Haruyuki Minamitani

Platelet and leukocyte adhesion in the microvasculature at the cerebral surface immediately after subarachnoid hemorrhage.

OBJECTIVEPathophysiology after subarachnoid hemorrhage (SAH) caused by aneurysmal rupture has not been well examined. The purpose of this study was to observe platelet-leukocyte-endothelial cell interactions as indexes of inflammatory and prothrombogenic responses in the acute phase of SAH, using an in vivo cranial window method. METHODSSubarachnoid hemorrhage was induced in C57Bl/6J mice by using the endovascular perforation method. Intravital microscopy was used to monitor the rolling and adhesion of platelets and leukocytes that were labeled with different fluorochromes. Regional cerebral blood flow was measured with laser Doppler flowmetry. The platelet-leukocyte-endothelial cell interactions were observed 30 minutes, 2 hours, and 8 hours after SAH. The effect of P-selectin antibody and apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, on these responses was examined at 2 hours after SAH, and compared with a different SAH model in which autologous blood was injected into the foramen magna. RESULTSSAH was accompanied by a 60% decrease in regional cerebral blood flow, whereas no changes in regional cerebral blood flow were observed on the contralateral side. SAH elicited time- and size-dependent increases in rolling and adherent platelets and leukocytes in cerebral venules. All of these interactions were attenuated by treatment with a P-selectin antibody or apocynin. There was no significant blood cell recruitment observed in the blood-injected SAH model. CONCLUSIONSAH at the skull base induced P-selectin- and oxygen radical-mediated platelet-leukocyte-endothelial cell interactions in venules at the cerebral surface. These early inflammatory and prothrombogenic responses may cause a whole-brain injury immediately after SAH.

Development of catheter-type optical oxygen sensor and applications to bioinstrumentation

A catheter-type optical oxygen sensor based on phosphorescence lifetime was developed for medical and animal experimental use. Since the sensor probe should have biocompatibility and high oxygen permeability in vivo, we focused attention on acceptable polymer materials for contact lenses as the substrates of probes. Pd-porphyrin was doped in silicone-based polymer, and was fixed at the edge of an optical fiber inserted in a catheter tube. The shape of the probe was 600 microm in diameter and 100 microm in thickness, and the probe had high oxygen permeability of Dk value 455. In accuracy evaluation, there found an excellent correlation between the pO2 values measured through phosphorescence lifetime using the oxygen sensors and those measured as the calibrating data using oxygen electrodes. The response time required to achieve 90% from reversible default value to be from 150 to 0 mmHg, and from 0 to 150 mmHg was 15.43 and 7.52 s, respectively. In addition, other properties such as temperature and pH dependency, response, and durability of our optical oxygen sensor were investigated. In animal experiments, the catheter-type oxygen sensor was inserted via the femoral artery of a rat, and arterial oxygen pressure was monitored under asphyxiation. The sensor was valid in the range of oxygen concentration sufficient for biometry, and expected to be integrated with an indwelling needle.

A modified back-propagation method to avoid false local minima

The back-propagation method encounters two problems in practice, i.e., slow learning progress and convergence to a false local minimum. The present study addresses the latter problem and proposes a modified back-propagation method. The basic idea of the method is to keep the sigmoid derivative relatively large while some of the error signals are large. For this purpose, each connecting weight in a network is multiplied by a factor in the range of (0,1], at a constant interval during a learning process. Results of numerical experiments substantiate the validity of the method.

Human standing posture control system depending on adopted strategies

Control of the standing posture of humans involves at least two distinct modes of operation to restore the body balance in the sagittal plane: the ankle strategy and the hip strategy. The objective of the study was to estimate the contribution of vestibular, visual and somatosensory feedbacks to these distinct strategies. The body dynamics was described as the motion of two linked rigid segments that represented the legs and the rest of the body. The posture controller received the inclination angles of the two body segments as inputs and regulated the moments around the ankle and hip joints. The controller had four feedback paths that were characterised by transfer functions connecting the two inputs and the two outputs. To evoke the distinct strategies, the floor conditions were varied by narrowing the support surface under the feet. A continuous pseudo-random external disturbing force was applied to the waist and the thigh independently. The inclination angles of the body segments and the ground reaction force were measured, and the transfer functions of the controller were estimated with the maximum-likelihood system identification procedure. Six healthy male adult subjects participated in the experiment. When the hip strategy became evident under the narrow support surface conditions, the transfer function relating the leg inclination angle and the ankle joint moment decreased its DC gain (16%), whereas the other three transfer functions increased the gains (20–140%) (ANOVA, p<0.05). Based on a criterion for simplicity in the modification of the posture controller, these changes suggest a new hypothesis that, when posture control becomes difficult, the central nervous system selectively activates the somatosensory feedback paths from the hip joint angle to the moments around the ankle and hip joints.

Characteristics of somatosensory feedback in postural control during standing

In the present study, the function of the somatosensory feedback system in postural control was investigated. For the sake of simplicity the present study considered only balancing in the anteroposterior direction using the ankle strategy, in which the ankle moment is mainly used to maintain balance. To suppress the vestibular and visual feedback paths, a subject stood on a force-measuring platform with a fixed back support. Because the subjects body was immovable under these conditions, the subject controlled a computer model that simulated the subjects load at the ankles, Information about the sway angle of the model was fed through the somatosensory feedback path. Frequency response functions of the ankle moment in response to the sway angle were calculated. The experimental results suggest that the human somatosensory feedback system has derivative characteristics and, consequently, can maintain an upright posture by itself. The results were compared with those of previous studies on vestibular and visual feedback systems. The comparison reveals that subject-to-subject variance in the somatosensory system is significantly smaller than that in the other systems. This may indicate that the somatosensory feedback is the most automatic of the systems and plays a dominant role when a subject maintains an upright posture using the ankle strategy.

