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Biomedical subjects

J Davis

Publications and source records attributed to J Davis.

At least 37 records · Page 2Linked to original sources

First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis.

OBJECTIVE: To update the international recommendations for use of anti-tumour necrosis factor (TNF) agents in the treatment of ankylosing spondylitis. METHODS: The published recommendations on anti-TNF treatment in ankylosing spondylitis formed the basis of the update. A questionnaire was sent to the ASAS (assessment in ankylosing spondylitis) members before the final decisions were agreed upon at an international meeting of the ASAS working group. RESULTS: Only minor changes to the original consensus statement were required. For the initiation of anti-TNF treatment, there should be: a diagnosis of definitive ankylosing spondylitis (normally based on modified New York criteria); active disease for at least four weeks, as defined by a sustained Bath ankylosing spondylitis disease activity index (BASDAI) of > or =4 on a 0-10 scale and expert opinion based on clinical findings; refractory disease, defined by failure of at least two non-steroidal anti-inflammatory drugs during a three month period, failure of intra-articular steroids (if indicated), and failure of sulfasalazine in patients with predominantly peripheral arthritis; and application of the usual precautions and contraindications for biological treatment. For monitoring anti-TNF treatment: both the ASAS core set for clinical practice and the BASDAI should be followed after the initiation of treatment. Discontinuation of anti-TNF treatment in non-responders should be considered after 6-12 weeks. Response is defined by improvement of at least 50% or 2 units (on a 0-10 scale) of the BASDAI. CONCLUSIONS: This updated consensus statement is recommended in guiding clinical practice and as a basis for developing national guidelines. Evaluation and regular update of this consensus statement is subject to further research by the ASAS group.

Antirheumatic Agents↗

Relationship between diabetes mellitus and adenocarcinoma of the oesophagus and gastric cardia.

BACKGROUND: Obesity is a risk factor for adenocarcinomas of the oesophagus and gastric cardia. Diabetes mellitus might mediate that association. AIM: To estimate the risk of diabetes mellitus on the development of adenocarcinoma of distal oesophagus and gastric cardia beyond that of gastro-oesophageal reflux disease. METHODS: A case-control study was performed using a national administrative database of the Veterans Administration. RESULTS: A total of 311 cases of cancer and 10,154 controls were identified. Gender, age, and race were risks for cancer. Diabetes was diagnosed in 36% of cases, and 32% of controls (P = 0.15). Diabetic complications were diagnosed in 14% of cases and 13% of controls (P = 0.60). Multiple logistic regression confirmed the absence of an association between cancer and diabetes (odds ratio 1.1, 95% confidence interval 0.8-1.5) or diabetic complications (odds ratio 0.8, 95% confidence interval 0.6-1.3), adjusting for age, gender, and race. CONCLUSIONS: Within the limitations of this case-control study, there is no evidence of an association between diabetes and adenocarcinoma of the oesophagus or gastric cardia among US veterans with gastro-oesophageal reflux disease.

Adenocarcinoma↗

Modeling of clusters in a strong 248-nm laser field by a three-dimensional relativistic molecular dynamic model.

A relativistic time-dependent three-dimensional particle simulation model has been developed to study the interaction of intense ultrashort KrF (248 nm) laser pulses with small Xe clusters. The trajectories of the electrons and ions are treated classically according to the relativistic equation of motion. The model has been applied to a different regime of ultrahigh intensities extending to 10(21) W/ cm(2). In particular, the behavior of the interaction with the clusters from intensities of approximately 10(15) W/cm(2) to intensities sufficient for a transition to the so-called "collective oscillation model" has been explored. At peak intensities below 10(20) W/cm(2), all electrons are removed from the cluster and form a plasma. It is found that the "collective oscillation model" commences at intensities in excess of 10(20) W/cm(2), the range that can be reached in stable relativistic channels. At these high intensities, the magnetic field has a profound effect on the shape and trajectory of the electron cloud. Specifically, the electrons are accelerated to relativistic velocities with energies exceeding 1 MeV in the direction of laser propagation and the magnetic field distorts the shape of the electron cloud to give the form of a pancake.

