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Yasuo Sugiura

Publications and source records attributed to Yasuo Sugiura.

At least 19 recordsLinked to original sources
PubMed2006

Fibroblast growth factor-2 enhances functional recovery of reinnervated muscle.

Long-term denervation of muscles results in fibrosis and fat replacement, which prevent muscles from regaining contractile function despite reinnervation. Therefore, prevention of muscle atrophy between nerve repair and muscle reinnervation may improve the functional outcome. A variety of growth factors play significant roles in muscle mass modulation and muscle regeneration. The purpose of the present study was to investigate the effect of fibroblast growth factor-2 (FGF2) and nerve growth factor (NGF) on muscle mass modulation after denervation and reinnervation using a nerve-to-muscle neurotization model. Growth factors were injected into the anterior tibial muscle after direct neurotization of muscles every 7 days up to 4 weeks after surgery. FGF2 significantly increased the amplitude of compound muscle action potentials (CMAPs), wet muscle weight, and the number of motor endplates, especially at higher concentration, compared to the vehicle. In contrast, NGF did not increase either the amplitude of CMAPs or muscle weight, although it significantly increased the number of motor endplates. These findings indicate that both growth factors enhance reinnervation of muscles; however, only FGF2 is involved in muscle mass modulation.

Action Potentials↗
PubMed2006

Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats.

UNLABELLED: We developed a rat model of oral cancer pain by inoculating cancer cells into the lower gingiva. A squamous cell carcinoma (SCC) derived from Fisher rats, SCC-158, was inoculated into the subperiosteal tissue on the lateral side of the lower gingiva in male Fisher rats. Inoculation of cancer cells induced marked mechanical allodynia and thermal hyperalgesia in the ipsilateral maxillary and mandibular nerve area. Infiltration of the tumor cells into the mandible and the completely encompassed inferior alveolar nerve was observed. Calcitonin gene-related peptide (CGRP)-, substance P (SP)-, ATP receptor (P2X(3))-, and capsaicin receptor (TRPV1)-immunoreactive cells strikingly increased in the small-cell group of trigeminal ganglia (TGs) after tumor cell inoculation. The TRPV1-immunoreactive cells also increased in the medium- and large-cell groups. Retrograde tracing combined with immunofluorescence techniques revealed the increased expression of peptides and the receptors in maxillary nerve afferent neurons. These results suggest that inoculation of SCC cells into the lower gingiva produces mechanical allodynia and thermal hyperalgesia, indicating the establishment of a novel rat model of oral cancer pain. Increased expression of CGRP, SP, P2X(3), and TRPV1 in the TG may be involved in the behavioral changes in this model. PERSPECTIVE: To clarify the mechanisms of oral cancer pain, we examined the expression of calcitonin gene-related peptide, substance P, ATP receptor P2X(3), and capsaicin receptor TRPV1 in trigeminal ganglia. Characterizations of these molecular systems which mediate pain perception are important to develop novel clinical tools for promoting relief of oral cancer pain.

Animals↗
PubMed2005

Murine glycosyltransferases responsible for the expression of globo-series glycolipids: cDNA structures, mRNA expression, and distribution of their products.

Biological functions of globo-series glycosphingolipids are not well understood. In this study, murine cDNAs of two glycosyltransferases responsible for the synthesis of globo-series glycolipids and mRNA expression of those genes were analyzed. Distribution of their products was also analyzed. Murine cDNAs for Gb3/CD77 synthase and Gb4 synthase predicted that both of them are type II membrane proteins with 348 and 331 amino acids, respectively. In northern blotting, Gb3/CD77 synthase gene was mainly expressed in kidney and lung but also detected in many other tissues. Gb4 synthase was expressed in brain, heart, kidney, liver, skin, and testis. In the immunohistological analysis, Gb3/CD77 was mainly expressed in the proximal tubules as revealed with coincidental expression with angiotensin-converting enzyme (ACE). In spleen, it was detected in pre-B cells in the peripheral region of the white pulp, as suggested with coincidental expression with CD10. It was also expressed on the endothelia of the alveolar capillaries in lung and on the sebaceous ducts aside of the hair follicles. Gb4 was also detected mainly on the proximal tubules in kidney and on the endothelia of the alveolar capillaries in lung as Gb3/CD77. But it was also detected on the epithelium of the bronchus, seminiferous tubules and tails of spermatozoa in testis, blood vessels of choroids plexus and endothelial cells in brain, and central and hepatoportal veins in liver. The expression patterns of two genes and their products almost corresponded with some exception. The results would provide essential information for the functional studies of globo-series glycolipids.

