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Biomedical subjects

R L Jones

Publications and source records attributed to R L Jones.

At least 19 recordsLinked to original sources
PubMed2006

Investigation of the prostacyclin (IP) receptor antagonist RO1138452 on isolated blood vessel and platelet preparations.

BACKGROUND AND PURPOSE: The current study examined the utility of the recently described prostacyclin (prostanoid IP) receptor antagonist RO1138452 (2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline) as a tool for classifying prostanoid receptors. EXPERIMENTAL APPROACH: pA(2) values were determined on isolated smooth muscle and platelet preparations. KEY RESULTS: RO1138452 antagonized relaxation of human pulmonary artery, guinea-pig aorta and rabbit mesenteric artery induced by the selective IP agonist cicaprost. Schild plots had slopes close to unity, generating pA(2) values of 8.20, 8.39 and 8.12 respectively. Non-surmountable antagonism was sometimes found with the higher concentrations of RO1138452, attributable to the EP(3) contractile action of cicaprost. RO1138452 did not block relaxation of guinea-pig trachea induced by the EP(2)-selective agonist butaprost. In contrast, there was a modest inhibition of butaprost-induced relaxation of human pulmonary artery by RO1138452, implying activation of both EP(2) and IP receptors by butaprost. RO1138452 did not affect relaxation induced by PGE(2) (EP(4) agonist) and substance P (NK(1)/endothelium-dependent agonist) in rabbit mesenteric artery. In human and rat platelet-rich plasmas, RO1138452 antagonized cicaprost-induced inhibition of platelet aggregation in a surmountable manner; pA(2) values may have been affected by binding of RO1138452 to plasma protein. RO1138452 did not affect the inhibitory actions of PGD(2) (DP(1) agonist) and NECA (adenosine A(2A) agonist) in human platelets. CONCLUSIONS AND IMPLICATIONS: The data indicate that RO1138452 is a potent and selective IP receptor antagonist. RO1138452 represents an important addition to our armoury of prostanoid receptor antagonists and a potential clinical agent in situations where prostacyclin has a pathophysiological function.

Alprostadil↗
PubMed2006

Pathological complete response and residual DCIS following neoadjuvant chemotherapy for breast carcinoma.

Patients who have no residual invasive cancer following neoadjuvant chemotherapy for breast carcinoma have a better overall survival than those with residual disease. Many classification systems assessing pathological response to neoadjuvant chemotherapy include residual ductal carcinoma in situ (DCIS) only in the definition of pathological complete response. The purpose of this study was to investigate whether patients with residual DCIS only have the same prognosis as those with no residual invasive or in situ disease. A retrospective analysis of a prospectively maintained database identified 435 patients, who received neoadjuvant chemotherapy for operable breast cancer between February 1985 and February 2003. Of these, 30 (7%; 95% CI 5-9%) had no residual invasive disease or DCIS and 20 (5%; CI 3-7%) had residual DCIS only. With a median follow-up of 61 months, there was no statistical difference in disease-free survival, 80% (95% CI 60-90%) in those with no residual invasive or in situ disease and 61% (95% CI 35-80%) in those with DCIS only (P=0.4). No significant difference in 5-year overall survival was observed, 93% (95% CI 75-98%) in those with no residual invasive or in situ disease and 82% (95% CI 52-94%) in those with DCIS only (P=0.3). Due to the small number of patients and limited number of events in each group, it is not possible to draw definitive conclusions from this study. Further analyses of other databases are required to confirm our finding of no difference in disease-free and overall survival between patients with residual DCIS and those with no invasive or in situ disease following neoadjuvant chemotherapy for breast cancer.

Adult↗
PubMed2005

Cytokines, chemokines and growth factors in endometrium related to implantation.

