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Biomedical subjects

S Wakisaka

Publications and source records attributed to S Wakisaka.

At least 37 records · Page 2Linked to original sources

Immunohistochemical detection of heme oxygenase-2 in the periodontal Ruffini ending of the rat incisor.

The present study was carried out to examine the occurrence of heme oxygenase-2 (HO-2) in the periodontal ligament of the rat incisor. HO-2-like immunoreactive (-IR) structures showed dendritic profiles, resembling the Ruffini endings, in the alveolar half of the ligament of rat incisor. Neither thin nerve fibers nor perivascular nerve fibers displayed HO-2-like immunoreactivity (-LI). No non-neural elements exhibited HO-2-LI. Electron microscopy revealed that immunoreactions were diffusely observed in the axon terminals of the Ruffini endings, but neither terminal Schwann cells nor Schwann sheaths contained immunoreactions for HO-2. Both most neurons in the trigeminal ganglion and trigeminal mesencephalic nucleus showed HO-2-LI. The presence of HO-2 in the periodontal Ruffini endings and its absence in the periodontal thin nerve fibers suggest the involvement of carbon monoxide produced by HO-2 in mechanoreception in the periodontal ligament.

Animals↗

Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR.

Neuropoletic cytokines such as ciliary neurotrophic factor (CNTF) can activate multiple signaling pathways in parallel, including those involving Janus kinase (JAK)-signal transducers and activators of transcription (STATs), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI 3-kinase) and mammalian target of rapamydn (mTOR)-p70 S6 kinase . Crosstalk occurs between these pathways, because studies have shown that STAT3 requires phosphorylation on tyrosine and serine residues by independent protein kinase activities for maximal activation of target gene transcription. Members of the JAK/Tyk family of tyrosine kinases mediate phosphorylation of STAT3 at Tyr705 during CNTF signaling; however, the kinase responsible for phosphorylation at STAT3 Tyr727 appears to depend on both the extracellular stimulus and the cellular context. Here we investigate the kinase activity responsible for phosphorylation of STAT3 on Ser727 in CNTF-stimulated neuroblastoma cells. We found that CNTF-induced phosphorylation of Ser727 was inhibited by the mTOR inhibitor rapamycin, but not by inhibitors of MAPK and protein kinase C (PKC) activation. A STAT3 peptide was efficiently phosphorylated on Ser727 in a CNTF-dependent manner by mTOR, but not by a kinase-inactive mTOR mutant or by p70 S6 kinase. In agreement with these biochemical studies, rapamycin treatment of cells transfected with a STAT-responsive promoter reporter decreased activation of the reporter to the same degree as a STAT3 Ser727Ala mutant The ability of mTOR to contribute to activation of STAT3 extends the function of mTOR in mammalian cells to include transcriptional regulation.

Cell Line↗

A Stump of Occluded Posterior Cerebral Artery Mimicking a Ruptured Aneurysm: Case Report.

We report on a 63-year-old female with subarachnoid hemorrhage who had a stump of occluded posterior cerebral artery (PCA) mimicking a ruptured aneurysm of the basilar bifurcation. Intraoperatively, the aneurysmal opacification on preoperative angiograms proved to be the residual lumen of the occluded right P1 segment. Because of the nodular appearance and upward direction of the stump of the right P1 segment, it was misinterpreted as an aneurysm. During operation, a tiny ruptured aneurysm missed on preoperative angiograms was found in the left A1-A2 junction and was clipped safely.

Journal Article↗

Poststenotic signal attenuation on 3D phase-contrast MR angiography: a useful finding in haemodynamically significant carotid artery stenosis.

We performed blinded visual evaluation of MR angiography (MRA) films in 44 patients with unilateral carotid artery stenosis to determine whether a flow gap and poststenotic signal attenuation on 3D-PC MRA were useful signs of severe carotid artery stenosis. Although nine patients with a flow gap alone had various degrees of stenosis ranging from 22.2 to 77.3% without any decrease in regional cerebral blood flow (rCBF), 13 patients with both a flow gap and poststenotic signal attenuation had severe stenoses of 80% or more, with a definite decrease in baseline rCBF. The presence of both a flow gap and poststenotic signal attenuation on 3D-PC MRA appeared to be a reliable marker of severe carotid artery stenosis with a decrease in rCBF.

