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Biomedical subjects

R E Jones

Publications and source records attributed to R E Jones.

At least 19 recordsLinked to original sources
PubMed2006

Complex hydrological controls on wet dune slacks: the importance of local variability.

Dune slacks are a species-rich habitat controlled largely by water chemistry and fluctuations in groundwater. Changes in water chemistry and water table level were analysed in 8 piezometers and 15 ephemeral surface water locations at a large UK dune system over a 12-month period. Total nitrogen concentrations in groundwater varied from 0.27-8.21 mg N L(-1), where dissolved organic nitrogen was dominant at the low nitrogen locations and nitrate was dominant at the high nitrogen locations. Principal components analysis of the water chemistry suggests at least four chemically distinct groundwater signatures. Water levels showed strong temporal heterogeneity. Comparisons of water levels with antecedent rainfall identified a component of year-round groundwater feed and differing seasonal responses overlain by a complex series of lags. In summer, there were lags of four, six and seven months with an additional rapid peaky response to daily rainfall with a one-day lag. In winter, water levels were strongly influenced by exogenous groundwater supply, but again exhibited multiple lags. This study shows that local variations in water chemistry and in hydrological regime can be more complicated than previously thought, with clear implications for optimum management of these high priority habitats for conservation.

Nitrates↗
PubMed2006

Evidence for p-type doping of InN.

The first evidence of successful p-type doping of InN is presented. It is shown that InN:Mg films consist of a p-type bulk region with a thin n-type inversion layer at the surface that prevents electrical contact to the bulk. Capacitance-voltage measurements indicate a net concentration of ionized acceptors below the -type surface. Irradiation with 2 MeV He+ ions is used to convert the bulk of InN:Mg from p to n-type, at which point photoluminescence is recovered. The conversion is well explained by a model assuming two parallel conducting layers (the surface and the bulk) in the films.

Journal Article↗
PubMed2006

Rhizome phyllosphere oxygenation in Phragmites and other species in relation to redox potential, convective gas flow, submergence and aeration pathways.

Underground rhizomes of emergent aquatic macrophytes are important for perennation, vegetative spread, competition and anchorage. In four species we examined the potential for the development of oxidized phyllospheres around rhizome apical buds, similar to the protective oxygenated rhizospheres around roots. Redox potentials and polarographic measurements of radial oxygen loss were recorded using platinum cathodes around the apical buds. The aeration pathway from atmosphere to phyllosphere was investigated anatomically and by applied pressurized gas flow. Redox potentials increased by +400, +45, +200 and +340 mV around rhizome apices of Phragmites australis, Oryza rhizomatis, Carex rostrata and Glyceria maxima, respectively. Radial oxygen loss from rhizome apices of Phragmites was increased by convective gas flow through the rhizome and by shoot de-submergence, and decreased by resistances applied within the aeration pathway and by shoot submergence. We conclude that oxygen passes via internal gas-space connections between aerial shoot, rhizome and underground buds and into the phyllosphere regions via scale-leaf stomata and surfaces on the buds. We suggest that oxidized phyllospheres may protect rhizome apices against phytotoxins in waterlogged soils, just as oxidized rhizospheres protect roots.

Cyperaceae↗
PubMed2004

Changes in vegetation and soil characteristics in coastal sand dunes along a gradient of atmospheric nitrogen deposition.

A field survey was conducted to detect signals of atmospheric nitrogen (N) in 11 dune systems along a nitrogen deposition gradient in the United Kingdom. In the mobile and semi-fixed dunes, above-ground biomass was positively related to N inputs. This increase was largely due to increased height and cover of Ammophila arenaria. In the long term, this increased biomass may lead to increased organic matter accumulation and consequently accelerated soil development. In the fixed dunes, above ground biomass also showed a positive relationship with N inputs as did soil C : N ratio while soil available N was negatively related to N inputs. Plant species richness was negatively related to N inputs. In the dune slacks, while soil and bulk vegetation parameters showed no relationship with N inputs, cover of Carex arenaria and Hypochaeris radicata increased. Site mean Ellenberg N numbers showed no relationship with N deposition either within habitats or across the whole dataset. Neither abundance-weighting nor inclusion of the Siebel numbers for bryophytes improved the relationship. The survey reveals that the relationships of soil and vegetation with atmospheric N deposition vary between sand dune habitats but, despite this variability, clear correlations with N inputs exist. While this survey cannot establish causality, on the basis of the relationships observed we suggest a critical load range of 10 - 20 kg N ha(-1) yr(-1) for coastal sand dunes in the UK.