Amino Acid Sequence↗
PubMed2005

alpha-Melanophore-stimulating hormone (alpha-MSH) antagonizes interleukin-1beta-induced hyperalgesia and Fos expression in the paraventricular and arcuate nucleus of the rat.

It is known that intracerebroventricular (ICV) administration of a low dose of interleukin-1beta (IL-1beta) induces hyperalgesia and that this effect can be inhibited by alpha-melanophore-stimulating hormone (alpha-MSH). To identify the part of the brain that is affected by hyperalgesia-induced IL-1beta and the possible site of alpha-MSH inhibition, we have examined Fos expression in the rat brain in response to ICV microinjection of alpha-MSH and/or IL-1beta. Following injection of 10 pg IL-1beta, hyperalgesia was induced and Fos became expressed in the paraventricular nucleus (PVN) of the hypothalamus and in the arcuate nucleus (ARC), which contains alpha-MSH-producing neurons. IL-1beta injection did not induce Fos expression in the pars intermedia of the pituitary gland, which contains endocrine melanotrope cells that release alpha-MSH into the systemic circulation. ICV co-injection of IL-1beta with 30 ng alpha-MSH fully inhibited both hyperalgesia and Fos expression in the PVN and the ARC. We conclude that PVN neurons are activated by hyperalgesic IL-1beta and propose that this effect is abolished by alpha-MSH possibly released from the ARC but not from the pituitary gland.

Animals↗
PubMed2005

Changes in P2X3 receptor expression in the trigeminal ganglion following monoarthritis of the temporomandibular joint in rats.

The pathophysiological mechanisms of orofacial deep-tissue pain is still unclear. Previously, P2X receptors (P2XR) in sensory neurons have been shown to play a role in the signal transduction of cutaneous pain. We investigated the functional significance of P2X3R in relation to orofacial deep-tissue pain caused by monoarthritis of the temporomandibular joint (TMJ). Monoarthritis was induced by the injection of complete Freund's adjuvant (CFA) into the unilateral TMJ of the rat. The pain associated with monoarthritis was assessed by the pressure pain threshold (PPT), which was defined as the amount of pressure required to induce vocalization. Fifteen days after CFA-treatment, changes in PPT were examined after injection of P2XR agonists or antagonists into the TMJ. The number of cells expressing P2X3R in trigeminal ganglia (TG) was investigated by immunohistochemistry. Inflamed TMJ showed a continuous decline in PPT during the experimental period (P<0.001). Injection of alpha,beta-meATP, an agonist of P2X1,3,2/3R, dramatically reduced the bilateral PPTs of both inflamed and non-inflamed TMJs (P<0.01) although beta,gamma-me-l-ATP, a selective agonist of P2X1R, did not. The decreased PPTs of inflamed TMJ were reversed either by PPADS, an antagonist of P2X1,2,3,5,1/5,4/5R, or by TNP-ATP, an antagonist of P2X1,3,2/3,1/5R. Immunohistochemically, the number of P2X3R-positive cells increased in the small cell group in TG (P<0.01), whereas there was no change in medium or large cell groups after the CFA-injection. Retrograde tracing confirmed that TMJ neurons in the TG exhibited P2X3R immunoreactivity. Our results suggested that P2X3R plays an important role in orofacial pressure pain caused by monoarthritis of TMJ.

Adenosine Triphosphate↗
PubMed2005

Heat and mechanical hyperalgesia in mice model of cancer pain.

