selective inhibition of p38 MAPK by SB203850 or SB202190 also blocked PE-induced scattering, whereas treatment of TFG2 cells with the PI3 kinase inhibitors LY294002 or wortmannin did not inhibit PE-induced scattering. Blocking JNK activation with a dominant negative mutant of JNK or blocking AP1 activation with a dominant negative mutant of c-jun (TAM67) significantly inhibited PE-induced cell scattering. These data indicate that PE-induced scattering of TFG2 cells is mediated by complex mechanisms, including activation of p42/44 MAPK, p38 MAPK, and JNK. Cell spreading has been reported to play important roles in wound repair, tumor invasion, and metastasis. Therefore, catecholamines acting via the (alpha1)AR may modulate these physiological and pathological processes.

Adrenergic alpha-Agonists↗
PubMed2000

First-principles determination of hybrid bilayer membrane structure by phase-sensitive neutron reflectometry.

The application of a new, phase-sensitive neutron reflectometry method to reveal the compositional depth profiles of biomimetic membranes is reported. Determination of the complex reflection amplitude allows the related scattering length density (SLD) profile to be obtained by a first-principles inversion without the need for fitting or adjustable parameters. The SLD profile so obtained is unique for most membranes and can therefore be directly compared with the SLD profile corresponding to the chemical compositional profile of the film, as predicted, for example, by a molecular dynamics simulation. Knowledge of the real part of the reflection amplitude, in addition to enabling the inversion, makes it possible to assign a spatial resolution to the profile for a given range of wavevector transfer over which the reflectivity data are collected. Furthermore, the imaginary part of the reflection amplitude can be used as a sensitive diagnostic tool for recognizing the existence of certain in-plane inhomogeneities in the sample. Measurements demonstrating the practical realization of this phase-sensitive technique were performed on a hybrid bilayer membrane (self-assembled monolayer of thiahexa (ethylene oxide) alkane on gold and a phospholipid layer) in intimate contact with an aqueous reservoir. Analysis of the experimental results shows that accurate compositional depth profiles can now be obtained with a spatial resolution in the subnanometer range, primarily limited by the background originating from the reservoir and the roughness of the film's supporting substrate.

Biophysics↗
PubMed2000

The mechanism of cellulase action on cotton fibers: evidence from atomic force microscopy.

Two cellulases from Trichoderma reesei--an exoglucanase, CBH I, and an endoglucanase, EG II--alone and in combination were incubated with cotton fibers. The effects of the cellulases on the surfaces of the cotton fibers were examined by atomic force microscopy. At high magnification, the physical effects on the fibers caused by the two types of enzymes were considerably different. Treatment with CBH I resulted in the appearance of distinct pathways or tracks along the length of the macrofibril. Treatment with EG II appeared to cause peeling and smoothing of the fiber surface. In combination, their effect was observed to be greatest when both enzymes were present simultaneously. When fibers smoothed by treatment with EG II were treated subsequently with CBH I, further evidence of path way formation caused by the action of CBH I along the fibers was observed. Incubation with a cellulase from Thermotoga maritima that lacks a cellulose binding domain had no effect on the surface of cotton fibers. These images provide the first physical evidence of differences in the effect of cellulase components action on the surface of cotton fibers and provide evidence for the movement or tracking of CBH I along the fibers. The first AFM image of CBH I molecules are presented.

Cellulase↗
PubMed2000

In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate.

Supplements of glucosamine hydrochloride, low molecular weight chondroitin sulfate, and manganese ascorbate were tested separately and in combination for their ability to retard progression of cartilage degeneration in a rabbit instability model of osteoarthrosis. Computerized quantitative histologic evaluation of safranin O stained sections of the medial femoral condyles measured the grade and extent of tissue involvement of lesions. Severe lesions (Mankin grade greater than 7) were absent in all animals supplemented with a dietary mixture of glucosamine, chondroitin sulfate, and manganese ascorbate. Total linear involvement (mm of lesioned surface) and total grade (mean grade x number of lesions per animal) were reduced significantly in animals given the combination compared with controls (59% and 74% respectively). Animals supplemented with glucosamine, chondroitin sulfate, or manganese ascorbate alone had less moderate and severe tissue involvement than controls but not to the extent of the combined group. In vitro, a combination of glucosamine hydrochloride and chondroitin sulfate acted synergistically in stimulating glycosaminoglycan synthesis (96.6%). Chondroitin sulfate and manganese ascorbate but not glucosamine were effective in inhibiting degradative enzyme activity. These data suggest that the disease modifying effect (the ability to retard progression of cartilage degeneration) of a mixture of glucosamine, chondroitin sulfate, and manganese ascorbate is more efficacious than either agent alone.

Animals↗
PubMed1999

Glucose and lactate metabolism after severe human head injury: influence of excitatory neurotransmitters and injury type.

The survival of traumatized brain tissue depends on energy substrate delivery and consumption. Excitatory amino acids produce a disturbance of ion homeostasis and thus, increase energy demand. In head-injured patients, massive release of glutamate has been reported, especially in patients with focal contusions. Therefore, we studied the interrelationship between glutamate, glucose and lactate in relation to the type of injury. We investigated 37 severely head-injured patients in which a microdialysis probe was placed next to a focal contusion (n = 14) or together with a ventricular catheter in diffusely injured tissue (n = 23). Within-subject Spearman-rank correlation revealed an overall strong relationship between glutamate and lactate (p < 0.001) and glutamate and glucose (p < 0.01), but not between glucose and lactate (n.s.). The interrelationship was more pronounced in diffusely injured brain (normal CT appearance) compared to the contused tissue. The results demonstrate that glutamate clearly influences the release of lactate following injury, supporting the hypothesis that glutamate "drives" glycolysis in astrocytes. The strong positive correlation between glutamate and glucose might indicate an effect of glutamate upon glucose uptake by cells which differs according to the type of injury.

Adult↗
PubMed1999

Evidence for time-dependent glutamate-mediated glycolysis in head-injured patients: a microdialysis study.

In the brain, lactate is not only a marker of anaerobic glycolysis due to hypoxia/ischemia, but also a neuronal energy source which is provided by glutamate-induced astrocytic glycolysis. In the present study we wanted to investigate the relationship between glutamate release and lactate production during the entire time-course and during three time periods of microdialytic monitoring in 54 severely head injured patients. Within-subject Spearman rank correlations were calculated in each period for glutamate and lactate, for each patient and the mean of all correlation coefficients were analyzed for difference from zero by a one-sample t-test. The results show a strong overall positive relationship between glutamate and lactate. However, during the first 12 hours after injury, there was no significant correlation. Thereafter, good correlation was seen. The splitting of patients into groups with good (Glasgow Outcome Scale; GOS 0-2) and poor outcome (GOS 3-4) showed a similar strong correlation for patients with good outcome, but this was lost for patients with poor outcome. The results clearly indicate that glutamate "drives" astrocytic lactate production in head-injured patients. The contribution of glutamate to overall lactate release is thus time-dependent. During the first 12 hours after injury, factors such as hypoxia, ischemia or edema overshadowed glutamate-induced glycolysis in astrocytes. In addition, the effect of glutamate is more pronounced in patients with good outcome.

Adult↗