Atmosphere↗
PubMed2003

Stem cell differentiation and the effects of deficiency.

Stem cells have several unique attributes, the key features being their potency and plasticity. They have the ability to give rise to multiple cell lineages and to transdifferentiate into totally different cell type(s) when relocated to a novel stem cell niche. Most self-renewing tissues are served by stem cells. At the ocular surface, the corneo-scleral limbus is believed to provide the niche for corneal epithelial stem cells. A large body of circumstantial evidence, both clinical and basic, supports this view. However, specific identification of limbal stem cells has proved elusive. Cytokeratin markers, vimentin, epidermal growth factor receptors, p63, and others have been used to identify epithelial cell populations at the limbus, which could harbour putative stem cells. In contrast, none of the known haematopoietic stem cell markers namely, CD34 and CD133, stain any specific subset of corneal or limbal epithelial cells. Singly or collectively, none of these markers point to any unique cell(s) that could be regarded as stem cells, supporting the notion that the corneal epithelium is served by 'committed progenitors' rather than by stem cells. Disease or destruction of the corneo-scleral limbus is associated with consequential events that eventually lead to visual impairment or blindness. Conjunctivalisation and vascularisation of the corneal surface and persistent or recurring epithelial defects are hallmarks of limbal deficiency.

Cell Differentiation↗
PubMed2001

The synthesis of a prodrug of doxorubicin designed to provide reduced systemic toxicity and greater target efficacy.

Doxorubicin (Dox) can provide some stabilization in prostate cancer; however, its use is limited because of systemic toxicities, primarily cardiotoxicity and immunosuppression. The administration of a prodrug of doxorubicin, designed to permit selective activation by the tumor, would reduce general systemic exposure to the active drug and would thereby increase the therapeutic index. Prostate specific antigen (PSA) is a serine protease with chymotrypsin-like activity that is a member of the kallikrein gene family. PSA's putative physiological role is the liquefaction of semen by virtue of its ability to cleave the seminal fluid proteins semenogelins I and II. Serum PSA levels have been found to correlate well with the number of malignant prostate cells. The use of a prodrug which is cleaved by the enzyme PSA in the prostate should in principle produce high localized concentrations of the cytotoxic agent at the tumor site while limiting systemic exposure to the active drug. Cleavage maps following PSA treatment of human semenogelin were constructed. Systematic modification of the amino acid residues flanking the primary cleavage site led to the synthesis of a series of short peptides which were efficiently hydrolyzed by PSA. Subsequent coupling of selected peptides to doxorubicin provided a series of doxorubicin-peptide conjugates which were evaluated in vitro and in vivo as targeted prodrugs for PSA-secreting tumor cells. From these studies we selected Glutaryl-Hyp-Ala-Ser-Chg-Gln-Ser-Leu-Dox, 27, as the peptide-doxorubicin conjugate with the best profile of physical and biological properties. Compound 27 has a greater than 20-fold selectivity against human prostate PSA-secreting LNCaP cells relative to the non-PSA-secreting DuPRO cell line. In nude mouse xenograft studies, 27 reduced PSA levels by 95% and tumor weight by 87% at a dose below its MTD. Both doxorubicin and Leu-Dox (13) were ineffective in reducing circulating PSA and tumor burden at their maximum tolerated doses. On the basis of these results, we selected 27 for further study to assess its ability to inhibit human prostate cancer cell growth and tumorigenesis.

Animals↗
PubMed2001

Computerized medical records in the Department of Veterans Affairs.

The VA Medical Center in Washington, DC, was the nexus for a number of computerization projects that were initiated by the Department of Veterans Affairs. The culmination of these initiatives is a software package that presents the complete electronic patient record in an easy-to-use graphic user interface. This record combines text data from the legacy data base, diagnostic images from patient procedures, electrocardiograms from a commercial server, an Internet connection, and a hospital web site with pertinent reference information. The information is available in over 1000 places in the hospital and can be accessed remotely using a remote access server. The computerization of the medical record has improved hospital efficiency, has made physician access to patient information more reliable, has opened new opportunities for patient education, and has given healthcare providers more time to care for patients.

Diagnostic Imaging↗
PubMed2001

T lymphocytes promote the development of bone marrow-derived APC in the central nervous system.

