Real-time observation of integrin bending/unbending conformational changes on living cells

<正>Introduction Integrins are a large family of adhesion molecules broadly expressed on the surface of a wide variety of cells as heterodimers. Binding of integrins to ligands provides not only mechanical anchorage for the cell to another cell or extracellular     

TIME-DEPENDENT PLASTICIRY PRODUCED BY LTP OF C-FIBER EVOKED FIELD POTENTIALS IN SPINAL DORSAL HORN

<正> Aim: Hippocampal long-term potentiation (LTP), an activity-dependent plasticity in synaptic transmission, is believed as a fundamental mechanism of learning and memory. This form of plasticity also exists in spinal dorsal horn. Our previous work showed that electrical as well as natural noxious stimulation of afferent C-fibers or acute injury of the sciatic nerve produces LTP of C-fiber evoked field potentials in spinal dorsal horn.     

MECHANISMS OF CONTRALATERAL HEAT HYPERALGESIA INDUCED BY SUBCUTANEOUS INTRAPLANTAR BEE VENOM INJECTION IN RATS

<正> Aim: It has been found that subcutaneous intraplantar injection of bee venom (BV) unilaterally could produce contralateral heat hyperalgesia as well as primary heat and mechanical hyperalgesia in adult rats. The aim of the present study is to investigate: (1) whether contralateral heat hyperalgesia is a consequence of central sensitization, and whether, if it is the case, establishment of central sensitization is dependent upon a time     

AVP-independent high osmotic water permeability of frog urinary bladder and autacoids

 In the isolated frog urinary bladder a 20- to 50-fold increase of the osmotic water permeability has been revealed in the absence of arginine vasopressin (AVP) as a result of several successive changes of the serosal Ringer solution. This increase of the osmotic water permeability was of the same magnitude as that of the effect of 1 nM AVP. Similarly to the effect of AVP, the amount of adenosine 3′,5′-cyclic monophosphate (cAMP) in the cells rose, and aggregates of intramembraneous particles were formed in the apical plasma membrane of granular cells (as shown by the freeze-fracture method). Immunocytochemical studies using anti-actin monoclonal antibodies indicated depolymerization of F-actin following the AVP-independent change in water permeability. It was possible to decrease the high level of osmotic permeability to the initial level if 10 μl/ml of frog blood serum or a lipid extract of this blood serum, or 1 μM arachidonic acid or 1 nM prostaglandin E₂ was added to the serosal Ringer solution. The rapid restoration of the osmotic water impermeability of the epithelium after the AVP- evoked effect was achieved by the addition to the serosal Ringer solution of Ringer solution in which intact frog urinary bladders had been previously incubated for 1 h. The data obtained indicate that the maintenance of the impermeability to water of the osmoregulating epithelium and the restoration of the initial low level of the osmotic permeability after the effect of AVP are due to participation of prostaglandin E₂ and other autacoids as well as, probably, some physiologically active substances of a lipid nature that are present in the blood serum. Received: 5 December 1995 / Accepted 22 July 1996     

Design of Calibration Device for Pulse Oximeter Simulator

Saturation of peripheral oxygen （SpO2） is one of the most important parameters of vital signs. Pulse oximeter based on near-infrared spectroscopy is commonly used as a non-invasive method to measure SpO2 yl. Currently, medical device manufacturers as well as metrology measurement agencies in China usually use pulse oximeter simulator as the commonly accepted functional calibration equipment for pulse oximeters. So far, no experimental protocol or devices can be used to test the accuracy and reliability of a pulse oximeter simulator. Therefore, a set of new metrology apparatus with the name of calibration device for pulse oximeter simulator have been designed in order to make a traceable system for the calibration or verification of pulse oximeter simulators. The principles and some research methods of this calibration device for pulse oximeter simulator will be discussed in this paper. Besides that, many experiments have been applied in order to guarantee the accuracy as well as traceability of this set of device.     

