Biomedical subjects

R A Jones

Publications and source records attributed to R A Jones.

At least 19 recordsLinked to original sources

PubMed2006

Reactive oxygen species and erectile dysfunction: possible role of NADPH oxidase.

Erectile dysfunction (ED) is a widespread condition, the incidence of which is increasing globally. ED is also indicative of underlying vasculopathy and represents a predictor of more serious cardiovascular disorders. Understanding the aetiology of ED may therefore provide invaluable pointers to the pathobiology of other cardiovascular diseases (CVDs) and syndromes. It follows, too, that therapeutic interventions that are successful in treating ED may, ipso facto, be effective in treating the early stages of conditions that include atherosclerosis, angina, plaque rupture and diabetic angiopathy. One common pathological denominator in both CVD and ED is oxidative stress, that is, the overproduction of reactive oxygen species (ROS), in particular, superoxide (O(2)(*-)) and hydrogen peroxide (H(2)O(2)). In this review, therefore, we consider the aetiology and pathobiology of O(2)(*-) in promoting ED and focus on NADPH oxidase as an inducible source of O(2)(*-) and H(2)O(2). Therapeutic strategies aimed at reducing oxidative stress to improve erectile function are also discussed.

Animals↗

PubMed2006

Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation.

Overexpression and hyperactivation of the type I insulin-like growth factor receptor (IGF-IR) has been observed in human breast tumor biopsies. In addition, in vitro studies indicate that overexpression of IGF-IR is sufficient to transform cells such as mouse embryo fibroblasts and this receptor promotes proliferation and survival in breast cancer cell lines. To fully understand the function of the IGF-IR in tumor initiation and progression, transgenic mice containing human IGF-IR under a doxycycline-inducible MMTV promoter system were generated. Administration of 2 mg/ml doxycycline in the animals' water supply beginning at 21 days of age resulted in elevated levels of IGF-IR in mammary epithelial cells as detected by Western blotting and immunohistochemistry. Whole mount analysis of 55-day-old mouse mammary glands revealed that IGF-IR overexpression significantly impaired ductal elongation. Moreover, histological analyses revealed multiple hyperplasic lesions in the mammary glands of these 55-day-old mice. The formation of palpable mammary tumors was evident at approximately 2 months of age and was associated with increased levels of IGF-IR signaling molecules including phosphorylated Akt, Erk1/Erk2 and STAT3. Therefore, these transgenic mice provide evidence that IGF-IR overexpression is sufficient to induce mammary epithelial hyperplasia and tumor formation in vivo and provide a model to further understand the function of IGF-IR in mammary epithelial transformation.

Animals↗

PubMed2005

Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth.

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.

Animals↗

PubMed2004

The wear and fracture behaviour of ultra high molecular weight polyethylene subjected to gamma-irradiation in an atmosphere of acetylene.

The wear and mechanical properties of GUR 1020 (Perplas IMP 2000-2) Ultra High Molecular Weight Polyethylene (UHMWPE) subjected to gamma-irradiation in an atmosphere of acetylene, were evaluated for a range of processing conditions of irradiation, annealing and ageing. The results were compared with those obtained for the virgin UHMWPE material and material processed using conventional gamma-irradiation in nitrogen. Cross-linking produced by irradiation in acetylene, followed by subsequent annealing was found to be significantly more effective in improving the mechanical and wear properties of UHMWPE compared to when the material was irradiated in nitrogen. Gel fraction analysis on its own, while being able to detect the degree of cross-linking, was found to be insufficient in determining the effectiveness of the cross-links and the resulting mechanical properties of the UHMWPE material. The results suggest that gamma-irradiation in an atmosphere of acetylene may provide significant advantages over conventional UHMWPE processing and irradiation cross-linking techniques.

Acetylene↗

PubMed2004

Radioactivity in cathode ray tubes.

While surveying used computer equipment out of a zone posted as a Contamination Area, 100% of the computer monitors surveyed had levels of radioactivity that were significantly above background. The radioactivity was primarily on the front face of the cathode ray tube and was not amenable to decontamination. Hot spots were found also along the edges and seals of the cathode ray tube. Similar surveys of computer monitors that were never in Contamination Areas confirmed that radioactivity was incorporated into the monitor. Surveys were made of recently manufactured television sets with similar results. Gamma spectroscopy indicates that the radioactivity is due to naturally occurring radioactive materials. Since most surveys of cathode ray tubes in the literature were made while the units were energized and indicated low-energy x-rays, the use of naturally occurring radioactive materials in the manufacture of cathode ray tubes has not been widely recognized. This paper presents the results of these surveys, the results of gamma spectroscopy, and a method for releasing existing computer equipment having naturally occurring radioactive materials.