Journal Article↗

Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis before and after therapy with the tumor necrosis factor alpha receptor fusion protein etanercept.

OBJECTIVE: To assess spinal inflammation by magnetic resonance imaging (MRI) before and after treatment with the tumor necrosis factor receptor fusion protein etanercept compared with placebo. METHODS: As part of a recently published randomized, controlled trial, 40 patients with ankylosing spondylitis (AS) underwent MRI of the lower thoracic and lumbar spine at 4 different time points: baseline, 12 weeks, 24 weeks, and 48 weeks. Nineteen patients received subcutaneous etanercept twice weekly (25 mg twice daily) for 1 year, and 21 patients received placebo for 6 months before being switched to etanercept. The mean age of the patients was 39.7 years, 75% were male, 89% were HLA-B27 positive, and the mean disease duration was 13 years. MRI examinations included T1-weighted sequences before and after application of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) and T2-weighted fat-saturated sequences. MRI sequences were scored with an adjusted AS spinal MRI score, using predefined vertebral units (VUs) as a basis. RESULTS: After 12 weeks, spinal inflammation (as assessed by T2-weighted MRI with fat saturation) regressed by 54% in the etanercept group (mean score 1.33 per VU at baseline and 0.61 per VU at 12 weeks; P = 0.002) but worsened by 13% in the placebo group (0.94 at baseline and 1.06 at 12 weeks) (P < 0.001 between groups). After switching to etanercept, placebo patients improved similarly. T1-weighted Gd-DTPA MRI sequences performed equally well in detecting spinal changes. At baseline, >50% of all active lesions were detected in the thoracic spine. Deterioration of chronic changes was significant only in patients treated with placebo. CONCLUSION: Etanercept treatment of patients with active AS results in regression of spinal inflammation as assessed by spinal MRI. Inclusion of the thoracic spine in MRI examinations of patients with AS may be of particular importance.

Adult↗

Karyometry in the early detection and chemoprevention of intraepithelial lesions.

The ideal chemopreventive agent targets pre-neoplastic changes and intraepithelial neoplasia, preventing progression over time without notable side effects. Assessment of success of chemopreventive intervention in the short and medium term remains a challenge, and in this review the suggestion is investigated that karyometric measurements constitute suitable markers of chemopreventive efficacy. Karyometry provides the sensitivity required to detect small differences amidst relatively high biological variability. It can help establish progression curves of intraepithelial neoplasia (IEN) to invasive cancer, and thus detect chemopreventive effects. Such effects can be observed in two ways, at the group level (intervention vs. placebo), and at the case (or patient) level. The latter is more difficult to establish, necessitating the development of specialised statistical methods. Analysis of between-case and within-case heterogeneity can reveal useful information about cancer progression and prevention. We suggest that karyometry can objectively quantify IEN progression, providing a framework for statistically securing chemopreventive effects. It can act as an integrating biomarker by detecting chemopreventive activity even when the mechanism for a given progression pathway is unknown, or when multiple pathways exist. The sensitivity of karyometric detection can help optimise the design of clinical trials of novel chemopreventive agents by decreasing trial duration and/or sample size.

Antineoplastic Agents↗

Soy protein influences insulin sensitivity and cardiovascular risk in male lean SHHF rats.

Previous investigations have demonstrated a marked effect of soy protein on multiple physiological parameters associated with the metabolic syndrome (MS). This preliminary study investigated the physiological effects of soy-based diets on cardiovascular risk in a unique rodent model that reflects early stages of MS. Briefly, lean male SHHF (+/cp) rats were randomly assigned to the following treatment groups: casein (control, C); low-isoflavone (LIS) soy protein isolate; high-isoflavone (HIS) soy protein isolate; or C+ 0.01 % rosiglitazone (CR). Rats were fed for thirty-six weeks. Liver weight, heart weight, total plasma cholesterol, fasting blood glucose were lower in soy-fed animals compared to control (p < 0.01). Body weight, kidney weight, alanine aminotransferase (ALT), fasting plasma insulin, and homeostasis model assessment (HOMA) score were also lower in LIS-fed rodents (p < 0.05) compared to casein treatment. All diet groups exhibited lower urine protein (p < 0.01) and small arteriole content (p < 0.05) compared to controls. LIS feed had a slightly more profound influence on body weight, liver metabolism, and insulin sensitivity. However, both soy diets exhibited marked improvements over a casein-based diet.

