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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
PubMed2000

Aerosolized Syk antisense suppresses Syk expression, mediator release from macrophages, and pulmonary inflammation.

Syk protein tyrosine kinase (PTK) is involved in signaling in leukocytes. In macrophages, Fcgamma-receptor cross-linking induces Syk PTK phosphorylation and activation, resulting in Syk-dependent events required for phagocytosis and mediator release. We hypothesized that Syk antisense oligodeoxynucleotides (ASO) delivered by aerosol to rat lungs in vivo would depress Syk PTK expression, mediator release from alveolar macrophages, and Syk-dependent pulmonary inflammation. RT-PCR and RT-in situ PCR demonstrated that aerosolized Syk ASO administration reduced Syk mRNA expression from alveolar macrophages compared with cells isolated from sham-treated rats. Western blot analysis confirmed that Syk PTK expression was reduced after Syk ASO treatment. Compared with sham-treated rats (scrambled oligodeoxynucleotide), Syk ASO treatment suppressed Fcgamma-receptor-mediated nitric oxide (86.0 +/- 8.3%) and TNF (73.1 +/- 3.1%) production by alveolar macrophages stimulated with IgG-anti-IgG complexes. In contrast, Fcgamma-receptor-induced IL-1beta release was unaffected by Syk ASO treatment. Additionally, Syk ASO suppressed Ag-induced pulmonary inflammation, suggesting that Syk ASO may prove useful as an anti-inflammatory therapy in disorders such as asthma.

Aerosols↗
PubMed2000

Posterior shoulder dislocation: avoiding a missed diagnosis.

Posterior shoulder dislocation is a relatively uncommon event, with an incidence of 1% to 4% of all shoulder dislocations. Because of the infrequency of this condition, the diagnosis is often missed, with significant consequences to the patient Injury in the athlete is usually from a direct blow or fall onto an outstretched arm. After such an injury, symptoms may be confused with a shoulder contusion or rotator cuff injury. Significant complications such as chronic posterior dislocation and degenerative disease of the shoulder can occur if the diagnosis is missed. A careful history and physical examination, complete radiographic evaluation, and a high level of suspicion are required to identify posterior shoulder dislocation. Treatment consists of prompt closed reduction, or operative repair if this is unsuccessful.

Accidental Falls↗
PubMed2000

Characterization of prostanoid receptors mediating inhibition of histamine release from anti-IgE-activated rat peritoneal mast cells.

1. Prostanoid receptors mediating inhibition of anti-IgE induced histamine release from rat peritoneal mast cells have been characterized pharmacologically. PGD2 and the specific DP receptor agonists BW 245C and ZK 118182 were the most potent inhibitors with half-maximal concentrations of 0.26, 0.06 and 0.02 microM respectively. The maximum inhibition attainable was 60-65% with 10(-5) M BW 245C and ZK 118182. 2. Among several EP receptor agonists investigated, only PGE2 and the EP2/EP3 receptor agonist misoprostol induced significant inhibition (46.8 +/- 4.7% at 10(-4) M and 18.7 +/- 6.8% at 10(-5) M respectively). The IP receptor agonists cicaprost and iloprost were both less potent than the DP agonists in inhibiting histamine release (45.2 +/- 3.3% and 35.1 +/- 2.5% inhibition respectively at 10(-5) M), whereas PGF2 alpha and the TP receptor agonist U-46619 were only marginally effective. 3. The EP4/TP receptor antagonist AH 23848 failed to affect the inhibitory actions of PGD2 or PGE2 even at 10(-5) M, whereas the DP/EP1/EP2 receptor antagonist AH 6809 slightly enhanced the effect of PGD2 at 10(-6) M. 4. At concentrations of 3 x 10(-6) to 10(-5) M, the putative DP receptor antagonist ZK 138357 dose-dependently suppressed the inhibitory activities of the DP agonists, PGE2 and cicaprost. The antagonism of ZK 138357 against the DP receptor agonists appeared to be competitive with pA2 values of around six. 5. In conclusion, these data support our earlier proposal that an inhibitory DP receptor is the predominant prostanoid receptor in rat peritoneal mast cell. The properties of this receptor in relation to putative DP receptor subtypes reported in the literature are discussed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Non-prostanoid prostacyclin mimetics as neuronal stimulants in the rat: comparison of vagus nerve and NANC innervation of the colon.

