Search PubMed⌕ Search

Biomedical subjects

J E Davis

Publications and source records attributed to J E Davis.

At least 37 records · Page 2Linked to original sources
PubMed1999

T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-alpha production in a manner distinct from LPS activation of monocytes.

p38 mitogen-activated protein kinase (MAPK) (p38) is involved in various cellular responses, including LPS stimulation of monocytes, resulting in production of proinflammatory cytokines such as TNF-alpha. However, the function of p38 during antigenic stimulation of T cells is largely unknown. Stimulation of the human Th cell clone HA-1.70 with either the superantigen staphylococcal enterotoxin B (SEB) or with a specific antigenic peptide resulted in p38 activation and the release of TNF-alpha. MAPK-activated protein kinase-2 (MAPKAPK-2), an in vivo substrate for p38, was also activated by T cell signaling. SB 203580, a selective inhibitor of p38, blocked p38 and MAPKAPK-2 activation in the T cell clone but did not completely inhibit TNF-alpha release. PD 098059, a selective inhibitor of MAPK kinase 1 (MEK1), blocked activation of extracellular signal-regulated kinase (ERK) and partially blocked TNF-alpha production by the clone. In human peripheral T cells, p38 was not activated by SEB, but rather by CD28 cross-linking, whereas in the human leukemic T cell line Jurkat, p38 was activated by CD3 and CD28 cross-linking in an additive fashion. TNF-alpha production by peripheral T cells in response to SEB and anti-CD28 mAb correlated more closely with ERK activity than with p38 activity. Therefore, various forms of T cell stimulation can activate the p38 pathway depending on the cells examined. Furthermore, unlike LPS-stimulated monocytes, TNF-alpha production by T cells is only partially p38-dependent.

Antibodies, Monoclonal↗
PubMed1999

Sensations experienced during removal of tubes in acute postoperative patients.

The major purpose of this study was to determine the types and intensity of sensations that patients experience when chest tubes (CTs) and Jackson-Pratt (JP) abdominal tubes are removed. A convenience sample of 62 hospitalized subjects, 31 with CTs and 31 with JP tubes, participated. Each subject was interviewed after tube removal. Sensations were identified, and intensity of sensation was marked on a 100-mm Visual Analogue Scale. Similar sensations were reported by both groups. Intensity of sensation was consistently higher in the JP group. The most frequently reported sensations were pain (77%) on JP tube removal and pulling (90%) upon CT removal.

Adult↗
PubMed1999

Anti-viral strategies of cytotoxic T lymphocytes are manifested through a variety of granule-bound pathways of apoptosis induction.

Cytotoxic T cells and natural killer cells together constitute a major defence against virus infection, through their ability to induce apoptotic death in infected cells. These cytolytic lymphocytes kill their targets through two principal mechanisms, and one of these, granule exocytosis, is essential for an effective in vivo immune response against many viruses. In recent years, the authors and other investigators have identified several distinct mechanisms that can induce death in a targeted cell. In the present article, it is postulated that the reason for this redundancy of lethal mechanisms is to deal with the array of anti-apoptotic molecules elaborated by viruses to extend the life of infected cells. The fate of such a cell therefore reflects the balance of pro-apoptotic (immune) and anti-apoptotic (viral) strategies that have developed over eons of evolutionary time.