Adult↗

A combination of wrapping and clipping using a collagen-impregnated dacron fabric (Hemashield).

BACKGROUND: We describe techniques combining wrapping and clipping using a collagen-impregnated Dacron knitted fabric (Hemashield) for accidental arterial perforations and broad-based aneurysms. The results of these techniques in seven patients are presented. METHODS: Clip-reinforced wrapping was performed to obtain hemostasis in two patients with arterial perforations and in a patient with a ruptured broad-based aneurysm in the internal carotid artery. Clipping of the broad neck of the aneurysm and wrapping with Hemashield (wrap-clipping) was performed in four patients with unruptured aneurysms (one internal carotid artery, two middle cerebral artery, one basilar artery). RESULTS: In the three patients treated with clip-reinforced wrapping, complete hemostasis was obtained just after clip application. In the patient with a ruptured broad-based aneurysm, postoperative angiography demonstrated that the dome of the aneurysm was well compressed. In the four patients treated with wrap-clipping, postoperative angiography revealed successful clipping of the broad neck of the aneurysm. CONCLUSION: In this early experience, there were no problems in the use of Hemashield for clip-reinforced wrapping or wrap-clipping.

Aged↗

Intrathecal lithium reduces neuropathic pain responses in a rat model of peripheral neuropathy.

We tested the ability of lithium (Li(+)) to block heat hyperalgesia, cold allodynia, mechanical allodynia and mechanical hyperalgesia in rats experimentally subjected to painful peripheral neuropathy. Chronic constrictive injury (CCI) to the sciatic nerve induced persistent hyperalgesia and allodynia. Intrathecal injection of Li(+) (2.5-40 micromol) into the region of lumbar enlargement dose-dependently reduced heat hyperalgesia, cold allodynia and mechanical allodynia for 2-6 h after injection, but had no effect on mechanical hyperalgesia. Li(+) had no significant effect on responses from control and sham-operated animals. Intrathecal injection of myo-inositol (2.5 mg) significantly reversed both the anti-hyperalgesic and anti-allodynic effect of Li(+). These findings suggest that intrathecal Li(+) suppresses neuropathic pain response in CCI rats through the intracellular phosphatidylinositol (PI) second messenger system in spinal cord neurons. Lithium (Li(+)) has already found widespread clinical application; these results suggest that its therapeutic utility may be extended to include treatment of neuropathic pain syndromes resulting from peripheral nerve injury.

Animals↗

Parathyroid hormone-related peptide is involved in protection against invasion of tooth germs by bone via promoting the differentiation of osteoclasts during tooth development.

In order to elucidate the role of parathyroid hormone-related peptide (PTHrP) in tooth development, we treated tooth germ explants of mouse molars with antisense phosphorothioate-oligodeoxynucleotide (ODN) against PTHrP. Antisense ODN-treatment of the explants resulted in the invasion of the tooth germs by bone. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells around the tooth germs in antisense ODN-treated explants was much lower than that of the control explants. Electron microscopic examination suggested that the antisense ODN-treatment inhibited differentiation of osteoclasts. Treatment of the explants with bisphosphonate or vitamin K2, inhibitors of the differentiation of osteoclasts, induced the invasion by bone into the tooth germs as observed in the antisense ODN-treated explants. The results obtained suggest that PTHrP is involved in the mechanism protecting tooth germs from bone invasion by promoting the differentiation of osteoclasts around them.

Animals↗

Altered expression level of calbindin D28k in the periodontal ligament of rat molar in response to changes in occlusal force.