The complexity of the events of embryo implantation and placentation is exemplified by the number and range of cytokines with demonstrated roles in these processes. Disturbance of the normal expression or action of these cytokines results in complete or partial failure of implantation and abnormal placental formation in mice or humans. Of known importance are members of the gp130 family such as interleukin-11 (IL-11) and leukaemia inhibitory factor (LIF), the transforming growth factor beta (TGFbeta) superfamily including the activins, the colony-stimulating factors (CSF), the IL-1 system and IL-15 system. New data are also emerging for roles for a number of chemokines (chemoattractive cytokines) both in recruiting specific cohorts of leukocytes to implantation sites and in trophoblast differentiation and trafficking. This review focuses on those cytokines and chemokines whose expression pattern in the human endometrium is consistent with a potential role in implantation and placentation and for which some relevant actions are known. It examines what is known of their regulation and action along with alterations in clinically relevant situations.

Activins↗
PubMed2005

Investigation of the agonist activity of prostacyclin analogues on prostanoid EP4 receptors using GW 627368 and taprostene: evidence for species differences.

The possibility that the prostacyclin analogues AFP-07 and cicaprost relax saphenous vein preparations of pig, guinea-pig and rabbit by simultaneously activating prostanoid EP4 and IP (prostacyclin) receptors was investigated using the high-affinity EP4 antagonist GW 627368. The IP receptor system in each preparation was suppressed with the partial agonist taprostene. The results indicate that AFP-07 and cicaprost are moderately potent EP4 agonists on pig saphenous vein, but much weaker EP4 agonists on guinea-pig saphenous vein. GW 627368 did not antagonise AFP-07- and cicaprost-induced relaxation of rabbit saphenous vein, which contrasts with a previous study using the EP4 blocker AH 23848. However, treatment with taprostene was of less value due to poorer antagonism of the rabbit IP system; this may be related to the presence of a sensitive EP2 relaxant system. Relaxation of each preparation induced by the selective EP2 agonist ONO-AE1-259 was unaffected by GW 627368, with and without taprostene.

Animals↗
PubMed2005

Small scale structure in the atmosphere: implications for chemical composition and observational methods.

Non-linearities in chemical processes are recognised as being important in a number of areas of atmospheric science. In this paper we show simulations using an idealised plume model which describes the relaxation of an urban plume into the background atmosphere. As might be anticipated, the initial conditions of NOx, O3 and VOCs within the plume and background are important in determining the chemistry downstream of the source, but crucially for this study, the rate of mixing (on timescales appropriate to the real atmosphere) is found to alter the composition of the atmosphere significantly. The model shows that NO3 chemistry can play a major role in the oxidation of biogenic VOCs present in the background atmosphere. In addition, the reaction of hydrocarbons with NO3 potentially has important implications for NOy speciation because a significant fraction of organic nitrates thus formed are sufficiently long-lived to leave the planetary boundary layer. A particularly critical result of the model is that under certain NOx conditions, O3 surface deposition can be significantly inhibited, with consequent effects on the O3 budget.

Aerosols↗
PubMed2005

Urinary mercury concentrations associated with dental restorations in adult women aged 16-49 years: United States, 1999-2000.

BACKGROUND: Mercury amalgam dental restorations have been used by dentists since the mid 19th century and issues on safety continue to be periodically debated within the scientific and public health communities. Previous studies have reported a positive association between urine mercury levels and the number of dental amalgams, but this relation has never been described in a nationally representative sample in the United States. AIMS AND METHODS: Using household interview, dietary interview, dental examination, and laboratory data from the 1999-2000 National Health and Nutrition Examination Survey (NHANES), the association between mercury concentrations and dental restorations was examined in US women of reproductive age. RESULTS: In women of childbearing age, approximately 13% of all posterior dental surfaces were restored with amalgams and the average urinary mercury level in women was low (1.34 microg/l). It is estimated that an increase of 1.8 microg/l in the log transformed values for mercury in urine would occur for each 10 dental surfaces restored with amalgam. CONCLUSIONS: Although the findings do not address the important issues of adverse health effects at low thresholds of mercury exposure, they do provide important reference data that should contribute significantly to the ongoing scientific and public health policy debate on the use of dental amalgams in the USA.

Adolescent↗
PubMed2004

Agonists can discriminate between cloned human and mouse prostacyclin receptors.