Animals↗

Soy protein influences the development of the metabolic syndrome in male obese ZDFxSHHF rats.

Previous investigations have demonstrated a marked effect of soy protein on the metabolic syndrome (MS). The purpose of this preliminary study was to identify the effects of soy-based diets on male obese ZDFxSHHF (fa/ fa-cp/?) rats. Animals were randomly assigned to one of four diets: control, casein (C); low-isoflavone (LIS) soy protein; high-isoflavone (HIS) soy protein; or casein + rosiglitazone (CR). Physiological, biochemical, and molecular parameters were determined at sacrifice. Body weight (p < 0.01) and food intake (p < 0.05) were lower in LIS-fed rodents. Rosiglitazone-treated animals had higher body weight and adiposity (p < 0.05). LIS and CR groups exhibited better glycemic control (p < 0.05), but with a limited effect in rosiglitazone-treated animals. HIS fed rats had higher glucose and triacylglyceride levels (p < 0.01), and lower plasma insulin (p < 0.01). Renal function parameters with the exception of an increase in systolic blood pressure (p < 0.05) were all suppressed in the LIS group (p < 0.01). The CR group had twofold PPARalpha and PPARgamma mRNA abundance (p < 0.01). LIS-fed animals also exhibited greater abundance of PPARgamma mRNA (p < 0.001), and nearly threefold FAS and CPT-1 mRNA levels (p < 0.05). HIS-fed rats also had higher abundance of CPT-1 mRNA, as well as a lower abundance of ACC mRNA (p < 0.05). Soy-based diets, influenced by isoflavone content and distinct from rosiglitazone, improved several metabolic parameters in obese ZDFxSHHF rats.

Animals↗

Optimization of power compression and stability of relativistic and ponderomotive self-channeling of 248 nm laser pulses in underdense plasmas.

The controlled formation in an underdense plasma of stable multi-PW relativistic micrometer-scale channels, which conduct a confined power at 248 nm exceeding 10(4) critical powers and establish a peak channel intensity of approximately 10(23) W/ cm(2) , can be achieved with the use of an appropriate gradient in the electron density in the initial launching phase of the confined propagation. This mode of channel formation optimizes both the power compression and the stability by smoothing the transition from the incident spatial profile to that associated with the lowest channel eigenmode, the dynamically robust structure that governs the confined propagation. A chief outcome is the ability to stably conduct coherent energy at fluences greater than 10(9) J/ cm(2) .

Journal Article↗

Lack of association of matrix metalloproteinase 3 (MMP3) genotypes with ankylosing spondylitis susceptibility and severity.

OBJECTIVE: To study the linkage and association of ankylosing spondylitis (AS) with genotypes for matrix metalloproteinase 3 (MMP3), a gene located at chromosome 11q22.3 and lying within the 101-124 cM region observed in a recent genome-wide scan as a region associated with AS susceptibility. METHODS: MMP3 genotypes were examined in 229 pedigrees with AS, 131 sporadic AS cases and 87 Caucasian controls. Eight single-nucleotide polymorphisms (SNPs) were selected and genotyped using Taqman. Non-parametric linkage (NPL) analysis was conducted between the eight MMP3 SNPs and AS using the NPL-all statistic and two-point parametric linkage analysis using GeneHunter Plus. Unrelated AS cases and controls were compared using chi2 statistics, and family-based controls using the transmission disequilibrium test and pedigree disequilibrium test. RESULTS: None of the eight MMP3 SNPs were significantly associated with AS, either using the 131 sporadic cases alone or in analyses which combined these cases with the 226 unrelated affected AS patients derived from the pedigrees. Analysis of linkage disequilibrium (LD) demonstrated that seven of the eight SNPs studied were in strong LD except for rs626750, which is about 6 kb upstream of the 5' end of the gene. No significant linkage was observed using NPL and LODs in the families. No association was seen of any of the MMP3 SNPs with disease severity (defined by patient functioning), as measured either by the Bath Ankylosing Spondylitis Functional Index or the modified Health Assessment Questionnaire. CONCLUSION: These data suggest that MMP3 genotypes are not involved in AS susceptibility or severity.

