Isolation and characterization of an unknown restriction endonuclease.
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DNA Restriction Enzymes↗
Biomedical subjects
R J Williams
Publications and source records attributed to R J Williams.
Trichostatin A, an inhibitor of histone deacetylase, inhibits hypoxia-induced angiogenesis.
Trichostatin A (TSA), a hydroxamate-type inhibitor of mammalian histone deacetylases has been reported to inhibit angiogenesis both in vitro and in vivo. TSA inhibits hypoxia-induced production of the angiogenic mediator vascular endothelial cell growth factor (VEGF) by tumour cells and also inhibits directly endothelial cell migration and proliferation. HDAC inhibitors such as TSA are currently of major interest as potential anticancer therapeutics, largely because of their well-documented properties of inhibiting proliferation and inducing apoptosis of tumour cells. The finding that HDAC appears to be a critical regulator of angiogenesis in addition to tumour cell growth will heighten interest in the development of HDAC inhibitors as potential anticancer drugs.
Angiogenesis Inhibitors↗
Reliability, validity, and responsiveness of four knee outcome scales for athletic patients.
BACKGROUND: Many patient-based knee-rating scales are available for the evaluation of athletic patients. However, there is little information on the measurement properties of these instruments and therefore no evidence to support the use of one questionnaire rather than another. The goal of the present study was to determine the reliability, validity, and responsiveness of four knee-rating scales commonly used for the evaluation of athletic patients: the Lysholm scale, the subjective components of the Cincinnati knee-rating system, the American Academy of Orthopaedic Surgeons sports knee-rating scale, and the Activities of Daily Living scale of the Knee Outcome Survey. METHODS: All patients in the study had a disorder of the knee and were active in sports (a Tegner score of 4 points). Forty-one patients who had a knee disorder that had stabilized and who were not receiving treatment were administered all four questionnaires at baseline and again at a mean of 5.2 days (range, two to fourteen days) later to test reliability. Forty-two patients were administered the scales at baseline and at a minimum of three months after treatment to test responsiveness. The responses of 133 patients at baseline were studied to test construct validity. RESULTS: The reliability was high for all scales, with the intraclass correlation coefficient ranging from 0.88 to 0.95. As for construct validity, the correlations among the knee scales ranged from 0.70 to 0.85 and those between the knee scales and the physical component scale of the Short Form-36 (SF-36) and the patient and clinician severity ratings ranged from 0.59 to 0.77. Responsiveness, measured with the standardized response mean, ranged from 0.8 for the Cincinnati knee-rating system to 1.1 for the Activities of Daily Living scale. CONCLUSIONS: All four scales satisfied our criteria for reliability, validity, and responsiveness, and all are acceptable for use in clinical research.
Adolescent↗
Six-year follow-up of the Toronto stentless porcine valve.
Stentless valves in the aortic position have been shown to have superior hemodynamic performance to stented valves and have now been shown to increase survival. We report the medium-term results from a single center of 229 Toronto (SPV) aortic valve replacements between 1994 and 2000. The mean age of the patients was 72 years (range, 41-87 years). The mean Euroscores were 6.2 (+/-0.13) and Parsonnet scores of 16.8 (+/-0.5). Concomitant coronary artery bypass grafting was performed in 125 (55%) of patients, eight patients had additional mitral valve replacements and ten were redo procedures. Hospital mortality was 3.5%. The mean follow-up period was 45 (7-81) months. The actuarial survival was 92.4% (+/-1.4%) at one year and 76.2% (+/-3.5%) at five years. There were 37 late deaths (4.7% per patient years). There were 3 patients with prosthetic valve endocarditis (0.38% per patient years), two of whom died. Stroke occurred in 13 patients (1.6% per patient years), five of whom died. None of these events were known to be valve related. There was no incidence of structural valve dysfunction and no valves have been explanted. At follow-up, the mean transvalvular gradient was 4.2 mm Hg (range, 0.9-12.7 mm Hg). No aortic incompetence (AI) was seen in 88% of patients with trivial or mild AI in 11% of patients and moderate AI in one patient. This series shows acceptable early and medium-term results in an elderly population with a high incidence of coronary artery disease.
Adult↗
A survey of the sixth European symposium on calcium-binding proteins. Calcium: its flow, its proteins and genomes.
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Animals↗
Phenolic antioxidants attenuate neuronal cell death following uptake of oxidized low-density lipoprotein.