The ability of prostacyclin analogues to stimulate adenylyl cyclase (AC) and phospholipase C (PLC) in Chinese hamster ovary (CHO) cells expressing cloned human (hIP) or cloned mouse (mIP) prostacyclin receptors has been compared. For hIP, the order of potency (pEC(50)) for stimulating AC and PLC pathways was similar: AFP-07 (9.3, 8.4)>cicaprost (8.3, 6.9), iloprost (7.9, 6.8)>taprostene (7.4, 6.8)>carbacyclin (6.9, 6.6), PGE(1) (6.6, 5.1). Although the standard IP agonists cicaprost and iloprost behaved similarly in both hIP and mIP receptor-expressing cells, carbacyclin and PGE(1) showed significantly higher potency at the mIP receptor, suggesting that the agonist recognition sites on hIP and mIP receptors are not identical. A further distinction between hIP and mIP receptors was found with taprostene, which had greater efficacy at hIP receptors (AC 94%, PLC 14%) than at mIP receptors (AC 77%, PLC 0%) (cicaprost=100% in each assay).

Adenylyl Cyclases↗
PubMed2004

Urinary cadmium levels predict lower lung function in current and former smokers: data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: A study was undertaken to determine the relation between urinary cadmium levels and lung function in a nationally representative cohort of current, former, and never smokers in the US. Urinary cadmium levels reflect the total body burden of cadmium. METHODS: The following data from the Third National Health and Nutrition Examination Survey were analysed: urinary cadmium (adjusted for urinary creatinine), lung function, sex, race/ethnicity, age, education level, job category, body mass index, serum cotinine level, and smoking history. Linear regression models were developed to predict lung function using urinary cadmium as the main predictor, adjusting for other covariates and stratified by smoking status. RESULTS: Data were available on 16 024 adults. Current smokers had higher mean (SE) urinary cadmium/creatinine levels (0.46 (0.01) micro g/g) than former (0.32 (0.01) micro g/g) or never smokers (0.23 (0.01) micro g/g). Higher levels of urinary cadmium were associated with significantly lower forced expiratory volumes in 1 second (FEV(1)) in current (-2.06%, 95% confidence interval (CI) -2.86 to -1.26 per 1 log increase in urinary cadmium) and former smokers (-1.95%, 95% CI -2.87 to -1.03) but not in never smokers (-0.18%, 95% CI -0.60 to 0.24). Similar results were obtained for forced vital capacity (FVC) and FEV(1)/FVC. CONCLUSIONS: Cadmium, which is known to cause emphysema in occupational settings, may also be important in the development of tobacco related lung disease.

Adolescent↗
PubMed2004

Tumour vaccine associated lymphadenopathy and false positive positron emission tomography scan changes.

A patient receiving intradermal injections of vaccine directed towards carcinoembryonic antigen-bearing metastases from colorectal cancer showed uptake of 18F-fluorodeoxyglucose in local draining lymph nodes during the course of treatment. This appearance should be considered as a possible false positive in patients undergoing such treatment who are being investigated with PET scans.

Adenocarcinoma↗
PubMed2003

Complex regulation of decidualization: a role for cytokines and proteases--a review.

Decidualization of the endometrial stroma is a precondition for successful establishment of pregnancy. While the local molecular mechanisms driving decidualization are still largely unknown, a number of autocrine/paracrine factors have been identified as differentiation factors in this process. These include the cytokines, interleukin 11, activin A and monoclonal non-specific suppressor factor beta (MNSFbeta). Furthermore, locally produced proteases, including proprotein convertase 6 and matrix metalloproteinases, enable expansion of the tissue and processing of regulatory molecules. This article reviews recent work from our laboratory on the roles of these factors in decidualization.

Activins↗
PubMed2003

Environmental health collaboration: United States and Russia.

Developed nations share similar challenges to human health from commercial and agricultural chemicals that are released into the environment. Although Russia and the United States are historically distinct and unique, both countries are geographically large and economically dependent on emission-producing surface transportation. This paper describes U.S.-Russian collaborative activities that grew from a 1995 conference in Moscow that brought together environmental health investigators from both countries to discuss common concerns about the human health impact of environmental pollutants. Lead, pesticides, volatile organic compounds, and mercury were identified as contaminants of greatest concern. Collaborative studies were initiated that included collecting blood and hair samples and splitting samples for analyses in both countries, and introducing and sharing new portable blood and environmental sample analyses instruments. The findings demonstrated that hair analysis was not a good predictor of BLL and that Russian children in the first city sampled had a mean BLL of 7.7 microg/dl. Although higher than the U.S. mean, this level was below the 10.0 microg/dl CDC level of concern. This manuscript summarizes additional study results and describes their impacts on Russian policy. On-going collaborative environmental investigations are described.

