Initiation of the alternative pathway of complement and the history of “tickover”

The evolutionary history of complement suggests that the alternative pathway arose prior to the arrival of the classical and lectin pathways. In these pathways, target specificity is provided by antibodies and sugar specific lectins. While these efficient initiation systems dominate activation on most targets, the alternative pathway produces most of the C3b and 80%-90% of the C5b-9. While the tickover process, originally proposed by Peter Lachmann, provided ancient hosts with a crude self/non-self-discriminatory system that initiated complement attack on everything foreign, tickover clearly plays a more minor role in complement activation in modern organisms possessing classical and lectin pathways. Spontaneous activation of the alternative pathway via tickover may play a major role in human pathologies where tissue damage is complement-mediated. The molecular mechanism of tickover is still not convincingly proven. Prevailing hypotheses include (a) spontaneous hydrolysis of the thioester in C3 forming the C3b-like C3(H₂O) in solution and (b) “enhanced tickover” in which surfaces cause specific or non-specific contact activated conformational changes in C3. Theoretical considerations, including computer simulations, suggest that the latter mechanism is more likely and that more research needs to be devoted to understanding interactions between biological surfaces and C3.     

Effects of 17 days bedrest on the maximal voluntary isometric torque and neuromuscular activation of the plantar and dorsal flexors of the ankle

Maximal voluntary isometric torque values of the ankle plantar (T _im,_PF) and dorsal flexors (T _im,_DF) were assessed in eight healthy adult males at 5° and 15° of dorsal flexion (DF) and at 5°, 15° and 25° of plantar flexion (PF) with the knee at right angles, before (two times), during (three times) and after (three times) 17 days of 6° head-down tilt bedrest (BR). Integrated electromyograms (iEMG) were also recorded from the gastrocnemius medialis and tibialis anterior. T _im,_PF and the iEMG of the gastrocnemius medialis were significantly larger (by 14% and by 27%, respectively) at the end of recovery than before BR. This was probably the consequence of training and/or habituation leading to: (1) increased activation of the plantar flexors; and (2) decreased co-activation of the antagonist muscles. Neither T _im,_DF nor the tibialis anterior iEMG changed significantly. The effects of BR on muscle performance were evaluated as follows. The net torque generated by a given muscle group was assumed to be the algebraic sum of the torque generated by the agonists and by the antagonists. Thus, for the plantar flexors T_im,PF=αiEMG_Gm − βiEMG_Ta, where: (1) iEMG_Gm and iEMG_Ta are the iEMGs of gastrocnemius medialis and of tibialis anterior during maximal PF; and (2) the constants α and β represent the electromechanical coupling of the plantar (α) and dorsal (β) flexors. Similarly for the dorsal flexors: T_im,DF=βiEMG_Ta − αiEMG_Gm, where iEMG_Ta and iEMG_Gm are the iEMGs of tibialis anterior and gastrocnemius medialis during maximal DF. Torque and iEMG values were assessed for all subjects under all experimental conditions. Thus, since the biomechanical leverage of the system was constant, α and β could be calculated. During BR, α decreased by 25% and it dropped by a further 30% during recovery. In contrast, β remained almost unchanged. This suggests that, in spite of training and/or habituation, BR significantly impaired the maximal isometric performance of the plantar flexors, an effect that continued during the initial 10 days of recovery. Accepted: 4 February 2000     

Comparative Study of the Characteristics of the P300 Wave and the Event-Related θ Rhythm in Schizophrenia and Personality Disorders

Neuroscience and Behavioral Physiology - Objectives. The amplitude and latency of the P300 wave are regarded as basic neurophysiological correlates in studies of cognitive functions. The...     