We developed a mouse model of cancer pain to investigate its underlying mechanisms. SCC-7, squamous cell carcinoma (SCC) derived from C3H mice, was inoculated subcutaneously into either the plantar region or thigh in male C3H/Hej mice. Heat and mechanical sensitivity as well as spontaneous behavior were measured at the plantar surface of the ipsilateral hind paw after the inoculation. Inoculated sites were histologically examined, and the expression of capsaicin receptors (TRPV1) was examined in the dorsal root ganglia (DRG) to clarify their potential contribution to pain sensitivity. Inoculation of cancer cells induced marked heat hyperalgesia and mechanical allodynia in the ipsilateral hind paw for two weeks in both plantar- and thigh-inoculation models. Signs of spontaneous pain, such as lifting, licking and flinching of the paw were also observed. However, further growth of the tumor reversed the mechanical allodynia in both plantar- and thigh-inoculation models, and heat hyperalgesia in thigh-inoculation models. Histologically, no infiltration of the tumor cells into the nerve was observed. TRPV1 immunoreactive cells increased in the L5 DRG on day 7, but returned to the control level on day 15 post-inoculation. Intraperitoneal administration of the competitive TRPV1 antagonist capsazepine inhibited hyperalgesia induced by tumor cell-inoculation in either plantar- or thigh-inoculated animals. This study indicated that inoculation of SCC resulted in spontaneous pain, heat hyperalgesia and mechanical allodynia. The altered expression of TRPV1 in the DRG may be involved in behavioral changes in this model.

Animals↗
PubMed2005

GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation.

Gangliosides are a family of sialic acid-containing glycosphingolipids that are highly enriched in the mammalian nervous system. In particular, b- and c-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to play important roles in adhesion, toxin-binding, neurite extension, cell growth and apoptosis. However, the neurobiological functions of these series of gangliosides remain largely unknown. To clarify the function of b- and c-series gangliosides in pain sensation in vivo, we generated mice in whom the gene for the alpha-2,8-sialyltransferase (GD3 synthase), which is responsible for the generation of all b-series gangliosides as well as c-series gangliosides, was disrupted. Compared to the wild-type mice, the mutant mice exhibited increased sensory responses to thermal and mechanical stimuli as measured by a hot plate test and von Frey test. In contrast, the mutant mice showed decreased responses during the late phase of the formalin test. Paw edema and Fos expression in the spinal cord after formalin injection were significantly decreased in the mutant mice compared to the wild-type mice. No significant differences in the conduction velocity of the sciatic nerve, and no apparent morphologic differences in the spinal cord and the sciatic nerve were detected between the wild-type and the mutant mice. These results suggested that b- and c-series gangliosides are critical in the development and/or maintenance of the sensory nervous system responsible for the transmission of acute pain sensation and pain modulation. Moreover, they play an important role in the development of hyperalgesia induced by inflammation.

Analysis of Variance↗
PubMed2004

Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis.

BACKGROUND: Although both interleukin-4 (IL-4) and IL-13 induce immunoglobulin E (IgE) production in vitro, the relative contribution of the two cytokines in various skin lesions of atopic dermatitis remains unclear. OBJECTIVE: We examined the relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis for IgE production. METHODS: The study group comprised 28 atopic dermatitis patients with serum IgE levels more than 2000 IU/ml. The expression levels of IL-4 mRNA and IL-13 mRNA versus that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) method in samples of normal-appearing skin from seven patients, very mild lesions from eight patients, subacute lesions from ten patients and lichenified lesions from ten patients with atopic dermatitis, and in samples of normal skin from six healthy control subjects. RESULTS: IL-4 mRNA expression was identified in only two of the eight very mild lesions, one of the ten subacute lesions, and none of the ten lichenified lesions, whereas IL-13 mRNA expression was identified in 27 of the 28 skin lesions of atopic dermatitis. The IL-13 mRNA/GAPDH mRNA ratios (x100) in the subacute lesions (94.4+/-20.6) and lichenified lesions (71.4+/-40.4) were significantly greater than in the skin of healthy controls (13.1+/-17.7; P<0.01, P<0.05, respectively). CONCLUSIONS: Upregulation of IL-13 mRNA in subacute and chronic lesions of atopic dermatitis along with scant expression of IL-4 mRNA suggest that IL-13 is a crucial cytokine in lesional skin.

