Relationship between the changes in blood flow and volume in the finger during a Braille character discrimination task.

PURPOSE: We hypothesized that skin blood flow (SBF) of fingers are modulated during concentrated finger perception and that the changes in SBF reflect fluctuations in finger volume (FV). The aim of this study, therefore, was examine the relationship between the changes in SBF and FV during Braille reading. METHODS: We measured SBF of the finger, cutaneous vascular conductance (CVC), FV, and arterial blood pressure during Braille reading performed under blind conditions in thirty healthy subjects. The subjects were instructed to read a flat plate with raised letters (Braille reading) for 15 seconds using their forefinger, and to touch a blank plate as a control for the Braille discrimination procedure. RESULTS: Arterial blood pressure slightly increased during Braille reading but remained unchanged during the touching of the blank plate. SBF, CVC, and FV were reduced during Braille reading (decreased by -26%, -29%, and -0.3 mL/100 mL respectively). Furthermore, a significant relationship was observed between the changes in SBF and FV (r=.613) during Braille reading. CONCLUSION: These results suggested that SBF of fingers is modulated during concentrated finger perception, and that the variability of blood flow reflects the response in FV.

Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study.

BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.

Infrared thermography and odour composition of the Amorphophallus gigas (Araceae) inflorescence: the cooling effect of the odorous liquid.

During the second blooming of a cultivated Amorphophallus gigas Teijsm and Binnend in the Botanical Gardens of the University of Tokyo, the surface temperature of the inflorescence was measured using an infrared camera. Contrary to studies of other species in the genus Amorphophallus, the surface of the inflorescence showed only very faint thermogenesis and had a lower temperature than that of the background. This cooling effect appeared to be due to a loss of heat through evaporation, which was caused by the secretion of a very large amount of odorous liquid. Chemical analysis revealed that the major components of this liquid were acetic acid, propionic acid, butyric acid and valeric acids. The composition of the odorous liquid was slightly different between the spathe surface and the sterile appendix. The major component(s) of the odorous material from the spathe was butyric acid, and from the sterile appendix was valeric acids. These components would play dual roles of adding the characteristic smell to the inflorescence and cooling the inflorescence.

A rare case of a glass foreign body in the parapharyngeal space: pre-operative assessment by contrast-enhanced CT and three-dimensional CT images.

The parapharyngeal space is an infrequent area for foreign bodies to lodge. However, the presence of trauma or inflammation near or within the space is dangerous because of its anatomical proximity to the bifurcation of the maxillary artery, carotid artery and jugular vein. We encountered a rare case, when a glass flask burst, in which intraparotid damage to the facial nerve was seen, as well as a glass foreign body lodged in the parapharyngeal space close to the above named great vessels. We emphasise the usefulness of contrast-enhanced CT and three-dimensional CT images for pre-operative evaluation of the locational relationship between the foreign body and great vessels in the parapharyngeal space.

Multiple nodules on the face and in the nasal cavity are the symptoms of vegetative pyoderma gangrenosum complicated with myelodysplastic syndrome.

We have encountered and treated an unusual case of pyoderma gangrenosum (PG) characterized by multiple nodular lesions on the face and in the nasal meatus, which was complicated by myelodysplastic syndrome.

Noninvasive evaluation of cardiac output during postural change and exercise in humans: comparison between the modelflow and pulse dye-densitometry.

