Biomedical subjects

Chris Bell

Publications and source records attributed to Chris Bell.

6 recordsLinked to original sources

PubMed2006

Concepts and possibilities in forensic intelligence.

Forensic intelligence can be viewed as comprising two parts, one directly concerning intelligence delivery in forensic casework, the other considering performance aspects of forensic work, loosely termed here as business intelligence. Forensic casework can be viewed as processes that produce an intelligence product useful to police investigations. Traditionally, forensic intelligence production has been confined to discipline-specific activity. This paper examines the concepts, processes and intelligence products delivered in forensic casework, the information repositories available from forensic examinations, and ways to produce within- and across-discipline casework correlations by using information technology to capitalise on the information sets available. Such analysis presents opportunities to improve forensic intelligence services as well as challenges for technical solutions to deliver appropriate data-mining capabilities for available information sets, such as digital photographs. Business intelligence refers primarily to examination of efficiency and effectiveness of forensic service delivery. This paper discusses measures of forensic activity and their relationship to crime outcomes as a measure of forensic effectiveness.

Data Collection↗

PubMed2006

Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and-effect relationship.

The functional relevance of autoantibodies (Abs) against cardiac myosin (CM) in clinical idiopathic dilated cardiomyopathy (DCM) remains controversial. The study sought to determine effects of human Abs affinity-purified (AF) by immunoaffinity column chromotography on excitation-contraction coupling in isolated myocytes. Effects of CM-Abs from heart failure patients with DCM (n=19) and ischemic heart disease (IHD, n=19) on contractility, L-type Ca2+ current, and Ca2+ transients in continuously perfused rat ventricular myocytes were studied. Immunofluorescence studies using confocal microscopy were carried out to determine whether Abs were internalized. AF-Abs from either group did not differ in IgG titer but differed in their elution profiles. The IgG3 subclass response was higher in AF fractions from DCM (21%) than IHD (5%) patients. The Abs reduced the capacity of field-stimulated myocytes to contract in a dose-dependent manner. Inhibition of contraction, as a percentage of untreated cells, was greater with DCM than IHD-Abs (P=0.004), and the effect was independent of Ab titer. An increase in frequency of the beating myocytes (0.2 to 3.0 Hz) raised peak systolic and diastolic levels of [Ca2+]i of cells treated with DCM but not IHD-Abs (P<0.005). The AF-Abs were not internalized by myocytes and had no effect on L-type Ca2+ currents. The altered sensitivity of the myofilaments to [Ca2+]i by CM-Abs may represent a potential mechanism of autoantibody-mediated impairment in clinical DCM.

Adult↗

PubMed2005

Inverse vs. forward breast IMRT planning.

Breast intensity-modulated radiation therapy (IMRT) improves dose distribution homogeneity within the whole breast. Previous publications report the use of inverse or forward dose optimization algorithms. Because the inverse technique is not widely available in commercial treatment planning systems, it is important to compare the 2 algorithms. The goal of this work is to compare them on a prospective cohort of 30 patients. Dose distributions were evaluated on differential dose-volume histograms using the volumes receiving more than 105% (V(105)) and 110% (V(110)) of the prescribed dose, and on the maximum dose (D(max)) or hot spot and the sagittal dose gradient (SDG) being the gradient between the dose on inframammary crease and the dose prescribed. The data were analyzed using Wilcoxon signed rank test. The inverse planning significantly improves the V(105) (mean value 9.7% vs. 14.5%, p=0.002), and the V(110) (mean value 1.4% vs. 3.2%, p=0.006). However, the SDG is not statistically significantly different for either algorithm. Looking at the potential impact on skin acute reaction, although there is a significant reduction of V(110) using an inverse algorithm, it is unlikely this 1.6% volume reduction will present a significant clinical advantage over a forward algorithm. Both algorithms are equivalent in removing the hot spots on the inframammary fold, where acute skin reactions occur more frequently using a conventional wedge technique. Based on these results, we recommend that both forward and inverse algorithms should be considered for breast IMRT planning.

Algorithms↗

PubMed2005

Plasmid-encoded regulator of extracellular proteases in Bacillus anthracis.