Adult↗
PubMed2004

[Immunohistochemistry study of calcitonin gene-related peptide and substance P levels between end-to-end and end-to-side neurorrhaphy].

OBJECTIVE: To explore the changes of calcitonin gene-related peptide (CGRP) and substance P (SP) levels after end-to-end and end-to-side neurorrhaphy. METHODS: Twenty female Wistar rats were divided into 4 experimental groups and control group. In the experimental groups, common peroneal nerves were transected on both sides. End-to-side coaptation was performed on the left, while end-to-end coaptation on the right. After 1, 2, 4 and 27 weeks, the rats were sacrificed, and immunoreactivities of CGRP and SP in suture sites, lumbar spine and dorsal root ganglia (DRGs) were evaluated respectively. RESULTS: The expression of CGRP and SP decreased in dorsal horn and DRGs within 1 week postoperatively. After 4-27 weeks, CGRP and SP in dorsal horn could return to almost normal level, but they had little recovery in DRGs. Although the trend of change between end-to-end and end-to-side was coincident, in most experimental groups, there existed differences in the dorsal horn between end-to-end and end-to-side. The sciatic nerve stained by acetylcholinesterase, SP, CGRP and PGP 9.5 showed that the fibers could pass through the suture site of either end-to-end or end-to-side. CONCLUSION: Nerve regeneration can be achieved by end-to-side neurorrhaphy, and the mechanism of sensory nerve recovery of these two methods is similar. But the recovery in end-to-side coaptation is insufficient to some degree.

Anastomosis, Surgical↗
PubMed2004

A quantitative study of nerve fiber density in the submandibular gland of rats.

The route and three dimensional distribution of nerve terminals in the submandibular gland were investigated in rats using immunohistochemistry for the protein gene product (PGP) 9.5, as a marker of neuronal elements. Thick fiber bundles were found along the wall of the excretory duct. Many fine fibers from these thick bundles were distributed each lobule of the submandibular gland. A large number of single fibers terminated in the area around the striated, intercalated ducts and the acini. The densities of PGP 9.5 immunoreactive terminals were measured by a computer aided analysis system in the three areas: the striated duct, the intercalated duct, and the acini, whose densities (microm/microm2) were 0.23, 0.39 and 0.05 respectively. The relatively high density of nerve terminals in the intercalated duct suggests that the duct system probably plays an unexpectedly important role in the functional aspects.

Animals↗
PubMed2003

Origin and course of nerves immunoreactive for calcitonin gene-related peptide surrounding the femoral artery in rat.

Appreciation of anatomic relationships between perivascular nerve fibers and blood vessels is essential in reconstructive surgery. We examined the origin and neural connections of perivascular nerve fibers containing calcitonin gene-related peptide surrounding the femoral artery that regulate vascular tone. We used immunohistochemistry, denervation, and retrograde labeling methods. Peptide-immunoreactive fibers surrounding the femoral artery formed a complex network, with numerous small fibers extending from nerve fiber bundles located in the perivascular connective tissue. In middle and distal arterial segments, these fibers originated from the femoral nerve, the artery's main accompanying nerve. More proximally, fibers arose from the genitofemoral nerve and sympathetic nerves. Nerve branches terminating in various arterial segments had origins corresponding to those of somatic sensory nerve fibers, although pathways innervating the femoral artery took different courses.

Animals↗
PubMed2003

Central projection of unmyelinated (C) primary afferent fibers from gastrocnemius muscle in the guinea pig.