Animals↗
PubMed1999

RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by activated monocytes/macrophages and T lymphocytes, has been implicated in several disease states, including rheumatoid arthritis, inflammatory bowel disease, septic shock, and osteoporosis. Monocyte/macrophage production of TNF-alpha is dependent on the mitogen-activated protein kinase p38. RWJ 67657 (4-[4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-(4-pyridinyl)-1H-imidazol -2-yl]-3-butyn-1-ol) inhibited the release of TNF-alpha by lipopolysaccharide (a monocyte stimulus)-treated human peripheral blood mononuclear cells with an IC(50) of 3 nM, as well as the release of TNF-alpha from peripheral blood mononuclear cells treated with the superantigen staphylococcal enterotoxin B (a T cell stimulus), with an IC(50) value of 13 nM. This compound was approximately 10-fold more potent than the literature standard p38 kinase inhibitor SB 203580 in all p38 dependent in vitro systems tested. RWJ 67657 inhibited the enzymatic activity of recombinant p38alpha and beta, but not gamma or delta, in vitro and had no significant activity against a variety of other enzymes. In contrast, SB 203580 significantly inhibited the tyrosine kinases p56 lck and c-src (IC(50) = 5 microM). RWJ 67657 did not inhibit T cell production of interleukin-2 or interferon-gamma and did not inhibit T cell proliferation in response to mitogens. RWJ 67657 inhibited TNF-alpha production in lipopolysaccharide-injected mice (87% inhibition at 50 mg/kg) and in rats (91% inhibition at 25 mg/kg) after oral administration. Based on these favorable biological properties, RWJ 67657 may have use as a treatment for inflammatory diseases.

Animals↗
PubMed1998

The development of novel and selective p56lck tyrosine kinase inhibitors.

Early T-cell receptor mediated signal transduction involves the activation of several tyrosine protein kinases. One of these tyrosine kinases, p56lck, is expressed primarily in T-cells and Natural Killer (NK) cells and has been shown to be critical for their proliferative and effector functions. Indandiones have been identified as a potent and selective chemical class that inhibits p56lck.

CSK Tyrosine-Protein Kinase↗
PubMed1998

An innovation in the assessment of future dentists.

'The assessment of students is a serious and often tragic enterprise.' The central question in assessment is 'What is one trying to assess?'. Is it factual knowledge, ability to apply and problem solve, clinical competencies or indeed other attributes? The domain being assessed requires appropriate methods. Professionals involved in examination development have identified three characteristics which all assessment methods demand: reliability, validity and feasibility. This article sets out to describe these features.

Attitude of Health Personnel↗
PubMed1998

Postliver transplant allograft reinfection with a lamivudine-resistant strain of hepatitis B virus: long-term follow-up.

Lamivudine is a nucleoside analogue with efficacy in the suppression of hepatitis B viral (HBV) replication. In a previously reported study, lamivudine was administered to patients with chronic, actively replicating HBV infection who subsequently underwent liver transplantation. Patients became serum HBV DNA-negative in response to lamivudine before transplantation, which was continued in the post-transplant period. Two of four patients surviving the immediate postoperative period developed allograft reinfection 240 and 409 days post-transplant. The strain of the reinfecting virus was analyzed, and a mutation in the YMDD region of the viral polymerase conferring resistance to lamivudine was discovered. The long term follow-up of these two patients is reported. The first patient developed ascites 16.5 months after allograft reinfection. A transjugular liver biopsy performed 18 months after the emergence of the lamivudine-resistant strain revealed cirrhosis and lobular hepatitis without rejection. The gradient between hepatic vein wedged and free pressures was 13 mmHg, consistent with portal hypertension. The second patient, 16 months after allograft reinfection with the lamivudine-resistant strain, is without clinical evidence of portal hypertension, although liver enzymes remain elevated. Both patients were given a trial of famciclovir, which did not significantly suppress HBV viremia. In conclusion, lamivudine-resistant HBV strains with the YMDD mutation may have an aggressive clinical course with rapid progression to cirrhosis. Famciclovir did not appear to be an effective rescue agent in these two patients.

2-Aminopurine↗
PubMed1998

A novel Alcian yellow-toluidine blue (Leung) stain for Helicobacter species: comparison with standard stains, a cost-effectiveness analysis, and supplemental utilities.