The spontaneous activity of the rat isolated colon is suppressed by prostacyclin analogues such as cicaprost (IC(50)=4.0 nM). Activation of prostanoid IP(1)-receptors located on NANC inhibitory neurones is involved. However, several non-prostanoids, which show medium to high IP(1) agonist potency on platelet and vascular preparations, exhibit very weak inhibitory activity on the colon. The aim of the study was to investigate this discrepancy. Firstly, we have demonstrated the very high depolarizing potency of cicaprost on the rat isolated vagus nerve (EC(50)=0.23 nM). Iloprost, taprostene and carbacyclin were 7.9, 66, and 81 fold less potent than cicaprost, indicating the presence of IP(1) as opposed to IP(2)-receptors. Three non-prostanoid prostacyclin mimetics, BMY 45778, BMY 42393 and ONO-1301, although much less potent than cicaprost (195, 990 and 1660 fold respectively), behaved as full agonists on the vagus nerve. On re-investigating the rat colon, we found that BMY 45778 (0.1 - 3 microM), BMY 42393 (3 microM) and ONO-1301 (3 microM) behaved as specific IP(1) partial agonists, but their actions required 30 - 60 min to reach steady-state and only slowly reversed on washing. This profile contrasted sharply with the rapid and readily reversible contractions elicited by a related non-prostanoid ONO-AP-324, which is an EP(3)-receptor agonist. The full versus partial agonism of the non-prostanoid prostacyclin mimetics may be explained by the markedly different IP(1) agonist sensitivities of the two rat neuronal preparations. However, the slow kinetics of the non-prostanoids on the NANC system of the colon remain unexplained, and must be taken into account when characterizing neuronal IP-receptors.

Acetates↗
PubMed2000

Hypercapnic ventilatory response in patients with and without obstructive sleep apnea: do age, gender, obesity, and daytime PaCO(2) matter?

STUDY OBJECTIVE: To evaluate the relationship between obstructive sleep apnea (OSA) and ventilatory responsiveness to carbon dioxide in both men and women. DESIGN: An analysis of 219 patients referred to an university-based sleep center between 1989 to 1994 was conducted (104 with OSA and 115 without OSA; 43 women and 176 men). These patients had spirometry and a daytime hypercapnic ventilatory response (HCVR) test that was corrected to the patient's ability to attain maximal ventilation. Comparisons between OSA and no-OSA groups, as well as between men and women, were made using multivariate modeling techniques. RESULTS: There was no significant difference in the slope of correlated HCVR (cHCVR) between those with and without OSA (1.57 +/- 0.57 vs 1.63 +/- 0.66; p = 0.48). In men, an inverse correlation between daytime PCO(2) and cHCVR was observed in both crude and multivariate analyses (crude beta-coefficient = - 0.04 +/- 0.02, p = 0.02; adjusted beta-coefficient = 0.07 +/- 0.02, p < 0.01). Although age and cHCVR did not share a significant relationship in the crude analysis (crude beta-coefficient = - 0.01 +/- 0.01, p = 0.10), with adjustments for confounding variables, a significant inverse relationship between age and cHCVR was observed (beta-coefficient = - 0.02 +/- 0.01, p = 0.04). On the other hand, in women, only body mass index (BMI) was positively correlated with cHCVR (crude beta-coefficient = 0.03 +/- 0.01, p = 0.01; adjusted beta-coefficient = 0.04 +/- 0.01, p < 0.01). CONCLUSION: OSA disorder is not associated with a blunted ventilatory chemoresponsiveness to carbon dioxide. Elevated PaCO(2) and older age are significant correlates for a low cHCVR in men. For women only, BMI was associated with cHCVR. These findings suggest that men and women may have different ventilatory control mechanisms.