Certain cells within the CNS, microglial cells and perivascular macrophages, develop from hemopoietic myelomonocytic lineage progenitors in the bone marrow (BM). Such BM-derived cells function as CNS APC during the development of T cell-mediated paralytic inflammation in diseases such as experimental autoimmune encephalomyelitis and multiple sclerosis. We used a novel, interspecies, rat-into-mouse T cell and/or BM cell-transfer method to examine the development and function of BM-derived APC in the CNS. Activated rat T cells, specific for either myelin or nonmyelin Ag, entered the SCID mouse CNS within 3-5 days of cell transfer and caused an accelerated recruitment of BM-derived APC into the CNS. Rat APC in the mouse CNS developed from transferred rat BM within an 8-day period and were entirely sufficient for induction of CNS inflammation and paralysis mediated by myelin-specific rat T cells. The results demonstrate that T cells modulate the development of BM-derived CNS APC in an Ag-independent fashion. This previously unrecognized regulatory pathway, governing the presence of functional APC in the CNS, may be relevant to pathogenesis in experimental autoimmune encephalomyelitis, multiple sclerosis, and/or other CNS diseases involving myelomonocytic lineage cells.

Animals↗
PubMed2001

Total knee arthroplasty using the S-ROM mobile-bearing hinge prosthesis.

A retrospective study was performed on 15 patients receiving 16 S-ROM mobile-bearing hinge total knee prostheses that were evaluated with at least a 2-year follow-up (range, 27-71 months). Indications for its use included severe instability and bone loss. The average patient age was 63 years (range, 33-83 years). There were 15 revision arthroplasties and 1 primary arthroplasty. Knee Society scores showed notable improvement in pain, motion, and stability (33.6 preoperatively vs 76.5 postoperatively; P <.0001) and approached significant improvement in function (29.2 preoperatively vs 43.5 postoperatively; P =.11). After excluding a patient with a traumatically ruptured patellar tendon, the probability of the latter comparison improved (P <.01). There was no evidence of loosening, and complete bone apposition was seen in nearly all cases. A high percentage of satisfactory results can be achieved when using this mobile-bearing hinge knee prosthesis for these indications.

Adult↗
PubMed2001

Modular, mobile-bearing hinge total knee arthroplasty.

Early reports of hinge total knee arthroplasty showed high rates of complications and implant failure. Third-generation modular, mobile-bearing, hinge knee arthroplasty systems have evolved to decrease the deleterious stresses that contributed to the failures of earlier designs. The combined series of Barrack et al and Jones et al documents midterm results using the S-ROM Hinge Knee System for patients with significant soft and hard tissue deficiencies not suitable for standard, less constrained, revision knee systems. The combined series included 30 knees with a mean followup of 49 months. Knee Society clinical scores improved from 52 to 134 points. There were no mechanical failures of the implants. The knee system used provides press-fit diaphyseal stems and metaphyseal filling and loading sleeves, all of which showed apposition and positive remodeling of bone at followup radiographic analysis. The excellent midterm results of this modular, mobile-bearing, linked knee system suggest the orthopaedic surgeon can display increasing confidence in the selection of such a knee system when confronted with catastrophic, salvage knee arthroplasty.

Arthroplasty, Replacement, Knee↗
PubMed2001

PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites.

Tumor-selective delivery of doxorubicin by a prostate-specific antigen (PSA)-targeted peptide conjugate prodrug of doxorubicin was demonstrated in a nude mouse xenograft model of human prostate cancer. The prodrug (referred to as doxorubicin conjugate) contains doxorubicin linked to a seven-amino acid peptide conjugate that was designed to increase delivery of doxorubicin to tumor sites through the hydrolytic properties of PSA, which prostate tumors express in high amounts. Following i.p. administration of the doxorubicin conjugate to mice, tumor exposure to doxorubicin was increased 2.5-fold as compared with that achieved after an equimolar dose of doxorubicin itself. However, in heart tissue, the site of clinical dose-limiting toxicity, doxorubicin concentrations observed after administration of doxorubicin conjugate were substantially lower than those in mice that received doxorubicin itself. While the prodrug provided selective delivery of doxorubicin to tumor tissue, there was substantial non-PSA-specific formation of doxorubicin in laboratory animals, a factor that would limit the extent of therapeutic gain of the prodrug. Following i.v. administration to mice, rats, dogs, and monkeys, about one-third of the dose was metabolized to doxorubicin. In tumor-bearing mice, the fraction of the dose metabolized to doxorubicin appeared even higher. This is likely the result of conjugate conversion to doxorubicin by both PSA-specific (in tumor) and non-PSA-specific proteolytic activities. In vitro studies provided further support for the PSA specificity of metabolism; LNCaP cells mediated rapid metabolism of the conjugate, while DuPRO-1 cells, which are deficient in PSA, were incapable of metabolism.