Helicobacter pylori (Hp) gastritis is a worldwide problem significantly associated with duodenal and gastric peptic ulcer disease, gastric carcinomas, and MALT-type lymphomas. A simple, rapid, reproducible, reliable, and inexpensive stain to detect the organism in gastric biopsy specimens is thus of great value. To assess the reliability and cost-effectiveness of a novel Alcian yellow-toluidine blue (Leung) stain for Hp, we stained 60 endoscopic mucosal biopsy specimens from patients with Hp gastritis and measured time to detection of organism, Hp numbers (scale, 1-5), and technical costs. We also stained serial 5-microm step sections of 17 of these cases with the Giemsa and modified Steiner (MS) methods, and similar measurements were made. Also, specimens from various normal gastrointestinal sites and metaplastic lesions, as well as four cases each of giardiasis and cryptosporidiosis, were stained with the Leung method. In the subset of 17 cases, the Leung stain enhanced detection time and compared favorably with the Giemsa method, though the MS method was somewhat superior. Hp scores were similar among all groups. Mean time to detection and Hp scores were similar in the larger (n = 60) group stained with hematoxylin and eosin and the Leung stain. Material costs and technologist's time for Giemsa stains, however, were greater than for the Leung stain, and technologist's time for MS was nearly fourfold that of the Leung stain. With the Leung method, mucus from all gastrointestinal sites and metaplastic lesions stained yellow, and this stain provided excellent contrast and morphologic definition in giardiasis and cryptosporidiosis. We suggest that the newly developed Alcian yellow-toluidine blue (Leung) histochemical stain is a good choice as the standard for routine Hp staining because it is the cheapest and easiest to prepare and because pathologists' detection with this stain compares favorably with detection times achieved with more traditional and established methods.

Coloring Agents↗
PubMed1997

Alteration of the dismal natural history of fibrosing cholestatic hepatitis secondary to hepatitis B virus with the use of lamivudine.

BACKGROUND: Fibrosing cholestatic hepatitis (FCH) is a severe form of hepatitis B virus (HBV) infection occurring as either primary allograft reinfection after liver transplantation for HBV or as severe HBV reactivation induced by immunosuppression in patients with previously latent infection. Without treatment, FCH is universally fatal within a few months of diagnosis. Some improvement has been reported with long-term ganciclovir, with and without foscarnet, but an effective and easily available treatment has not yet been reported. METHODS: We report the prolonged survival of a renal transplant recipient who developed histologically confirmed FCH 6 months after transplantation and was treated with lamivudine. RESULTS: At the time of diagnosis, the patient had jaundice, ascites, and a serum HBV-DNA level of 3868 pg/ml. Lamivudine was instituted 2 months later, and after 6 months of treatment, the HBV-DNA level was undetectable with the serum bilirubin within the normal range. Twelve months after the diagnosis of FCH, the patient remains stable without progression of liver dysfunction. CONCLUSION: Our experience demonstrates that lamivudine therapy can improve the dismal natural history of FCH.

Antiviral Agents↗
PubMed1997

Mge1 functions as a nucleotide release factor for Ssc1, a mitochondrial Hsp70 of Saccharomyces cerevisiae.

Mge1, a GrpE-related protein in the mitochondrial matrix of the budding yeast Saccharomyces cerevisiae, is required for translocation of precursor proteins into mitochondria. The effect of Mge1 on nucleotide release from Ssc1, an Hsp70 of the mitochondrial matrix, was analyzed. The release of both ATP and ADP from Ssc1 was stimulated in the presence of Mge1, therefore we conclude that Mge1 functions as a nucleotide release factor for Ssc1. Mge1 bound stably to Ssc1 in vitro; this interaction was resistant to high concentrations of salt but was disrupted by the addition of ATP. ADP was much less effective in releasing Mge1 from Ssc1 whereas ATP gamma S and AMPPNP could not disrupt the Ssc1/Mge1 complex. Ssc1-3, a temperature sensitive SSC1 mutant protein, did not form a detectable complex with Mge1. Consistent with the lack of a detectable interaction, Mge1 did not stimulate nucleotide release from Ssc1-3. A conserved loop structure on the surface of the ATPase domain of DnaK has been implicated in its interaction with GrpE. Since the single amino acid change in Ssc1-3 lies very close to the analogous loop in Ssc1, the role of this loop in the Ssc1:Mge1 interaction was investigated. Deletion of the loop abolished the physical and functional interaction of Ssc1 with Mge1, suggesting that the loop in Ssc1 is also important for the Ssc1:Mge1 interaction. Two mutants with single amino acid changes within the loop did not eliminate the stable binding of Mge1, yet the binding of Mge1 did not stimulate the release of nucleotides from the mutant SSC1 proteins. We propose that the loop region of Ssc1 is important for the physical interaction between Mge1 and Ssc1, and for generation of a conformational change necessary for Mge1-induced nucleotide release.