We have demonstrated the central projections of muscle C or group IV afferent fibers in the guinea pig by tracing arborizations in the spinal cord. C afferent fibers from the gastrocnemius muscle (GCM) were electrophysiologically identified by conduction velocity (less than 1 m/second). A single neuron in the lumbar 5 dorsal root ganglion (L5 DRG) was intracellularly labeled with Phaseolus vulgaris leucoagglutinin (PHA-L). After iontophoretic injection of PHA-L, we processed the lumbar cord and L5 DRG for PHA-L immunohistochemistry. Six muscle C afferent fibers from 40 animals were labeled, and whole trajectories were recovered. Labeled fibers were reconstructed by tracing of the arbor in serial parasagittal sections. The GCM C afferents projected rostrocaudally for two or three segments and ran at the surface of the dorsal funiculus, giving off collaterals into laminae I and II and sometimes into parts of lamina III. We determined, based on the branching pattern and form of the terminal plexus, that the branching of muscle C afferent fibers showed an intermediate pattern that fell morphologically between the terminal patterns of somatic and visceral afferents. The numbers and sizes of fiber swellings and terminal swellings were measured on all collateral branches. We found that the area of distribution of the terminal swellings of muscle C afferent fibers is larger than that of somatic terminals but that the density of terminal swellings in the terminal area was lower than that of the somatic terminals.

Afferent Pathways↗
PubMed2003

Innervation and functional characteristics of connective tissues, especially elastic fibers, in human fetal thoracic intervertebral articular capsule and its surroundings.

The articular capsules between the thoracic vertebrae, which have physiologically different functions from those of other levels of the vertebrae, have yet to be subjected to neuro-anatomical and fine structural analysis. In the present study, we analyzed serial frozen sections of decalcified thoracic vertebrae in human fetuses, and identified the articular capsule tissue with its unique distribution of elastic fibers. The fine structure of the elastic fibers was studied by transmission electron microscopy. In the early-stage fetus, the fibrous membrane forming the lateral intervertebral articular capsule contained abundant thin elastic fibers consisting of microfibrils. In the late-stage fetus, the lateral capsule of fibrous membrane was occupied by thick elastic fibers. A medial articular capsule, namely the ligamenta flava, contained numerous thick elastic fibers in both early and late-stage fetuses. The distributional differences in nerve fibers between early and late-stage fetuses were determined by immunostaining, using antibodies raised against protein gene product 9.5 (PGP 9.5; ubiquitin carboxyl-terminal hydrolase). Innervation by PGP 9.5 immunoreactive fibers was limited to the areas of the articular capsules near the blood vessels, which may indicate their functional relation with blood flow. No PGP 9.5 immunoreactive fibers were found in the ligamenta flava of the late-stage fetus. Innervation might be directly involved in the development of the intervertebral articular capsules in normal human fetuses.

Antibodies↗
PubMed2003

Nerve terminals extend into the temporomandibular joint of adjuvant arthritic rats.

The innervation of the temporomandibular joint (TMJ) has attracted particular interest because of the close association with complex mandibular movement. Although the pathological changes of disk innervation may have a crucial role in the development of TMJ pain, the innervation of the TMJ disk by experimentally induced arthritis has rarely been examined in detail. Arthritic rats were induced by injection with 0.1ml solution of Complete Freund's adjuvant (CFA). We investigated three-dimensional distribution of nerve fibers in the TMJ disk using immunohistochemistry for protein gene product-9.5 (PGP-9.5) and calcitonin gene-related peptide (CGRP) in naive and arthritic rats. To clarify the possible role of nerve growth factor (NGF) and its receptor on changes in peripheral innervation of the TMJ, the expressions of trkA and p75 receptor in trigeminal ganglia were examined. Although PGP-9.5 and CGRP immunoreactive (ir) fibers were seen in the peripheral part of the TMJ disk, they were not seen in its central part. The total length and the length density of PGP-9.5 ir and CGRP ir nerve fibers increased in arthritic rats. The innervation area of fibers proliferating in the rostro-medial part merged with that of fibers in the rostro-lateral part in the arthritic rats. In addition, the ratio of trkA- and p75-positive small- and medium-sized cells increased in trigeminal ganglia. It is assumed that increasing innervation of the TMJ disk may be important for the pathophysiology of TMJ pain. NGF and its receptors are likely involved in pathological changes of the TMJ disk.

