Biomedical subjects

J Murata

Publications and source records attributed to J Murata.

At least 19 recordsLinked to original sources

PubMed2001

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.

Animals↗

PubMed2001

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.

Computer Simulation↗

PubMed2001

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.

Alleles↗

PubMed2001

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.

Calcitonin Gene-Related Peptide↗

PubMed2001

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.

Animals↗

PubMed2001

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.

Animals↗

PubMed2001

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.

Acetylation↗

PubMed2001

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.

Adrenal Medulla↗

PubMed2001

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.

Journal Article↗

PubMed2001

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.

Animals↗

PubMed2001

[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.

Anesthesia, Intravenous↗

PubMed2000

Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) on prostate cancer cell lines.

Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase, which activates proMMP-2 and expressed on the cell surface in many invasive cancer cells. We investigated the expression of MT1-MMP in prostate cancer cell lines. MT1-MMP protein and mRNA were expressed in PC-3, DU-145 and TSU-pr1 cells (androgen-independent prostate cancer cell lines), but in LNCaP cells (androgen-dependent prostate cancer cell line). MT1-MMP protein was negative and mRNA was low to detect by RT-PCR. Cell lysate of PC-3 cleaved proMMP-2 to the active form. In addition, both hepatocyte growth factor (HGF) and gastrin-releasing peptide (GRP) increased Matrigel invasion and induced the expression of MT1-MMP protein in DU-145 prostate cancer cells. These results suggest that MT1-MMP is indeed the tumor-specific activator of proMMP-2 in androgen-independent prostate cancer cells and plays an important role in the invasive properties of prostate cancer cells.

Catalysis↗

PubMed2000

Deep brain stimulation of subthalamic area for severe proximal tremor.

Proximal tremors are often refractory to nucleus ventrointermedius thalami thalamotomy. Subthalamotomy has been suggested to be effective for treatment of tremor, although this procedure is associated with considerable adverse effects, and has rarely been considered a suitable treatment modality. The authors demonstrate the efficacy and safety of subthalamic deep brain stimulation in two patients, one with a severe, refractory proximal essential tremor and one with tremor with dystonia.

Aged↗

PubMed2000

Social isolation stress enhanced liver metastasis of murine colon 26-L5 carcinoma cells by suppressing immune responses in mice.

We investigated the effect of social isolation stress on the formation of experimental liver metastasis resulted from intraportal vein (i.p.v.) injection of colon 26-L5 carcinoma cells in male Balb/c mice, and elucidated some of the underlying mechanism involving the effects of this stress on cellular immunity. Increases in the colony number and tumor burden were observed in the mice socially isolated before and/or after tumor cell challenge, as compared with the group-housed mice. In addition, exposure of mice to 2 weeks of preisolation resulted in decreases in the thymus weight and number of thymocytes by 35.8% and 40.2%, respectively, in comparison with the controls. Reduced proliferative response of splenocytes to various stimuli and suppressed splenic NK activity, as well as decreased macrophage-mediated cytotoxicity, were also found in the mice exposed to social isolation. Thus, these results suggest that social isolation stress enhances tumor metastasis in part via its suppressive effect on the immune system of the host.

Animals↗

PubMed2000

Universal learning network and its application to chaos control.

Universal Learning Networks (ULNs) are proposed and their application to chaos control is discussed. ULNs provide a generalized framework to model and control complex systems. They consist of a number of inter-connected 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. Therefore, physical systems, which can be described by differential or difference equations and also their controllers, can be modeled in a unified way, and so ULNs may form a super set of neural networks and fuzzy neural networks. In order to optimize the ULNs, a generalized learning algorithm is derived, in which both the first order derivatives (gradients) and the higher order derivatives are incorporated. The derivatives are calculated by using forward or backward propagation schemes. These algorithms for calculating the derivatives are extended versions of Back Propagation Through Time (BPTT) and Real Time Recurrent Learning (RTRL) of Williams in the sense that generalized node functions, generalized network connections with multi-branch of arbitrary time delays, generalized criterion functions and higher order derivatives can be deal with. As an application of ULNs, a chaos control method using maximum Lyapunov exponent of ULNs is proposed. Maximum Lyapunov exponent of ULNs can be formulated by using higher order derivatives of ULNs, and the parameters of ULNs can be adjusted so that the maximum Lyapunov exponent approaches the target value. From the simulation results, it has been shown that a fully connected ULN with three nodes is able to display chaotic behaviors.

Artificial Intelligence↗

PubMed2000

Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice.

We have previously shown that tumor necrosis factor-alpha (TNF-alpha), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-alpha was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-alpha exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-alpha, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation.

Animals↗

PubMed2000

[Vestibular symptoms and ENG findings during periods of convalescence after endolymphatic sac drainage and steroid-instillation surgery (EDSS)].

Understanding the appearance of vestibular symptoms during periods of convalescence after surgery for the treatment of Meniere's disease is important for determining when a patient can return to work as well as the long-term results of the operation. We have treated 20 cases of intractable Meniere's disease with endolymphatic sac drainage & steroid-instillation surgery (EDSS) [Kitahara T, et al., Ann Otol Rhlnol Laryngol in press, 2000] and observed the subjective symptoms and objective vestibular findings using electronystagmogram (ENG) during the subsequent period of convalescence. The average postoperative durations of subjective static and evoked vestibular symptoms were 1.7 and 6.7 days, respectively. Those of spontaneous, positional and positioning nystagmus observed using ENG were 1.2, 2.0 and 7.9 days, respectively. In cases with a long history of Meniere's disease, postoperative static vestibular sensation and positional nystagmus lasted significantly longer than in cases with short histories. In cases with poorly developed temporal bony pneumatization in the area behind the posterior semicircular canal, postoperative evoked vestibular sensations and positioning nystagmus lasted significantly longer than in cases with well developed temporal bony pneumatization. Vestibular symptoms resulting from direct invasion during EDSS were considered to be slighter than those resulting from vestibular neurectomy or gentamicin treatment and almost the same as those resulting from endolymphatic sac surgery.

Adult↗

PubMed2000

[Management of the acoustic tumor in an only/better hearing ear].

Because profound bilateral hearing impairment is a catastrophic event, the management and care of an individual with an 8th nerve lesion in an only/better hearing ear remains a significant challenge for both patient and physician. Current options regarding the treatment of the acoustic tumor in an only/better hearing ear include: observation, attempted hearing preservation surgery and stereotactically guided radiation therapy. In this article, we present 3 cases of acoustic tumor within the internal auditory canal in an only/better hearing ear diagnosed by gadolinium-enhanced MRI and discuss the recommendations, especially observation, available in the care of these cases. In one patient, hearing disturbance caused by the tumor in a better hearing ear made the patient quite depressive and desperate. One of the most important consideration is for the physician to provide the patient with adequate informed consent regarding the possibility of profound bilateral hearing loss caused by either the natural growth or surgical removal of the tumor in the future, and alternative methods of communication with others such as: hearing aid and lip reading, cochlear implant and brainstem implant.

Aged↗