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Biomedical subjects

S Wakisaka

Publications and source records attributed to S Wakisaka.

At least 55 records · Page 3Linked to original sources

Unilateral middle cerebral artery stenosis in an adult with Down's syndrome--case report.

A 29-year-old male with Down's syndrome presented with severe headache and vomiting. Computed tomography demonstrated subarachnoid hemorrhage. Left carotid angiography showed severe stenosis of the middle cerebral artery 2 cm distal to its origin, as well as abnormal hyper-vascularization near the stenosis site similar to that seen in moyamoya disease. Right carotid angiography showed no abnormalities. However, slight stenosis of the distal part of the bilateral vertebral arteries was noted. There was no aneurysm. We judged that the subarachnoid hemorrhage had been caused by rupture of the moyamoya-like vessel. Some patients with Down's syndrome have anatomical vascular abnormality and vascular fragility. The cerebral vascular abnormality found in this case may be part of the systemic vascular abnormalities associated with Down's syndrome. The vascular changes in some adult patients with Down's syndrome may be a sign of premature aging, and long-term studies with periodic vascular examination of patients with Down's syndrome need to be performed.

Adult↗

Radiographic and scintigraphic courses of union in cervical interbody fusion: hydroxyapatite grafts versus iliac bone autografts.

UNLABELLED: This study investigated the radiographic and scintigraphic courses of union in cervical interbody fusion using hydroxyapatite (HA) grafts or iliac bone autografts. METHODS: Twelve patients underwent both serial plain radiography and bone scintigraphy during the 12 mo after surgery. Serial plain radiographs were obtained every month until the end of the study period. Bone scintigrams with 99mTc-hydroxymethylene diphosphonate (HMDP) were obtained at 2 wk and at 1, 2, 3, and 6 mo. Uptake of 99mTc-HMDP in the graft was expressed as a ratio of the counts in the graft to those in the axis. RESULTS: In the HA graft group, the plain radiographs of all patients showed a radiolucent stripe that disappeared 7.3 +/- 1.5 (mean +/- SD) months after surgery. In the autograft group, a radiolucent stripe around the graft was not seen for any patient, and union was confirmed by follow-up radiographs within 6 mo after surgery. The serial changes in the 99mTc-HMDP uptake ratio showed no difference between the 2 groups. The 99mTc-HMDP uptake ratio peaked 1 mo after surgery and decreased rapidly to a plateau within 2 mo. CONCLUSION: In the HA graft group, despite the presence of a radiolucent stripe around the graft for more than 6 mo, the scintigraphic course of union was not different from that in the autograft group. The likelihood is that the presence of a radiolucent stripe around the HA graft in the early months after surgery is not always a sign of pseudoarthrosis.

Biocompatible Materials↗

Altered distribution of Schwann cells in the periodontal ligament of the rat incisor following resection of the inferior alveolar nerve: an immunohistochemical study on S-100 proteins.

The present study employed immunohistochemistry for the detection of S-100 proteins to reveal the alteration in the distribution of Schwann cells in the periodontal ligament of the rat incisor following resection of the inferior alveolar nerve (IAN). In normal animals, S-100-immunostaining demonstrated the profiles of Ruffini endings, primary mechanoreceptors in the periodontal ligament, in the alveolus-related part of the ligament. Under the electron microscope, S-100-like immunoreactivity (-LI) was observed in the cytoplasm of the terminal Schwann cell elements and in some axon profiles of the Ruffini endings. During the regeneration, S-100-like immunoreactive (-IR) terminal Schwann cells in the alveolus-related part of the ligament gradually decreased in number. In contrast, S-100-LI was found in the spindle-shaped cells at the shear zone (the border between alveolus-related and tooth-related parts) and in the tooth-related part, where S-100-LI was rarely detected in normal animals. Immunoelectron microscopic observations revealed that some S-100-IR spindle-shaped cells contained fibrous long spacing (FLS) fibers, suggesting that they were Schwann cells. Some regenerating axons were observed at the shear zone, but were rarely found in the tooth-related part. With the progress of the regeneration of the periodontal Ruffini endings, S-100-IR terminal Schwann cells became rearranged in the alveolus-related part by 42-56 days post injury, whereas the S-100-IR spindle-shaped Schwann cells in the shear zone and tooth-related part disappeared when the regeneration was complete.

