Biomedical subjects

J M Parker

Publications and source records attributed to J M Parker.

At least 19 recordsLinked to original sources

PubMed2001

Head-to-tail oligomerization of calsequestrin: a novel mechanism for heterogeneous distribution of endoplasmic reticulum luminal proteins.

Many proteins retained within the endo/sarcoplasmic reticulum (ER/SR) lumen express the COOH-terminal tetrapeptide KDEL, by which they continuously recycle from the Golgi complex; however, others do not express the KDEL retrieval signal. Among the latter is calsequestrin (CSQ), the major Ca2+-binding protein condensed within both the terminal cisternae of striated muscle SR and the ER vacuolar domains of some neurons and smooth muscles. To reveal the mechanisms of condensation and establish whether it also accounts for ER/SR retention of CSQ, we generated a variety of constructs: chimeras with another similar protein, calreticulin (CRT); mutants truncated of COOH- or NH2-terminal domains; and other mutants deleted or point mutated at strategic sites. By transfection in L6 myoblasts and HeLa cells we show here that CSQ condensation in ER-derived vacuoles requires two amino acid sequences, one at the NH2 terminus, the other near the COOH terminus. Experiments with a green fluorescent protein GFP/CSQ chimera demonstrate that the CSQ-rich vacuoles are long-lived organelles, unaffected by Ca2+ depletion, whose almost complete lack of movement may depend on a direct interaction with the ER. CSQ retention within the ER can be dissociated from condensation, the first identified process by which ER luminal proteins assume a heterogeneous distribution. A model is proposed to explain this new process, that might also be valid for other luminal proteins.

Amino Acid Sequence↗

PubMed2000

Regulatory and educational initiatives fail to promote discussions regarding end-of-life care.

We conducted an observational cohort study to determine if hospital-based, reinforcing regulatory and educational interventions could encourage physicians to discuss end-of-life (EOL) care with their patients. Specifically, we measured the effect of (1) administrative prompts to encourage discussions about EOL care and (2) a mandatory educational seminar focusing on EOL issues. Study subjects were patients consecutively admitted to the medicine service who faced an anticipated 3-year mortality rate of at least 50%. The main study endpoint was the frequency of documented EOL discussions between physicians and patients. In the inception cohort of 184 patients, physicians discussed EOL care with 64 patients (34. 8%), and in the follow-up cohort of 121 patients, 41 individuals (33. 9%) had documented discussions regarding EOL issues (P = 0.90). Actual "Do Not Resuscitate"(DNR) orders were written for 53 patients (28.8%) in the inception cohort and for 33 persons (27.3%) in the follow-up cohort (P = 0.71). We conclude that enhanced, mutually reinforcing regulatory and educational efforts focusing on EOL care proved ineffectual at promoting either discussions about EOL issues or the use of DNR orders.

Aged↗

PubMed2000

Computer keyboards and faucet handles as reservoirs of nosocomial pathogens in the intensive care unit.

PURPOSE: We postulate that computer keyboards and faucet handles are significant reservoirs of nosocomial pathogens in the intensive care unit (ICU) setting. METHODS: Sterile swab samples were obtained from 10 keyboards and 8 pairs of faucet handles in the medical ICU at Tripler Army Medical Center during a period of 2 months. Methicillin-resistant Staphylococcus aureus (MRSA) obtained from the environmental and patient specimens were sent for DNA identification by using pulsed-field gel electrophoresis. RESULTS: A total of 144 samples were obtained (80 keyboards and 64 faucet handles), yielding 33 isolates. The colonization rate for keyboards was 24% for all rooms and 26% in occupied rooms. Rates for faucet handles in all rooms and occupied rooms were 11% and 15%, respectively. The environmental isolates annd their prevalence were: MRS, 49%; Enterococcus, 18%; Enterobacter, 12%; and all other gram-negative rods, 21%. Fourteen individual patient isolates were recorded: MRSA, 43%; Enterobacter, 21%; other gram-negative rods, 36%; and Enterococcus, 0%. By using pulsed-field gel electrophoresis, an indistinguishable strain of MRSA was identified in two patients, the keyboards and faucet handles in their respective rooms, and on other keyboards throughout the ICU, including the doctors' station. CONCLUSIONS: The colonization rate for keyboards and faucet handles, novel and unrecognized fomites, is greater than that of other well-studied ICU surfaces in rooms with patients positive for MRSA. Our findings suggest an associated pattern of environmental contamination and patient infection, not limited to the patient's room. Pulsed-field gel electrophoresis results have documented an indistinguishable strain of MRSA present as an environmental contaminant on these two fomites and in two patients with clinical infections patients during the same period. We believe these findings add evidence to support the hypothesis that these particular surfaces may serve as reservoirs of nosocomial pathogens and vectors for cross-transmission in the ICU setting. New infection control policies and engineering plans were initiated on the basis of our results.

