Complement receptor type two (CR2,CR21)

Cellular receptors for complement C3 fragments deposited on antigens are important bricks in the wall defending against microbial pathogens. The part of complement receptor type 2 (CR2; CD21) deals with enhancing humoral immune responses and with long-term trapping of C3d-coated antigen by follicular dendritic cells. CR2 is also pivotal for Epstein-Barr virus (EBV) infection. Here, the current understanding, how CR2 interacts with its ligands C3d, EBV, and CD23 is summarized. The potential to target CR2 for clinical therapy or immunization purposes are discussed.     

The use of detective quantum efficiency (DQE) in evaluating the performance of gamma camera systems

The imaging properties of an imaging system can be described by its detective quantum efficiency (DQE). Using the modulation transfer function calculated from measured line spread functions and the normalized noise power spectrum calculated from uniformity images, DQE was calculated with the number of photons emitted from a plane source as a measure for the incoming SNR2. Measurements were made with 99mTc, using three different pulse height windows at 2 cm and 12 cm depths in water with high resolution and all purpose collimators and with two different crystal thicknesses. The results indicated that at greater depths a 15% window is the best choice. The choice of collimator depends on the details in the organ being investigated. There is a break point at 0.5 cycles cm-1 and 1.2 cycles cm-1 at 12 cm and 2 cm depths, respectively. A difference was found in DQE between the two crystal thicknesses, with a slightly better result for the thick crystal for measurements at 12 cm depth. At 2 cm depth, the thinner crystal was slightly better for frequencies over 0.5 cm-1. The determination of DQE could be a method to optimize the parameters for different nuclear medicine investigations. The DQE could also be used in comparing different gamma camera systems with different collimators to obtain a figure of merit.     

Effects of x-ray spectra on the DQE of a computed radiography system

The effect of incident x-ray beam quality on the measured detective quantum efficiency (DQE) of a computed radiography system was investigated. The incident x-ray beams used had peak tube potentials of 70, 95, and 120 kVp, were filtered with various thicknesses of a "patient equivalent phantom" (PEP), aluminum, and copper, and provided a consistent exposure to the storage phosphor. For each peak tube potential and filter combination, the one-dimensional modulation transfer function and noise power spectrum were measured and the square of the incident signal-to-noise ratio was estimated. The spatial frequency dependent DQE was calculated from these data. The DQE was integrated to provide an overall estimate of the efficiency and frequency response of the computed radiography system for the various x-ray beams. There was found to be a wide range of integral DQE (IDQE) values for the peak tube potential and filter combinations used. For example, the IDQE ranged from 3.0 to 0.9 mm(-2) using the peak tube potential and filter combinations 70 kVp with 5.1 cm PEP and 120 kVp with 30.3 cm PEP, respectively. Finally, peak tube potential and filter combinations 70 kVp with 10.2 cm PEP and 120 kVp with 20.2 cm PEP were chosen as standard x-ray beams that will be used at our facility to measure the DQE of digital radiographic imaging systems for evaluation and acceptance testing.     

Expression of complement receptors type 1 (CR1) and type 3 (CR3) on circulating granulocytes in experimentally provoked asthma

Neutrophils demonstrate increased complement receptor activity, measured by rosetting of C3b-coated erythrocytes, after asthma that was provoked experimentally. However, it is not clear whether the increased rosetting is due simply to increase in receptor numbers or whether other factors, such as cell adhesiveness, are involved. We have therefore enumerated granulocyte complement receptors, after asthma provoked experimentally, with monoclonal antibodies against the receptors and flow cytometry. There was a maximal 28.2 +/- 7.5% and 33.4 +/- 9.5% (mean +/- SEM; n = 15) increase in granulocyte CR1 and CR3, respectively, at 3 hours after asthma induced by antigen. There was a maximal 32.0 +/- 7.3% (mean +/- SEM; n = 7) increase in granulocyte CR1, but no change in granulocyte CR3, at 1 hour after exercise-induced asthma. No significant changes in granulocyte CR1 or CR3 were observed up to 6 hours after methacholine challenge, or after exercise in subjects who did not develop exercise-induced asthma. There was a maximal 33 +/- 9% (mean +/- SEM; n = 8) increase in granulocyte CR1 at 30 minutes, but no increase in granulocyte CR3, after histamine challenge of subjects with asthma. Incubation of whole blood with histamine in vitro did not lead to any enhancement in expression of granulocyte CR1. This suggests that antigen- and exercise-induced release of histamine may augment granulocyte CR1 expression through an indirect mechanism. These data indicate that there is increase in the numerical expression of CR1 on granulocytes, after asthma provoked experimentally, which is accompanied by increases in granulocyte CR3 after bronchoprovocation with antigen, but not histamine or exercise.     