Beta Particles↗

PubMed2001

Thermodynamic versus kinetic products of DNA alkylation as modeled by reaction of deoxyadenosine.

Alkylating agents that react through highly electrophilic quinone methide intermediates often express a specificity for the weakly nucleophilic exocyclic amines of deoxyguanosine (dG N(2)) and deoxyadenosine (dA N(6)) in DNA. Investigations now indicate that the most nucleophilic site of dA (N1) preferentially, but reversibly, conjugates to a model ortho-quinone methide. Ultimately, the thermodynamically stable dA N(6) isomer accumulates by trapping the quinone methide that is transiently regenerated from collapse of the dA N1 adduct. Alternative conversions of the dA N1 to the dA N(6) derivative by a Dimroth rearrangement or other intramolecular processes are not competitive under neutral conditions, as demonstrated by studies with [6-(15)N]-dA. Both a model quinone methide precursor and its dA N1 adduct yield a similar profile of deoxynucleoside products when treated with an equimolar mixture of dC, dA, dG, and T. Consequently, the most readily observed products of DNA modification resulting from reversible reactions may reflect thermodynamic rather than kinetic selectivity.

Alkylation↗

PubMed2001

Character of the glass transition in thin supported polymer films.

We have used ellipsometry to study the thermal expansivity of thin polystyrene films on silicon substrates with thicknesses of 10-200 nm. We find well-defined glass transitions, and detailed analysis of the expansivities shows that for thinner films the transition width is broadened, while the strength of the transition, defined by the difference between the expansivities in the liquid and glassy state, is reduced; the expansivity in the glassy state is higher than in the bulk. These phenomena are consistent with the idea that a layer of roughly constant thickness, of order 10 nm, near the surface of the film has liquidlike thermal properties at all experimental temperatures.

Journal Article↗

PubMed2001

Role of the cross-linking enzyme tissue transglutaminase in the biological recognition of synthetic biodegradable polymers.

The calcium-dependent cross-linking enzyme tissue transglutaminase (tTgase, type II) is a potential novel player at the cell surface, where its contribution to cell adhesion and stabilization of the extracellular matrix is becoming increasingly recognized. We investigated whether tTgase enhances the biological recognition of poly (DL lactide co-glycolide) (PLG), poly (epsilon-caprolactone) (PCL), and poly (L lactide) (PLA), biomaterials widely used in medical implants. Three cell-model systems consisting of human osteoblasts, endothelial cells (ECV-304), and Swiss 3T3 fibroblasts were utilized, in which tTgase expression was modulated by gene transfer, and the ability of cells to spread on these polymers was quantified in relation to the altered level of expressed tTGase. Results show that over-expression of tTgase in human osteoblasts positively correlated with cell spreading on PLG, while no attachment and spreading was found on PCL and PLA. Antisense silencing of tTgase in the endothelial cells led to a marked reduction of cell spreading on all polymers. The hydrophobic nature of PLC also appeared to favor endothelial cell attachment. Spreading of Swiss 3T3 fibroblasts on these biomaterials was only slightly affected by increased expression of tTgase, although cell spreading on control glass was increased. We propose that the consideration of tTgase-mediated bioactivity in novel biomaterials may improve cell attachment and promote biocompatibility.

3T3 Cells↗

PubMed2001

Diffusion tensor MRI of the human kidney.

This study characterizes the diffusion anisotropy of the human kidney using a diffusion-weighted, single-shot echo planar imaging (EPI) sequence in order to access the full apparent diffusion tensor (ADT) within one breathhold. The fractional anisotropy (FA) of the cortex and the medulla were found to be 0.22 +/- 0.12 and 0.39 +/- 0.11, respectively (N = 10), which emphasizes the need for rotationally invariant diffusion measurements for clinical applications. Additional limitations for clinical diffusion imaging on the kidney are the strong susceptibility variations within the abdomen that restrict the use of imaging techniques employing long echo trains, and the severe motion sensitivity that limits the available imaging time to one breath-hold. To overcome these problems an isotropic, diffusion-weighted, segmented EPI protocol that facilitates the acquisition of high-resolution diffusion-weighted images within a single breath-hold was implemented. Using this method, the apparent diffusion coefficient (ADC) of the cortex and medulla were found to be 2.89 +/- 0.28. 10(-9) m2/s and 2.18 +/- 0.36. 10(-9) m2/s (N = 10).