Editorial commentary on the special issue of CRISPR Trends in Biomedical Research

In 2012,the laboratories of Drs.Emmanuelle Charpentier and Jennifer Doudna reported the repurposing of a bacterial adaptive immune system,known as CRISPR,as a programmable,RNA guided DNA editing system in eukaryotic cells.Over the next 12 months,a tsunami of research papers emerged demonstrating the facile utilization of this newfound genome editing platform in a variety of cell types and animal models.Since 2013.     

Effects of mesaconitine on [3H]noradrenaline uptake and neuronal excitability in rat hippocampus

Mesaconitine, one of the main alkaloids contained in Aconiti tubers, is a centrally acting analgesic without affinity to opioid receptors. It has been reported that the antinociception is due to an interaction with the noradrenergic system. In the present study, the effect of mesaconitine on the uptake of noradrenaline and on neuronal activity was examined in rat hippocampus. Experiments were performed as a tudy of [³H]noradrenaline uptake into rat hippocampal synaptosomes. Mesoconitine inhibited [³H]noradrenaline uptake in a concentration-dependent manner with a K _i of 111.95±18 nM. In a further series of experiments, the effects of mesaconitine on the extracellularly recorded population spike were investigated in rat hippocampal slices. At a concentration of 10 nM, mesaconitine increased the amplitude of the postsynaptic population spike by 31.10%±6.7% of control and elicited one or two additional spikes. The presynaptic fiber spike and the field excitatory postsynaptic potential were not affected by this alkaloid. The enhancement of neuronal activity was abolished by 1 μM propranolol as well as by 1 μM timolol. It is concluded that mesoconitine increased the excitability in rat hippocampal pyramidal cells by an involvement of the noradrenergic system, with at least one mechanism being inhibition of noradrenaline uptake leading to an enhanced extraneuronal noradrenaline level. Received: 25 August 1997 / Accepted: 3 March 1998     

Chemerin,a novel player in inflammatory bowel disease

Inflammatory bowel disease （IBD） manifests during Crohn＇s disease and ulcerative colitis as well as in a group of inflammatory disorders of the gastrointestinal tract.1 The etiology of IBD is thought to be a combination of genetics and environmental factors, including the microbiome and immune system of the individual.     

Expression of NMDA receptors in multipotent stromal cells of human adipose tissue under conditions of retinoic acid-induced differentiation

The system of NMDA glutamate receptors in human adipose tissue multipotent stromal cells and SH-SY5Y human neuroblastoma cells was used as a model for studies of NMDA receptor expression during neurodifferntiation. Glutamate NMDA receptors were detected in multipotent stromal cells of human adipose tissue. The expression of NR1 subunits of NMDA receptors increased significantly after 6-day incubation of multipotent stromal cells of human adipose tissue with 10 μM retinoic acid. Only NR1 subunits of NMDA receptors were expressed in SH-SY5Y neuroblastoma cells. Incubation with retinoic acid did not promote the appearance of mRNA of other subunits (NR2A-D, NR3). The results indicate that expression of NMDA receptors can serve as an indicator of neuronal differentiation of cells and as a marker of the efficiency of neuronal differentiation protocol. __________ Translated from Kletochnye Tehnologii v Biologii i Medicine, No. 4, pp. 216–220, October, 2007     

The development of a multichannel electrode array for retinal prostheses

The development of a multielectrode array is the key issue for retinal prostheses. We developed a 10 × 10 platinum electrode array that consists of an 8-μm polyimide layer sandwiched between 5-μm polymonochloro-para-xylylene (parylene-C) layers. Each electrode was formed as a 30-μm-high bump by Pt/Au double-layer electroplating. We estimated the charge delivery capability (CDC) of the electrode by measuring the CDCs of two-channel electrode arrays. The dimensions of each electrode of the two-channel array were the same as those of each electrode formed on the 10 × 10 array. The results suggest that for cathodic-first (CF) pulses, 80% of electrodes surpassed our development target of 318 μC/cm², which corresponds to the charge density of pulses of 500 μs duration and 200 μA amplitude for a 200-μm-diameter planar electrode.     