DQE analysis on a dual detector phase x-ray imaging system

This study presents the characterization results of a newly developed dual detector in-line phase x-ray imaging prototype. Comparison of modulation transfer function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE) for both detectors was conducted when they worked in the dual detection mode, in which two images are acquired simultaneously at a single exposure. The MTFs of the two detectors are almost identical, showing that the blurring caused by detector1 does not significantly weaken the resolving power of detector2. With a 40 kVp and 4 cm thick BR-12 phantom filtered x-ray beam, the transmittance of detector1 was measured to be 32%. The characteristic response and DQE of the two detectors almost coincide, showing that the two detectors have similar imaging performance under the imaging conditions of this study. The DQE of detector2 at the different source to detector distances (SID) also demonstrate a high level of agreement, implying that the reduced exposure level caused by elongated SID did not degrade the performance significantly. The study validated the design of the dual detection configuration for phase x-ray imaging, which has the potential for improving the accuracy of diagnostics at clinically acceptable radiation doses.     

DQE and eDQE of the KARS-BKS2 Digital Slot Scan X-Ray System

Biomedical Engineering - DQE and eDQE were evaluated for a slot scan X-ray system using four standard radiation qualities: RQA3, RQA5, RQA7, and RQA9. The results showed that the system under...     

The identification and evaluation of ATP binding cassette systems in the intracellular bacterium Francisella tularensis

Francisella tularensis is a facultative intracellular bacterium responsible for the disease tularemia. Analysis of the fully sequenced genome of the virulent F. tularensis strain SCHU S4 has led to the identification of twenty ATP binding cassette (ABC) systems, of which five appear to be non-functional. The fifteen complete systems comprise three importers, five exporters, four systems involved in non-transport processes, and three systems of unknown or ill-defined function. The number and classification of the ABC systems in F. tularensis is similar to that observed in other intracellular bacteria, indicating that some of these systems may be important for the intracellular lifestyle of these organisms. Among the ABC systems identified in the genome are systems that may be involved in the virulence of F. tularensis SCHU S4. Six ABC system proteins were evaluated as candidate vaccine antigens against tularemia, although none provided significant protection against F. tularensis. However, a greater understanding of these systems may lead to the development of countermeasures against F. tularensis.     

Complement receptor type two (CR2,CR21): a target for influencing the humoral immune response and antigen-trapping

Cellular receptors for complement C3 fragments deposited on antigens are important bricks in the wall defending against microbial pathogens. The part of complement receptor type 2 (CR2; CD21) deals with enhancing humoral immune responses and with long-term trapping of C3d-coated antigen by follicular dendritic cells. CR2 is also pivotal for Epstein-Barr virus (EBV) infection. Here, the current understanding, how CR2 interacts with its ligands C3d, EBV, and CD23 is summarized. The potential to target CR2 for clinical therapy or immunization purposes are discussed.     

Immune complexes and erythrocyte CR1 (complement receptor type 1): effect of CR1 numbers on binding and release reactions.

We performed experiments to investigate whether immune complexes opsonized with C3b and iC3b transferred from CR1 on one erythrocyte to CR1 on others, and studied the effect of variation in erythrocyte CR1 number on the transfer reaction. We used populations of cells of different blood groups to study this phenomenon which were separated by differential agglutination with monoclonal anti-group antibodies. The rate of transfer of immune complexes between erythrocytes was related to CR1 concentration of both donor and recipient cells; fastest transfer occurred from donor cells of low CR1 numbers to recipient cells of high CR1. These results were not explained by a difference in the binding constant of immune complexes to erythrocytes bearing different numbers of CR1. In the absence of factor I, complexes partitioned between erythrocytes according to their relative concentrations of CR1 with no release of complexes into solution. In serum, the proportion of complexes bound to donor and recipient erythrocytes was similarly related to their respective CR1 numbers with progressive release of complexes into solution. Erythrocyte CR1 may act as a dynamic buffering system which prevents immune complexes that have bound complement from fixing to vascular endothelium.     