Recommendations for the classification and nomenclature of the DNA-β satellites of begomoviruses

The symptom-modulating, single-stranded DNA satellites (known as DNA-β) associated with begomoviruses (family Geminiviridae) have proven to be widespread and important components of a large number of plant diseases across the Old World. Since they were first identified in 2000, over 260 full-length sequences (∼1,360 nucleotides) have been deposited with databases, and this number increases daily. This has highlighted the need for a standardised, concise and unambiguous nomenclature for these components, as well as a meaningful and robust classification system. Pairwise comparisons of all available full-length DNA-β sequences indicate that the minimum numbers of pairs occur at a sequence identity of 78%, which we propose as the species demarcation threshold for a distinct DNA-β. This threshold value divides the presently known DNA-β sequences into 51 distinct satellite species. In addition, we propose a naming convention for the satellites that is based upon the system already in use for geminiviruses. This maintains, whenever possible, the association with the helper begomovirus, the disease symptoms and the host plant and provides a logical and consistent system for referring to already recognised and newly identified satellites.     

Continuous remote monitoring of COPD patients—justification and explanation of the requirements and a survey of the available technologies

Remote patient monitoring should reduce mortality rates, improve care, and reduce costs. We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers. Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field. We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain. Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO₂) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients. We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise. We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters. The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems.

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Evaluation of the combination of the NucliSENS easyMAG® and the EasyQ® applications for the detection of Mycoplasma pneumoniae and Chlamydia pneumoniae in respiratory tract specimens

Mycoplasma pneumoniae and Chlamydia pneumoniae are respiratory tract pathogens frequently involved in community-acquired pneumonia, but are fastidious microorganisms. Their direct detection mainly requires molecular amplification techniques. A nucleic acid extraction system, NucliSENS easyMAG®, and a real-time nucleic acid sequence-based amplification (NASBA) technique, NucliSENS EasyQ®, were recently developed by bioMérieux to detect both bacteria. The aim of our study was to compare the easyMAG/EasyQ combination with our in-house combination, MagNA Pure extraction (Roche) and real-time polymerase chain reaction (PCR), to detect both bacteria in respiratory tract specimens. The analytical specificities of both combinations were similar. A higher analytical sensitivity was found for C. pneumoniae using the easyMAG/EasyQ combination, since the easyMAG/EasyQ system detected nucleic acid extracts 10⁶ times more diluted than the in-house combination. Both combinations were equivalent when detecting M. pneumoniae in positive respiratory tract samples. Finally, the easyMAG/EasyQ combination is a potential useful tool for the detection of both bacteria regarding sensitivity, specificity, monitoring, and standardization of the procedure.     

Racial and ethnic harassment and discrimination: in the eye of the beholder?

The nature, rate, and higher-order relationships among facets of racial/ethnic harassment (REH) and discrimination (RED) were examined across five racial/ethnic groups in a sample of 5,000 US military personnel. Using a hierarchical, multigroup confirmatory factor analysis approach, results suggest that the nature of REH and RED do not differ by race, with behavioral items equally representing REH and RED across the different groups. Further, higher-order relationships among the facets of REH and RED do not vary across race, with a single second-order factor accounting for the relationships. This single factor is theorized to represent a root intergroup prejudice that leads to harassment and discrimination. However, as anticipated, individuals from minority groups generally reported higher levels of REH and RED once measurement equivalence has been established. Together, the results suggest that both intergroup prejudice (which is multidirectional) and racism (which originates in powerful groups against other groups) are operating in REH and RED experiences.     

Observation of the effect of cleaning the smear layer and tubule plugs with SEM

The smear layeris membrane-like substance,which adhere to the prepared cavity enamel ofsurface of the dentin tightly and could only be cleaned by special drugs.As wish to not onlycom pletely clean the smear layer,but also reduce the stimulation to the pulp tissure,we mustclean the enam el and the smearlayer,m eanwhile,reserve the partial tubule plugs.In thisexperiment,we applied the study observing the cleanup of surface smear layer of dental cariesand the tubule plugs reserving effect after u…     

The effect of ACTH on the development of the athüs phenomenon and on the morphological composition of the inflammatory exudate