The present immunohistochemical study was designed to investigate the alteration in the expression level of calbindin D28k in the periodontal ligament of the rat molar in response to changes in occlusal force to clarify the physiological role(s) of this protein in the ligament. In normal periodontal ligament of the lower first molar, immunoreactivity for calbindin D28k was found in the spindle-shaped cells, presumably fibroblasts, at the alveolar portion of the ligament at the distal side of the mesial root and mesial side of the distal root. Following the overload of occlusal force to the upper first molar by bite-raising, the number and immunoreactivity of the positive cells in the periodontal ligament of the lower first molar increased gradually. A more significant increase was detected at 7 d following the bite-raising compared to the normal animals. When occlusal force was removed by the extraction of the upper first molar, the expression level of calbindin D28k in the periodontal ligament of the lower first molar rapidly decreased, however a subsequent gradual increase was recognized. Statistical analysis of the spatial immunoreactivity of calbindin D28k in the periodontal ligament was performed and showed statistically significant differences. The present results suggest that calbindin D28k may play important roles in the homeostasis and cytoprotection of the periodontal fibroblasts against occlusal force.

Analysis of Variance↗

Angiographic cerebral circulation time before and after endovascular therapy for symptomatic vasospasm.

AIM: To investigate the correlation between angiographic cerebral circulation time (CCT) and cerebral blood flow (CBF) evaluated by single photon emission computed tomography (SPECT) before and after endovascular treatment for symptomatic vasospasm. MATERIALS AND METHODS: Seven patients with unilateral vasospasm as demonstrated by catheter angiography who underwent pre- and post-treatment SPECT were selected. All patients had angiographic vasospasm of unilateral middle cerebral artery (MCA). Eight vessels in seven patients underwent intra-arterial papaverine infusion and three vessels underwent percutaneous transluminal angioplasty. Angiographic CCT was defined as the interval from the first image in which contrast medium was visible at the origin of MCA to its disappearance from the cortical arteries in the MCA territory. In SPECT studies, the ischaemic degree in MCA territory was analysed by side to side comparison with calculating the asymmetry index (AI). RESULTS: The pre-treatment mean CCT was 4.1 +/- 0.8 s. The mean CCT immediately after treatment was 2.7 +/- 0.5 s. In the control subjects (n = 15) with unruptured aneurysm, mean CCT was 3.5 +/- 0.2 s. The pre-treatment mean CCT was significantly prolonged compared with that in the control subjects (P = 0.02). The post-treatment mean CCT was significantly shortened compared with that in the control subjects (P = 0.001). The pre-treatment mean AI was 71.2 +/- 7.4%, and that immediately after treatment was 90.5 +/- 3.6%. AI increased in all territories treated with endovascular treatment; the mean change was 19.3%. Angiographic CCT was closely correlated with AI in both pre- (r = - 0.95) and post-treatment (r = - 0.79). CONCLUSION: Measurement of CCT is useful in evaluating cerebral haemodynamics of endovascular treatments in patients with cerebral vasospasm.

Adult↗

Oral findings in DiGeorge syndrome: clinical features and histologic study of primary teeth.

OBJECTIVE: For the purpose of supplementing the shortage of dental information about DiGeorge syndrome, we report two cases of the syndrome seen in Japanese boys. STUDY DESIGN: Two cases were compared with respect to orofacial and dental findings; one was a case of complete DiGeorge syndrome and the other a case of partial DiGeorge syndrome. Extracted deciduous teeth from the two boys underwent histologic study. RESULTS: Each patient showed systemic developmental delay, hypocalcemia, and slight mental retardation. In the orofacial area, hypertelorism, a short philtrum, thick and reflected lips, and hypoplasia of the nasopharynx were also observed. A dental examination showed delayed formation and eruption of permanent teeth, aplasia of the nasopharynx, and enamel hypoplasia along with enamel hypocalcification. Structural streaks with increased calcification were histologically detected in the deciduous tooth from the patient with complete DiGeorge syndrome. CONCLUSIONS: Common characteristic orofacial and dental findings were noted in the two DiGeorge syndrome cases. Furthermore, histologic study of the deciduous tooth from the boy with complete DiGeorge syndrome suggests that there was some relationship between transient relative hypercalcemia and dentinal hypermineralized streaking of the tooth.

Adolescent↗

Intravenous low-dose native tissue plasminogen activator for distal embolism in the middle cerebral artery divisions or branches: a pilot study.

