A novel variant fibrinogen, deletion of B beta 111Ser in coiled-coil region, affecting fibrin lateral aggregation

ArticleCLINICA CHIMICA ACTA. 365(1-2): 160-167 (2006)journal articl

Sequential therapy of anti-Nogo-A antibody treatment and treadmill training leads to cumulative improvements after spinal cord injury in rats

Intense training is the most clinically successful treatment modality following incomplete spinal cord injuries (SCIs). With the advent of plasticity enhancing treatments, understanding how treatments might interact when delivered in combination becomes critical. Here, we investigated a rational approach to sequentially combine treadmill locomotor training with antibody mediated suppression of the fiber growth inhibitory protein Nogo-A. Following a large but incomplete thoracic lesion, rats were immediately treated with either anti-Nogo-A or control antibody (2 weeks) and then either left untrained or step-trained starting 3 weeks after injury for 8 weeks. It was found that sequentially combined therapy improved step consistency and reduced toe dragging and climbing errors, as seen with training and anti-Nogo-A individually. Animals with sequential therapy also adopted a more parallel paw position during bipedal walking and showed greater overall quadrupedal locomotor recovery than individual treatments. Histologically, sequential therapy induced the greatest corticospinal tract sprouting caudally into the lumbar region and increased the number of serotonergic synapses onto lumbar motoneurons. Increased primary afferent sprouting and synapse formation onto lumbar motoneurons observed with anti-Nogo-A antibody were reduced by training. Animals with sequential therapy also showed the highest reduction of lumbar interneuronal activity associated with walking (c-fos expression). No treatment effects for thermal nociception, mechanical allodynia, or lesion volume were observed. The results demonstrate that sequential administration of anti-Nogo-A antibody followed in time with intensive locomotor training leads to superior recovery of lost locomotor functions, which is probably mediated by changes in the interaction between descending sprouting and local segmental networks after SCI

Conveyance Test by Oscillation and Rotation to a Permanent Magnet Repulsive-Type Conveyor

Various applications of a single-axis controlled repulsive-type magnetic bearing have been proposed earlier. However, most conventional systems are equipped with a set of passive magnetic bearings and an active magnetic bearing. In this paper a new repulsive-type conveyor system with many passive magnetic bearing pairs is proposed. This system enables an easy rotation with negligible friction and soft conveyance by radial stiffness between the rotor and the stator permanent magnets. This paper also reports a conveyance test using ellipse motion of each shaft

High prevalence of multidrug-resistant Pneumococcal molecular epidemiology network clones among Streptococcus pneumoniae isolates from adult patients with community-acquired pneumonia in Japan

AbstractA total of 141 Streptococcus pneumoniae isolates from patients with community-acquired pneumonia were collected from May 2003 through October 2004. The strains were tested for antimicrobial agent susceptibility, serotype and genotype by multilocus sequence typing (MLST) and the presence of the pilus rlrA islet. MLST analysis identified 49 sequence types (STs), of which 19 were novel. eBURST analysis using the MLST database (3773 STs) grouped the isolates into 27 clonal complexes and three singletons. A total of 92 (65.2%) isolates were related to ten of the 43 international Pneumococcal Molecular Epidemiology Network (PMEN) clones; major clones found were multidrug-resistant Netherlands3-31 [clonal complex (CC) 180], Taiwan19F-14 (CC271), Taiwan23F-15 (CC242), and Colombia23F-26 (CC138) (the latter new to Asia). We adopted univariate and multiple logistic regression models to identify factors associated with PMEN CCs. Multivariate analysis showed that multidrug resistance (OR 6.3; 95% CI 2.0–22.9), carriage serogroups (OR 7.2; 95% CI 2.5–23.7), prevalence of rlrA (OR 12.6; 95% CI 3.6–59.7) and central nervous system-related disorders (OR 7.7; 95% CI 1.8–48.4) were independently associated with PMEN CCs. Our data indicate that multidrug-resistant PMEN clones are highly prevalent, contributing to the high frequency of resistance to antimicrobial agents in Japan, and suggest that certain predisposing factors in patients contribute to the high frequency of these clones

Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation.

