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Biomedical subjects

J Pennington

Publications and source records attributed to J Pennington.

At least 19 recordsLinked to original sources
PubMed2001

Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization.

Critical to homeostasis of blood cell production by hematopoietic stem/progenitor (HSC/P) cells is the regulation of HSC/P retention within the bone marrow microenvironment and migration between the bone marrow and the blood. Key extracellular regulatory elements for this process have been defined (cell-cell adhesion, growth factors, chemokines), but the mechanism by which HSC/P cells reconcile multiple external signals has not been elucidated. Rac and related small GTPases are candidates for this role and were studied in HSC/P deficient in Rac2, a hematopoietic cell-specific family member. Rac2 appears to be critical for HSC/P adhesion both in vitro and in vivo, whereas a compensatory increase in Cdc42 activation regulates HSC/P migration. This genetic analysis provides physiological evidence of cross-talk between GTPase proteins and suggests that a balance of these two GTPases controls HSC/P adhesion and mobilization in vivo.

Animals↗
PubMed2001

Understanding urban child mental health l service use: two studies of child, family, and environmental correlates.

The results of two studies identifying child, family, and environmental correlates of initial and ongoing mental health service use by urban minority children and their families are presented. In the first study, data from a sample of 405 adult caregivers of children revealed no predictive power of child demographic characteristics in relation to initial or ongoing service usage. Only parental ratings of child impulsive-hyperactive behavior were significantly related to ongoing involvement in services. In the second study, a new sample of 100 urban caregivers of children was interviewed. Parental discipline efficacy and attitudes about mental health services were found to relate significantly to initial attendance. Relative to ongoing service use, level of family stress, presence of another adult in the home, and parental discipline efficacy were significant. Implications for research and child mental health service organizations are highlighted.

Adolescent↗
PubMed2001

Residual subset population analysis in WBC-reduced blood components using real-time PCR quantitation of specific mRNA.

BACKGROUND: Implementation of WBC reduction of the blood supply increases the importance of measurement of residual WBC subtypes responsible for immunologic and infectious complications of transfusion. STUDY DESIGN AND METHODS: Real-time RT-PCR assays were developed to detect mRNA encoding lineage-specific WBC markers. Primers and fluorescent probes were designed for CD45 (pan-WBC), CD3 (T-lymphocyte), CD19 (B-lymphocyte), CD14 (monocyte), and CD66 (granulocyte), and the specificity was assessed by comparison with flow cytometric analysis of enriched cell populations. WBC subsets were examined in WBC-reduced whole blood prepared with filters (WBF2, Pall; and RZ2000, Baxter) and in platelet concentrates prepared with other filters (Autostop, Pall; and PLX-5, Baxter) and apheresis (COBE Spectra LRS, Gambro). RESULTS: All real-time RT-PCR assays were linear over >5 log concentration range, allowing pre-WBC-reduction and post-WBC-reduction comparisons. Sensitivity limits ranged from 10 cells per mL (CD45) to 200 cells per mL (CD19). Assay specificity was confirmed by the close correlation of real-time RT-PCR and immunophenotyping results by flow cytometry. For all subsets, >3.8 log and >3.1 log reduction was obtained during WBC reduction of whole blood and platelets, respectively. CONCLUSION: Real-time RT-PCR assays are suitable for analysis of subset removal during WBC reduction. There was no significant difference between the two whole-blood filters or between platelet filtration and apheresis in the removal of any WBC subset.

Antigens, CD↗
PubMed2000

Localization of arrhythmogenic triggers of atrial fibrillation.

INTRODUCTION: Mapping procedures to identify triggers of atrial fibrillation from pulmonary veins (PVs) are not well established. We sought to determine the value of multipolar recordings from the coronary sinus (CS) and crista terminalis (CT) for identifying the origin of paced and atrial premature depolarizations (APDs) initiating atrial fibrillation from left versus right PVs. METHODS AND RESULTS: Fifteen patients with paroxysmal atrial fibrillation refractory to medications had decapolar catheters (5-mm electrode, 2-mm interelectrode spacing) placed in the CS and posterior medial to the CT. Bipolar electrograms were recorded at each site. Electroanatomic left atrial endocardial maps were created in sinus rhythm, and each PV was identified and paced. During spontaneous APDs initiating atrial fibrillation and PV pace maps, the atrial activation and the earliest electrogram at CS and CT were compared. PV sites were designated as sites of origin of APDs when (1) intracardiac electrograms in the CS and CT during arrhythmogenic APDs matched those of PV pace maps, (2) local activation preceded CS and CT recordings by at least 40 msec (all sites), and (3) atrial depolarizations were eliminated by application of radiofrequency energy (24/26 sites). Pacing from each of the 30 right PV sites resulted in proximal to distal CS activation and later recordings at the CS than the CT (earliest CS-CT activation range: -15 to -58 msec, mean -32 +/- 12). In contrast, pacing from the left PV sites typically (28/30 sites) activated the CS from the distal to proximal poles and demonstrated simultaneous or earlier (CS-CT range: -14 to +54 msec, mean 13 +/- 17) recordings of the CS than the CT (P < 0.0001). For 13 APDs mapped to the right PVs, CS minus CT activation was -17 to -49 msec (mean -31 +/- 8). For 13 APDs localized to the left PVs, the CS minus CT activation time ranged from -8 to +28 msec (mean 14 +/- 15). CONCLUSION: Activation sequence mapping from multipolar catheters placed in the CS and along the posterior medial CT rapidly differentiates right and left PV sites of origin of atrial depolarization.