Cross Infection↗

PubMed2000

Citrate enhances olfactory receptor responses and triggers oscillatory receptor activity in the channel catfish.

Citrate, a normal constituent of cellular metabolism, in a binary mixture with an amino acid enhanced asynchronous olfactory receptor responses in the channel catfish, Ictalurus punctatus. In addition, high concentrations of either citrate (> or =3 mM) alone or an amino acid (> or =0.1 mM) in a binary mixture with citrate (> or =1 mM) triggered synchronized voltage oscillations of olfactory receptor neurons (ORNs) known as "peripheral waves" (PWs). Binary mixtures containing lower concentrations of an amino acid also triggered PW activity if the concentration of citrate in the mixture was increased. Both the enhancement of asynchronous activity and the generation of PW activity were the result of citrate chelating calcium, which lowers the surface potential of ORNs making them hyperexcitable. These effects of citrate are replicated by EGTA. Inactivation of the chelating ability of citrate and EGTA with 1 mM calcium chloride, barium chloride, or strontium chloride abolished both the enhancement of asynchronous olfactory responses and PW activity, while not affecting olfactory receptor responses to the amino acids alone.

Action Potentials↗

PubMed2000

Symptomatic vascular rings in adulthood: an uncommon mimic of asthma.

Symptomatic thoracic vascular rings presenting in adulthood are thought to be rare. During a 3-year time period, we diagnosed four cases of symptomatic vascular rings, which had been treated unsuccessfully for suspected asthma. Spirometry was characterized by normal forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and FEV1/FVC, decreased peak expiratory flow (PEF), and truncation of the expiratory flow volume loop. Chest radiographs revealed a right aortic arch in each case with computed tomography (CT) or magnetic resonance imaging (MRI) confirming the diagnosis of a vascular ring. The specific abnormalities consisted of right aortic arch with mirror branching of the main arteries and persistent ligamentum arteriosum; right aortic arch with diverticulum and a fibrous embryonic left arch; right aortic arch with aberrant left subclavian artery arising from a diverticulum of Kommerell; and a right aortic arch with persistent ligamentum arteriosum. Although they are uncommon, vascular rings first presenting in adulthood as a mimic of asthma are not rare. This diagnosis should be considered in adults when abnormal truncation of the flow-volume loop occurs or when radiographic aortic arch abnormalities are found.

Adult↗

PubMed1999

Acquisition of electrophysiologic signals during magnetic resonance imaging.

We describe a low cost system for acquiring electrophysiological signals during magnetic resonance imaging. The system consists of high common-mode-rejection and low noise operational amplifiers, coupled by fiber optic cables to a receiver located at the periphery of the magnetic field. The system minimizes noise introduction which would contaminate image signals.

Electrophysiology↗

PubMed1999

Impediments to writing do-not-resuscitate orders.