Oxidative stress is implicated in neuronal loss associated with neurodegeneration such as in Parkinson's disease, Alzheimer's disease and age-related cognitive decline. Recent reports indicate that the consumption of flavonoid-rich fruits partly reverses the age-related neuronal and cognitive decline. In this study, cultured striatal neurons were exposed to oxidized lipids in the form of low-density lipoprotein (oxLDL) as a model for the induction of oxidative injury, and the abilities of phenolic antioxidants, flavonoids and hydroxycinnamic acid derivatives, to attenuate this neuronal damage were examined. OxLDL was demonstrated to enter neuronal cells and to be capable of eliciting neurotoxicity in a dose- and time-dependent manner, inducing DNA fragmentation and cell lysis. Flavonoids exert protective effects, which appear to be related to specific structural characteristics, particularly relevant being those defining their reduction potentials and partition coefficients. In summary, these data suggest a possible role for flavonoids in reducing neurodegeneration associated with chronic disorders in which oxidative stress is implicated.
Animals↗
Conclusions to the special issue of Science of the Total Environment concerning 'The water quality of UK rivers entering the North Sea'.
This paper presents an overview of the water quality functioning of eastern UK rivers draining into the North Sea. It summarises the results of three special issues of Science of the Total Environment and related work and complements a companion bibliography (Neal and Turner, 2000, this volume). The rivers are described in straightforward broad terms, and the reader is guided via the bibliography to the special volumes for the detailed findings. The water quality is shown to be highly variable over space and time. The changes over the past 300 years reflect first the transition from a rural society to the major impact of the industrial revolution and subsequently to one of the worlds' most successful environmental cleanups. The present water quality reflects the relative impacts of diffuse agricultural sources, urban and industrial point source discharges together with background inputs associated with geology: all these can be modified by within-river processes associated with physical mixing, biology and inorganic reactions. The work is set within the context of water quality, modelling and flux outputs to the North Sea and contemporary and future environmental research and management needs. A range of environmental impact studies is included. The detailed information is now available on a major and easily accessible database.
Agriculture↗
The water quality of the River Kennet: initial observations on a lowland chalk stream impacted by sewage inputs and phosphorus remediation.
The water quality of seven sites on the upper reaches of the River Kennet round the market town of Marlborough is described and related to the introduction of phosphorus treatment of effluent from Marlborough sewage treatment works (STW). The River Kennet is mainly groundwater-fed from a Cretaceous chalk aquifer and hence the river water is calcium- and bicarbonate-bearing and has a relatively constant composition of many major water quality determinants. In-stream biological activity gives rise to marked diurnal fluctuations in pH (of approx. 0.8 units). Dissolved carbon dioxide and dissolved oxygen also show marked diurnal fluctuations. Dissolved carbon dioxide varies from approximately 10 to 70 times atmospheric pressure, indicating net release of carbon dioxide and the dominance of heterotrophic (respiratory) processes over autotrophic processes (photosynthesis). Much of the excess carbon dioxide is probably associated with carbon dioxide laden groundwater inputs and the relatively short within-stream residence times ensures only limited degassing to the atmosphere. Diurnal fluctuations in dissolved oxygen vary from approximately 20% to 200% saturation. For both dissolved carbon dioxide and dissolved oxygen, the amplitude of fluctuations is much lower during the winter period, when biological activity is at its lowest. The concentrations of soluble reactive phosphorus (SRP), total phosphorus (TP) and boron increase markedly just downstream of the sewage works as a result of this point source input. These concentrations slowly decline further downstream as additional groundwater inputs dilute the effluent further. The introduction of chemical treatment of sewage effluent for phosphorus reduction at Marlborough STW resulted in a marked decrease in within-river SRP and TP concentrations to levels approximately the same as those upstream of the STW. A comparison of SRP and boron concentrations reveals a reduction in in-stream SRP concentrations by approximately 75% following effluent treatment. In terms of within-river processes controlling in-stream phosphorus concentrations, previous studies have indicated that one potentially important mechanism within calcium bicarbonate bearing rivers may be related to co-precipitation of phosphorus with calcium carbonate (calcite). The present study shows that the waters are oversaturated with respect to calcium carbonate, that no equilibrium conditions exist and that phosphorus removal has led to undetectable changes in calcium carbonate oversaturation. Hence, it is concluded that the primary changes in phosphorus levels within the river is directly associated with changing point source contributions from the STW and physical dilution within the river. However (1) the results relate to only the first year of study and subsequent differences may become apparent and (2) reactions between the water column and plant and bottom sediment interfaces may be important in regulating phosphorus fluxes within the river. The results presented in this paper mark a pilot phase of a longer-term initiative and this paper provides a background setting. The paper discusses the longer-term objectives and important gaps in knowledge of the system that requires further address.