Sensitivity analysis of a thin-film optical waveguide biochemical sensor using evanescent field absorption

A multichannel thin-film optical waveguide sensor for determining aqueous biochemical concentration with a high dynamic range of measurement is proposed. The sensitivity dependence of the proposed sensor on interaction length and waveguide thickness is investigated for dye solutions and three different hemoglobin concentration levels of carboxyhemoglobins. The sensitivity is inversely proportional to the waveguide thickness while proportional to the interaction length. As a consequence the variability of the interaction length makes the proposed sensor a flexible tool for concentration measurements. Moreover, an efficient method for determining the absorption coefficient is discussed.

Re-evaluation of tropicamide in the pupillary response test for Alzheimer’s disease

In 1994, a pupillary response test using very dilute (0.01%) tropicamide, a cholinergic antagonist, evoked remarkable pupil dilation in subjects with Alzheimers disease (AD) and has since been considered a diagnostic tool for AD. However, since this test was first reported, there have been studies suggesting it cannot provide a differential diagnosis of AD. Thus, the present study re-evaluated the pupillary dilation of AD (n=17) and non-AD (n=20) subjects at a 0.01% concentration of tropicamide and found that non-AD subjects, including young subjects, showed the same extent of pupil dilation as AD subjects. Furthermore, there was no significant difference between the average dilation rate of the two groups (P>0.05). When the tropicamide concentration was diluted to half of the initial concentration and performed for AD (n=14), vascular dementia (VD) (n=14), and young (n=16) subjects, the AD subjects showed a large dilation (mean pupil dilation rate: 133.8+/-15%) while the non-AD subjects did not show hypersensitivity to the new concentration of eye drops (105.4+/-9%). These differences in pupillary dilation between AD and non-AD patients were statistically significant (P<0.001). Based on these results, the most effective cutoff point of 0.005% tropicamide for differential diagnosis was 114.5% of the average pupil dilation rate for 60 min.

Direct activation of glomerular endothelial cells by anti-moesin activity of anti-myeloperoxidase antibody

BACKGROUND Glomerular neutrophil infiltration has been thought to be a key pathological event in the development of myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis involving glomerulonephritis. Accordingly, we sought to explore the molecules responsible for glomerular neutrophil accumulation. METHODS Glomerular neutrophil infiltration and renal chemokine expression in mice treated with anti-MPO IgG were evaluated. Chemokine expression in vitro induced by anti-MPO IgG was measured in the primary mouse glomerular endothelial cells (mGEC). The target molecule reacted with anti-MPO IgG on the mGEC was determined by peptide mass fingerprint analysis. RESULTS A significant glomerular neutrophil infiltration was observed in the mice administered with anti-MPO IgG. The expressions of CXC chemokines, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2), were significantly increased in the renal cortex, indicating that these chemokines contribute to the neutrophil infiltration. Based on the previous findings of upregulation of adhesion molecule expression in mGEC treated with anti-MPO IgG, we examined whether mGEC secrete these chemokines in response to anti-MPO IgG. Indeed, anti-MPO IgG induced secretion of KC and MIP-2, leading to neutrophil chemotaxis in vitro. Furthermore, complete depletion of MPO in mGEC and serum using MPO-deficient mice showed an upregulation of intercellular adhesion molecule-1, indicating cross-reactive molecule(s) were existing on mGEC. We identified the molecule as moesin by a proteomic approach. CONCLUSIONS The endothelial CXC chemokines, KC and MIP-2, contribute to infiltration of neutrophils in MPO-ANCA-associated vasculitis involving glomerulonephritis. The activation of glomerular endothelial cells by anti-MPO IgG appeared to directly involve a signaling through moesin.

Ion-sensitive and selective active waveguide optodes

Abstract A novel polymer waveguide (active waveguide) type optode possessing the advantages of both selective analyte determination and optical signal propagation was developed. The noteworthy concept of this active waveguide is the integration of plural functions into the planar waveguide itself, such as molecular recognition, color change, and light propagation. In order to demonstrate this concept, the analyte sensing layer is utilized as the light propagating layer. An ion-selective optode membrane consisting of a plasticized poly(vinylchloride) (PVC) membrane containing a neutral ionophore and a color changeable lipophilic anionic dye was used as the planar active waveguide sensing layer. The principle of the response of this active waveguide is based on the measurement of the output light signal intensity in which this light is propagated through the color changeable PVC membrane phase, and its intensity is decreased by interaction with the analyte ions. In this report, calcium and sodium ion-sensitive waveguides were prepared based on our developed neutral ionophores. Comparison of the experimental responses between the novel active waveguide optode and a commonly utilized conventional waveguide optode based on evanescent wave spectrometry demonstrated that the sensitivity of the active waveguide optode is obviously greater than that of the conventional waveguide optode. This concept of an active waveguide fully demonstrates the advantageous property of a planar waveguide with respect to highly sensitive and selective optical chemical sensing.

Characteristics of visual feedback in postural control during standing

In the present study, the visual feedback system in postural control was investigated. To suppress the vestibular and proprioceptive feedback paths, a subject stood on a force-measuring plate with a fixed back support. Because the subjects body was immovable under these conditions, the subject controlled a computer model which simulated body dynamics. Information on the sway angle of the model was fed visually. Under this condition, frequency response functions for the ankle moment in response to the sway angle were calculated. The experimental results suggest that the visual feedback system contains a large time delay and, consequently, the visual system does not by itself allow a subject to maintain an upright posture. Index Terms- Feedback control, frequency characteristics, identification, posture, visual sensory feedback.