Bacillus anthracis Sterne cured of the pXO1 plasmid had enhanced secreted protease activity during the postexponential phase but no change in hemolytic or lecithinase activities. A zymogen profile revealed at least six proteases, including serine, metal, and perhaps cysteine types. There were similar amounts of protease secreted by the closely related species Bacillus cereus and Bacillus thuringiensis, but the patterns differed. Among the pXO1 plasmid-encoded proteins, there is a tetratricopeptide protein designated Cot43 that is related to the Rap proteins of Bacillus subtilis and the PlcR pleiotropic regulator of secreted enzymes and toxins in B. thuringiensis. A disruption of the cot43 gene resulted in overproduction of several proteases to a somewhat greater extent than in the plasmid-cured strain. Transformation of either of these strains with a clone of the cot43 gene resulted in the inhibition of accumulation of some of the proteases and induction of at least one. On the basis of lacZ fusions, transcription of the cot43 gene increased in late exponential cells at the time of protease accumulation. The expression of lacZ fusions to the upstream regions of two B. anthracis extracellular protease genes was greater in the strain with the disruption of cot43 than in the Sterne strain, indicating regulation at the level of transcription. In B. anthracis, a pXO1 plasmid-encoded protein directly modulates or indirectly regulates the transcription of genes for several chromosomally encoded extracellular proteases.

Bacillus anthracis↗

PubMed2004

Different domains of Pseudomonas aeruginosa exoenzyme S activate distinct TLRs.

Some bacterial products possess multiple immunomodulatory effects and thereby complex mechanisms of action. Exogenous administration of an important Pseudomonas aeruginosa virulence factor, exoenzyme S (ExoS) induces potent monocyte activation leading to the production of numerous proinflammatory cytokines and chemokines. However, ExoS is also injected directly into target cells, inducing cell death through its multiple effects on signaling pathways. This study addresses the mechanisms used by ExoS to induce monocyte activation. Exogenous administration resulted in specific internalization of ExoS via an actin-dependent mechanism. However, ExoS-mediated cellular activation was not inhibited if internalization was blocked, suggesting an alternate mechanism of activation. ExoS bound a saturable and specific receptor on the surface of monocytic cells. ExoS, LPS, and peptidoglycan were all able to induce tolerance and cross-tolerance to each other suggesting the involvement of a TLR in ExoS-recognition. ExoS activated monocytic cells via a myeloid differentiation Ag-88 pathway, using both TLR2 and the TLR4/MD-2/CD14 complex for cellular activation. Interestingly, the TLR2 activity was localized to the C-terminal domain of ExoS while the TLR4 activity was localized to the N-terminal domain. This study provides the first example of how different domains of the same molecule activate two TLRs, and also highlights the possible overlapping pathophysiological processes possessed by microbial toxins.

ADP Ribose Transferases↗

PubMed2002

Oxygen uptake kinetics for moderate exercise are speeded in older humans by prior heavy exercise.

This study examined the effect of heavy-intensity warm-up exercise on O(2) uptake (VO(2)) kinetics at the onset of moderate-intensity (80% ventilation threshold), constant-work rate exercise in eight older (65 +/- 2 yr) and seven younger adults (26 +/- 1 yr). Step increases in work rate from loadless cycling to moderate exercise (Mod(1)), heavy exercise, and moderate exercise (Mod(2)) were performed. Each exercise bout was 6 min in duration and separated by 6 min of loadless cycling. VO(2) kinetics were modeled from the onset of exercise by use of a two-component exponential model. Heart rate (HR) kinetics were modeled from the onset of exercise using a single exponential model. During Mod(1), the time constant (tau) for the predominant rise in VO(2) (tau VO(2)) was slower (P < 0.05) in the older adults (50 +/- 10 s) than in young adults (19 +/- 5 s). The older adults demonstrated a speeding (P < 0.05) of VO(2) kinetics when moderate-intensity exercise (Mod(2)) was preceded by high-intensity warm-up exercise (tau VO(2), 27 +/- 3 s), whereas young adults showed no speeding of VO(2) kinetics (tau VO(2), 17 +/- 3 s). In the older and younger adults, baseline HR preceding Mod(2) was elevated compared with Mod(1), but the tau for HR kinetics was slowed (P < 0.05) in Mod(2) only for the older adults. Prior heavy-intensity exercise in old, but not young, adults speeded VO(2) kinetics during Mod(2). Despite slowed HR kinetics in Mod(2) in the older adults, an elevated baseline HR before the onset of Mod(2) may have led to sufficient muscle perfusion and O(2) delivery. These results suggest that, when muscle blood flow and O(2) delivery are adequate, muscle O(2) consumption in both old and young adults is limited by intracellular processes within the exercising muscle.

Adult↗