Influence of minor thermal injury on expression of complement receptor CR3 on human neutrophils.

Thermal injury is well known to inhibit functions of the circulating neutrophil related to its role in host defense against infection, but the mechanism(s) of this phenomenon are not fully understood. To gain further clues to these mechanisms, the authors have studied patients with thermal injury in terms of altered expression of neutrophil cell membrane receptors for the opsonic complement-derived ligand C3bi--complement receptor Type 3, or CR3. CR3 expression was selected for study because an increase in the number of receptors on the cell surface can be stimulated by products of complement activation known to accumulate after thermal injury and because of the role of CR3 in phagocytic and adherence functions of the neutrophil. Expression of CR3 was monitored semiquantitatively by flow cytometry with the use of a murine monoclonal antibody (OKM1) specific for an antigen (CD11) associated with this receptor. Patients evaluated were limited in this study to those with minor degrees of thermal injury (second-degree burn involving less than 20% of total body surface area) so that possible confounding effects of major injury and its complications could be eliminated. It was observed that patient neutrophil CR3 becomes significantly up-regulated during the first week, as early as 1 day after injury. The maximum level of expression of CR3 averaged greater than 150% (range, 70-314%) of the respective minimum level observed for each patient. The minimum levels of expression of CR3 on patient neutrophils, reached 11-37 days after injury for 7 of 8 patients, were comparable to the level of expression of CR3 on unstimulated control neutrophils. Such temporal up-regulation of patient neutrophil CR3 suggests the early generation of stimuli of CR3 mobilization in response to thermal injury. Increased numbers of CR3 on patient neutrophils may augment microbicidal function and enhance or inhibit delivery of cells to the burn site.     

An association between ATP binding cassette systems, genome sizes and lifestyles of bacteria

Comparative bioinformatic analyses of ATP binding cassette (ABC) systems encoded in bacterial genomes have been undertaken in order to examine whether the range and distribution of these systems correlates with niches occupied by different organisms. In general, bacteria with larger genomes were found to encode more ABC systems than those with smaller genomes. Environmental bacteria, generally containing the largest genomes, showed the greatest number and diversity of ABC systems. Extracellular bacteria have larger genomes and show higher relative numbers of ABC transporters in comparison to intracellular bacteria. Similar results were obtained when comparing bacteria with different respiratory requirements since aerobic bacteria have larger genomes and also display greater numbers of ABC systems than anaerobes. These results suggest that the number of ABC systems encoded in bacterial genomes correlates with genome size and also with the physiological niche in which bacteria live. Furthermore, the distribution of the ABC systems into families indicates that the process of reductive evolution is responsible for retaining particular types of ABC systems as bacteria adapt to particular niches.     

4. Influence of classification systems on the treatment of leukemia

In this paper the influence of the newer aids to the classification of leukemia is considered in relation to the treatment of the disease.     

An image quality comparison of standard and dual-side read CR systems for pediatric radiology

An objective analysis of image quality parameters was performed for a computed radiography (CR) system using both standard single-side and prototype dual-side read plates. The pre-sampled modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) for the systems were determined at three different beam qualities representative of pediatric chest radiography, at an entrance detector air kerma of 5 microGy. The NPS and DQE measurements were realized under clinically relevant x-ray spectra for pediatric radiology, including x-ray scatter radiations. Compared to the standard single-side read system, the MTF for the dual-side read system is reduced, but this is offset by a significant decrease in image noise, resulting in a marked increase in DQE (+40%) in the low spatial frequency range. Thus, for the same image quality, the new technology permits the CR system to be used at a reduced dose level.     

Influence of lifestyle on the course of type 1 diabetes mellitus

Type 1 diabetes (T1DM) is an autoimmune disease that requires insulin treatment from the time of diagnosis. Its clinical course depends on both genetic and environmental factors, and the lifestyle of a patient modulates their interaction. The evidence about the influence of lifestyle on the course of T1DM is increasing. In this paper, we present evidence on the relationship between lifestyle parameters and diabetes-related outcomes. We discuss the most commonly addressed factors associated with lifestyle, such as physical activity, nutrition and smoking, and those with sparse evidence in T1DM, such as socioeconomic status, sleep duration, psychological stress and illicit drugs intake.     