Animals↗

Effects of cigarette smoking on Fas/Fas ligand expression of human lymphocytes.

Cigarette smoking has been shown to affect human immune responses. We have studied Fas/Fas ligand (FasL) expression, which is involved in the cytotoxic activity, immune privilege, and self-tolerance, and other apoptosis-associated molecule expression of peripheral blood lymphocytes (PBL) in healthy subjects with/without cigarette smoking. We found that expression of FasL protein was detected marginally in the fresh PBL and was induced upon mitogen activation in normal individuals without smoking. In contrast, fresh PBL from those with chronic cigarette smoking exhibited enhanced expression of FasL protein without in vitro mitogen stimulation. Moreover, mitogen stimulation failed to augment FasL protein expression of their lymphocytes, suggesting dysregulation of FasL expression of PBL in individuals with cigarette smoking. In contrast, Fas, Bcl-2, and p53 expression were not significantly different between normal individuals with chronic cigarette smoking and those without smoking. In addition, we found that in vitro brief treatment with nicotine induces and/or enhances FasL mRNA and protein expression of lymphocytes from normal donors without smoking. These results suggest that aberrant FasL expression of lymphocytes is, at least in part, involved in the immune impairment in individuals with chronic cigarette smoking.

Adult↗

Effects of morphine on the distribution of Fos protein in the trigeminal subnucleus caudalis neurons during experimental tooth movement of the rat molar.

The present study was undertaken to disclose temporal changes in the distribution of Fos-like immunoreactive (-IR) neurons in the trigeminal subnucleus caudalis (SpVc), one of the important relay nuclei for processing the nociceptive information from the oro-facial regions, following induction of experimental tooth movement in rat upper molars. Furthermore, the effect of morphine and naloxone on the levels of Fos-IR neurons in the SpVc was examined. The experimental tooth movement was induced by insertion of an elastic rubber between the first and second upper molars. In normal animals, Fos-IR neurons were rarely observed in the SpVc. Immediately after insertion of the elastic band, the distribution of Fos-IR neurons was comparable to that observed in normal animals. The number of Fos-IR neurons increased significantly from 1 to 4 h following the induction of experimental tooth movement, reaching a maximum at 2 h, and then decreasing gradually. Most of the neurons were localized in the dorsomedial portion of the superficial layers of the ipsilateral SpVc near the obex, but a few were observed at the ventral portion of the SpVc. The neurons at the superficial layers and ventral portion of the contralateral SpVc also showed Fos-like immunoreactivity, but their numbers were significantly smaller than those on the ipsilateral side. Pretreatment with morphine (3 and 10 mg/kg, i.p.) significantly reduced the induction of Fos-IR neurons at the superficial layers of the ipsilateral SpVc in a dose-dependent manner, and its effect was antagonized by the subsequent treatment of naloxone (2 mg/kg, i.p.). Naloxone pretreatment enhanced the expression of Fos-IR neurons on the ipsilateral SpVc. The present results of a reduction of Fos-IR neurons by morphine pretreatment suggest that the induction of Fos-IR neurons may be due to the noxious stimulation caused by induction of experimental tooth movement.

Analgesics, Opioid↗

Immunohistochemical localization of S-100beta in the dental pulp of the rat molar.

The present study was undertaken to reveal whether S-100alpha or S-100beta or both are present in the nerve fibers in the rat molar tooth pulp. No immunoreactivity for S-100alpha was observed in the molar pulp. In the root pulp, thick smooth-surfaced structures accompanying the blood vessel showed S-100beta-like immunoreactivity (-LI), and occasionally a very few thin beaded elements exhibited S-100beta-LI. In the coronal pulp, S-100beta-like immunoreactive (-IR) structures arborized repeatedly and extensively; they had a predominantly thick, smooth-surfaced appearance, though parts appeared thin and beaded. Numerous thin varicose S-100beta-IR structures ran through the odontoblast cell layer, and further penetrated into the predentin alongside the dentinal tubules. They could be traced for approximately 10-20 micrometers into the predentin from the pulp-predentin border. Immunoelectron microscopy revealed that the Schwann cells in the root pulp showed S-100beta-LI, and that S-100beta-LI was present in the axoplasm as well as Schwann cells in the coronal pulp. The S-100beta-IR axons were rarely surrounded by S-100beta-IR Schwann cells. In the predentin, S-100beta-IR nerve fibers terminated in a position close to the odontoblast processes. The present findings indicate that S-100beta, not S-100alpha, is present in the axon in the dental pulp and predentin as well as in the Schwann cells.