Adult↗

Spectroscopic diagnosis of nested-wire-array dynamics and interpenetration at 7 MA.

Nested-wire array experiments have been conducted at the 7 MA level with 150 ns implosion times from an outer diameter of 40 mm. Analysis of spectral data indicates that material from the outer array preferentially occupies the high temperature core of the stagnated pinch independent of the interwire gap in the range of 1.1 to 4.5 mm.

Journal Article↗

Efficient multi-keV X-ray sources from Ti-doped aerogel targets.

We have measured the production of hnu approximately 4.7 keV x rays from low-density Ti-doped aerogel (rho approximately 3 mg/cc) targets at the OMEGA laser facility (University of Rochester), with the goal of maximizing x-ray output. Forty OMEGA beams (lambda(L)=0.351 microm) illuminated the two cylindrical faces of the target with a total power that ranged from 7 to 14 TW. The laser fully ionizes the target (n(e)/n(crit)</=0.1), and a laser-bleaching wave excites, supersonically, the high-Z emitter ions in the sample. Ti K-shell x-ray emission was spectrally resolved with a two-channel crystal spectrometer and also with a set of filtered aluminum x-ray diodes; both instruments provide absolute measurement of the multi-keV x-ray emission. We find between 40 and 260 J of output with 4.67</=hnu</=5.0 keV.

Journal Article↗

Enhanced dizocilpine efficacy in heterozygous reeler mice relates to GABA turnover downregulation.

Reelin synthesized by cortical GABAergic interneurons throughout the telencephalon is secreted into the extracellular matrix (ECM) and binds with nM affinity to integrin receptors located at dendritic spine postsynaptic densities and positively modulates Arc and other dendritic resident mRNAs translation, thereby facilitating the onset of synaptic plasticity and LTP consolidation. Accordingly, the reelin haploinsufficient heterozygous reeler mice (HRM) express a marked decrease of cortical thickness, of cortical and hippocampal dendritic spine density, and of cortical GAD67 expression. Behaviorally, HRM manifest a sensorimotor deficit, an exaggerated response to fear, and a deficit in olfactory discrimination learning. HRM and wild-type mice (WTM) were trained to retrieve to criterion palatable chocolate-flavored food pellets in an eight-arm radial maze. In 9-14 days of training HRM and WTM learned the task equally well committing only a few errors. However, HRM, when compared with WTM, show a greater cognitive impairment following the administration of dizocilpine. Also, HRM are more susceptible to the increased locomotion and stereotypic behavior elicited by dizolcipine. The enhanced dizocilpine susceptibility of HRM is not due to differences in pharmacokinetics because the levels of dizocilpine in cortices of HRM and WTM were virtually equal. We also failed to detect differences between HRM and WTM in glutamate brain content and in the rate of 13C-glucose incorporation into the glutamate brain pools. In contrast we found that the conversion index of glutamate into GABA (an indirect measurement of GABA turnover rate) is decreased in cortex, hippocampus and striatum of HRM when compared to WTM. Thus, HRM recapitulate several neurochemical and behavioral endophenotypes reminiscent of schizophrenia and these mice can be proposed as a relevant animal model for the study of pharmacological treatments aimed at alleviating the sensory-motor and cognitive dysregulation associated with schizophrenia.

Animals↗

Concurrent ovarian-type primary peritoneal adenocarcinoma and peritoneal choriocarcinoma. A case report and review of the literature.