BACKGROUND: Physicians are frequently unaware of their patients' desires regarding end-of-life care. Consequently, opportunities to implement do-not-resuscitate (DNR) orders are often missed. OBJECTIVE: To determine the reasons attending physicians do not write DNR orders when patients face increased mortality. METHODS: Over 4 months, the medical records of all inpatients on the General Medicine Service were reviewed at the time of discharge to identify patients with conditions predicting increased mortality. These cases were presented to a 5-member panel who decided if a DNR order was indicated. Reasons for missing DNR orders were discussed with the attending physicians. RESULTS: Of 613 consecutive admissions, the panel identified 149 patients (24%) for whom DNR orders were indicated. In 88 (59%) of these, DNR orders were absent. The lack of a DNR order did not correlate with age (P = .95), sex (P = .61), or race (P = .80). The attending physicians' explanations for not writing DNR orders in these 88 cases included the belief that the patient was not in imminent danger of death (n = 49 [56%]), the belief that the primary physician should discuss DNR issues (n = 43 [49%]), and the lack of an appropriate opportunity to discuss end-of-life issues (n = 38 [43%]). In 11 (12%) of the 88 cases, patients or their families did not accept the recommendation for a DNR order. No physicians expressed concerns regarding the morality of DNR orders, discomfort discussing end-of-life issues, or the threat of litigation as reasons for not writing a DNR order. CONCLUSIONS: Limitations in the extent and depth of the physician-patient relationship appear to be the most frequent impediments to writing DNR orders in our institution.

Adult↗

PubMed1999

Structural predictions of AgfA, the insoluble fimbrial subunit of Salmonella thin aggregative fimbriae.

The unusually stable and multifunctional, thin aggregative fimbriae common to all Salmonella spp. are principally polymers of the fimbrin subunit, AgfA. AgfA of Salmonella enteritidis consists of two domains: a protease-sensitive, 22 amino acid residue N-terminal region and a protease-resistant, 109 residue C-terminal core. The unusual amino acid sequence of the AgfA core region comprises two-, five- and tenfold internal sequence homology patterns reflected in five conserved, 18-residue tandem repeats. These repeats have the consensus sequence, Sx5QxGx2NxAx3Q and are linked together by four or five residues, (x)xAx2. The predicted secondary structure for this unusual arrangement of tandem repeats in AgfA indicates mainly extended conformation with the beta strands linked by four to six residues. Candidate proteins of known structure with motifs of alternating beta strands and short loops were selected from folds described in SCOP as a source of coordinates for AgfA model construction. Three all-beta class motifs selected from the Serratia marcescens metalloprotease, myelin P2 protein or vitelline membrane outer protein I were used for initial AgfA homology build-up procedures ultimately resulting in three structural models; beta barrel, beta prism and parallel beta helix. The beta barrel model is a compact, albeit irregular structure, with the beta strands arranged in two antiparallel beta sheet faces. The beta prism model does not reflect the 5 or 10-fold symmetry of the AgfA primary sequence. However, the favored, parallel beta helix model is a compact coil of ten helically arranged beta strands forming two parallel beta sheet faces. This arrangement predicts a regular, potentially stable, C-terminal core region consistent with the observed tandem repeat sequences, protease-resistance and strong tendency of this fimbrin to oligomerize and aggregate. Positional conservation of amino acid residues in AgfA and the Escherichia coli AgfA homologue, CsgA, provides strong support for this model. The parallel beta helix model of AgfA offers an interesting solution to a multifunctional fimbrin molecular surface having solvent exposed areas, regions for major and minor subunit interactions as well as fiber-fiber interactions common to many bacterial fimbriae.

Amino Acid Sequence↗

PubMed1999

Regulation of monocyte survival in vitro by deposited IgG: role of macrophage colony-stimulating factor.

IgG deposition at tissue sites characteristically leads to macrophage accumulation and organ injury. Although the mechanism by which deposited IgG induces tissue injury is not known, we have recently demonstrated that deposited IgG stimulates the release of IL-8 and monocyte chemoattractant protein-1 from normal human monocytes, which may drive inflammation. Since IgG also induces macrophage accumulation in these diseases, we hypothesized that deposited IgG protects monocytes from apoptosis. As an in vitro model of the effect of deposited IgG on monocyte survival, monocyte apoptosis was studied after FcgammaR cross-linking. Monocytes cultured on immobilized IgG, which induces FcgammaR cross-linking, were protected from apoptosis, whereas monocytes cultured with equivalent concentrations of F(ab')2 IgG or 50 times higher concentrations of soluble IgG, neither of which induces FcgammaR cross-linking, were not protected. Moreover, this protection was transferable, as supernatants from immobilized IgG-stimulated monocytes protected freshly isolated monocytes from apoptosis and contained functional M-CSF, a known monocyte survival factor. M-CSF mediated the monocyte survival induced by FcgammaR cross-linking, as neutralizing anti-human M-CSF Abs blocked the monocyte protection provided by either immobilized IgG or IgG-stimulated monocyte supernatants. These findings demonstrate a novel mechanism by which deposited IgG targets tissue macrophage accumulation through FcgammaR-mediated M-CSF release. This pathway may play an important role in promoting and potentiating IgG-mediated tissue injury.