Although fluoroquinolones or other antibiotics are commonly used to prevent bacterial infections after hematopoietic cell transplantation (HCT), because of the growing presence of multidrug-resistant microorganisms, it is important to identify patients who are more likely to benefit from antibacterial prophylaxis. To evaluate risk factors for early bacterial infection after allogeneic HCT, we retrospectively analyzed clinical data for 112 consecutive adult patients with hematological malignancies who received transplants without any antibacterial prophylaxis. The cumulative incidence of bacterial infection at 30 days after transplantation was 16%. Among various pre-transplant factors, only high serum ferritin (>700 ng/mL, 47 patients) and high C-reactive protein (CRP) (>0.3 mg/dL, 28 patients) levels were significantly associated with the development of bacterial infection in a multivariate analysis (hazard ratio (95% confidence interval): ferritin, 4.00 (1.32-12.17); CRP, 3.64 (1.44-9.20)). In addition, septic shock and sepsis with organ failure were exclusively observed in patients who had high ferritin and/or high CRP levels. These results suggest that pretransplant serum ferritin and CRP levels can be useful markers for predicting the risk of early bacterial infection after allogeneic HCT. It may be prudent to limit antibacterial prophylaxis to patients with predefined risk factors to ensure the safety of HCT with the use of fewer antibiotics

Training locomotor networks

For a complete adult spinal rat to regain some weight-bearing stepping capability, it appears that a sequence of specific proprioceptive inputs that are similar, but not identical, from step to step must be generated over repetitive step cycles. Furthermore, these cycles must include the activation of specific neural circuits that are intrinsic to the lumbosacral spinal cord segments. For these sensorimotor pathways to be effective in generating stepping, the spinal circuitry must be modulated to an appropriate excitability level. This level of modulation is sustained from supraspinal input in intact, but not spinal, rats. In a series of experiments with complete spinal rats, we have shown that an appropriate level of excitability of the spinal circuitry can be achieved using widely different means. For example, this modulation level can be acquired pharmacologically, via epidural electrical stimulation over specific lumbosacral spinal cord segments, and/or by use-dependent mechanisms such as step or stand training. Evidence as to how each of these treatments can “tune” the spinal circuitry to a “physiological state” that enables it to respond appropriately to proprioceptive input will be presented. We have found that each of these interventions can enable the proprioceptive input to actually control extensive details that define the dynamics of stepping over a range of speeds, loads, and directions. A series of experiments will be described that illustrate sensory control of stepping and standing after a spinal cord injury and the necessity for the “physiological state” of the spinal circuitry to be modulated within a critical window of excitability for this control to be manifested. The present findings have important consequences not only for our understanding of how the motor pattern for stepping is formed, but also for the design of rehabilitation intervention to restore lumbosacral circuit function in humans following a spinal cord injury

Refining rodent models of spinal cord injury.

This report was produced by an Expert Working Group (EWG) consisting of UK-based researchers, veterinarians and regulators of animal experiments with specialist knowledge of the use of animal models of spinal cord injury (SCI). It aims to facilitate the implementation of the Three Rs (Replacement, Reduction and Refinement), with an emphasis on refinement. Specific animal welfare issues were identified and discussed, and practical measures proposed, with the aim of reducing animal use and suffering, reducing experimental variability, and increasing translatability within this critically important research field

Macrophages fine-tune pupil shape during development

Tissue macrophages, which are ubiquitously present innate immune cells, play versatile roles in development and organogenesis. During development, macrophages prune transient or unnecessary synapses in neuronal development, and prune blood vessels in vascular development, facilitating appropriate tissue remodeling. In the present study, we identified that macrophages contributed to the development of pupillary morphology. Csf1op/op mutant mice, in which ocular macrophages are nearly absent, exhibited abnormal pupillary edges, with abnormal protrusions of excess iris tissue into the pupillary space. Macrophages located near the pupillary edge engulfed pigmented debris, which likely consisted of unnecessary iris protrusions that emerge during smoothening of the pupillary edge. Indeed, pupillary edge macrophages phenotypically possessed some features of M2 macrophages, consistent with robust tissue engulfment and remodeling activities. Interestingly, protruding irises in Csf1op/op mice were only detected in gaps between regressing blood vessels. Taken together, our findings uncovered a new role for ocular macrophages, demonstrating that this cell population is important for iris pruning during development

Genetic, Pathophysiological and Clinical Aspects of Nephrocalcinosis

Nephrocalcinosis describes the ectopic deposition of calcium salts in the kidney parenchyma. Nephrocalcinosis can result from a number of acquired causes, but also an even greater number of genetic diseases, predominantly renal, but also extra-renal. Here we provide a review of the genetic causes of nephrocalcinosis, along with putative mechanisms, illustrated by human and animal data