Animals↗

Immunohistochemical localization of calbindin D28k during root formation of rat molar teeth.

The present study was undertaken to examine the localization of calbindin D28k (CB)-like immunoreactivity (-LI) during the root formation of the rat molar. In the adult rat, CB-LI was detected in some of the cells of the epithelial rest of Malassez at the bifurcational region and in certain cells between the root dentin and cementum at the apical region. These cells had indented nuclei and many tonofilaments, and cementocytes lacked CB-LI. Moreover, CB-LI was observed in the periodontal fibroblasts in the alveolar half of the apical region. During root formation, the cells in the Hertwig's epithelial root sheath (HERS) lacked CB-LI, but most fragmented cells along the root surface began to express CB-LI when HERS was disrupted. Preodontoblasts and odontoblasts at the apical portion of the root also showed CB-LI. After the formation of cellular cementum, the CB-immunoreactive (-IR) cells were entrapped between the root dentin and cementum in the apical portion of the root. The number of CB-IR cells at the root surface decreased gradually, while that between the root dentin and cementum increased. The fibroblasts in the periodontal ligament began to express CB-LI after commencement of the occlusion, and the number and the staining intensity of CB-IR fibroblasts increased gradually with the passage of time. The present results suggest that CB may play an important role in the survival of the epithelial cells, in the cellular responses of periodontal fibroblasts against mechanical forces caused by the occlusion, and in the initial mineralization by the odontoblasts through the regulation of intracellular Ca(2+) concentration.

Animals↗

Clinical usefulness of and problems with three-dimensional CT angiography for the evaluation of arteriosclerotic stenosis of the carotid artery: comparison with conventional angiography, MRA, and ultrasound sonography.

BACKGROUND: Prevention of stroke is aided by determination of the degree of carotid artery stenosis and progression of arterial sclerosis. Three-dimensional computed tomography (CT) angiography (3D-CTA) is a new method for evaluating the degree of arterial stenosis. The purpose of this study was to compare the accuracy of 3D-CTA with the "gold standard": conventional angiography, magnetic resonance angiography (MRA), and ultrasound sonography (US). METHODS: A total of 128 carotid bifurcations in 64 patients (42 men and 22 women; mean age, 68.5 years) were examined by 3D-CTA because of symptoms of cerebral infarction, carotid bruit, or findings suggestive of arteriosclerotic carotid artery stenosis on MRA screening. The following were used to compare 3D-CTA with conventional angiography, MRA and US: 1) estimation of the degree of stenosis; 2) depiction of irregularities in arterial walls, including calcification, intimal thickening, ulcers and plaque; and 3) surgical planning for carotid endarterectomy (CEA) and percutaneous transluminal angioplasty (PTA), and postoperative evaluation. RESULTS: A strong correlation was found between the degrees of stenosis estimated by conventional angiography and 3D-CTA MIP image (r = 0.987/p < 0.0001). On the other hand, stenosis was generally overestimated by MRA, which, however, has the advantage of being able to scan the carotid siphon to the middle cerebral artery at one time. Calcification and ulceration of the artery wall could be evaluated with 3D-CTA, whereas with US, progression of arterial sclerosis could be evaluated by differentiation of homogenous and heterogenous plaque. The anatomical relationships between the site of stenosis and the internal jugular vein and bony structures, which must be known before CEA, were confirmed by observation of rotated images using the shaded surface reconstruction (SSR) method. Because the hemodynamics of cross and collateral flows cannot be clearly imaged with 3D-CTA, standard angiography is needed to determine suitability for bypass surgery. CONCLUSIONS: The current method used in our hospital for the diagnosis of stenosis of the internal carotid artery includes MRA or US for initial screening, 3D-CTA for evaluation of the degree of stenosis and for preoperative and postoperative evaluation of CEA and PTA, and conventional angiography for evaluation of hemodynamics and determination of the indications for a bypass surgery.