Antigen-Antibody Complex↗

PubMed1999

Patient or customer?

This paper investigates caring in practice within the context of the global imperative of increasing rationalisation of care based on an economic ethic. The notion of the global marketplace has spread to the domain of health services, so that 'health' has come to be seen as a commodity, with the body as its site, and the 'patient' a customer; clinicians work to construct standard pathways through the healthcare supermarket. The challenge for nurses is to work within but also to challenge and resist the reductionist impetus of economically based and commercially driven approaches to health care. They must retain the sense of the value of the wholeness of the person, the deeply personal and profoundly significant professional-recipient relationship, and find ways of demonstrating their capacity to deliver high-quality care in a cost-effective way. Proper and appropriate accountability is a key strategy to maintaining quality nursing as a significant aspect of care. The expansion of the role of the advanced practice nurse is very useful in providing holistic and cost-effective care, though there are currently limitations to scope of practice that need to be removed. The metaphor of the marketplace, underpinned by powerful global economic forces, can draw us into unthinking compliance with its imperatives--but other metaphors are available. Metaphor and creativity are linked, and we need to consider how the creative use of language can facilitate the emergence of new ways of understanding in health care.

Cost-Benefit Analysis↗

PubMed1999

Nursing town and nursing gown: time, space, and the reinvention of nursing through collaboration.

This paper argues that nursing can reinvent itself through collaboration between the clinical domain and the university and that this reinvention requires new ways of thinking about the relationship between town and gown. The paper analyzes the metaphor of the town/gown distinction and the constitution of time and space and their changing interrelationship. It offers a description of the learning environment of collaboration, which identifies some of the challenges that face nursing in each area. It then presents a way of envisioning the reinvention of nursing in this context, which will facilitate learning.

Clinical Competence↗

PubMed1998

Nitric oxide modulates respiratory-related neural activity in the isolated brainstem of the bullfrog.

The effects of nitric oxide (NO) on respiratory-related neural activity were investigated using the isolated brainstem preparation from bullfrogs (Rana catesbeiana). Addition of the NO donor, sodium nitroprusside (SNP), or the amino acid precursor for NO synthesis, L-arginine (L-Arg), produced significant increases in respiratory-related burst frequency. Inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NA), a non-selective NOS inhibitor, 7-nitro indazole (7-NI), reversibly abolished burst activity. These results suggest that production of NO, probably via neuronal NOS (nNOS), provides a facilitatory input to the respiratory central pattern generator (CPG) in the amphibian brainstem. Endogenous production of NO may be a necessary inter- or intracellular messenger for neurotransmission and/or neuromodulation of central respiratory drive to motor effectors in the bullfrog.

Animals↗

PubMed1998

Lymphocytes produce IL-1beta in response to Fcgamma receptor cross-linking: effects on parenchymal cell IL-8 release.