To investigate whether the Model-flow method, by simulating the aortic input impedance model from a noninvasive monitoring of arterial blood pressure, reflected a reliable measure of cardiac output (CO) during postural change and whole-body exercise occurring in daily life, we compared the Modelflow-estimated CO with a simultaneous reference determined by the pulse dye-densitometry. Nine healthy volunteers performed postural change from supine to upright and dynamic stepping exercise. The Modelflow-estimated CO decreased to 4.8 +/- 0.5 l/min, from 5.8 +/- 0.6 l/min, during the postural change and increased to 12.8 +/- 1.3 l/min during a stepping exercise, returning to 5.1 +/- 0.4 l/min at 5 min after exercise. When comparing the pooled data of CO during resting and following exercise between the Modelflow and pulse dye-densitometry, we found that the average CO did not differ between the two estimates and that there was a significant correlation between them; the slope of the linear regression line corresponded to approximately 1.0. Although such linear relationship was also observed in an individual subject, the slope of the regression line varied from 0.737 to 1.588 among the subjects. The calibration of the Modelflow-estimated CO with the dye-densitometry value at supine or upright improved a correlation between the two estimates. Thus it is likely that the noninvasive Modelflow simulation from arterial blood pressure can provide a reliable estimation of group-average cardiac output during postural change and stepping exercise occurring in daily life. It will be recommended for a more accurate estimation of cardiac output in a given subject to calibrate the Modelflow data with an independent measure.

Reflex responses in plasma catecholamines caused by static contraction of skeletal muscle.

To examine a hypothesis of whether static muscle contraction produces a release of catecholamines from the adrenal medulla via reflex stimulation of preganglionic adrenal sympathetic nerve activity induced by receptors in the contracting muscle, we compared the reflex responses in a concentration of epinephrine (Ep) and norepinephrine (NEp) in arterial plasma during static contraction and during a mechanical stretch of the hindlimb triceps surae muscle in anesthetized cats. Static contraction was evoked by electrically stimulating the peripheral ends of the cut L(7) and S(1) ventral roots at 20 or 40 Hz. Mean arterial pressure (MAP) and heart rate (HR) increased 23 +/- 3.1 mmHg and 19 +/- 4.3 beats/min during static contraction. Ep in arterial plasma increased 0.18 +/- 0.072 ng/ml over the control of 0.14 +/- 0.051 ng/ml within 1 min from the onset of static contraction, and NEp increased 0.47 +/- 0.087 ng/ml over the control of 0.71 +/- 0.108 ng/ml. Following a neuromuscular blockade, although the same ventral root stimulation failed to produce the cardiovascular and plasma catecholamine responses, the mechanical stretch of the muscle increased MAP, HR, and plasma Ep, but not plasma NEp. With bilateral adrenalectomy, the baseline Ep became negligible (0.012 +/- 0.001 ng/ml) and the baseline NEp was lowered to 0.52 +/- 0.109 ng/ml. Neither static contraction nor mechanical stretch produced significant responses in plasma Ep and NEp following the adrenalectomy. These results suggest that static muscle contraction augments preganglionic adrenal sympathetic nerve activity, which in turn secretes epinephrine from the adrenal medulla into plasma. A muscle mechanoreflex from the contracting muscle may play a role in stimulation of the adrenal sympathetic nerve activity.

Social isolation stress impairs the resistance of mice to experimental liver metastasis of murine colon 26-L5 carcinoma cells.

Our previous study has demonstrated that the exposure of male BALB/c mice to social isolation stress caused a suppressed immune response and enhanced liver metastasis of colon 26-L5 carcinoma cells. To more precisely understand the influence of psychosocial factors on the metastatic process, here we have investigated the effect of social isolation stress on the vulnerability of the host to develop liver metastasis of colon 26-L5 cells, including the time span and incidence of metastatic formation, survival time and chemotherapy response. Isolation stress decreased the time period required for the metastasis formation relative to that in controls. On day 7 after the tumor injection, the 75% incidence of tumor metastasis in the stressed mice was 5 times the 15% incidence in the unstressed mice. When exposed to the challenge of lower cell numbers (0.025, 0.05, 0.1 x 10(4)/mouse) of colon 26-L5 cells, mice subjected to isolation stress developed an elevated incidence of metastasis (33.3, 66.6, and 100%, respectively) as compared with the controls (0, 33.3 and 50%, respectively). The survival time following the tumor inoculation was also shorter in the stressed mice (21.83 +/- 1.59d) than in the control mice (24.08 +/- 1.68 d). Furthermore, the response of liver metastasis to chemotherapy consisting of 2 mg/kg cisplatin (CDDP) was worse in the stressed mice than that in unstressed mice. These findings suggested that social isolation stress could significantly impair the resistance of mice to the development of metastasis.