Summary Arthüs phenomenon was induced in 42 rabbits by the classical method. ACTH (10–20 units) was injected into 33 of them before the injection of the booster dose of horse serum, as well as beginning from the 3rd–4th administration of sensitizing doses. In the majority of experiments Arthüs phenomenon did not develop at all, or was much weaker than in control animals.The second group of experiments dealt with the cellular composition of the exudate in rats in experimental aseptic peritonitis caused by injecting sterile broth into the peritoneal cavity. Experimental results demonstrated that in animals which received ACTH (2.5 units) prior to broth injection the exudate was of thicker consistency and its cellular composition differed from control. Neutrophil percentage was much lower and lymphocytic phase occurred much earlier.The data obtained indicates the effect of ACTH both on the manifestation of allergic inflammation and on the exudative reaction during usual inflammation.(Presented by Active Member AMN SSSR P. S. Kupalov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 55, No. 5, pp. 51–53, May, 1963     

Expression and Localization of α-amylase in the Submandibular and Sublingual Glands of Mice

In the major salivary glands of mice, acinar cells in the parotid gland (PG) are known to be the main site for the production of the digestive enzyme α-amylase, whereas α-amylase production in the submandibular gland (SMG) and sublingual gland (SLG), as well as the cell types responsible for α-amylase production, has been less firmly established. To clarify this issue, we examined the expression and localization of both the mRNA and protein of α-amylase in the major salivary glands of male and female mice by quantitative and histochemical methods. α-amylase mRNA levels were higher in the order of PG, SMG, and SLG. No sexual difference was observed in α-amylase mRNA levels in the PG and SLG, whereas α-amylase mRNA levels in the female SMG were approximately 30% those in the male SMG. Using in situ hybridization and immunohistochemistry, signals for α-amylase mRNA and protein were found to be strongly positive in acinar cells of the PG, serous demilune cells of the SLG, and granular convoluted tubule (GCT) cells of the male SMG, weakly positive in seromucous acinar cells of the male and female SMG, and negative in mucous acinar cells of the SLG. These results clarified that α-amylase is produced mainly by GCT cells and partly by acinar cells in the SMG, whereas it is produced exclusively by serous demilune cells in the SLG of mice.     

Chemotherapy of Chagas’ disease: the how and the why

Current developments in experimental chemotherapy of Chagas’ disease are reviewed, in particular the demonstration that fourth-generation azole derivatives (inhibitors of sterol C14α demethylase), with particular selectivity against Trypanosoma cruzi and special pharmacokinetic properties, are capable of inducing radical parasitological cures in murine models of both acute and chronic disease. These are the first reports of parasitological cure of this disease in its chronic phase. We also discuss the relevance of etiological treatment in the clinical outcome of patients with chronic Chagas’ disease. Although previous studies have suggested an important autoimmune component in the pathogenesis of this disease, recent results obtained using highly sensitive polymerase chain reaction based detection methods and detailed immunological characterization of the inflammatory process associated with chagasic cardiomyopathy indicate a positive correlation between tissue parasitism and the severity of cardiac pathological findings. Effective antiparasitic treatment can lead to regression of the inflammatory heart lesions and fibrosis in experimental animals and to stop the progression of the disease in humans. Taken together, these findings support the notion that the presence of the parasite is a necessary and sufficient condition for chagasic cardiomyopathy and confirm the importance of specific etiological treatment in the management of chronic chagasic patients. Received: 30 March 1998 / Accepted: 6 November 1998     

Evaluation of the CELL-DYN® 3500 haematology instrument for the analysis of the mouse and rat blood