Neutrophils mediate tissue injury in response to immune complexes, although the factors that induce their recruitment are incompletely understood. We have reported that lymphocytes may be important regulators of monocyte and macrophage IL-8 release in the presence of immobilized IgG. Since tissue parenchymal cells are important local producers of IL-8 but are not directly stimulated by FcgammaR cross-linking, we hypothesized that lymphocytes may also regulate parenchymal IL-8 release. Supernatants from lymphocytes incubated on immobilized IgG induced primary human fibroblasts and human mesangial cells to produce IL-8 (17 +/- 3.5 and 44 +/- 8 ng/ml, respectively). Fibroblast and mesangial cell IL-8 mRNA levels were similarly increased by the conditioned lymphocyte supernatant. Immobilized anti-human FcgammaRIII, but not FcgammaRI or FcgammaRII Abs, could stimulate this IL-8-inducing activity in lymphocytes, suggesting that FcgammaRIII-bearing lymphocytes were responsible. Supernatants from lymphocytes incubated on immobilized IgG contained 2.2 +/- 0.8 ng/ml of IL-1beta, while enriched monocyte preparations from the same donors incubated on immobilized IgG released only 0.1 +/- 0.04 ng/ml of IL-1beta (p = 0.05). Consistent with the identification of IL-1beta as the lymphocyte factor, fibroblast or mesangial cell IL-8 release induced by the IgG-stimulated lymphocyte supernatants was inhibited by 1) the combination of IL-1R antagonist and soluble type II IL-1R, 2) an IL-1-converting enzyme inhibitor, or 3) anti-IL-1beta but not preimmune Abs. These data suggest that targeted deposits of IgG can stimulate FcgammaRIII-bearing lymphocytes to produce IL-1beta, which induces parenchymal cell IL-8 release.

Cells, Cultured↗

PubMed1998

Truth, virtue and beauty: midwifery and philosophy.

In this paper, we outline three moments in the history of Western philosophy--Classical Greek, Modernity, Postmodernity--and the ways in which issues of truth, virtue and beauty have been understood within these philosophical formations. In particular, we investigate the ways in which notions of truth, virtue and beauty influenced the orthodoxy of birthing practices at these different moments. Finally, we examine current, critical reflections on the role of the intellectual in postmodern society and use these reflections as a heuristic for understanding the role of the contemporary midwife. We suggest that midwifery must reconcile two divergent demands. The first is to mobilise the positive, instrumental benefits of Western medical science to improve mortality and morbidity outcomes. The second is to remain sensitive to the cultural and social meanings attached to traditional birthing practices and to understand the roles these play in the well-being of mother and child.

Adult↗

PubMed1998

Metabotropic glutamate receptor expression in olfactory receptor neurons from the channel catfish, Ictalurus punctatus.

Metabotropic glutamate receptors (mGluRs) were identified in olfactory receptor neurons of the channel catfish, Ictalurus punctatus, by polymerase chain reaction. DNA sequence analysis confirmed the presence of two subtypes, mGluR1 and mGluR3, that were coexpressed with each other and with the putative odorant receptors within single olfactory receptor neurons. Immunocytochemical data showed that both mGluR subtypes were expressed in the apical dendrites and some cilia of olfactory neurons. Pharmacological analysis showed that antagonists to each mGluR subtype significantly decreased the electrophysiological response to odorant amino acids. alpha-Methyl-L-CCG1/(2S,3S,4S)-2-methyl-2-(carboxycyclopropyl++ +)glycine (MCCG), a known antagonist to mGluR3, and (S)-4-carboxyphenylglycine (S-4CPG), a specific antagonist to mGluR1, each significantly reduced olfactory receptor responses to L-glutamate. S-4CPG and MCCG reduced the glutamate response to 54% and 56% of control, respectively, which was significantly greater than their effect on a neutral amino acid odorant, methionine. These significant reductions of odorant response by the antagonists, taken with the expression of these receptors throughout the dendritic and ciliated portions of some olfactory receptor neurons, suggest that these mGluRs may be involved in olfactory reception and signal transduction.

Amino Acid Sequence↗

PubMed1997

IL-1 beta-converting enzyme (ICE) is present and functional in human alveolar macrophages: macrophage IL-1 beta release limitation is ICE independent.

