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Biomedical subjects

R L Jones

Publications and source records attributed to R L Jones.

At least 55 records · Page 3Linked to original sources

Clostridial enterocolitis.

Equine clostridial enterocolitis is being recognized with increasing frequency. It has been identified in foals with diarrhea, antibiotic-associated enterocolitis, or nosocomial enterocolitis. The sporadic occurrence of clostridial enterocolitis, the variety of types of clostridia involved, and the difficulty of experimentally reproducing the disease suggest that it is a poorly defined multifactorial syndrome. The risk factors associated with susceptibility to colonization and progressive infection are largely based on anecdotal observations and extrapolation from human studies. Quantitative studies are needed to decipher the complex interactions between host and indigenous microflora that provide for and maintain a healthy colonization resistance environment. It seems that such studies might be more beneficial in furthering our understanding of the pathogenesis of clostridial enterocolitis than attempting to implicate another agent or toxin as the sole cause of the disease in equids. Treatment protocols that interrupt the pathogenesis of the disease need to be devised and critically evaluated to complement the present protocols emphasizing supportive care. Perhaps it is time to consider clostridial enterocolitis as yet another consequence of the use of antimicrobials analogous to the selective pressures that result in the emergence of multiple drug-resistant pathogens.

Animals↗

Vacuoles and prevacuolar compartments.

Plant vacuoles are complex and dynamic organelles. Important advances have been made in our understanding of the transporters present in the tonoplast and of the molecular interactions that allow targeting to vacuoles. Despite these advances, markers that permit vacuoles to be defined unambiguously have not yet been identified.

Biological Transport↗

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↗

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↗

Morphological and functional changes in human endometrium following intrauterine levonorgestrel delivery.

The levonorgestrel releasing intrauterine system (LNG-IUS) provides a novel contraceptive method. Intrauterine LNG induces a dramatic transformation of the endometrium, characterized by extensive decidualization. This is associated with strong expression of local factors associated with decidualization, including prolactin receptor and insulin-like growth factor binding protein-1. A striking discovery was the down-regulation of oestrogen and progesterone receptors in all components of the endometrium after insertion of the LNG-IUS, with a gradual return between 6 and 12 months post-insertion. Preliminary findings suggest that androgen receptors are expressed during this time. Elevated leukocyte infiltrate is observed 1 month after insertion of the device, comprising large granular lymphocytes and macrophages. We examined a number of local mediators implicated in menstruation and breakthrough bleeding episodes. Expression of the chemokine interleukin-8 was enhanced after insertion of the device, with a notable decrease apparent 6 months post-insertion. Cyclooxygenase-2 was similarly strongly expressed in the first months after LNG-IUS insertion, in contrast to an initial suppression of prostaglandin dehydrogenase activity. By deduction it appears that higher local concentrations of prostaglandins are present in the initial period of local LNG exposure. Taken together these data suggest that in the first months following LNG-IUS insertion steroid receptor content is significantly decreased, resulting in the altered expression of many locally acting mediators which may be involved in breakthrough bleeding episodes.

Contraceptive Agents, Female↗

Inhibin and activin subunits are differentially expressed in endometrial cells and leukocytes during the menstrual cycle, in early pregnancy and in women using progestin-only contraception.

Inhibins and activins are dimeric hormones which share common subunits and which have diverse endocrine and paracrine roles in regulating reproductive function. Endometrial expression of inhibin alpha, ssA and ssB subunits was examined by immunohistochemistry and in-situ hybridization, across the menstrual cycle and in early pregnancy. All three subunits were found to be expressed in endometrium, primarily by glandular epithelium in the early stages of the cycle. Following the onset of decidualization, expression of alpha, ssA and ssB subunits was up-regulated in decidualized stromal cells. A marked down-regulation of alpha subunit was detected in glandular epithelium, whilst expression of ssA and ssB subunits was maintained. This pattern was consistent in decidua from early pregnancy and additionally in endometrium from women using progestin-only contraceptives, either subdermal implants (Norplant((R))) or levonorgestrel-releasing intrauterine systems (Lng-IUS). Immunostaining was also observed for both ssA and ssB subunits in subpopulations of endometrial leukocytes, identified to be distinct subsets of macrophages, neutrophils and mast cells. Potential paracrine roles for activins may be envisaged in facilitating tissue remodelling during decidualization, in tissue repair following menstruation, and additionally in modulating premenstrual inflammatory events.

Activins↗

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↗

Recall of a lead-contaminated vitamin and mineral supplement in a clinical trial.

PURPOSE: The Treatment of Lead-exposed Children (TLC) trial tested whether developmental outcome differed between children treated for lead poisoning with succimer or placebo. On 7 July 1997, TLC was informed that the vitamin and mineral supplements it gave to all children were contaminated with about 35 microg of lead per tablet. METHODS: TLC recalled the contaminated supplements and measured the children's exposure. RESULTS: The families of 96% of the children were contacted with 30 days. Among the 571 children to whom the contaminated supplements were dispensed, the mean increase in blood lead was 0.06+/-0.01 micromol/L (1.2+/-0.2 microg/dL); among 78 children to whom they were not, it was 0.09+/-0.03 micromol/L (1.8+/-0.7 microg/dL). There was no evidence of a dose-response relation between estimated supplement consumption and increase in blood lead concentration. CONCLUSIONS: The children's blood lead concentrations were not detectably affected by the contamination. Since the association of cognitive delay with lead exposure is best described for blood lead, we believe that the trial's inference about the effect of drug therapy on lead induced cognitive delay should be unaffected.

Journal Article↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