Animals↗
PubMed2000

Osteonecrosis in HIV: a case-control study.

BACKGROUND: Osteonecrosis (avascular necrosis) has been infrequently reported in HIV-infected patients. It is not known whether HIV itself is an independent risk factor for osteonecrosis. METHODS: We identified 25 patients with osteonecrosis from 1984 to 1999 from a large county teaching hospital and two large practices in Dallas County that specialize in HIV-disease related therapy. A retrospective chart review was performed to evaluate potential risk factors for osteonecrosis. Each case was matched with two controls for HIV positive status and date of osteonecrosis diagnosis. RESULTS: In the study, 22 of 25 (88%) case patients had at least one osteonecrosis risk factor compared with 24 of 50 (48%) controls, p =.003. The most common osteonecrosis risk factors were hyperlipidemia (32%), alcoholism (28%), pancreatitis (16%), corticosteroids (12%), and hypercoaguability (12%). Of the cases, 12% were idiopathic. Multiple joints were involved in 72% of cases. Four of the case patients compared with none of the controls received megesterol acetate before the diagnosis of osteonecrosis, p =.01. No significant differences were found between cases and controls with respect to liver function tests, testosterone levels, triglyceride levels, cholesterol levels, or CD4 cell counts. Saquinavir was independently associated with osteonecrosis, p <.05. However, no differences in overall use of protease inhibitors among cases and controls were noted: 79% versus 76%, respectively. CONCLUSIONS: The increased incidence of osteonecrosis in HIV/AIDS may be due to an increased frequency of risk factors previously associated with osteonecrosis such as hyperlipidemia, corticosteroid use, alcohol abuse, and hypercoaguability. Use of protease inhibitors was not independently associated with osteonecrosis.

Adult↗
PubMed2000

UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions.

The cAMP-specific phosphodiesterases (PDE4) enzymes contain unique "signature" regions of amino acid sequence, called upstream conserved regions 1 and 2 (UCR1 and UCR2). UCR1 and UCR2 are located between the extreme amino-terminal region and the catalytic region of the PDE4 enzymes. The UCR1 of the PDE4D3 isoform was used as a "bait" in a two-hybrid screen, which identified a PDE4D cDNA clone containing UCR2 and the catalytic region but not UCR1. Two-hybrid and "pull down" analysis of constructs incorporating various regions of the PDE4D3 cDNA demonstrated that the carboxyl-terminal region of UCR1 interacted specifically with the amino-terminal region of UCR2. The interaction was blocked by mutations of two positively charged amino acids (Arg-98 and Arg-101 to alanine) located within an otherwise largely hydrophobic region of UCR1. Mutation of three negatively charged amino acids in UCR2 (Glu-146, Glu-147, and Asp-149, all to alanine) also blocked the interaction. The phosphorylation of UCR1 by cAMP-dependent protein kinase (PKA) in vitro attenuated the ability of UCR1 to interact with UCR2. Mutation of the PKA substrate site in UCR1 (Ser-54) to aspartic acid, which mimics the activation of PDE4D3 by PKA, profoundly reduced the interaction between UCR1 and UCR2. Our data are consistent with a model in which UCR1 and UCR2 act as independent domains whose interaction is determined by electrostatic interactions and which may be disrupted by PKA phosphorylation. We suggest that the UCR1 and UCR2 domains may form a module that interacts with and regulates the PDE4 catalytic region.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Distribution of beta-amyloid and amyloid precursor protein in the brain of spawning (senescent) salmon: a natural, brain-aging model.

Brain amyloid precursor protein (APP), a normal constituent of neurons, glial cells and cerebrospinal fluid, has several proposed functions (e.g., in neuronal growth and survival). It appears, however, that altered processing of APP is an initial or downstream step in the neuropathology of brain aging, Alzheimer's disease (AD), and Down's syndrome (DS). Some studies suggest that proteolytic cleavage of APP, producing beta-amyloid (Abeta(1-42)), could have neurotoxic or neuroprotective effects. In this study, we utilized antibodies to human APP(695) and Abeta(1-42,) and Congo red staining, to search for amyloid deposition in the brain of semelparous spawning kokanee salmon (Oncorhynchus nerka kennerlyi). Intracellular APP(695) immunoreactivity (APP-ir) was observed in brain regions involved in gustation (glomerulosus complex), olfaction (putative hippocampus, olfactory bulb), vision (optic tectum), the stress response (nucleus preopticus and nucleus lateralis tuberis), reproductive behavior (nucleus preopticus magnocellularis, nucleus preopticus periventricularis, ventral telencephalon), and coordination (cerebellum). Intra- and extra-neuronal Abeta(1-42) immunoreactivity (Abeta-ir) were present in all APP-ir regions except the nucleus lateralis tuberis and Purkinje cells of the cerebellum (coordination). Thus, the relationship between APP and Abeta deposition during brain aging could shed light on the processing of APP into Abeta, neurodegeneration, and possible protection of neurons that are functioning in spawning but senescent salmon. Pacific salmon, with their predictable and synchronized life history, could provide research options not available with the existing models for studies of brain aging and amyloidosis.