Stilbenoids in lianas of Gnetum parvifolium.

Five new stilbene dimers were isolated from the lianas of Gnetum parvifolium in addition to known stilbenoids. The structures of the compounds were established on the basis of spectroscopic evidence, including long-range coupling and nuclear Overhauser effect experiments, in NMR spectrum. Among the isolates, 2b-hydroxyampelopsin F showed potent inhibitory activity in the Maillard reaction.

Accumulation of extracellular matrix in the liver induces high metastatic potential of hepatocellular carcinoma to the lung.

The liver undergoes pathogenic changes such as hepatitis, fibrosis and cirrhosis under continuous stimulation by hepatitis virus or alcohol intake, leading to the development of hepatocellular carcinoma. The metastatic potential of HCC can be positively or negatively regulated by pathogenic alterations of liver. We investigated whether the metastatic abilities of HCC after orthotopic implantation can be influenced in the fibrotic liver by continuous injection of carbon-tetrachloride (CCl4) for seven weeks. The incidence of lung metastasis after orthotopic implantation of murine HCC (CBO140C12) fragments into CCl4-treated livers was higher than into normal livers. The amount of mRNA for MMP-2 increased in the CCl4-treated livers as compared with normal livers, and CBO140C12 cells constitutively expressed mRNA for MT1-MMP in early amplification cycles by RT-PCR. In addition, we found that the culture of CBO140C12 cells on the substrates pre-coated with ECM components increased the expression of MMP-2 mRNA. Thus, enhanced incidence of lung metastasis in the fibrotic liver might be partly due to: i) over-expression of MMP-2 in the fibrotic liver in cooperation with MT1-MMP on the CBO140C12 cell surface, ii) over-expression of MMP-2 in CBO140C12 cells, possibly mediated by the interaction of tumor cells (surface integrins) with accumulated ECM in the fibrotic liver. This is the first report showing that increase of MMP-2 in the fibrotic liver can influence the metastatic potential of HCC cells.

[Minimally invasive stereotactic functional surgery using an intravenous anesthetic propofol and applying Image Fusion and AtlasPlan].

Image-guided stereotactic surgery of the ventralis intermedius nucleus of the thalamus, globus pallidus, and subthalamic nucleus is a prevailing modality as a treatment of movement disorders. This technical note describes a method of minimally-invasive stereotactic functional surgery for patients with parkinsonian symptom or various tremors. Patients were administered propofol, an intravenous anesthetic, during placement of a burr hole and a stereotactic frame, but not the period when the patients were necessary to be awake. The intravenous anesthesia was very beneficial to relieve local pain and mental stress of the patients. Radionics ImageFusion and AtlasPlan were used for defining the target localization without an intraoperative ventriculography. ImageFusion efficiently fused high-resolution MR images on CT images. AtlasPlan accurately corrected the localization of the tentative target point after measurements from the midpoint of the anterior commissure-posterior commissure line on the modified MRI, and enabled us to reduce the degree of an intraoperative correction to fix a final target. Stereotactic functional surgery has been thought to be less-invasive, however further modifications of surgical procedure and intraoperative medication can make this type of surgery much more less-invasive.

Phylogenetic relationships and evolution in Chrysosplenium (Saxifragaceae) based on matK sequence data.