Animals↗
PubMed2003

Retrograde tracing and electrophysiological findings of collateral sprouting after end-to-side neurorrhaphy.

The aim of this study was to seek more potent evidences of collateral sprouting for both motor and sensory nerve fibres after end-to-side neurorrhaphy using a modified double-labelling retrograde tracing method and to investigate the function of regenerated motor axons with electrophysiological evaluation. Four groups (n=4 for each group) were used: end-to-end coaptation (six months postoperatively), end-to-side coaptation (four months and six months postoperatively) and normal control. Two fluorescent tracers (true blue and diamidino yellow) were applied to the proximal ends of tibial and common peroneal nerves, respectively after four or six months of nerve coaptation. Five days later, we only found single-labelled motor and sensory neurons in the normal and end-to-end coaptation groups, while some dual-labelled neurons can be identified in end-to-side coaptation groups. Four months after surgery, the motor nerve conduction velocity in end-to-side coaptation was significantly slower than in the normal control. But no difference was found in the sixth month. These results suggest that end-to-side neurorrhaphy can induce the functional collateral sprouting of both motor and sensory axons in the peripheral nerve.

Amidines↗
PubMed2003

Morphological study of disordered myelination and the degeneration of nerve fibers in the spinal cord of mice lacking complex gangliosides.

Gangliosides, a family of glycosphingolipids that contain sialic acid, are abundant on the neuronal cell membranes, but their precise functions in the central nervous system remain largely undefined. In a previous study of GalNAc-T(-/-) mice engineered to lack beta1,4-N-acetylgalactos-aminyltransferase (GM2/GD2 synthase) to abolish any, complex gangliosides, we observed the reduction of nerve conduction velocity but did not find any obvious morphological change in the brain. In the present study, we observed morphological changes in the nerve fiber tracts of the spinal cord in these mice. In GalNAc-T(-/-) mice, the number of degenerated axons was markedly increased in the dorsal funiculus, tract of Lissauer, and dorsolateral funiculus of the cervical segment of the spinal cord as well as the dorsal funiculus and tract of Lissauer of the lumbar segment of the spinal cord. There were also increased numbers of unmyelinated fibers in GalNAc-T(-/-) mice. Loosened myelin sheaths and myelin sheaths separated from axons by wide spaces were also observed in GalNAc-T(-/-) mice. These results provide a morphological basis for the previously observed reduction in the nerve conduction velocity and suggest that complex gangliosides are essential for the maintenance of myelin and the integrity of nerve fibers of the spinal cord.

Animals↗
PubMed2002

Refractory skin injury in complex knock-out mice expressing only the GM3 ganglioside.

We generated double knock-out mice lacking the GM2/GD2 and the GD3 synthase gene by mating single gene mutants, and we analyzed the abnormal phenotypes of the mutant mice expressing only the GM3 ganglioside. We observed a refractory skin lesion that appeared primarily on the face of the mutant mice at 25 weeks after birth or later. Frequent scratching of the wound sites was observed in mutant mice with the skin injury, suggesting that it is a triggering factor that exacerbates the injury. This was confirmed by isolating mice in special cages for metabolic study in which the skin injury developed more rapidly. Characteristic proliferation of nerve fibers was found in the epidermis and subepidermis at the injured sites of the mutants, probably a result of continuous skin injury. Peripheral nerve degeneration was observed in young mutant mice, suggesting that reduced sensory function induced over-scratching and the resulting skin lesion. The fact that sensory response to mechanical stimuli decreased while that to hot stimuli increased in the mutant mice supports this interpretation. Thus, only GM3-expressing mice displayed the important role of gangliosides in maintaining skin integrity via regulation of the peripheral nerves.

Animals↗