OBJECTIVE: We prospectively evaluated the safety and efficacy of an intravenous infusion of low-dose native tissue plasminogen activator for distal embolisms in the middle cerebral artery divisions or branches. METHODS: Twenty patients were selected according to the following computed tomographic and angiographic criteria and treated with intravenous infusion of 7.2 mg of tisokinase: 1) no early ischemic changes on the initial computed tomographic scan, and 2) embolic occlusion of the middle cerebral artery divisions or branches without the involvement of the lenticulostriate arteries. For comparison, the records of 12 patients from previous years who met the above inclusion criteria but underwent no thrombolytic therapy were reviewed retrospectively. The degree of neurological recovery was assessed using the National Institutes of Health Stroke Scale at 24 hours after admission. Major neurological improvement was defined as a decrease in the stroke score by 4 points or more. RESULTS: There was no significant difference in stroke scores at the time of admission between the treatment group (mean +/- standard deviation, 12.8 +/- 2.8) and the untreated group (14.0 +/- 2.4). In the treatment group, major neurological improvement was seen in 17 (85%) of 20 patients, whereas in the untreated group only 5 (41.7%) of 12 patients showed major neurological improvement (P < 0.05). The mean score at 24 hours in the treatment group (3.6 +/- 3.5) was significantly lower than that in the untreated group (9.4 +/- 7.3) (P < 0.05). There was no hemorrhagic complication with neurological exacerbation in the treatment group. CONCLUSION: Even with delayed initiation (>3 h after symptom onset), intravenous infusion of low-dose tisokinase may be safe and effective for small distal emboli in the middle cerebral artery divisions or branches, when early ischemic changes on computed tomographic scans and involvement of the lenticulostriate arteries are absent.

Aged↗

Thresholds of ischemia salvageable with intravenous tissue plasminogen activator therapy: evaluation with cerebral blood flow single-photon emission computed tomographic measurements.

OBJECTIVE: This study investigated the cerebral blood flow (CBF) thresholds of ischemic cortices that were salvageable with intravenous tissue plasminogen activator (t-PA) infusion therapy. METHODS: We retrospectively reviewed data for 20 patients who were treated with intravenous low-dose (7.2 mg) native t-PA infusion therapy for distal embolic occlusions of middle cerebral artery divisions or branches, without early computed tomographic ischemic changes. All patients underwent pretreatment single-photon emission computed tomographic CBF measurements using (99m)Tc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethylester. Intravenous t-PA infusion was initiated within 6 hours (average, 3 h) after symptom onset for 14 patients and 6 to 14 hours (average, 8.8 h) after the last time the patient was noted to be in normal condition for the other 6 patients. Pretreatment single-photon emission computed tomographic and 3-month post-treatment computed tomographic scans were compared using computerized coregistration. Ischemic cortices in single-photon emission computed tomographic scans were divided into areas of reversible and irreversible ischemia. The degree of hypoperfusion was analyzed with an asymmetry index (AI). The AI was calculated as C(a)/C(b) x 100%, where C(a) represents the mean reconstructed counts for the ipsilateral ischemic area and C(b) represents the mean reconstructed counts for the corresponding contralateral area. RESULTS: Partial recanalization, with clinical improvement, at 60 minutes was confirmed by angiography for 14 of the 20 patients (70%). Seventeen of the 20 patients (85%) exhibited major neurological improvements (defined as decreases in National Institutes of Health Stroke Scale scores of > or =4 points) at 24 hours, suggesting that recanalization occurred within 24 hours for almost all patients. AIs for the 25 irreversible lesions ranged from 15.0 to 53.4% (37.3 +/- 11.6%), whereas AIs for the 38 reversible lesions ranged from 45.0 to 83.1% (69.3 +/- 8.6%). There was a significant difference in the AIs for these two groups (P < 0.0001). The ischemia in tissue with AIs of more than 53.4% was reversible. In contrast, ischemic tissue with AIs of less than 45.0% could not escape cerebral infarction with our treatment. The ischemia in tissue with AIs between 45.0 and 53.4% was reversible in some patients and irreversible in others. CONCLUSION: To save ischemic tissue with our intravenous t-PA infusion therapy, residual CBF should be at least 45% of the contralateral presumed normal CBF value. CBF thresholds for ischemia that would be surely salvageable with our intravenous t-PA infusion therapy might be approximately 50 to 55% of the contralateral presumed normal CBF values.