Tissue macrophages readily produce intracellular pro-IL-1beta in response to stimuli such as LPS, but are limited in mature IL-1beta release compared with blood monocytes. The mechanism of this IL-1beta control may provide important insights into the physiology of IL-1beta at the tissue level. Since it has been hypothesized that IL-1beta processing by the IL-1beta-converting enzyme (ICE) regulates IL-1beta release, we compared human alveolar macrophages and human blood monocytes for relative ICE expression and activation. Using immunoblots and enzyme-linked immunoassay for ICE, we demonstrate that alveolar macrophages do not differ from blood monocytes in antigenic p45 ICE. Furthermore, an indirect assay for functional ICE documents similar ICE activities in both monocytes and alveolar macrophages, i.e., similar concentrations of soluble synthetic ICE inhibitor (IC50 values of 0.3 +/- 0.01 and 0.6 +/- 0.2 microM, respectively) are required to block mature IL-1beta generation. However, as has been reported for THP-1 myelomonocytic cells, neither alveolar macrophages nor blood monocytes contain directly quantifiable levels of functional ICE forms (p22/p20 and p10) when assayed by immunoblots or by a sensitive capture ELISA that uses an irreversible, biotinylated ICE inhibitor. These findings document that the macrophage limitation in mature IL-1beta release is not due to a lack of ICE or to an inability to activate ICE. Finally, using a staged release assay, the time to half-maximum mature IL-1beta release is significantly depressed in macrophages compared with that in monocytes. Taken together, these findings suggest that macrophage IL-1beta export is regulated independently of ICE activation.

Adenosine Triphosphate↗

PubMed1997

Serum angiotensin converting enzyme does not correlate with radiographic stage at initial diagnosis of sarcoidosis.

Serum levels of angiotension converting enzyme (ACE) are elevated in many patients who suffer from sarcoidosis. Few studies have correlated ACE levels at diagnosis with the radiographic stage of the disease. The present authors reviewed the charts of all patients who had the diagnosis of sarcoidosis made between 1990 and 1995, and correlated ACE level at diagnosis with radiographic stage. Only patients with biopsy-proven sarcoid were included. One hundred and sixteen cases were identified, and complete data were available for 104 individuals. Serum ACE levels were increased in approximately 63.5% of the study population. The relationships between both stage and ACE level, and stage and percentage of individuals with elevated ACE levels within that stage were not statistically significant (P > 0.05). This large, retrospective study of patients with histologic evidence of sarcoidosis demonstrated no association between serum ACE level and radiographic stage.

Biomarkers↗

PubMed1997

Dissociation of the Jak kinase pathway from G-CSF receptor signaling in neutrophils.

Activation of the granulocyte colony-stimulating factor receptor (G-CSFR) induces rapid tyrosine phosphorylation of multiple intracellular substrates in proliferating cells and nonproliferating, terminally differentiated neutrophils. The kinases that couple ligand binding to tyrosine phosphorylation of cellular substrates by the G-CSFR with activation of specific functional programs are largely unknown. In this study, we examined early signaling events in proliferating and terminally differentiated cells following G-CSF stimulation to determine whether identical signaling cascades are activated. In murine Ba/F3 cells transfected with the human G-CSFR and NFS-60 cells constitutively expressing the murine G-CSFR, G-CSF induced tyrosine phosphorylation and activation of Jak1, Jak2, and Tyk2. Tyrosine phosphorylation of Stat3 and, to a lesser extent, Stat1 was also detected following G-CSF stimulation. Using a mitogenically incompetent human G-CSFR mutant in which Pro639 and Pro641 were substituted by alanine, the box 1 PDP motif was found to be required for activation of Jak kinases, tyrosine phosphorylation of the G-CSFR, and recruitment of Stat proteins. Notably, no activation of Jak1, Jak2, Tyk2, Stat1, or Stat3 was observed in neutrophils following G-CSF stimulation. In addition, there was no detectable activation in neutrophils of the recently cloned Jak3 kinase, which has been reported to be expressed at high levels as myeloid cells undergo terminal neutrophilic maturation. These results indicate a lack of involvement of Jak kinases in signaling by the G-CSFR in neutrophils, and suggest utilization of alternative signal transduction pathways distinct from those in proliferating cells. Activation of the Jak-Stat pathway correlates with proliferative signaling by the G-CSFR and requires the membrane-proximal box 1 PXP motif, which is conserved in members of the cytokine receptor superfamily.

Animals↗