Adult↗
PubMed1999

The effect of percutaneous oestradiol on atheroma formation in ovariectomized cholesterol-fed rabbits.

OBJECTIVE: The aim of this study was to examine the effect of percutaneous oestradiol on the lipid profile and on atheroma formation using an animal model. METHODS: The study was of 12 weeks duration. Fifty sexually mature female New Zealand White rabbits were divided into five groups of equal size. Two groups acted as controls and received normal rabbit chow. Rabbits in one of these groups were ovariectomized. The remaining three groups were ovariectomized but received 1% cholesterol enriched rabbit chow. One of these cholesterol-fed groups received 0.3 mg/kg percutaneous oestradiol daily whilst another received 0.1 mg/kg oral oestradiol daily. Measurements of concentrations of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were made at the beginning and end of the study. Aortic atheroma formation was measured using computerized image analysis of uptake of Sudan III staining. RESULTS: After 12 weeks there were significant increases in the mean concentrations of TC in the three cholesterol-fed groups compared with controls (P < 0.001). Changes in HDL-C and TG concentrations were less consistent. The mean area of aortic atheroma formation was significantly less in both the percutaneous oestradiol group (4.9%) and the oral oestradiol group (8.6%) compared with the non-oestrogen-treated cholesterol-fed group (19.5%) (P < 0.001, < 0.01 respectively). CONCLUSION: These results suggest that percutaneous oestradiol has a direct protective effect on atheroma formation independent of serum concentrations of total cholesterol.

Administration, Oral↗
PubMed1999

No difference in iron status between children with low and moderate lead exposure.

We compared the iron status between children 11 to 33 months old with confirmed blood lead levels of 20 to 44 microg/dL and demographically similar children with blood lead levels of <10 microg/dL. There were no differences. Laboratory investigation or empirical treatment for iron deficiency is not justified on the basis of moderately elevated blood lead levels alone.

Anemia, Iron-Deficiency↗
PubMed1999

Evaluating students on an interdisciplinary primary care clerkship at the Pennsylvania State University College of Medicine.

With funding from The Robert Wood Johnson Foundation's Generalist Physician Initiative, the Pennsylvania State University College of Medicine created a community-based primary care clerkship in general pediatrics, general internal medicine, and family and community medicine, in which third-year students spend a month in a small town, rural area, or urban underserved medical community. In addition to linking students with preceptors who would teach the clinical skills essential to primary care practice, the medical school set out to teach and to evaluate knowledge, attitudes, and behaviors unique to primary care. This paper describes the three-part teaching tool/evaluation developed to address (1) a student's recognition of the characteristics of primary care (learning objectives assignment), (2) a student's ability to appreciate the multiple nonmedical factors influencing a patient's health and experience of illness (family project), and (3) a student's ability to solve clinical problems (clinical reasoning examination). The authors describe how these evaluation methods are linked with the clerkship's goals and objectives and how they yield a richer portrait of the student's performance than the traditional preceptor's evaluation alone can provide. They also discuss the relationship between students' performances on the primary care clerkship and their performances in other clinical clerkships. Similar clinical experiences in primary care should focus on features unique to primary care medicine in both teaching and evaluation.

Clinical Clerkship↗
PubMed1999

Who is a generalist? An analysis of whether physicians trained as generalists practice as generalists.

Accurate data on the number of generalist physicians are needed to monitor the physician workforce and to plan for future requirements in the changing health care system. This study assessed the relationship between two frequently used definitions of a generalist physician: completion of graduate medical education (GME) in only a generalist discipline and physician's self-report of practicing as a generalist. Data for 4,808 physician graduates from six Pennsylvania medical schools from 1986 to 1991 were analyzed using information from the GME tracking census of the Association of American Medical Colleges and the Physician Masterfile of the American Medical Association. Of 1,291 physicians trained in a generalist discipline, 1,205 (93%) reported practicing as generalists. Conversely, of the 3,517 not trained in a generalist discipline, 3,358 (95%) were not practicing as generalists. These results indicate GME training is a valid predictor of self-reported practice and provide baseline data to monitor future changes.