Chrysosplenium (Saxifragaceae) consists of 57 species widely distributed in temperate and arctic regions of the Northern Hemisphere, with two species restricted to the southern part of South America. Species relationships within the genus are highly problematic. The genus has traditionally been divided into two groups, sometimes recognized as sections (Oppositifolia and Alternifolia), based on leaf arrangement, or, alternatively, into 17 series. Based on morphological features, Hara suggested that the genus originated in South America and then subsequently migrated to the Northern Hemisphere. We conducted phylogenetic analyses of DNA sequences of the chloroplast gene matK for species of Chrysosplenium to elucidate relationships, test Hara's biogeographic hypothesis for the genus, and examine chromosomal and gynoecial diversification. These analyses revealed that both sections Oppositifolia and Alternifolia are monophyletic and form two large sister clades. Hence, leaf arrangement is a good indicator of relationships within this genus. Hara's series Pilosa and Macrostemon are each also monophyletic; however, series Oppositifolia, Alternifolia, and Nepalensia are clearly not monophyletic. MacClade reconstructions suggest that the genus arose in Eastern Asia, rather than in South America, with several independent migration events from Asia to the New World. In one well-defined subclade, species from eastern and western North America form a discrete clade, with Old World species as their sister group, suggesting that the eastern and western North American taxa diverged following migration to that continent. The South American species forms a clade with species from eastern Asia; this disjunction may be the result of ancient long-distance dispersal. Character mapping demonstrated that gynoecial diversification is dynamic, with reversals from inferior to half-inferior ovaries, as well as to ovaries that appear superior. Chromosomal evolution also appears to be labile with several independent origins of n = 12 (from an original number of n = 11) and multiple episodes of aneuploidy.

Allozyme analysis of the hybrid origin of Arisaema ehimense (Araceae).

Allozyme diversity was examined in the Japanese jack-in-the pulpit species, Arisaema serratum and A. tosaense, and their putative hybrid species, A. ehimense (all diploid). Arisaeme ehimense contains mostly alleles found in one or both of the putative parent species but few unique alleles, partially supporting the hypothesis that A. ehimense is of hybrid origin from the two species, although the possibility that A. ehimense arose via divergent speciation cannot be excluded. Because only limited information was gained from the survey of allozyme variation, additional taxon-specific markers from A. serratum and A. tosaense are required to test rigorously the hybrid origin of A. ehimense. A phenogram based on allele frequencies suggested that introgression occurs between A. serratum and A. tosaense where these species are sympatric.

Effect of prostatic neuropeptides on migration of prostate cancer cell lines.

BACKGROUND: A previous study by the same authors demonstrated that among various neuropeptides in the prostate, calcitonin gene-related peptide (CGRP) and gastrin-releasing peptide (GRP) increased the invasive capacity of PC-3 prostate cancer cells through enhancement of cell motility, while substance P (SP) inhibited the invasiveness through suppression of motile response. METHODS: The effect of 10 kinds of neuropeptides were investigated, including CGRP, GRP, SP, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), methionine-enkephalin (M-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of DU-145 prostate cancer cells through a reconstituted basement membrane (Matrigel) and the haptotactic migration of DU-145, TSU-pr1 and LNCaP prostate cancer cells using a Transwell cell culture chamber assay. RESULTS: It was found that GRP, CGRP and PTH-rP increased the invasive capacity of tumor cells. In contrast, SP, VIP, CT, L-ENK, M-ENK, NPY and glucagon had no significant effect. These three neuropeptides also increased the haptotactic migration of tumor cells to fibronectin. In addition VIP, CGRP and GRP increased the haptotactic migration of LNCaP prostate cancer cells and GRP and PTH-rP increased the migration of TSU-pr1 cells. CONCLUSION: The results indicated that some prostatic neuropeptides increased the invasive potential of prostate cancer cells partially through enhancement of cell motility.

Carrier and dose effects on the pharmacokinetics of T-0128, a camptothecin analogue-carboxymethyl dextran conjugate, in non-tumor- and tumor-bearing rats.