Acute Disease↗

Delayed expression of calbindin D28k during regeneration of the periodontal Ruffini endings of the rat incisor following injury to the inferior alveolar nerve.

Expression of calbindin D28k (CB)-like immunoreactivity (-LI) was compared with that of protein gene product 9.5 (PGP 9.5), a general neuronal marker, in the periodontal ligament of the rat lower incisor following resection of the inferior alveolar nerve (IAN). In normal animals, the periodontal nerve fibers showing PGP 9.5-LI formed either Ruffini endings with expanded arborization or thin free nerve endings in the alveolar half of the ligament. Thick CB-like immunoreactive (-IR) nerve fibers terminated in a dendritic fashion in the same region, but thin CB-IR nerve fibers were rarely detected. During the 3 days following resection of the IAN, most of the PGP 9.5-IR and all CB-IR nerve fibers disappeared. Regenerated PGP 9.5-IR nerve fibers appeared around 7 days after resection, in contrast to the very small number of regenerated CB-IR nerve fibers. Around 21-28 days following resection, the number and terminal morphology of regenerated PGP 9.5-IR nerve fibers were comparable to those observed in normal animals, but the number of regenerated CB-IR nerve fibers was still smaller. The terminal morphologies of these regenerated CB-IR nerve fibers showed less expansion compared with normal animals at these post-injured periods. The number of regenerated CB-IR nerve fibers increased gradually to return to normal by 56 days following injury. The delayed expression of CB in the regenerated periodontal Ruffini endings suggests that the functional recovery of periodontal Ruffini endings occurred after the regeneration of periodontal Ruffini endings had been completed.

Animals↗

Characterization of tissue outgrowth developed in vitro in patients with rheumatoid arthritis: involvement of T cells in the development of tissue outgrowth.

BACKGROUND: The aim of this study was to analyze cellular and cytokine interactions governing the development of synovial tissue outgrowth in patients with rheumatoid arthritis (RA). METHODS: A single-cell suspension of dissociated synovial tissues of RA patients was cultured for a long period to develop tissue outgrowth. The resulting tissue outgrowth was characterized by immunohistochemical staining and ELISA. RESULTS: The tissue outgrowth developed in vitro included various cell types, such as macrophage-like synovial cells, fibroblast-like synovial cells and lymphocytes. Even after prolonged cultivation, synovial cells devoid of infiltrating T lymphocytes did not form tissue outgrowth. The outgrowth contained CD3+ cells, LeuM3 (CD14)+ cells and HLA-DR+ cells. The T cells expressed lymphocyte function-associated antigen (LFA)-1 and CD2, and the synovial cells expressed intracellular adhesion molecule (ICAM)-1 and LFA-3, suggesting possible interactions via LFA-1/ICAM-1 and CD2/LFA-3. Production of T-cell derived IFN-gamma and IL-17 and synovial-cell-derived fibroblast growth factor (FGF)-1 and IL-15 was confirmed in the tissue outgrowth as well as in RA synovial tissue. These cell types stimulate each other by secreting cytokines, leading to the secretion of proinflammatory cytokines and matrix metalloproteinase (MMP)-1 by the tissue outgrowth and proliferation of both lymphocytes and synovial cells. CONCLUSION: This study emphasizes the importance of cellular interactions between T cells and synovial cells, via adhesion molecules and the secretion of cytokines with stimulatory activity towards other cell types, for the hyperactivity of RA synovial cells.

Arthritis, Rheumatoid↗

Transient expression of heat shock protein (Hsp)25 in the dental pulp and enamel organ during odontogenesis in the rat incisor.