England↗
Temporal and small-scale spatial variations of dissolved oxygen in the Rivers Thames, Pang and Kennet, UK.
Small-scale spatial dissolved oxygen concentrations were measured on three rivers by taking a number of transects along a river reach. Temporal (diurnal) variations were measured by use of continuous (15-min) monitors located at the mid-transect of the spatial observations. Spatial variation of dissolved oxygen concentrations were found to be relatively small (approx. +/- 10% dissolved oxygen) and biologically insignificant compared to diurnal changes under conditions of high productivity (approx. +/- 60% dissolved oxygen). The diurnal curves were analysed in order to estimate values of reaeration, photosynthesis and respiration on a daily basis for almost 3 months using process-based analytical techniques (the Delta and Hornberger and Kelly methods). The River Kennet was shown to be the most productive river followed by the River Pang and then the River Thames. The patterns of reaeration, photosynthesis and respiration and the behaviour of the three rivers are discussed.
England↗
The water quality of UK rivers entering the North Sea.
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Environmental Monitoring↗
Simple rules yield complex food webs.
Several of the most ambitious theories in ecology describe food webs that document the structure of strong and weak trophic links that is responsible for ecological dynamics among diverse assemblages of species. Early mechanism-based theory asserted that food webs have little omnivory and several properties that are independent of species richness. This theory was overturned by empirical studies that found food webs to be much more complex, but these studies did not provide mechanistic explanations for the complexity. Here we show that a remarkably simple model fills this scientific void by successfully predicting key structural properties of the most complex and comprehensive food webs in the primary literature. These properties include the fractions of species at top, intermediate and basal trophic levels, the means and variabilities of generality, vulnerability and food-chain length, and the degrees of cannibalism, omnivory, looping and trophic similarity. Using only two empirical parameters, species number and connectance, our 'niche model' extends the existing 'cascade model and improves its fit ten-fold by constraining species to consume a contiguous sequence of prey in a one-dimensional trophic niche.
Ecology↗
Copper coordination in blue proteins.
The spectroscopic and electrochemical properties of blue copper proteins are strikingly different from those of inorganic copper complexes in aqueous solution. Over three decades ago this unusual behavior was ascribed to constrained coordination in the folded protein; consistent with this view, crystal structure determinations of blue proteins have demonstrated that the ligand positions are essentially unchanged on reduction as well as in the apoprotein. Blue copper reduction potentials are tuned to match the particular function of a given protein by exclusion of water from the metal site and strict control of the positions of axial ligands in the folded structure. Extensive experimental work has established that the reorganization energy of a prototypal protein, Pseudomonas aeruginosa azurin, is approximately 0.7 eV, a value that is much lower than those of inorganic copper complexes in aqueous solution. The lowered reorganization energy in the protein, which is attributable to constrained coordination, is critically important for function, since the driving forces for electron transfer often are low (approximately 0.1 eV) between blue copper centers and distant (>10 A) donors and acceptors.
Bacterial Proteins↗
Mitochondria and chloroplasts: localized and delocalized bioenergetic transduction.
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Adenosine Triphosphate↗
Crimean-congo haemorrhagic fever: a seroepidemiological and tick survey in the Sultanate of Oman.
In 1995 and 1996, 4 persons from the Sultanate of Oman were confirmed with clinical Crimean-Congo haemorrhagic fever (CCHF). To assess the prevalence of CCHF virus infection in Oman, a convenience sample of imported and domestic animals from farms, abattoirs and livestock markets was examined by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to CCHF virus. Ticks were collected from selected animals, identified, pooled by species, host and location and tested for evidence of infection with CCHF virus by antigen-capture ELISA. Serum samples from individuals working in animal and nonanimal contact-related jobs were also tested for CCHF antibodies. Serological evidence of infection was noted in 108 (22%) of 489 animals. Most of the ticks collected (618 of 912) from all species of sampled livestock were Hyalomma anatolicum anatolicum, a competent vector and reservoir of CCHF virus. 243 tick pools were tested for CCHF antigen, and 19 pools were positive. Of the individuals working in animal contact-related jobs, 73 (30.3%) of 241 non-Omani citizens and only 1 (2.4%) of 41 Omani citizens were CCHF antibody-positive. Butchers were more likely to have CCHF antibody than persons in other job categories. The presence of clinical disease and the serological results for animals and humans and infected Hyalomma ticks provide ample evidence of the presence of CCHF virus in yet another country in the Arabian Peninsula.