Atrial Fibrillation↗
PubMed2000

Inhibiting cadherin function by dominant mutant E-cadherin expression increases the extent of tight junction assembly.

Previous studies have shown that induction of cadherin-mediated cell-cell adhesion leads to tight junction formation, and that blocking cadherin-mediated cell-cell adhesion inhibits tight junction assembly. Here we report analysis of tight junction assembly in MDCK cells overexpressing a mutant E-cadherin protein that lacks an adhesive extracellular domain (T151 cells). Mutant E-cadherin overexpression caused a dramatic reduction in endogenous cadherin levels. Despite this, tight junction assembly was extensive. The number of tight junction strands observed by freeze-fracture electron microscopy significantly increased in T151 cells compared to that in control cells. Our data indicate that the hierarchical regulation of junctional complex assembly is not absolute, and that inhibition of cadherin function has both positive and negative effects on tight junction assembly.

Animals↗
PubMed1999

The promoter of a novel human papillomavirus (HPV77) associated with skin cancer displays UV responsiveness, which is mediated through a consensus p53 binding sequence.

An aetiological role has been proposed for human papillomavirus (HPV) in skin carcinogenesis within the immunosuppressed patient population. To examine this possibility, we have focused on an HPV type that, to date, has been identified only in the cutaneous lesions of renal transplant recipients despite a high degree of sequence homology with other HPVs commonly found in warts in the general population. We report that the non-coding region of this virus, HPV type 77, contains a consensus binding site for the tumour suppressor protein p53, and we show by gel-retardation analysis that this sequence does indeed bind p53. Furthermore, using reporter gene assays, we demonstrate that HPV77 promoter activity is stimulated by UV radiation and that this response is mediated through the p53 binding site. This is the first report of a p53-dependent positive response element within a viral genome. Our results suggest a possible novel mechanism by which specific types of HPV might act as cofactors with UV radiation in cutaneous transformation.

Adult↗
PubMed1998

Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group.

BACKGROUND: Despite the availability of potent antibiotics and intensive care, mortality rates from septic shock are 40-70%. We assessed the safety and efficacy of murine monoclonal antibody to human tumour necrosis factor alpha (TNF alpha MAb) in the treatment of septic shock. METHODS: In a randomised, multicentre, double-blind, placebo-controlled clinical trial in 105 hospitals in the USA and Canada, we randomly assigned 1879 patients a single infusion of 7.5 mg/kg TNF alpha MAb (n=949) or placebo (0.25% human serum albumin n=930). Our main outcome measurement was the rate of all-cause mortality at 28 days. FINDINGS: 382 (40.3%) of 948 patients who received TNF alpha MAb and 398 (42.8%) of 930 who received placebo had died at 28 days (95% CI -0.02 to 0.07, p=0.27). We found no association between therapy with TNF alpha MAb and increased rapidity in reversal of initial shock or prevention of subsequent shock. Similarly, baseline plasma interleukin-6 concentrations of more than 1000 pg/mL or detectable circulating TNF concentrations were not associated with improvement in survival after TNF alpha MAb therapy. Coagulopathy but not other organ or system failures, was significantly decreased in the TNF alpha MAb group compared with placebo (day 7, p<0.001; day 28, p=0.005). Serious adverse events were reported in 55.2% of patients given placebo and 54.1% in the TNF alpha MAb group. INTERPRETATION: We did not find an improvement in survival after septic shock with TNF alpha MAb. Therapy not solely dependent on TNF alpha blockade may be required to improve survival.

Adult↗
PubMed1998

Role of glycosylation in the lipid-binding activity of the exchangeable apolipoprotein, apolipophorin-III.