Aged↗

Simultaneous up-regulation of urokinase-type plasminogen activator (uPA) and uPA receptor by hepatocyte growth factor/scatter factor in human glioma cells.

Several lines of evidence indicate that hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, may play an important role in progression of human glioma. In this study, effects of HGF/SF on urokinase- type plasminogen activator (uPA)-mediated proteolysis network were examined in c-Met-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of uPA proteins accompanying increased transcription of uPA mRNA in a dose dependent fashion. The levels of uPA receptor (uPAR) mRNAs were also elevated simultaneously upon HGF/SF stimulation, and the cell-surface associated uPA activity was also elevated by the treatment. Since concomitant expression of HGF and its receptor c-Met are frequently observed in malignant gliomas, these results suggest that HGF/SF participates in invasive process of malignant glioma cells not only by its motility-stimulating activity but also through enhanced degradation of the extracellular matrix induced by autocrine activation of uPA proteolysis network.

Central Nervous System Neoplasms↗

Immunohistochemical localization of carbonic anhydrase isozyme II in the gustatory epithelium of the adult rat.

The distribution of carbonic anhydrase isozyme II (CA II)-like immunoreactivity (-LI) in the gustatory epithelium was examined in the adult rat. In the circumvallate and foliate papillae, CA II-LI was observed in the cytoplasm of the spindle-shaped taste bud cells, with weak immunoreaction in the surface of the gustatory epithelium. No neuronal elements displayed CA II-LI in these papillae. There was no apparent difference in the distribution pattern between the anterior and posterior portions of the foliate papillae. In immunoelectron microscopy, immunoreaction products for CA II were diffusely distributed in the entire cytoplasm of the taste bud cells having dense round granules at the periphery of the cells. No taste bud cells displaying CA II-LI were detected in the fungiform papillae, but a few thick nerve fibers displayed CA II-LI. In the taste buds of the palatal epithelium, neither taste bud cells nor neuronal elements exhibited CA II-LI. The present results indicate that CA II was localized in the type I cells designated as supporting cells in the taste buds located in the posterior lingual papillae of the adult animal.

Animals↗

The usefulness of Tc-99m MIBI for evaluating brain tumors: comparative study with Tl-201 and relation with P-glycoprotein

PURPOSE: This study was undertaken to determine the usefulness of Tc-99m methoxyisobutylisonitrile (MIBI) in brain tumors compared with TI-201 imaging. The authors evaluated the correlation between MIBI uptake and the presence of P-glycoprotein, and also the relation between MIBI uptake in response to combined radiotherapy and chemotherapy in glioblastoma. MATERIALS AND METHODS: Thirty-four brain tumors composed of 15 glioblastoma multiforme (GBM), 5 anaplastic astrocytomas, 5 low-grade astrocytomas, and 9 metastases were evaluated. Early and delayed images were obtained for MIBI and Tl-201 scintigraphy. P-glycoprotein status in all GBM, 2 anaplastic astrocytomas, 2 low-grade astrocytomas, and 2 metastases were evaluated immunohistochemically. Patients with GBM were divided into an effective and a noneffective group according to the change in tumor size. MIBI uptake indices were compared for these two groups. RESULTS: Both radiopharmaceuticals accumulated in all GBM and anaplastic astrocytomas. In low-grade astrocytomas, only one case showed tracer uptake. In metastasis, two cases showed high uptake on early images and marked washout on delayed images. Uptake ratio values (early uptake ratio and delayed uptake ratio) in all tumors were significantly higher in MIBI than in Tl-201. Immunohistochemical studies showed that the metastases were positive for P-glycoprotein but the GBM were not. In low-grade astrocytomas, a few cells were positively stained. In relation to the therapeutic outcome of GBM, both the early and delayed uptake ratios of MIBI were significantly greater in the noneffective group. CONCLUSIONS: Although diagnostic ability was comparable in MIBI and Tl-201, the imaging quality was better in MIBI. Both radiopharmaceuticals are useful in differentiating low-grade glioma from high-grade glioma. MIBI delayed imaging could also reflect the presence of P-glycoprotein. Intense MIBI uptake was also predictive of a poor clinical outcome in GBM.