Attitude of Health Personnel↗
PubMed1999

Role of inflammatory mediators in human endometrium during progesterone withdrawal and early pregnancy.

The role of progesterone (P4) in the regulation of inflammatory mediators interleukin-8 (IL-8), monocyte chemoattractant protein-1, and cyclooxygenase-2 (COX-2) and in the recruitment of leukocyte subpopulations in the endometrium has been examined, by employing a model of P4 withdrawal and maintenance in vivo. Messenger RNA and protein expression have been investigated in endometrial biopsies: 1) during the midsecretory phase (LH+8 to 10); during the maintained luteal phase (P4 administered vaginally for 4 days from LH+8) and biopsies collected 2) 24 h and 3) 48 h post withdrawal of P4; and 4) during pseudo pregnancy (lifespan of corpus luteum extended by 7 days with CG; (decidua collected from women with 5) an ectopic gestation and 6) from women undergoing first-trimester termination of pregnancy). CD56+ large granular lymphocytes remain the major leukocyte subtype, both 24 and 48 h after P4 withdrawal, and in decidua (CG supported or ectopic). Higher numbers (P < 0.05) of macrophages (CD68+) were present in endometrium 48 h post P4 withdrawal and in pseudo pregnant endometrium, compared with normal decidua. Significantly more macrophages (P < 0.01) were present in decidua from an ectopic pregnancy. A significant elevation of IL-8 (P < 0.01) and COX-2 (P < 0.05) messenger RNA was detected 48 h post P4 withdrawal. Evidence is provided for up-regulation of IL-8 and COX-2 in response to P4 withdrawal.

Chemokine CCL2↗
PubMed1999

Assurance: the power behind PCASSO security.

The need for security protection in Internet-based healthcare applications is generally acknowledged. Most healthcare applications that use the Internet have at least implemented some kind of encryption. Most applications also enforce user authentication and access control policies, and many audit user actions. However, most fall short on providing strong assurances that the security mechanisms are behaving as expected and that they cannot be subverted. While no system can claim to be totally "bulletproof," PCASSO provides assurance of correct operation through formal, disciplined design and development methodologies, as well as through functional and penetration testing. Through its security mechanisms, backed by strong system assurances, PCASSO is demonstrating "safe" use of public data networks for health care.

Computer Security↗
PubMed1999

Barley aleurone cell death is not apoptotic: characterization of nuclease activities and DNA degradation.

Barley aleurone cells undergo programmed cell death (PCD) when exposed to gibberellic acid (GA), but incubation in abscisic acid (ABA) prevent PCD. We tested the hypothesis that PCD in aleurone cells occurs by apoptosis, and show that the hallmark of apoptosis, namely DNA cleavage into 180 bp fragments, plasma membrane blebbing, and the formation of apoptotic bodies do not occur when aleurone cells die. We show that endogenous barley aleurone nucleases and nucleases present in enzymes used for protoplast preparation degrade aleurone DNA and that DNA degradation by these nucleases is rapid and can result in the formation of 180 bp DNA ladders. Methods are described that prevent DNA degradation during isolation from aleurone layers or protoplasts. Barley aleurone cells contain three nucleases whose activities are regulated by GA and ABA. CA induction and ABA repression of nuclease activities correlate with PCD in aleurone cells. Cells incubated in ABA remain alive and do not degrade their DNA, but living aleurone cells treated with GA accumulate nucleases and hydrolyze their nuclear DNA. We propose that barley nucleases play a role in DNA cleavage during aleurone PCD.

Abscisic Acid↗
PubMed1998

Characterization of a calmodulin-binding transporter from the plasma membrane of barley aleurone.