CR1 and CR1-like: the primate immune adherence receptors

Immune adherence describes the phenomenon in which complement‐opsonized substrates, such as immune complexes (IC), viruses, or bacteria, are bound by primate erythrocytes via erythrocyte complement receptors. In vivo studies have shown that this binding allows the erythrocyte to act as an inert shuttle, targeting IC to the monocyte phagocytic system and away from vulnerable tissue. Thus, immune adherence appears to play an integral role in the primate in promoting the safe clearance of circulating IC and preventing IC‐mediated pathologies. The complement receptors that mediate immune adherence comprise two unique but closely related gene products, either the type one complement receptor (CR1) in humans or CR1‐like in non‐human primates. This review focuses on the structure, function, and physiological role of the primate immune adherence receptors.     

Influence of type 2 diabetes on the inflammatory response in rats

OBJECTIVES AND DESIGN: To verify whether the inflammatory responses in animals with type 2 diabetes are altered to an extent similar to that in type 1 diabetes. MATERIALS: Male newborn (2 days old) Wistar rats were made diabetic by streptozotocin (160 mg/kg, i.p.) and used 8-10 weeks later (10 rats/group). METHODS: The inflammatory responses were evaluated using paw edema (induced by local injection of carrageenan or dextran), pleurisy (by pleural injection of carrageenan), increases in vascular permeability (induced by intradermal injection of histamine, serotonin and bradykinin) and leukocyte counts in peripheral blood and pleural exudate. RESULTS: Diabetic animals showed reduced inflammatory responses to carrageenan but not to dextran. The increase in vascular permeability induced by serotonin and bradykinin was reduced whereas that to histamine was not altered in diabetic compared to control rats. Although the pleural exudate was reduced, leukocyte counts were similar in diabetic and control rats. Insulin (2 IU, 4 h before), though effective in reducing blood sugar levels, did not restore the altered responses in diabetic rats. In contrast to that in rats with type 1 diabetes, in rats with type 2 diabetes, removal of the adrenal glands restored the reduced inflammatory responses. CONCLUSIONS: Insulin resistance in type 2 diabetic rats led to reduced inflammatory responses, which were partially corrected by adrenalectomy.     

Differences between methicillin-resistant Staphylococcus aureus bacteremic isolates harboring type IV and type V staphylococcal cassette chromosome mec genes based on prior patient healthcare exposure

This observational study enrolled adult patients with bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) who were treated at the emergency department of a teaching hospital from 2001 to 2007. MRSA isolates with type IV and type V staphylococcal cassette chromosome mec (SCCmec) genes (SCC IV/V-MRSA) were included in the final analysis. Healthcare-associated SCC IV/V-MRSA (HA-SCC IV/V-MRSA) and community-acquired SCC IV/V-MRSA (CA-SCC IV/V-MRSA) were defined as the identification of an SCC IV/V-MRSA isolate from a patient with and without healthcare-associated risk factors, respectively. Thirty-four cases of CA-SCC IV/V-MRSA (20 SCCmec type IV, 14 SCCmec type V) and 81 cases of HA-SCC IV/V-MRSA (59 SCCmec type IV, 22 SCCmec type V) bacteremia were identified. Vascular device-associated infections were a significant infection source in HA-SCC IV/V-MRSA bacteremia cases. SCCmec type IV HA-SCC IV/V-MRSA isolates (3.4%) were significantly less likely to carry the Panton–Valentine leukocidin (PVL) gene than SCCmec type IV CA-SCC IV/V-MRSA isolates (35.0%, p = 0.001). The 90-day cumulative probability of survival was 76% for patients with CA-SCC IV/V-MRSA bacteremia and 66% for patients with HA-SCC IV/V-MRSA bacteremia (p = 0.247, by the Wilcoxon rank-sum test). Significant differences in antimicrobial susceptibility were observed between bacterial isolates from patients with CA-SCC IV/V-MRSA bacteremia and HA-SCC IV/V-MRSA bacteremia.