Aging↗
PubMed2000

Cell density and intracellular translocation of glucocorticoid receptor-immunoreactive neurons in the kokanee salmon (Oncorhynchus nerka kennerlyi) brain, with an emphasis on the olfactory system.

This study tested the hypothesis that neurons in olfactory regions of the kokanee salmon brain contain glucocorticoid receptors. Distribution and neuronal number of glucocorticoid receptor-like immunoreactive (GRir) neurons were identified in the kokanee salmon brain using immunohistochemistry with an antibody to GR (polyclonal rabbit anti-human, dilution 1:1500; and monoclonal mouse, dilution 5 micrograms/ml). Distribution of GRir neurons similar to the mammalian pattern was observed in the brains of sexually immature (n = 8; 4 female and 4 male) as well as spawning (n = 8; 4 female and 4 male) salmon. Olfactory-related areas containing GRir positive neuronal bodies included the internal cell layer of the olfactory bulb, ventral-lateral and lateral parts of the dorsal telencephalon (homologue of the mammalian hippocampus), ventral area of the telencephalon (homologue of the mammalian amygdala), glomerulosus complex of the thalamus, the preoptic area, and inferior lobe of the hypothalamus. The pattern of GRir neuronal distribution in sexually immature and spawning fish was similar. However, spawning fish brains, compared to sexually immature brains, exhibited a significantly greater GRir neuronal number in several olfactory regions in paired immunohistochemical runs. There also were differences in intraneuronal location of GRir in olfactory regions, with staining being predominantly cytoplasmic in sexually immature fish but nuclear in spawning fish. These results are consistent with a role for cortisol in olfactory-mediated homing in kokanee salmon. Although GRir were identified in many nonolfactory regions, the focus of this study is on GRir present in brain regions involved in olfaction.

Animals↗
PubMed2000

Elevation of plasma cortisol during the spawning migration of landlocked kokanee salmon (Oncorhynchus nerka kennerlyi).

Kokanee salmon (Oncorhynchus nerka kennerlyi ), a landlocked subspecies of sockeye salmon, exhibited hypothalamic-pituitary interrenal (HPI, adrenal homologue) axis activation and an increase in plasma cortisol concentration up to 639 +/- 55.9 ng/ml in association with upstream migration in the upper Colorado River even though they were not exposed to a change in salinity and lengthy migration. Kokanee salmon were collected at various stages of migration and concomitant sexual maturation. The pattern of cortisol elevation in kokanee is similar to that in ocean-run sockeye salmon (O. nerka nerka). The presence of plasma cortisol elevation in an upstream migrating, landlocked Pacific salmon suggests that stressors previously considered to cause the cortisol increase, such as long-distance migration and changes in salinity, may not be primary causes of the HPI axis activation.

Animals↗
PubMed2000

A peptide-doxorubicin 'prodrug' activated by prostate-specific antigen selectively kills prostate tumor cells positive for prostate-specific antigen in vivo.

We covalently linked doxorubicin with a peptide that is hydrolyzable by prostate-specific antigen. In the presence of prostate tumor cells secreting prostate-specific antigen, the peptide moiety of this conjugate, L-377,202, was hydrolyzed, resulting in the release of leucine-doxorubicin and doxorubicin, which are both very cytotoxic to cancer cells. However, L-377,202 was much less cytotoxic than conventional doxorubicin to cells in culture that do not secrete prostate-specific antigen. L-377,202 was approximately 15 times more effective than was conventional doxorubicin at inhibiting the growth of human prostate cancer tumors in nude mice when both drugs were used at their maximally tolerated doses. Nude mice inoculated with human prostate tumor cells secreting prostate-specific antigen showed considerable reductions in tumor burden with minimal total body weight loss when treated with L-377, 202. This improvement in therapeutic index correlated with the selective localization of leucine-doxorubicin and free doxorubicin in tissues secreting prostate-specific antigen after exposure to L-377,202.

Animals↗