The expression of heat shock protein (Hsp) 25 during odontogenesis in the dental pulp and enamel organ of rat incisors was investigated by immunocytochemistry and confocal microscopy. In the process of dentin formation, immature odontoblasts first exhibited Hsp 25-immunoreactivity, and increased in immunointensity with the advance of their differentiation. In the dental pulp, in contrast, intense immunoreaction in the mesenchymal cells became weak or negative in parallel with the progress of cell differentiation. The immunoreaction for Hsp 25 in the enamel organ revealed a characteristic stage-related alteration during amelogenesis. In secretory ameloblasts, the immunoreaction for Hsp 25 was found throughout their cell bodies, intense reactivity being located near the proximal and distal terminal webs. At the maturation stage, ruffle-ended ameloblasts (RA) consistently showed Hsp 25-immunoreactivity throughout the cell bodies, whereas smooth-ended ameloblasts (SA) lacking a ruffled border were weak in immunoreaction at the distal cytoplasm. Other cellular elements of the enamel organ were negative. The subcellular localization of Hsp 25-immunoreactivity in this study appeared essentially identical to that of actin filaments as demonstrated by confocal microscopy using rhodamine-labeled phalloidin. These immunocytochemical data suggest that the Hsp 25 molecule is involved in reinforcement of the cell layer following cell movement during odontogenesis and in the formation and maintenance of the ruffled border of RA.

Actins↗

Effects of different types of injury to the inferior alveolar nerve on the behavior of Schwann cells during the regeneration of periodontal nerve fibers of rat incisor.

The present study reports on different regeneration patterns of axons and Schwann cells in the periodontal ligament of the rat incisor using immunohistochemistry of protein gene product 9.5 (PGP 9.5) and S-100 protein. Three kinds of injury (transection, crush and segmental resection) were applied to the inferior alveolar nerve. In normal animals, PGP 9.5- and S-100-immunoreactivities were detected in the axons and Schwann cell elements of periodontal Ruffini endings, respectively. They were restricted to the alveolus-related part, occurring only rarely in the tooth-related part and in the shear zone (the border between the alveolus-related and tooth-related parts). Both transection and segmental resection caused the complete disappearance of PGP 9.5-immunoreactive nerve fibers in the periodontal ligament, while a small number of them could be found following the crush injury. Regenerating PGP 9.5-reactive nerve fibers appeared at 5 days and 21 days following the transection and segmental resection, respectively. The regeneration of periodontal nerve fibers completed in a period of 21-28 days and 14-21 days following the transection and crush, respectively, but was not completed even at 56 days following the segmental resection. The behavior of Schwann cells during regeneration was similar after the different nerve injuries; spindle-shaped S-100-immunoreactive cells, presumably Schwann cells, appeared in the shear zone and the tooth-related part. These cells disappeared 5-7 days prior to the completion of the regeneration of axonal elements of the periodontal ligament following the transection and crush. Following the segmental resection, in contrast, spindle-shaped S-100-positive cells disappeared from the tooth-related part at 42 days, although the axonal regeneration of periodontal Ruffini endings proceeded even until 56 days. We thus conclude that the duration of the migration of Schwann cells depends on the state of the regeneration of axons.

Animals↗

Morphological and cytochemical characteristics of periodontal Ruffini ending under normal and regeneration processes.

Current knowledge on the Ruffini endings, primary mechanoreceptors in the periodontal ligament is reviewed with special reference to their cytochemical features and regeneration process. Morphologically, they are characterized by extensive ramifications of expanded axonal terminals and an association with specialized Schwann cells, called lamellar or terminal Schwann cells, which are categorized, based on their histochemical properties, as non-myelin-forming Schwann cells. Following nerve injury, the periodontal Ruffini endings of the rat incisor ligament can regenerate more rapidly than Ruffini endings in other tissues. During regeneration, terminal Schwann cells associated with the periodontal Ruffini endings migrate into regions where they are never found under normal conditions. Also during regeneration, alterations in the expression level of various bioactive substances occur in both axonal and Schwann cell elements in the periodontal Ruffini endings. Neuropeptide Y, which is not detected in intact periodontal Ruffini endings, is transiently expressed in their regenerating axons. Growth-associated protein-43 (GAP-43) is expressed transiently in both axonal and Schwann cell elements during regeneration, while this protein is localized in the Schwann sheath of periodontal Ruffini endings under normal conditions. The expression of calbindin D28k and calretinin, both belonging to the buffering type of calcium-binding proteins, was delayed in periodontal Ruffini endings, compared to their morphological regeneration. As the importance of axon-Schwann cell interactions has been proposed, further investigations are needed to elucidate their molecular mechanism particularly the contribution of growth factors during the regeneration as well as development of the periodontal Ruffini endings.

Animals↗