Adolescent↗
Impact on T-cell depletion and CD34+ cell recovery using humanised CD52 monoclonal antibody (CAMPATH-1H) in BM and PSBC collections; comparison with CAMPATH-1M and CAMPATH-1G.
BACKGROUND: Ex vivo T-cell depletion of allogeneic BM (BM) grafts can effectively reduce graft versus host disease (GvHD) and may also apply to transplantation of allogeneic peripheral blood stem cell (PBSC) transplants. METHODS: Here we have evaluated T-cell depletion and progenitor cell recovery by antibody-mediated cells lysis using three CD52 monoclonal antibodies (MAbs) at different concentrations and cell densities. RESULTS: CAMPATH-1M was superior to CAMPATH-1H for T-cell depletion of BM samples. Treatment with CAMPATH-1M resulted in up to 2.55 log depletion of CD3+ cells, with recoveries of >or=45% CD34+ cells, >or=67% CFU-GM and >or=65% BFU-E. CAMPATH-1H treatment resulted in up to 1.64 log depletion of CD3+ cells and similar recoveries of CD34+ cells, CFU-GM and BFU-E as seen with CAMPATH-1M. Depletion of CD19+ cells was similar to that observed for CD3+ cells while natural killer (NK) cells were relatively spared compared with the T and B cell populations. Log depletions of T cells from PBSC, as determined by immunofluorescence studies and limiting dilution analyses, were similar using CAMPATH-1M, -1H, and -1G. There were also no differences in the depletion of CD19+ cells or NK cells using the three MAbs. Similar results were obtained for recoveries of CD34+ cells, CFU-GM and BFU-E using all three MAbs, although the recovery of CD34+ cells using the highest concentration of MAbs was significantly greater in CAMPATH-1H treated samples. Increasing the number of PBSC treated with CAMPATH-1H and -1M had no effect on the log depletion of T, B or NK cells and there were no major differences in the log depletions achieved with CAMPATH-1H or -1M. Likewise, the higher PBSC density had no effect on the recoveries of CD34+ cells or committed progenitors and once again CAMPATH-1H gave similar recoveries to those obtained using CAMPATH-1M. DISCUSSION: Although CAMPATH-1M resulted in greater ex vivo T-cell depletion of BM than CAMPATH-1H, in all other respects, the humanised CAMPATH-1H was just as effective as CAMPATH-1M and -1G.
Alemtuzumab↗
Advances in our understanding of the bone and joint pathology caused by Staphylococcus aureus infection.
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Animals↗
Identification of a novel gene cluster encoding staphylococcal exotoxin-like proteins: characterization of the prototypic gene and its protein product, SET1.
We report the discovery of a novel genetic locus within Staphylococcus aureus that encodes a cluster of at least five exotoxin-like proteins. Designated the staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading frames have between 38 and 53% homology to each other. All five proteins contain consensus sequences that are found in staphylococcal and streptococcal exotoxins and toxic shock syndrome toxin 1 (TSST-1). However, the SETs have only limited overall sequence homology to the enterotoxins and TSST-1 and thus represent a novel family of exotoxin-like proteins. The prototypic gene in this cluster, set1, has been cloned and expressed. Recombinant SET1 stimulated the production of interleukin-1beta, interleukin-6, and tumor necrosis factor alpha by human peripheral blood mononuclear cells. PCR analysis revealed that set1 was distributed among other strains of S. aureus but not in the other staphylococcal species examined. Sequence analysis of the set1 genes from different strains revealed at least three allelic variants. The protein products of these allelic variants displayed a 100-fold difference in their cytokine-inducing potency. The distribution of allelic variants of the set genes among strains of S. aureus may contribute to differences in the pathogenic potential of this bacterium.
Amino Acid Sequence↗
Sex-role traits and self-monitoring as dimensions of control: women with bulimia nervosa vs. controls.
OBJECTIVE: The study investigated sex-role traits and self-monitoring styles as two dimensions of self-control amongst women with bulimia nervosa and normal controls. DESIGN AND METHODS: The participants were 30 women with bulimia nervosa and 40 normal controls who completed questionnaires, which assessed bulimic symptoms, sex-role traits, and Synder's Self-Monitoring Scale. RESULTS: Women with bulimia nervosa were found to identify more strongly than controls with negative feminine traits and Other Directedness, a style of self-monitoring that focuses on pleasing others. CONCLUSIONS: These findings reinforce the notion that women with bulimia nervosa lack assertiveness skills and that the strategies they have developed in their interactions with others can be described as a Negative Yielding style of self-control.
Adolescent↗