Anisotropy↗

PubMed2001

The effect of molecular orientation and acetylene-enhanced crosslinking on the wear of UHMWPE in total artificial joints.

This paper investigates the benefits of combining roll-drawing and acetylene-enhanced crosslinking to alter the mechanical properties of the ultra high molecular weight polyethylene (UHMWPE) used in total hip and knee replacements, with the aim of improving its resistance to wear. UHMWPE was processed via crosslinking, roll-drawing and a combination of crosslinking and roll-drawing and subjected to gel content analysis, tensile tests, X-ray diffraction and wear tests using different types of motion and smooth and rough counterfaces. Purely roll-drawn materials with length and width draw ratios of lambda l x lambda w = 1.3 x 1.0 and lambda1 x lambdaw = 1.6 x 0.9 respectively, were found to have lower wear factors in a unidirectional motion test with a rough counterface when compared to the virgin material. The crosslinked roll-drawn material, with length and width draw ratios of lambda1 x lambdaw = 1.6 x 0.9, was seen to possess five crosslinks per initial number average molecule. This crosslinked and roll-drawn material showed 5.5 times less wear than the virgin material in a multidirectional motion test with a smooth counterface and 1.4 times more wear than the virgin material in a unidirectional motion test with a rough counterface. Hence this study supports previous work by the authors that acetylene-enhanced crosslinked materials may show benefits for a total hip replacement, but only where the femoral head remains smooth. The improvements in wear with the roll-drawn material in unidirectional tests were smaller, but may prove to have some benefits in the knee.

Journal Article↗

PubMed2001

Relationship between function and perfusion early after acute myocardial infarction.

To assess the relationship between baseline left ventricle function, functional reserve and resting myocardial perfusion in patients with acute myocardial infarction (AMI). After AMI the presence of dysfunctioning but viable myocardium plays a determinant role in clinical outcome. Regional ventricular function was evaluated by echocardiography both in resting conditions and during dobutamine infusion (10 microg/kg/min). Perfusion was assessed by magnetic resonance imaging in a single slice approach where the first pass of an intravenously injected bolus of gadolinium-based contrast agent was followed through six regions of interest within the myocardium. In each patient a region with normal function was used as reference and the cross-correlation coefficient (CCC), which described the myocardial perfusion relatively to the reference region (CCC = 1 means equivalent perfusion), was obtained for the other five myocardial regions. Twenty-two patients were enrolled into the study. Sixty-one segments had normal function and normal perfusion (CCC = 0.92+/-0.23). The perfusion deficit was more marked in the 29 regions with resting akinesia-dyskinesia than in the 20 hypokinetic regions (CCC = 0.71+/-0.45 vs. 0.84+/-0.23; p < 0.05). Out of the 29 regions with resting akinesia-dyskinesia the 13 segments which showed functional improvement following dobutamine had a higher resting perfusion than the 16 segments which were unresponsive to dobutamine (CCC = 0.83+/-0.32 vs. 0.61+/-0.52, p < 0.05). Similarly, out of the 20 regions with resting hypokinesia the 11 segments having functional reserve showed an higher resting perfusion than the segments which did not (0.96+/-0.21 vs. 0.69+/-0.19; p < 0.05). Early after AMI, the perfusion deficit reflects the severity of the mechanical dysfunction. In regions with baseline dyssynergy resting perfusion is, in general, higher when contractile reserve can be elicited by stress-echo.

Adrenergic beta-Agonists↗

PubMed2001

Issues and trends in care of the hypertensive client.

This article discusses issues and trends in care of the hypertensive client that pertain to practice, education, research, and health policy. Clinical practice issues center around obtaining accurate blood pressure measurements and educating patients about health promotion interventions and use of medications. These topics are important in the education of the beginning nurse student as well. Researchers have studied risk factors, incidence, and prevalence in global populations; use of pharmacologic agents; and investigative methods employing technology. Researchers are beginning to explore more holistic approaches to controlling risk factors before hypertension occurs. Funding for public education regarding prevention and control of hypertension is a number one health policy issue.

Blood Pressure↗

PubMed2001

The health risk of hypertension in south Texas: a demographic profile.

This article provides a demographic profile of the hypertensive adult in South Texas. Hypertension, a silent disease because of its lack of overt signs and symptoms, poses a major public health problem. Few prevalence studies have been completed reflecting Mexican-American populations. South Texas hypertension trends are comparable to national trends. However, the awareness of hypertension in South Texas is lower than that of the national population. The density of risk factors may be responsible for the patterns of South Texas hypertension.

Adult↗

PubMed2000

The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells.