Journal Article↗

Serotonergic modulation of the hyperpolarizing spike afterpotential in rat jaw-closing motoneurons by PKA and PKC.

Intracellular recordings were obtained from rat jaw-closing motoneurons (JCMNs) in slice preparations to investigate the effects of serotonin (5-HT) on the postspike medium-duration afterhyperpolarization (mAHP) and an involvement of protein kinases in the effects. Application of 50 microM 5-HT caused membrane depolarization and increased input resistance in the most cells without affecting the mAHP, whereas not only membrane depolarization and an increase in input resistance, but also the suppression of the mAHP amplitude was induced by higher dose of 5-HT (100 or 200 microM). On the other hand, when the mAHP amplitude was increased by raising [Ca(2+)](o) from 2 to 6 mM, 5-HT-induced attenuation of the mAHP amplitude was enhanced, and even 50 microM 5-HT reduced the mAHP amplitude. This 5-HT-induced suppression of the mAHP could be mimicked by application of membrane-permeable cAMP analogue 8-Bromo-cAMP, potentiated by the cAMP-specific phosphodiesterase inhibitor Ro 20-1724 and antagonized by protein kinase A (PKA) inhibitor H89. The enhancement of the mAHP attenuation induced by 50 microM 5-HT under raised [Ca(2+)](o) was blocked by a protein kinase C (PKC) inhibitor chelerythrine, suggesting an involvement of PKC in this enhancement. On the other hand, the attenuation of the mAHP induced by PKC activator phorbol 12-myristate 13-acetate was blocked almost completely by H89, suggesting that the PKC action on the mAHP requires PKA activation. Neither 5-HT(1A) antagonist NAN-190 or 5-HT(4) antagonist SB 203186 blocked 5-HT-induced attenuation of the mAHP. We conclude that 5-HT induces dose-dependent attenuation of the mAHP amplitude through cAMP-dependent activation of PKA and that PKC-dependent PKA activation is also likely to be involved in the enhancement of 5-HT-induced attenuation of the mAHP under raised [Ca(2+)](o). Because the slope of the linear relationship between firing frequency and injected current was increased only when the mAHP amplitude was decreased by 5-HT, it is suggested that the relation between incoming synaptic inputs and firing output in JCMNs varies according to serotonergic effects on JCMNs and calcium-dependent modulation of its effects.

Animals↗

The Ruffini ending as the primary mechanoreceptor in the periodontal ligament: its morphology, cytochemical features, regeneration, and development.

The periodontal ligament receives a rich sensory nerve supply and contains many nociceptors and mechanoreceptors. Although its various kinds of mechanoreceptors have been reported in the past, only recently have studies revealed that the Ruffini endings--categorized as low-threshold, slowly adapting, type II mechanoreceptors--are the primary mechanoreceptors in the periodontal ligament. The periodontal Ruffini endings display dendritic ramifications with expanded terminal buttons and, furthermore, are ultrastructurally characterized by expanded axon terminals filled with many mitochondria and by an association with terminal or lamellar Schwann cells. The axon terminals of the periodontal Ruffini endings have finger-like projections called axonal spines or microspikes, which extend into the surrounding tissue to detect the deformation of collagen fibers. The functional basis of the periodontal Ruffini endings has been analyzed by histochemical techniques. Histochemically, the axon terminals are reactive for cytochrome oxidase activity, and the terminal Schwann cells have both non-specific cholinesterase and acid phosphatase activity. On the other hand, many investigations have suggested that the Ruffini endings have a high potential for neuroplasticity. For example, immunoreactivity for p75-NGFR (low-affinity nerve growth factor receptor) and GAP-43 (growth-associated protein-43), both of which play important roles in nerve regeneration/development processes, have been reported in the periodontal Ruffini endings, even in adult animals (though these proteins are usually repressed or down-regulated in mature neurons). Furthermore, in experimental studies on nerve injury to the inferior alveolar nerve, the degeneration of Ruffini endings takes place immediately after nerve injury, with regeneration beginning from 3 to 5 days later, and the distribution and terminal morphology returning to almost normal at around 14 days. During regeneration, some regenerating Ruffini endings expressed neuropeptide Y, which is rarely observed in normal animals. On the other hand, the periodontal Ruffini endings show stage-specific configurations which are closely related to tooth eruption and the addition of occlusal forces to the tooth during postnatal development, suggesting that mechanical stimuli due to tooth eruption and occlusion are a prerequisite for the differentiation and maturation of the periodontal Ruffini endings. Further investigations are needed to clarify the involvement of growth factors in the molecular mechanisms of the development and regeneration processes of the Ruffini endings.