Centers for Disease Control and Prevention, U.S.↗
PubMed2002

Evaluation of the comparative efficacy of selamectin against flea (Ctenocephalides felis felis) infestations on dogs and cats in simulated home environments.

The comparative efficacy of monthly administration of selamectin or lufenuron against Ctenocephalides felis felis on dogs and cats was evaluated over a 5-month period in flea-infested environments. Twenty-four dogs and 32 cats were randomly allocated to receiving a topical treatment with selamectin or an oral administration of tablets containing lufenuron/milbemycin oxime (for dogs) or lufenuron only (for cats). Each product was administered in accordance with the manufacturer's label recommendations. Eight dogs and four cats served as untreated sentinels. Treatments were administered on days 0, 30, 60, 90, and 120. Each animal received an application of 100 fleas on days -28 and -21, and then weekly applications of 20 fleas from days 91 through 147. Flea comb counts were performed on day -6, and every 2 weeks after day 0. From day 29 (dogs) or day 44 (cats) to day 150, geometric mean flea counts for selamectin were < or =0.4. Mean flea counts for animals assigned to treatment with selamectin were significantly lower (P=0.0001) than for animals assigned to treatment with lufenuron at all assessments after day 0.

Animals↗
PubMed2002

Lymphatics in leprosy: relationship to elastic fibres and observations following intra-lesional injections of colloidal carbon.

An investigation of skin lymphatics in leprosy has been undertaken. Examination of 62 skin biopsies from 31 patients with various classifications of leprosy has revealed dilated initial lymphatics within granulomas of lepromatous leprosy, but no significant abnormalities in non-lepromatous disease or in non-granulomatous skin. Colloidal carbon injected intra-lesionally failed to appear within granulomas, but could be seen in lymphatics in non-granulomatous dermis. Elastic fibres were also absent within granulomas. AFB were clearly identified within endothelial cells of initial lymphatics. We suggest lymphatic malfunction may be compartmental, existing only within the granulomas and not in the surrounding normal appearing dermis.

Carbon↗
PubMed2001

Immunogenicity, safety and lot consistency in adults of a chromatographically purified Vero-cell rabies vaccine: a randomized, double-blind trial with human diploid cell rabies vaccine.

The immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) was evaluated using US veterinary medical students. In the first study, 242 healthy adults were enrolled in a randomized, modified double-blind, multicenter trial and received five doses of either CPRV or human diploid cell vaccine (HDCV) by intramuscular injection on days 0, 3, 7, 14, and 28 concurrently with human rabies immunoglobulin in a simulated post-exposure prophylaxis regimen. Post-immunization titers in the CPRV and HDCV groups reached 0.5 IU/ml (the WHO-recommended minimally acceptable titer) or greater in all subjects in both vaccine groups by day 14 and remained above that level through day 90. In the second study, 438 healthy adults were enrolled in a randomized, double-blind, multicenter trial and assigned to receive five doses from one of three lots of CPRV by intramuscular injection on days 0, 3, 7, 14, and 28 in a simulated post-exposure prophylaxis regimen to evaluate lot consistency. Post-immunization titers rapidly increased to over 0.5 IU/ml by day 14 for all subjects and remained above that level through day 42 when the study was terminated. The three lots were considered equivalent. The percentage of subjects with at least one local reaction during the five-dose regimen was slightly lower in the CPRV group than in the HDCV group (P=0.06). The most frequently reported local reaction for all doses of vaccine was pain at the injection site. Headache, myalgia, and malaise were the most frequently reported systemic events. The percentage of subjects with at least one systemic event was significantly lower for CPRV (P=0.0084). No vaccine-related serious adverse reaction was reported in these studies. The results of these studies indicate that CPRV administered intramuscularly to healthy adults is immunogenic and is associated with fewer local and systemic reactions than HDCV.