T-0128 is a novel camptothecin (CPT) analogue (T-2513: 7-ethyl-10-aminopropyloxy-CPT)-carboxymethyl (CM) dextran conjugate via a Gly-Gly-Gly linker, with a molecular weight (MW) of 130 kDa. Our previous studies demonstrated that T-0128 has strong antitumor activity against human tumor xenografts that are highly refractory to CPT analogues attributable to the passive tumor targeting of released T-2513. This study examines the effects of carrier, dose, and tumor on T-0128 pharmacokinetics. To study carrier effect, tumor-bearing rats received one i.v. injection of fluorescein isothiocyanate (FITC)-labeled CM dextran with a different degree of substitution (DS) of the carboxymethylated groups and a different MW. Results showed that CM dextran from Dextran T-110 (MW 110 kDa) with a DS value of 0.4 is an appropriate drug carrier for T-0128 regarding plasma half-life and passive tumor targeting. To study dose and tumor effects, non-tumor- and tumor-bearing rats were treated with T-0128 doses ranging from 1 to 25 mg/kg (based on the amount of T-2513 bound to CM dextran). Dose-dependent pharmacokinetics of T-0128 were observed in both kinds of rats. The presence of tumor reduced the plasma half-life and systemic exposure of T-0128. The saturation of hepatic and splenic tissue uptake clearances (CLups), and a large contribution of the tumor CLup to the total body clearance explain these results. Overall, our data provide a rationale for the selection of the carrier for T-0128 and a need for pharmacokinetic studies to evaluate the influences of tumor on the drug disposition.

Cardiac vagal and sympathetic efferent discharges are differentially modified by stretch of skeletal muscle.

We directly measured cardiac vagal efferent nerve activity (CVNA) and cardiac sympathetic efferent nerve activity (CSNA) in cats decerebrated at the level of the precollicular-premammillary body while the hindlimb or the triceps surae muscle was passively stretched. CVNA gradually decreased during passive stretch of the hindlimb, and this decrease was sustained throughout the stretch. CSNA increased at the onset of passive stretch, but this increase was not sustained. CVNA and CSNA responded differentially to graded passive stretches of the triceps surae muscle as well as the hindlimb. The sustained decrease in CVNA but not the initial increase in CSNA became greater depending on muscle length and developed tension. The time course and direction of the cardiac autonomic responses to muscle stretch were not affected by partial sinoaortic denervation, although the magnitude of the CSNA response was augmented. We conclude that the muscle mechanoreflex contributes to differential regulation of cardiac parasympathetic and sympathetic efferent discharges during passive stretch of skeletal muscle irrespective of arterial baroreceptor input.

A new control method of nonlinear systems based on impulse responses of universal learning networks.

A new control method of nonlinear dynamic systems is proposed based on the impulse responses of universal learning networks (ULNs), ULNs form a superset of neural networks. They consist of a number of interconnected nodes where the nodes may have any continuously differentiable nonlinear functions in them and each pair of nodes can be connected by multiple branches with arbitrary time delays. A generalized learning algorithm is derived for the ULNs, in which both the first order derivatives (gradients) and the higher order derivatives are incorporated. One of the distinguished features of the proposed control method is that the impulse response of the systems is considered as an extended part of the criterion function and it can be calculated by using the higher order derivatives of ULNs. By using the impulse response as the criterion function, nonlinear dynamics with not only quick response but also quick damping and small steady state error can be more easily obtained than the conventional nonlinear control systems with quadratic form criterion functions of state and control variables.

Improvement of generalization ability for identifying dynamical systems by using universal learning networks.

This paper studies how the generalization ability of models of dynamical systems can be improved by taking advantage of the second order derivatives of the outputs with respect to the external inputs. The proposed method can be regarded as a direct implementation of the well-known regularization technique using the higher order derivatives of the Universal Learning Networks (ULNs). ULNs consist of a number of interconnected nodes where the nodes may have any continuously differentiable nonlinear functions in them and each pair of nodes can be connected by multiple branches with arbitrary time delays. A generalized learning algorithm has been derived for the ULNs, in which both the first order derivatives (gradients) and the higher order derivatives are incorporated. First, the method for computing the second order derivatives of ULNs is discussed. Then, a new method for implementing the regularization term is presented. Finally, simulation studies on identification of a nonlinear dynamical system with noises are carried out to demonstrate the effectiveness of the proposed method. Simulation results show that the proposed method can improve the generalization ability of neural networks significantly, especially in terms that (1) the robust network can be obtained even when the branches of trained ULNs are destructed, and (2) the obtained performance does not depend on the initial parameter values.