Acid Phosphatase↗

Effects of thyroid hormones on apoptotic cell death of human lymphocytes.

Apoptosis plays a critical role in the development and homeostasis of tissues, especially those with high cell turnover such as the lymphoid system. We have examined the effects of thyroid hormones, TSH and TRH, on apoptosis of human T lymphocytes. We found that T lymphocytes cultured with T3 and T4, but not TSH nor TRH, in vitro showed enhanced apoptosis, evidenced by DNA ladder formation and characteristic morphological changes. In addition, prolonged cultivation with thyroid hormones of the lymphocytes further enhanced the extent of apoptosis. We also found that treatment with thyroid hormones of T lymphocytes induced reduction of mitochondrial transmembrane potential (delta psi) and production of reactive oxygen species, both of which are intimately associated with apoptotic cell death. In addition, cellular expression of antiapoptotic Bcl-2 protein was clearly reduced by the treatment of lymphocytes with thyroid hormones in vitro. Thus, T lymphocytes treated with thyroid hormones accompany reduction of Bcl-2 protein expression, production of reactive oxygen species, and reduction of mitochondrial delta psi, resulting in apoptotic lymphocyte death. Moreover, we found that lymphocytes in patients with Graves' disease showed enhanced apoptosis compared with those in normal individuals. These results suggest that thyroid hormones have the potential to induce apoptotic cell death of human lymphocytes in vivo and in vitro.

Adult↗

Alteration in the expression level of calbindin D28k in the periodontal ligament of the rat molar during experimental tooth movement.

The present immunohistochemical study was designed to investigate changes in the distribution and expression level of calbindin D28k in the periodontal ligament during experimental tooth movement in the rat molar to clarify the physiological role of this protein in the ligament. In normal animals, calbindin D28k-like immunoreactivity appeared sparsely in spindle-shaped cells in the alveolar half of the periodontal ligament. Electron microscopic observations showed that these immunoreactive cells were characterized by well-developed rough-surfaced endoplasmic reticulum and phagosomes--which often contained collagen fibers--suggesting that these cells could be categorized as periodontal fibroblasts. Twelve hours following the onset of the experimental tooth movement, cells positive for calbindin D28k increased in number in the periodontal ligament, especially in the alveolar half of the pressured side. Immunoelectron microscopy showed that the calbindin D28k-immunopositive cells had morphological features similar to those of fibroblasts in the normal ligament, and that these cells occasionally made contact with immunonegative macrophage-like cells. Immunopositive cells gradually decreased in number, and the distribution of the cells and intensity of the immunoreactivity returned to normal levels by 14 days following the induction of the experimental tooth movement. The present results suggest that calbindin D28k plays an important role in the homeostasis and cyto-protection of fibroblasts in the periodontal ligament at the initial phase of experimental tooth movement.

Animals↗

Heterogeneous localizations of Trk B among individual periodontal Ruffini endings in the rat incisor.