Adult↗
PubMed2001

Controlled study of the efficacy of clavulanic acid-potentiated amoxycillin in the treatment of Chlamydia psittaci in cats.

Twenty-four specific pathogen-free cats were inoculated with 3 x 10(3) infectious units of a field isolate of Chlamydia psittaci on to the corneal surface. Seven days later they were assigned randomly to three groups of eight and treated orally for 19 days with either clavulanic acid-potentiated amoxycillin, doxycycline or a placebo. Both treated groups responded rapidly, with a marked reduction in isolation rates and clinical scores which were significantly lower than in the placebo group within two and four days, respectively. After two days the group treated with potentiated amoxycillin had a significantly lower isolation score than the group treated with doxycycline. Forty days after they were infected the clinical signs recurred in five of the eight cats treated with potentiated amoxycillin, but a four-week course of potentiated amoxycillin resulted in a complete clinical recovery with no evidence of a recurrence for six months.

Amoxicillin↗
PubMed2001

Chiral Ansa metallocenes with Cp ring-fused to thiophenes and pyrroles: syntheses, crystal structures, and isotactic polypropylene catalysts.

Syntheses, crystal structures, and polymerization data for new isospecific metallocenes (heterocenes) having cyclopentenyl ligands b-fused to substituted thiophenes (Tp) and pyrroles (Pyr) are reported. The C2- and C1-symmetric heterocenes are dimethylsilyl bridged, have methyl groups adjacent to the bridgehead carbon atoms, and have aryl substituents protruding in the front. rac-Me2Si(2,5-Me2-3-Ph-6-Cp[b]Tp)2ZrCl2/MAO (MAO = methyl alumoxanes) is the most active metallocene catalyst for polypropylene reported to date. rac-Me2Si(2,5-Me2-3-Ph-6-Cp[b]Tp)2ZrCl2 and rac-Me2Si(2,5-Me2-1-Ph-4-Cp[b]Pyr)2ZrCl2 have the same structure, and the former is 6 times more active, produces half the total enantiofacial errors, and is 3.5 times less regiospecific in propylene polymerizations at the same conditions. rac-Me2Si(2-Me-4-Ph-1-Ind)2ZrCl2/MAO is 3.5 times lower in activity than rac-Me2Si(2,5-Me2-3-Ph-6-Cp[b]Tp)2ZrCl2 catalyst, and while the former is the more stereospecific and the less regiospecific, the sum of these two enantioface errors is the same for both species. Fine-tuning the heterocene sterics by changing selected hydrogen atoms on the ligands to methyl groups influenced their catalyst activities, stereospecificites, regiospecificites, and isotactic polypropylene (IPP) Mw. Thus, both substituting a hydrogen atom adjacent to the phenyl ring with a methyl group on an azapentalenyl ligand system and replacing one and then two hydrogens on the phenyl ring with methyls on thiopentalenyl ligands provided increased polymer Tm and Mw with increasing ligand bulk. Polymer molecular weights are sensitive to and inversely proportional to MAO concentration, and the catalyst activities increase when hydrogen is added for molecular weight control. The polymer Tm values with the thiopentalenyls as TIBAL/[Ph3C][B(C6F5)4] systems were higher than with MAO as catalyst activator. A racemic C1, pseudo-meso complex with a hybrid dimethylsilyl-bridged 2-Me-4-Ph-1-Ind/2,5-Me2-4-Ph-1-Cp[b]Pyr ligand produced the first sample of IPP with all the steric pentad intensities fitting the enantiomorphic site control model. Speculative mechanistic considerations are offered regarding electronic effects of the heteroatoms and steric effects of the ligand structures, the preferred phenyl torsion angles, and anion effects.

Journal Article↗
PubMed2001

The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead.

BACKGROUND: Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment. METHODS: We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter (1.0 to 2.1 micromol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months. RESULTS: During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 microg per deciliter (0.2 micromol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter [0.2 to 0.3 micromol per liter]). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant. CONCLUSIONS: Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 microg per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels.

Chelating Agents↗