The objective of this study was to evaluate the performance of the CELL-DYN^® 3500 for rat and mouse blood analysis in a routine environment. The WBC (white blood cells), RBC (red blood cells), PLT (platelets) counts and the WBC differential were determined. In addition, the following aspects were studied: within-run precision, day-to-day precision, biasfree paired difference precision; extended ranges of linearity for RBC, HCT (haematocrit), WBC, PLT; carry-over, the fffect of blood ageing, cell stability with different anticoagulants; and the normal ranges, the out of range flagging and some typical pathology cases. The CELL-DYN^® 3500 is a multiparameter flow cytometer which counts and differentiates WBC, based on the principle of multi-angle polarised light scatter separation. RBC and PLT are determined by the impedance method. The WBC count is evaluated by both, optical and impedance methods. Reference methods used were according to the ICSH recommendations on blood cell analysis, including manual counts of WBC and platelets, a centrifugal microhaematocrit method and a haemoglobin measurement by spectrophotometry using the WHO haemoglobin standard. All cell counts were compared with the results obtained by our routine blood cell analyser (Contraves AL820), and the WBC differential was compared with the manual microscopic differentiation of the 400 WBC (200 cells differentiated by two technicians). The following coefficients of variation were obtained: within-run precision was 1.2% and 2.7% for WBC; 1.0% and 1.0% for RBC; 1.3% and 0.9% for haematocrit; 2.1% and 2.7% for platelets (rats and mice respectively). Day-to-day precision was performed using human trilevel control blood, and the CVs were found to be <1.7% for WBC, <1.4% for RBC, <1.2% for haemoglobin and <6.3% for platelets. The following ranges of measurement were found to be linear in the rat: WBC: 0.10–20.20×10³/μl; RBC: 0.016–14.3×10⁶/μl; haemoglobin: 0.08–26.8 g/dl; haematocrit: 5.0%–77%; platelets: 14.0–1670.0×10³/μl. Equal ranges were observed for mouse blood. Carry-over in rat blood was found to be 0.12% for WBC, 0.05% for RBC, 0.15% for haemoglobin and 0.46% for platelets. In mice, similar carry-over results were obtained. The correlation coefficients (Pearson, correlation coefficient) between the CELL-DYN^® 3500 and Contraves AL 820 using linear regression analysis were as follows: 0.988 and 0.997 for WBC; 0.986 and 0.920 for RBC; 0.995 and 0.984 for haemoglobin; 0.958 and 0.85 for haematocrit; 0.958 and 0.963 for platelets, for rats and mice, respectively. Correlation coefficients between the CELL-DYN^® 3500 and the manual differential of NEU (neutrophils) and LYM (lymphocytes) were higher than 0.8 in rats and higher than 0.9 in mice. Due to the relatively low absolute counts of MONO (monocytes), EOS (eosinophils) and BASO (basophils), only moderate correlation of methods was found. The CELL-DYN^® 3500 was judged to be reliable, accurate and easy-to-use for counting and identifying normal and most of the pathological blood specimens obtained from mice and rats. By using the CELL-DYN^® 3500, the time for blood sample analysis can be shortened significantly and provides extensive opportunities to characterise pathological samples.     

Disconnection of man and the soil: reason for the asthma and atopy epidemic?

Intense search has been going on to find factors responsible for the asthma and atopy epidemic in Western societies. Attention has increasingly been devoted to environmental saprophytes, which, in addition to gut commensals, might be the major players in the development and fine tuning of immunologic homeostasis. This review outlines current evidence for the role of environmental saprophytes in the development of atopic disease and considers the consequences of urbanization in reducing contacts with soil microorganisms. The major microbial components that have been shown to possess immunomodulatory capacity and their respective Toll-like receptors are also discussed, as are the possible mechanisms underlying the ability of saprophytes to confer protection against atopic disease.     

Understanding the influence of MgO and SrO binary doping on the mechanical and biological properties of β-TCP ceramics

The objective of this study was to evaluate the influence of MgO and SrO doping on the mechanical and biological properties of β-tricalcium phosphate (β-TCP). β-TCP was doped with two different binary compositions, 0.25 and 1.0 wt.% SrO along with 1.0 wt.% MgO. MgO and SrO doping increased the β phase stability at a sintering temperature of 1250 °C and marginally decreased the compressive strength of β-TCP. An in vitro cell–material interaction study, using human fetal osteoblast cells (hFOB), indicated that doped β-TCP was non-toxic, and MgO/SrO dopants improved cell attachment and growth. β-TCP implants doped with 1.0 wt.% MgO and 1.0 wt.% SrO showed good in vivo biocompatibility when tested in male Sprague–Dawley rats for 16 weeks. Histomorphology analysis indicated that MgO/SrO-doped β-TCP promoted more osteogenesis than pure β-TCP. In vivo osteocalcin and type I collagen assay also revealed faster bone formation in rats with doped β-TCP implant compared to rats with pure β-TCP implant. Low Ca²⁺ concentration in the urine of rats with doped β-TCP implant confirmed slower degradation of MgO/SrO-doped β-TCP than pure β-TCP.