The overall role of a proficiency testing program

Proficiency testing programs provide many benefits to participant laboratories, functioning as an integral component of total quality control, as a vehicle for self-improvement, as a mechanism for continuing education, and as a fulfillment of regulatory requirements. Proficiency testing should not be utilized as the sole indicator of acceptable laboratory performance; unacceptable results should serve as a trigger for further inquiry and corrective action as indicated. A proficiency testing program should be a broad-based program covering the usual spectrum of laboratory disciplines without commercial bias and it should possess continuous scientific input so as to be capable of adjusting promptly to technologic advancements as well as maintaining established participant benefits. It is important that proficiency testing programs continue to develop mechanisms of mutual interchange with accreditational bodies and regulatory agencies.     

Regulation of sodium pump endocytosis by cardiotonic steroids: Molecular mechanisms and physiological implications

We have previously shown that ouabain and other cardiotonic steroids interact with the plasmalemmal Na/K-ATPase and cause a time and dose dependent endocytosis of the Na/K-ATPase. This endocytosis is demonstrable using fluorescence imaging as well as conventional biochemical and biophysical cell separation methods. In proximal tubule cells, this process appears to regulate the density of basolateral Na/K-ATPase expression directly as well as indirectly modulate transepithelial sodium transport.

Work with genetic manipulations, as well as pharmacological agents with cell culture models, have demonstrated that the cardiotonic steroid stimulated endocytosis of the plasmalemmal Na/K-ATPase requires caveolin and clathrin as well as the activation of c-Src, transactivation of the EGFR and activation of PI3K. Interestingly c-Src, EGFR and ERK1/2 all appear to be endocytosed along with the plasmalemmal Na/K-ATPase. These observations suggest a close analogy between a subset of plasmalemmal Na/K-ATPase and signaling companions with conventional receptor tyrosine kinases. While further studies are necessary to delineate the role of this endocytosis in the generation as well as the limit of signal transduction through the Na/K-ATPase signal cascade, we propose that it has an important role in the regulation of renal sodium handling as well as other important processes.     

Hospital as a temple

The present concept of hospital health care has exhausted its purpose. In a personal view as well as experience the idea "Hospital as a temple" was studied in an attempt to reconcile modern and technical with older form of health care, the latter often labelled as alternative or complementary. Both from a historical perspective as well as nowadays situation this vision is pursued.     

Antithrombin III. Theory and clinical applications. H. P. Smith Memorial Lecture.

Antithrombin III is one of the main inhibitors in the blood coagulation mechanisms. Thrombin and factor Xa are slowly inactivated by it, as well as other serine proteinases of the coagulation mechanisms. Heparin tremendously accelerates the inhibitory function of antithrombin III. In the process antithrombin III activity is also reduced. Heparin retards the thrombin-fibrinogen reaction, but otherwise the effectiveness of heparin as an anticoagulant depends on antithrombin III in laboratory experiments, as well as in therapeutics. The activation of prothrombin is inhibited, and any thrombin or other vulnerable protease that might generate becomes inactivated. The measurement of antithrombin III concentration in blood is now achieved by research methods, as well as by methods that are practical for routine use. The tests require either thrombin or factor Xa as substrate, and could be specific for antithrombin III. There are congenital as well as acquired deficiencies of antithrombin III. The inhibitor is also found in tissues.     

nPKCdelta a new therapeutic marker for melanoma metastasis? (Review)

Melanoma metastasis is almost uniformly fatal. The identification of signal transduction as crucial effectors for tumorigenesis suggests modalities of gene therapy as well as design of specific drugs. the possible use of nPKCdelta as a therapeutic target is reviewed and discussed. Motivated by recent results, we propose a model in which nPKCdelta modulates melanin synthesis as well as metastasis.     

Regulation of L-carnitine metabolism in Escherichia coli

The metabolization of L-carnitine was studied using whole cells of Escherichia coli 044 K74. It showed features of an epigenetical control. L-carnitine and crotonobetaine were able to induce the carnitine-reducing system. Oxygen and nitrate as electron acceptors, gamma-butyrobetaine as final product of carnitine transformation in E. coli as well as glucose repress the carnitine metabolization. Other betaines and structurally related compounds did not show any effect neither as inductors nor as repressors.     