BACKGROUND: Nongestational choriocarcinomas are aggressive tumours occurring either as a global event or as a focal change in solid tumours. The latter is responsible for coexistence of trophoblastic histology with other malignancies. CASE: A 65-year old female with stage IV primary peritoneal carcinoma, ovarian type, underwent surgical cytoreduction followed by two courses of paclitaxel/carboplatin chemotherapy. A choriocarcinomatous component was later identified in the resection specimens, as chemotherapy resulted in a differential response of the two malignant variants. Commencement of EMA/CO chemotherapy (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) resulted in symptom palliation and tumour regression, further consolidated with platinum-based EP/EMA (etoposide, cisplatin, methotrexate, actinomycin D). Two months later, relentless choriocarcinomatous disease progression followed, leading to the patient's death while the peritoneal adenocarcinomatous variant remained biochemically quiescent. CONCLUSION: Choriocarcinomas may coexist with typical ovarian-type peritoneal cancer, creating diagnostic and therapeutic dilemmas. Aggressive weekly chorio-type chemotherapy appears to be warranted despite the low likelihood of cure, as it provides significant symptom palliation.

Adenocarcinoma↗

[Adenoviral vector expressing the TRAIL gene driven by the hTERT promoter].

BACKGROUND: Resistance can be overcome by modified adenoviral vectors containing an Arg-Gly-Asp (RGD) sequence. We constructed an adenoviral vector with RGD-modified fibers, expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter (designated Ad/TRAIL-F/RGD), and evaluated its antitumor activity in vitro and in vivo. METHODS: The induction of apoptosis by the new vector Ad/TRAIL-F/RGD was evaluated in human carcinoma cells derived from hepatocellular carcinoma (Hep G2, Hep 3b), pancreatic carcinoma (Panc-1, Capan-1), and colon carcinoma (LOVO, SW 620) . Cell viability was measured by the XTT assay and GFP expression and apoptosis induction by fluorescence-activated cell sorting (FACS) and Western blot. In vivo experiments were performed in an orthotopic pancreas tumor model in nu/nu nude mice. RESULTS: Treatment with Ad/TRAIL-F/RGD and Ad/gTRAIL resulted in significantly reduced cell viability in comparison to PBS and Ad/CMV-GFP treatment in all examined human carcinoma cell lines. In addition, mice treated with Ad/TRAIL-F/RGD showed a significantly decreased tumor growth than both control groups. CONCLUSIONS: Our results suggest that Ad/TRAIL-F/RGD may become a potent therapeutic agent for the treatment of different human solid carcinomas.

Adenoviruses, Human↗

CTLA4Ig: a novel inhibitor of costimulation.

T cell costimulatory pathways are believed to play important roles in the pathogenesis of various autoimmune diseases including systemic lupus erythematosus (SLE). Animal models of SLE support the role of T cell costimulation in B cell activation and the production of autoantibodies. CTLA4Ig is a novel fusion protein that interferes with T cell costimulation by inhibiting the CD28-B7 interaction. A pivotal study demonstrated the ability of CTLA4Ig to suppress the production of anti-dsDNA antibodies and decrease nephritis in lupus prone mice. In an additional study, the combination of CTLA4Ig and cyclophosphamide significantly reduced proteinuria and prolonged survival in mice with advanced nephritis. In small human studies of psoriasis and rheumatoid arthritis, CTLA4Ig improved clinical outcomes and was well tolerated. These promising experiences with CTLA4Ig have paved the way for future studies in human SLE.

Abatacept↗

The role of CD40 ligand in systemic lupus erythematosus.

CD40 ligand (CD40L, also known as CD154 or gp39) is a member of the tumor necrosis superfamily of transmembrane proteins. The interaction of CD40L on activated T cells with its receptor, CD40 on B cells, is necessary for normal immune function, including B cell differentiation, germinal center formation, and antibody isotype switching. Abnormal expression of CD40L in patients with systemic lupus erythematosus (SLE) may contribute to autoantibody production and disease pathogenesis. Although murine models of monoclonal antibodies directed against CD40L initially showed promise, human trials either have failed to demonstrate efficacy or have been associated with adverse events. This review will summarize in vitro and murine model data and human clinical trials involving anti-CD40L monoclonal antibody.

Animals↗