Interleukin-6 (IL-6) is reported to be central to the pathogenesis of myeloma, inducing proliferation and inhibiting apoptosis in neoplastic plasma cells. Therefore, abrogating IL-6 signaling is of therapeutic interest, particularly with the development of humanized anti-IL-6 receptor (IL-6R) antibodies. The use of such antibodies clinically requires an understanding of IL-6R expression on neoplastic cells, particularly in the cycling fraction. IL-6R expression levels were determined on plasma cells from patients with myeloma (n = 93) and with monoclonal gammopathy of undetermined significance (MGUS) or plasmacytoma (n = 66) and compared with the levels found on normal plasma cells (n = 11). In addition, 4-color flow cytometry was used to assess the differential expression by stage of differentiation and cell cycle status of the neoplastic plasma cells. IL-6R alpha chain (CD126) was not detectable in normal plasma cells, but was expressed in approximately 90% of patients with myeloma. In all groups, the expression levels showed a normal distribution. In patients with MGUS or plasmacytoma, neoplastic plasma cells expressed significantly higher levels of CD126 compared with phenotypically normal plasma cells from the same marrow. VLA-5(-) "immature" plasma cells showed the highest levels of CD126 expression, but "mature" VLA-5(+) myeloma plasma cells also overexpressed CD126 when compared with normal subjects. This study demonstrates that CD126 expression is restricted to neoplastic plasma cells, with little or no detectable expression by normal cells. Stromal cells in the bone marrow microenvironment do not induce the overexpression because neoplastic cells express higher levels of CD126 than normal plasma cells from the same bone marrow in individuals with MGUS. (Blood. 2000;96:3880-3886)

Aged↗

PubMed2000

Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats exposed to frequency-modulated microwave fields.

In a 2-year bioassay, we exposed Fischer 344 rats to a frequency-modulated (FM) signal (836.55 MHz +/- 12.5 KHz deviation) simulating radiofrequency exposures in the head of users of hand-held mobile phones. We tested for effects on spontaneous tumorigenicity of central nervous system (CNS) tumors in the offspring of pregnant rats and also for modified incidence of primary CNS tumors in rats treated with a single dose of the neurocarcinogen ethylnitrosourea (ENU) in utero. ENU dosage (4 mg/kg) was selected to give an expected brain tumor incidence of 10-15% over the mean life span of 26 months. Pregnant dams (n = 102) were randomly assigned to six groups. Their offspring were treated as cohorts in each of the six groups (n = 90 per group; total, n = 540): Sham ENU/Sham Field, Sham ENU/Field Exposed, ENU/Sham Field, ENU/Field Exposed, ENU/Cage Control, and Sham ENU/Cage Control. Intermittent field exposures began on gestation day 19 and continued until weaning at 21 days, resuming thereafter at 31 days and continuing until experiment termination at 731-734 days. Energy absorption rates (SARs) in the rats' brains were similar to localized peak brain exposures of a phone user (female, 236 g, 1.0 W/kg; male, 450 g, 1.2 W/kg). Of the original 540 rats, 168 died before the termination of the experiment. In these rats, ENU significantly reduced survival from a mean of 708 days in three groups without ENU treatment to 645 days in three groups treated with ENU (P < 0.0005). There were no effects on survival attributable to FM field exposure in either ENU-treated or in sham-treated groups. Spontaneous CNS tumor incidence in control groups was 1.1-4.4% but sharply higher in rats receiving ENU (14.4-22.2%; P < 0.0001). No FM field-mediated changes were observed in number, incidence, or histological type of either spontaneous or ENU-induced brain tumors, nor were gender differences detected in tumor numbers. These negative findings with FM fields contrast with our study using standard digital phone fields pulsed on and off at 50/se, where a trend was noted toward reduced incidence of both spontaneous and ENU-induced CNS tumors (W. R. Adey et al., Radiat. Res., 152: 293-302, 1999). Although consistent but not attaining significance in the experiment overall (spontaneous CNS tumors, P < 0.08 one-tailed; P < 0.16 two-tailed; ENU-induced CNS tumors, P < 0.08 one-tailed, P < 0.16 two-tailed), the trend was significant (P < 0.015 one-tailed, P < 0.03, two-tailed) in rats that received ENU and died prior to experiment termination, with a primary brain tumor as the cause of death. We discuss differences in the signaling structure of digital and FM fields. Certain bioeffects induced by either amplitude-modulated or pulsed radiofrequency fields at athermal levels have not been seen with fields of similar average power but unvarying in intensity (continuous wave or frequency-modulated fields).