A team effort: reply to Snyder and Elliott

This response to C.R. Snyder and T.R. Elliott's innovative proposals for training (this issue, pp. 1033-1054) highlights areas of agreement with the authors as well as encourages greater attention to several issues. These include counseling psychology and its historical emphasis on wellness, mentoring training for current faculty as well as graduate students, and appreciation for the diverse areas within psychology as well as within the broader social sciences (e.g., social work, marriage and family therapy) as contributors to such training.     

Hypothalamic modulation of baroreceptor afferent unit activity.

Unit responses to sinus nerve stimulation were recorded in the medulla. A conditioning stimulus to the posterior hypothalamus produced inhibition of 65% of unit responses to sinus nerve stimulation as early as 7 ms and extending as long as 790 ms after conditioning; 50% recovered after 300 ms. Unit responses to hypothalamic stimulation alone were also recorded in the medulla, some in the same loci as other unit responses to sinus nerve stimulation. They could be activated by contralateral as well as ipsilateral hypothalmic stimulation and showed recurrent bursts of firing over a 1,000-ms poststimulus interval. Evoked potentials and unit responses were recorded in the posterior hypothalamus, some occurring within 10--20 ms poststimulation of the sinus nerve, indicating that baroreceptor information is ascending in a time sufficiently short to involve the hypothalamus in reflex regulation of blood pressure as well as more generalized homeostatic responses which include the cardiovascular system.     

The genetics of osteoporosis: 'complexities and difficulties'

Osteoporosis is characterized by a decrease in bone mass as well as a deterioration of the bone architecture resulting in an increased risk of fracture. Although the disease is multifactorial, twin studies have shown that genetic factors account for up to 80% of the variance in bone mineral density, the best known predictor of the risk of osteoporosis. Some loci, such as the vitamin D and estrogen receptor genes, as well as the collagen type Ialpha1 locus, are promising genetic determinants of bone mass, and possibly other bone phenotypes, but this is controversial and the molecular basis of osteoporosis remains largely undefined. Considering that the effect of each candidate gene is expected to be modest, discrepancies between allelic association studies may have arisen because different populations carry different genetic backgrounds and exposure to environmental factors. Also, we realize the importance of gene-gene as well as gene-environment interactions as significant determinants of bone density and risk of osteoporosis. The use of new tools such as small nucleotide polymorphism maps now allows the possibility to perform allelic association studies in the context of whole-genome search. However, specific study design strategies in large epidemiological studies as well as the best statistical approach will need to be established. We may expect the development of population-specific at-risk profiles for osteoporosis that would include genetic and environmental factors, as well as their interactions. This should eventually lead to better prevention strategies and more adapted therapies against osteoporosis.     

Electron microscopic and immunohistochemical studies of gastrointestinal stromal tumors

Sixteen gastrointestinal stromal tumors (GISTs) were studied by immunohistochemical analysis and an ultrastructural procedure. The tumor locations were as follows: esophagus (2), stomach (7), small intestine (3), and large intestine (4). Four of the lesions were classified as malignant, 2 as borderline, and 10 as benign. On the basis of the immunohistochemical analysis, the tumors were classified as follows: 1 as myogenic type, 2 as Schwann cell type, 8 as Cajal cell type (including 2 gastrointestinal autonomic nerve tumors, GANTs), and 5 as mixed-cell type. In each subtype the phenotype was compared to the ultrastructural findings. Myogenic and Schwann cell type revealed ultrastructurally smooth muscle differentiation and schwannian tumor. All 8 tumors of the Cajal cell type revealed interdigitating cytoplasmic processes with occasional clusters of filopodia. Two tumors were subdivided as GANT. Five tumors of mixed-cell type were composed of a mixture of cells with variable myogenic features or variable neural differentiation. We confirmed in this study that immunohistochemical analysis reflected electron microscopic findings.