Non-glycosylated recombinant Locusta migratoria apolipophorin-III, apoLp-III, was expressed in E. coli and its physical-chemical properties were compared to those of the glycosylated native apoLp-III. Fluorescence quantum yield and acrylamide quenching studies indicated a slightly higher accessibility of the Trp residues in the recombinant apoLp-III. Far-UV CD spectroscopy indicated that the recombinant apoLp-III has a lower alpha-helical content than the glycosylated apoLp-III. Both proteins spontaneously formed discoidal recombinant lipoprotein particles when incubated with dimyristoylphosphatidylcholine (DMPC). Interaction with lipid promotes an increase in alpha-helical content. CD and fluorescence studies indicate that both proteins adopt the same conformation in the lipid-bound state. However, the kinetics of association of the recombinant protein with DMPC is 5-fold faster than that of the native protein. The results suggest that glycosylation inhibits the lipid binding activity by preventing the exposure of hydrophobic domains and/or decreasing the conformational flexibility of the protein.

Animals↗
PubMed1996

Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand.

Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of (+)-m-[125I]iodobenzyl)trozamicol(+)-[125I]MIBT), a novel radioligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[125I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction-system elements. Marked similarities existed between (+)-[125I]MIBT uptake and acetylcholinesterase-positive regions. Optical densitometric analysis of regional (+)-[125I]MIBT uptake revealed significantly greater (+)-[125I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 +/- 0.37; His bundle: 2.16 +/- 0.30; right bundle branch: 0.95 +/- 0.13; right atrium: 0.68 +/- 0.05; right ventricle: 0.57 +/- 0.03; and left ventricle: 0.57 +/- 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[125I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction-system elements. Thus, (+)-[125I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

Acetylcholinesterase↗
PubMed1995

Use of educational gaming to enhance theory learning.

Using educational games in the classroom can increase enthusiasm and reinforce previously presented didactic information in an innovative way. This article presents a game format for teaching and learning components of nursing theories. A discussion of the teaching objectives, the development of the game, rules of play, and an evaluation of the experience are presented. The use of educational games in the classroom can be a positive, interactive, alternative method of teaching and information sharing. Engaging students in a game that is structured to reinforce information presented in lectures and reading assignments can help students test and apply their knowledge of key concepts.

Education, Nursing↗
PubMed1994

Identification of the site of glycation of gamma-II-crystallin by (14C)-fructose.

Cataract formation in diabetes may be via non-enzymic glycosylation (glycation) of lens proteins due to increased concentrations of sugars present in the lenses of diabetic patients. The objective of this project was to identify the site(s) of glycation of bovine gamma-II-crystallin by [14C]fructose. gamma-II-crystallin was isolated from soluble lens nucleus proteins by gel chromatography, followed by ion-exchange chromatography and was then glycated by incubation with [14C]fructose. Radioactively labelled gamma-II-crystallin was cleaved with trypsin. Affinity chromatography of the tryptic peptides gave a single main peak containing the majority of the radioactivity. This indicated that fructose had reacted at a single site on the protein. Amino acid analysis of this peptide showed it to contain only lysine and a trace amount of glycine. By relating the results of the amino acid analysis to the amino acid sequence of gamma-II-crystallin, it was concluded that the labelled peptide corresponded to the N-terminal dipeptide. The site of glycation of bovine gamma-II-crystallin by fructose was thereby identified as the alpha-NH2 group of the N-terminal glycine.

Animals↗
PubMed1994

The triangle model of responsibility.

Responsibility acts as a psychological adhesive that connects an actor to an event and to relevant prescriptions that should govern conduct. People are held responsible to the extent that (a) a clear, well-defined set of prescriptions is applicable to an event (prescription-event link); (b) the actor is perceived to be bound by the prescriptions by virtue of his or her identity (prescription-identity link); and (c) the actor is connected to the event, especially by virtue of appearing to have personal control over it (identity-event link). Studies supported the model, showing that attributions of responsibility are a direct function of the combined strengths of the 3 linkages (Study 1) and that, when judging responsibility, people seek out information that is relevant to the linkages (Study 2). The model clarifies prior multiple meanings of responsibility and provides a coherent framework for understanding social judgment.

Analysis of Variance↗
PubMed1994

Bacteriological studies of open versus closed contrast medium delivery systems in angiography.

The aim of this study was to evaluate the safety of the 'open' method of contrast medium delivery in the angiographic theatre, in which contrast medium is decanted into open galley pots on sterile trolleys. The air bacterial load within the angiographic theatre was sampled before and during angiographic procedures. The relationship of staff and patient activity to bacterial load was assessed. Samples of Iopromide (Ultravist 370; Schering Pty Ltd, Sydney, NSW, Australia) decanted into galley pots were taken for bacterial culture at the end of seven patient procedures. Air bacterial loads were comparable with operating theatre levels and were heaviest during staff activity. Three of seven samples taken at the end of angiographic procedures from air-exposed galley pots yielded contaminants, but the number of bacteria was below that required to produce septicaemia under normal conditions. These results suggest that the open system of contrast medium delivery can be safely used, providing that bacterial checks of room contamination are performed and personnel entry into the theatre is strictly limited.