We have used Arabidopsis calmodulin (CaM) covalently coupled to horseradish peroxidase to screen a barley aleurone cDNA expression library for CaM binding proteins. The deduced amino acid sequence of one cDNA obtained by this screen was shown to be a unique protein of 702 amino acids with CaM and cyclic nucleotide binding domains at the carboxyl terminus and high similarity to olfactory and K+ channels. This cDNA was designated HvCBT1 (Hordeum vulgare CaM binding transporter). Hydropathy plots of HvCBT1 showed the presence of six putative transmembrane domains, but sequence alignment indicated a pore domain that was unlike the consensus domains in K+ and olfactory channels. Expression of a subclone of amino acids 482-702 in Escherichia coli generated a peptide that bound CaM. When a fusion protein of HvCBT1 and green fluorescent protein was expressed in barley aleurone protoplasts, fluorescence accumulated in the plasma membrane. Expression of HvCBT1 in the K+ transport deficient Saccharomyces cerevisiae mutant CY162 showed no rescue of the mutant phenotype. However, growth of CY162 expressing HvCBT1 with its pore mutated to GYGD, the consensus sequence of K+ channels, was compromised. We interpret these data as indicating that HvCBT1 acts to interfere with ion transport.

Amino Acid Sequence↗
PubMed1998

Calcium, magnesium, and potassium in hair of deer from areas of contrasting soil productivity.

Differences in mineral nutrient composition of soils have been considered to affect health and population characteristics of free-ranging animals, particularly herbivores. Contents of Ca, Mg, and K in hair of female fawn white-tailed deer (Odocoileus virginianus) were measured for eight consecutive years to determine if soil and annual effects occurred in two areas of contrasting soil productivity in Illinois. Soil differences may account for some of the autumnal weight difference (7.2 kg for 4 yrs of observation) observed in fawn does from the areas. Ca, Mg, and K were assayed, because these macronutrients were known to differ in soils of the areas and were presumed to differ in forages. In 6 of the 8 yrs, at least one element was significantly different (P < or = 0.05) between areas. Significant (P < or = 0.05) differences for K occurred in 5 yr, for Ca in 4 yr, and for Mg in 2 yr. Ca and Mg were lower in hair in 7 yr from deer collected from the area in which extractable Ca and Mg were higher in soils; that is, hair Ca and Mg levels tended to be inversely related to levels of plant-available Ca and Mg in soil. For 7 of the 8 yr, K content was lower in hair from the area of lower soil K content. Within one area, between-year differences occurred for Ca and K and for Ca and Mg in the other area. Between-year differences in diet selection and annual climatic effects on mineral uptake of forages, among other factors, may account for some of the latter differences. Results for hair analyses suggest that macronutrient differences in Ca, Mg, and K occur in the diets of these populations and may account for some of the weight difference observed between the areas.

Animals↗
PubMed1998

Nicotine and cotinine replacement when nicotine nasal spray is used to quit smoking.

Nicotine nasal spray (NNS) is generally considered to be an effective smoking cessation aid, but all studies to date of NNS effectiveness have also utilized group therapy sessions or frequent laboratory visits to support their subjects' stop smoking efforts. We studied 50 volunteers before they attempted to quit smoking and again at 1, 2 and 3 months after they received NNS to assist them in quitting smoking. No other stop smoking intervention was used, which more closely mimics the common practice of many individuals trying to stop smoking with the aid of a nicotine replacement product but without other supportive interventions. We found that 50% of the subjects quit smoking for the first month, 34% were still abstinent after 2 months and 32% quit smoking for 3 months. Those who quit smoking for the entire 3 months and who continued regular NNS use throughout had 67% cotinine replacement at the end of the first month, while another group which quit smoking for only the first month with the aid of NNS had 42% cotinine replacement at the end of that month. Our data confirm that NNS is an effective smoking cessation aid, but our abstinent rate at 3 months is slightly lower than in other studies in which group therapy was provided. Our data also indicate that higher NNS-induced cotinine replacement during the first month of quitting smoking (suggesting more frequent use of NNS) is associated with longer term quit-smoking success rate.

Administration, Intranasal↗
PubMed1998

Herniography in the investigation of groin pain in adults.

Herniography is a useful investigation in adults with unexplained groin pain in whom there is no clinical evidence of a hernia, thus ensuring appropriate surgery. The technique is described, normal anatomy and different types of hernias illustrated.

Adult↗