Adenine Nucleotides↗
PubMed1997

A case of massive thymolipoma.

A massive anterior mediastinal tumor was discovered in a 9-year-old girl with long-standing symptoms of asthma. Preoperative computed tomography (CT) scan and magnetic resonance imaging (MRI) results suggested the presence of a thymolipoma, a rare benign tumor of the thymus. Few cases have been reported in the literature, although the histological and radiographic features have been well described. This case confirms previously reported characteristics and also illuminates new aspects of clinical presentation and perioperative management.

Child↗
PubMed1997

Combined epicardial-transthoracic electrode paddle placement: a method for defibrillation during open-chest cardiac resuscitation.

We present a case of open-chest cardiac massage where ventricular fibrillation developed and a direct current shock was required. In the absence of 'surgical' electrode paddles, standard paddle electrodes were used; one small electrode was placed directly on the exposed epicardial surface and the second electrode was placed on the lateral chest wall. Defibrillation was achieved with a 100 J shock. This combined epicardial-transthoracic electrode paddle placement technique allows defibrillation to be accomplished when open chest cardiac massage is being performed and no 'surgical' electrode paddles are available.

Electric Countershock↗
PubMed1997

Effect of fluid ingestion on orthostatic responses following acute exercise.

Orthostatic tolerance is impaired following an acute bout of exercise. This study examined the effect of fluid ingestion following treadmill exercise in restoring the cardiovascular responses to an orthostatic stress. Five men (age, 29.6 +/- 3.4 yrs) were exposed to a graded lower body negative (LBNP) pressure protocol (0 to -50 mmHg) during euhydration without exercise (C), 20 minutes after exercise dehydration (D), 20 minutes after exercise and fluid ingestion (FI20), and 60 minutes after exercise and fluid ingestion (FI60). Fluid ingestion (mean +/- SE) consisted of water-ingestion equivalent to 50% of the body weight lost during exercise (520 +/- 15 ml). Exercise dehydration resulted in significantly higher heart rates (119 +/- 8 vs 82 +/- 7 bpm), lower systolic blood pressures (95 +/- 1.7 vs 108 +/- 2.3 mmHg), a smaller increase in leg circumference (3.7 +/- 4 vs 6.9 +/- 1.0 mm), and an attenuated increase in total peripheral resistance (2.58 +/- 1.2 vs 4.28 +/- 0.9 mmHg/L/min) at -50 mmHg LBNP compared to the C condition. Fluid ingestion (both 20 and 60), partially restored the heart rate, systolic blood pressure, and total peripheral resistance responses to LBNP, but did not influence the change in leg circumference during LBNP (4 +/- 0.3 for R20 and 2.8 +/- 0.4 mm for R60). These data illustrate the effectiveness of fluid ingestion on improving orthostatic responses following exercise, and suggest that dehydration is a contributing factor to orthostatic intolerance following exercise.

Adult↗
PubMed1997

Effects of exercise during head-down bed rest on postural control.