Air Microbiology↗
PubMed1994

Multiple doses of contrast medium from a single container: bacteriological studies.

Preparations of Iopromide (Ultravist 370; Schering Pty Ltd, Sydney, NSW, Australia), brain/heart infusion broth (BHI; positive growth control) and distilled water (negative control) were inoculated with 10(3) to 10(4) Pseudomonas aeruginosa, Escherichia coli or Staphylococcus aureus cells and incubated at 37 degrees C. Slow decreases (up to one log) were observed in each organism's count in Iopromide and distilled water at room temperature and in S. aureus and E. coli in Iopromide and distilled water at 35 degrees C until 6-8 h, when counts stabilized. BHI cultures showed logarithmic increases. P. aeruginosa counts increased (half log over 8 h) in Ultravist at 37 degrees C. Radiology laboratories were shown to have similar airborne bacterial loads to operating theatres. Samples from repeatedly entered Iopromide bottles showed no contamination. Multiple intravenous doses from a single bottle of non-ionic contrast medium can safely be used as a cost-saving measure provided scrupulous attention is paid to aseptic preparation. Unused decanted contrast medium should be discarded after 4 h.

Bacteria↗
PubMed1992

The effect of dietary yeast on the activity of stable chronic Crohn's disease.

The effect of dietary yeast on the activity of stable Crohn's disease was assessed in 19 patients. During the 1st month patients continued their usual diet (base-line period), but during the next 2 months dietary yeast was excluded except that during 1 month patients took baker's yeast capsules while for the other month they took placebo capsules. The patients' mean Pettit Crohn's disease activity index (CDAI) while taking baker's yeast (mean, 107.9; SE, 6.1) was significantly greater than during yeast exclusion (mean, 102.1; SE, 5.7; p less than 0.05). The mean of each patient's maximum CDAI during yeast exclusion (mean, 107.1; SE, 5.7) was significantly lower than those during the base-line (mean, 115.2; SE, 6.1; p less than 0.05) and baker's yeast inclusion periods (mean, 113.9; SE, 6.7; p less than 0.05). Patients with elevated yeast antibodies tended to develop a higher CDAI while receiving baker's yeast (13 of 15). These results suggest that dietary yeast may affect the activity of Crohn's disease.

Adult↗
PubMed1990

Cellular pharmacology of 5-fluorouracil in a human colon adenocarcinoma cell line selected for thymidine kinase deficiency.

A human colon adenocarcinoma cell line (GC3TK-) was selected for thymidine kinase (TK) deficiency from cloned parental cells (GC3C1) by exposure to 5-bromodeoxyuridine (BrdUrd). The cellular pharmacology of 5-fluorouracil (FUra) and the influence of physiological concentrations of thymidine (dThd; 0.1 to 1 microM) on FUra cytotoxicity during brief exposure in both cell lines were examined. The uptake of FUra during a 1-hr drug exposure, its metabolism to ribo- and deoxyribonucleotides, incorporation into RNA, and inhibition of thymidylate synthase were similar in GC3C1 and GC3TK- cells as were the IC50 values for FUra (26 and 23 microM respectively). TK deficiency did not reduce the intracellular concentrations of FdUMP generated from FUra. In GC3C1, at FUra concentrations up to 100 microM, cytotoxicity was prevented by co-administration of dThd (0.1 to 20 microM). The relationship between cell survival and thymidylate synthase inhibition was close under these conditions. At higher drug concentrations, less dThd protection was observed, and none was detected in GC3TK- cells. Thus, the metabolism of FUra did not appear to be altered substantially in GC3C1 cells selected for TK deficiency. Also in these cells, at concentrations of FUra less than 100 microM, FUra cytotoxicity appeared to be mediated via the inhibition of thymidylate synthase.

Adenocarcinoma↗
PubMed1990

Primary fallopian canal glomus tumors.

Primary fallopian canal glomus tumor has been reported only once previously, although the occurrence of glomus body tissue in the fallopian canal was documented many years ago. Facial paresis as a presenting symptom of glomus tumors is well known, as is facial nerve invasion by glomus tumors. However, a primary fallopian canal glomus tumor that extends extratemporally to the pes anserinus is unusual. Although facial nerve grafting may be necessary for removal of some glomus jugulare tumors, the need for facial nerve grafting appears to be uniform in the patients with primary fallopian canal glomus tumors. The primary fallopian canal glomus tumors that we report did not involve the jugular fossa or the Jacobson's branch of the glossopharyngeal nerve. Both tumors did extend to the middle ear and mastoid and followed the facial nerve extratemporally. The latter features appear to typify primary fallopian canal glomus tumors.

Adult↗