Animals↗

PubMed2000

Synthesis and characterization of 8-(dimethylamino)-1-naphthyl derivatives of aluminum, gallium, and indium.

The group 13 dichlorides of formula Ar'MCl2 [Ar' = 8-(dimethylamino)-1-naphthyl (8-(Me2N)C10H6)], M = Al (1), Ga (2), and In (3), have been prepared via the salt elimination reaction of 1 equiv of Ar'Li with MCl3 in toluene solution at -78 degrees C. The reaction of 1 with LiAlH4 in diethyl ether solution at -78 degrees C produced the dihydride [Ar'AlH2]2 (4). The X-ray crystal structures of 1-4 have been determined and show that 1 and 2 are monomeric while 3 and 4 are dimeric in the solid state. The reaction of 1 with RLi in toluene solution at -78 degrees C results in ligand redistribution and formation of Ar'2AlR (R = Me (5), t-Bu (6)). The chloride analogue of 5 and 6, Ar'2AlCl (7), can be prepared directly from the reaction of 2 equiv of Ar'Li with AlCl3 in toluene solution at -78 degrees C. The homoleptic derivative Ar'3Al (8) was obtained when 3 equiv of Ar'Li was employed. Crystal data for 1: monoclinic, space group P2(1), a = 6.534(1) A, b = 10.801(1) A, c = 9.631(2) A, beta = 105.57(2) degrees, V = 654.8(2) A3, Z = 2, R = 0.0453. Crystal data for 2: monoclinic, space group P2(1), a = 6.552(2) A, b = 10.833(2) A, c = 9.601(2) A, beta = 106.05(2) degrees, V = 654.9(3) A3, Z = 2, R = 0.0609. Crystal data for 3: monoclinic, space group P2(1)/c, a = 7.401(2) A, b = 15.746 A, c = 10.801(4) A, beta = 92.37(3) degrees, V = 1257.6(7) A3, Z = 2, R = 0.0712. Crystal data for 4: monoclinic, space group P2(1)/c, a = 13.343(2) A, b = 11.228(2) A, c = 7.505(1) A, beta = 100.64(1) degrees, V = 1105.0(4) A3, Z = 4, R = 0.0560.

Journal Article↗

PubMed2000

Frequency dependence of the functional MRI response after electrical median nerve stimulation.

Localizing sensorimotor areas with high resolution functional MRI is of considerable interest for a wide range of medical applications from the preoperative planning of neurosurgical interventions to determining the course of neuroplastic reorganisation after brain lesions. We examined the effect of the stimulation frequency on the blood oxygen level dependent (BOLD) fMRI response and on perfusion weighted fMRI using electrical median nerve stimulation at 5, 15, 40, and 100 Hz. BOLD fMRI was performed using a single shot gradient echo EPI sequence to acquire 15 contiguous slices. For the qualitative flow sensitive studies, a single slice inversion recovery prepared spin echo echoplanar sequence (IR-SE EPI) was used. In the primary sensorimotor cortex, a linear increase of the fMRI-BOLD response, affecting both the number of activated pixels and the amplitude of the signal changes, was seen with increasing stimulation frequencies. The qualitative in-flow sensitive studies, using the IR-SE EPI sequence, indicate that the tissue perfusion also increases over the same range of frequencies. This implicates that larger fMRI responses can be obtained if electrical median nerve stimulation is performed at higher frequencies. The results are compared with electrophysiological data, which show a decrease of the early somatosensory evoked potentials at higher frequencies.

Adult↗

PubMed2000

Diffusion tensor MRI of the spinal cord.

Apparent diffusion tensor (ADT) measurements on the spinal cord using a pulsed-field-gradient (PFG) multi-shot echo-planar imaging (EPI) sequence are presented. In a study of 10 healthy volunteers, the obtained rotationally invariant anisotropy information is compared to the results obtained by the rotationally dependent methods. The water diffusivity in the direction parallel to the fibers was found to be almost 2.5 times higher than the average diffusivity in directions perpendicular to the fibers and showed cylindrically symmetric anisotropy characteristics. The influence of partial volume effects and the point spread function on the measured results was evaluated, and it was the concluded that a resolution of 1 mm in the read and phase directions is required to obtain unbiased values. Possible clinical implications were demonstrated by investigating the diffusion characteristics of 10 patients suffering from narrowing of the cervical canal. The changes in the diffusion characteristics were found to be large enough to allow a robust detection of diffusion changes in the spine, even in cases in which conventional T(2) and T(1) weighted images were unable to detect any lesion.

Anisotropy↗