The present immunocytochemical study examined the localization of Trk B, a high affinity neurotrophin receptor, in the neural elements of the periodontal ligament of the rat incisor. In light microscopy, the immunoreactivity was demonstrated in dendritic profiles in the alveolar half of the periodontal ligament. Their location and morphological features indicated that they were periodontal Ruffini endings. Occasional rounded cells associated with periodontal Ruffini endings, which had immunonegative kidney-shaped nuclei, were immunoreactive; these were judged to be terminal Schwann cells. Immunoelectron microscopy revealed the heterogeneous localization of Trk B among individual Ruffini endings. Some terminal Schwann cells contained immunoreactive products for Trk B in the cytoplasm, while others did not. Similarly, a part of the Schwann sheaths covering the axon terminals showed Trk B immunoreactivity. Most axon terminals associated with periodontal Ruffini endings were immunopositive for Trk B, though a few of them were immunonegative. The ordinary Schwann cells did not contain Trk B immunoreactive products. These findings imply that Trk B is required for the maintenance of periodontal Ruffini endings. The different expression pattern of Trk B suggests that neuronal and glial elements comprising individual periodontal Ruffini endings are subject to heterogeneous conditions with regard to the requirement of Trk B.

Animals↗

Postnatal expression of calretinin-immunoreactivity in periodontal Ruffini endings in the rat incisor: a comparison with protein gene product 9.5 (PGP 9.5)-immunoreactivity.

The postnatal expression of immunoreactivity for calretinin, one of the calcium binding proteins, and for protein gene product 9.5 (PGP 9.5), a general neuronal marker, was investigated in mechanoreceptive Ruffini endings in the periodontal ligament of the rat incisor. Age-related changes in the expression of these two proteins in periodontal nerves were further quantified with a computerized image analysis. At 1 day after birth, a few PGP 9.5-immunoreactive nerve fibers and a still smaller number of calretinin-positive fibers were found in the periodontal ligament: they were thin and beaded in appearance and no specialized nerve terminals were recognized. Tree-like terminals, reminiscent of immature Ruffini endings, were recognizable in 4-day-old rats by PGP 9.5-immunohistochemistry, while calretinin-immunostaining failed to reveal these specialized endings. At postnatal 7-11 days when PGP 9.5-immunostaining could demonstrate typical Ruffini endings, calretinin-immunopositive nerve fibers merely tapered off without forming the Ruffini type endings. A small number of Ruffini endings showing calretinin-immunoreactivity began to occur in the periodontal ligament at 24-26 days after birth when the occlusion of the first molars had been established. At the functional occlusion stage (60-80 days after birth), the Ruffini endings showing calretinin-immunoreactivity drastically increased in number and density, but less so than those positive for PGP 9.5-immunoreaction. The delayed expression of calretinin suggests that the function of the periodontal Ruffini endings is established after the completion of terminal formation because Ca2+, which binds to calcium binding proteins including calretinin with high affinity, plays an important role in mechano-electric transduction.

Age Factors↗

Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in brain tumors: evidence for a role in progression of astrocytic tumors (Review).

Hepatocyte growth factor (HGF) is a multifunctional cytokine which is believed to have important roles in tissue development and regeneration, and tumor progression. It is indistinguishable from scatter factor (SF), a motility factor. HGF/SF is believed to be a mesenchymal cell-derived cytokine acting for epithelial cells bearing its receptor tyrosine kinase, c-Met. Recently, we found that glioblastoma multiforme (GBM), a highly malignant brain tumor of astrocytic origin, concomitantly express HGF/SF and c-Met. This finding indicates a presence of autocrine loop of HGF/SF signaling pathway in GBM. Moreover, GBM cells also co-express HGF activator, a recently identified serine proteinase having efficient HGF/SF activating activity. The expression of HGF/SF and c-Met was low or hardly detectable in low-grade astrocytoma, and c-Met immunoreactivity was correlated with the histological grade of the tumor suggesting that the creation of HGF/SF autocrine loop occurs along with the progression of astrocytic brain tumors. Experimental evidence indicated that HGF/SF exhibits potent migration/invasion-inducing activity for GBM cells bearing c-Met receptor. It is also a significant angiogenesis factor in GBM, and may serve as a cellular growth factor for certain GBM cells. These lines of evidence suggest that HGF/SF signaling pathway may serve as a promising new target of therapeutic intervention of GBM.

Brain Neoplasms↗