BACKGROUND: The effects of exercise on postural control during walking were evaluated following exposure to head-down bed rest (BR). METHODS: Two groups of male subjects (N = 18, mean age = 21.4 yr +/- SE 1.0) were exposed to 5 d of 6 degrees head-down bed rest. The experimental group (E) exercised 90 min.d-1 (n = 12 subjects) during the BR while the control group received no intervention (n = 6). The exercise treatment consisted of a combination of isotonic and isokinetic lower extremity exercise training. Electromyographic (EMG) activity in the tibialis anterior, gastrocnemius, vastus lateralis, and biceps femoris was measured during walking before and after BR. RESULTS: Following BR, EMG activity increased in both test subject groups for all muscles (p < 0.05). However, there were no significant differences in EMG activity between the C and E groups either before or after BR. CONCLUSIONS: These data suggest that the ability of the postural control system to adjust to the gravitational environment was compromised as a result of BR. In addition, we conclude that the exercise protocol used was not an effective countermeasure to the alterations in the postural control system.

Adult↗
PubMed1997

Health promotion and screening services reported by older adult patients of urban primary care physicians.

BACKGROUND: Adult preventive services provided at intervals recommended by expert panel guidelines may reduce morbidity and mortality. As part of an intervention trial to increase primary preventive services in urban primary care practices, baseline data were collected on primary prevention and screening test rates in older adults and on patient characteristics associated with provision of these services. METHODS: A questionnaire on preventive services offered or provided over the past 2 years was completed by patients aged 52 to 77 years and another by their 42 participating physicians. Logistic regression was used to identify patient characteristics associated with increased provision of these services. RESULTS: Usable questionnaires were completed by 1457 (80.9%) patients. Patient age and sex were not associated with the provision of primary preventive and counseling services. The presence of two or more chronic diseases was predictive of primary preventive services (P < .02), but was not associated with an increase in screening tests or procedures. Age was positively associated with delivery of prostate-specific antigen blood tests (P < .001) and rectal examinations (P < .001) in men, but was negatively associated with mammography (P < .001) and Papanicolaou (Pap) tests (P = .02) in women. The negative trend in screening mammography was evident even for women aged 50 to 65 years despite the national consensus regarding the benefits of screening for this age group. Patients with health management organization insurance reported significantly more mammography (P = .002), cervical Pap tests (P = .050), sigmoidoscopies (P = .002), and fecal occult blood tests (P = .035). CONCLUSIONS: In our study patients, the provision of primary preventive and screening services was closer to consensus guidelines than is typically reported in the literature. The data suggest that future investigations and interventions to improve primary prevention and screening services in older adults who have access to primary care do not need to be directed at fundamental changes in the way preventive services are delivered, but rather should target procedures of proven benefit, such as mammography, where rates remain below recommended guidelines.

Age Factors↗
PubMed1996

Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A.

A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta I, beta II, gamma, delta, epsilon and eta PKC isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b, was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.

Animals↗
PubMed1996

Development of a high volume screen to identify inhibitors of endothelial cell activation.

We have developed a high throughput screen to identify inhibitors of endothelial cell activation using E-selection cell-surface expression as a marker. Endothelial cell activation is an important component of both acute and chronic inflammatory disease. Inhibitors of this process represent potential therapeutic agents. A cell culture system for primary human umbilical vein endothelial cells was generated, including an analysis of donor variability, passage number, seeding density, and cost. The effects of IL-1 beta, TNF alpha, LPS, and an LPS-conditioned plasma product on E-selectin expression were characterized. E-selectin expression on the surface of IL-1-stimulated endothelial cells was quantified with a direct ELISA on fixed cell monolayers. Automation of the ELISA necessitated identification of methods for cell fixation, liquid handling, and compound addition which would maintain the integrity of the cell monolayer. The ELISA is inexpensive, reproducible, and suitable for high throughput primary cell assays, supporting a screening rate of 10,000 compounds/ week. The method is compatible with a broad chemical diversity, and the cellular format provides early information on the cellular uptake and cytotoxicity of compounds. We describe a screening paradigm which allowed us to identify inhibitors of endothelial cell activation and simultaneously discriminate their activity from their cytotoxic effects.

Cell Survival↗