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Biomedical subjects

K Kurisu

Publications and source records attributed to K Kurisu.

At least 55 records · Page 3Linked to original sources
PubMed2000

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↗
PubMed2000

Growth inhibition of human glioma cells by transfection-induced P21 and its effects on telomerase activity.

The aim of this study is to investigate the effect of the p21 gene transfection on the growth of cultured human glioma cell lines, and analyze the telomerase activity, and detection of telomerase components in p21 transfectant. The p21 gene was transfected into human glioma cell lines, U251MG and T98G with our novel liposome. The cell growth was assessed by counting the number of trypan blue-excluding cells in a hemocytometer and flow cytometry analysis. The expression of P21 protein and its mRNA were examined by Western and Northern blot analysis. The telomerase activity was assayed by TRAP (telomerase repeat amplification protocol)/TRAP-HPA (hybridization protection assay) method qualitatively and quantitatively. The length of telomere was measured by Southern blot analysis. The expression of telomerase components (hTERT, hTERC and TEP1) were examined by RT-PCR (reverse transcriptase-polymerase chain reaction). The p21 transfectant demonstrated the expression of P21 protein and its mRNA. The p21 transfection of human glioma cells results in growth inhibition and G0/G1 arrest. The p21 transfectant revealed a decrease of telomerase activity and hTERT expression as compared with control cells. These results suggest that p21 transfection induces G0/G1 arrest in human glioma cells which associates with the reduction in the telomerase activity and hTERT expression.

Blotting, Northern↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Local and chronic application of PTH accelerates tooth movement in rats.

We previously reported that whereas systemic continuous infusion of parathyroid hormone (PTH) accelerated orthodontic tooth movement, systemic but intermittent injection of PTH did not increase the rate of tooth movement. Analysis of these data suggested that continuous administration of PTH could be applicable for orthodontic therapy. In the present study, we investigated whether local and chronic application of PTH(1-34) would accelerate orthodontic tooth movement. To increase the residence time of PTH in the injected area, we used methylcellulose (MC) gel (2% W/V) for a slow-release formulation of PTH. MC gel containing PTH (PTH-MC) continuously released biologically active PTH into the acceptor medium for more than 72 hrs in vitro. When male rats received a local injection of PTH-MC into the subperiosteum in the mesio-palatal region of the maxillary first molar (M1) every other day, M1 movement, which was mesially drawn by an orthodontic coil spring attached to the maxillary incisors, was accelerated in a dose-dependent manner. PTH-MC injection at 1 microg/400 g body weight caused a 1.6-fold increase in the rate of tooth movement. The acceleration of tooth movement by PTH-MC injection was marked on days 6, 9, and 12. Local injection of PTH dissolved in saline without MC did not significantly accelerate tooth movement on day 6 or later. Histological examination revealed active osteoclastic bone resorption and a widened periodontal space on the compression side of the periodontal tissue in the PTH-MC-injected rats. These results suggest that local injection of PTH in a slow-release formulation is applicable to orthodontic therapy.

Animals↗
PubMed2000

Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation.

Sonic hedgehog (Shh) and Indian hedgehog (Ihh) are important regulators of skeletogenesis, but their roles in this complex multistep process are not fully understood. Recent studies have suggested that the proteins participate in the differentiation of chondrogenic precursor cells into chondrocytes. In the present study, we have tested this possibility more directly. We found that implantation of dermal fibroblasts expressing hedgehog proteins into nude mice induces ectopic cartilage and bone formation. Immunohistological and reverse-transcription polymerase chain reaction (RT-PCR) analyses revealed that the ectopic tissues derived largely if not exclusively from host cells. We found also that treatment of clonal prechondrogenic RMD-1 and ATDC5 cells in culture with Ihh or recombinant amino half of Shh (recombinant N-terminal portion of Shh [rShh-N]) induced their differentiation into chondrocytes, as revealed by cytoarchitectural changes, Alcian blue staining and proteoglycan synthesis. Induction of RMD-1 cell differentiation by Ihh or rShh-N was synergistically enhanced by cotreatment with bone morphogenetic protein 2 (BMP-2) but was blocked by cotreatment with fibroblast growth factor 2 (FGF-2). Our findings indicate that hedgehog proteins have the ability to promote differentiation of chondrogenic precursor cells and that their action in this process can be influenced and modified by synergistic or antagonist cofactors.

Animals↗
PubMed2000

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↗
PubMed2000

Sigmoid sinus thrombosis after mild closed head injury in an infant: diagnosis by magnetic resonance imaging in the acute phase--case report.

Intracranial sinus thrombosis following a mild closed head injury without a skull fracture or intracranial hematoma is extremely rare. A 23-month-old girl presented with vomiting and gait ataxia 1 day after occipital trauma. Computed tomography revealed a slightly increased density area in the region of the left sigmoid sinus. T1-weighted magnetic resonance (MR) imaging demonstrated an isointense area in the left sigmoid sinus and T2-weighted imaging showed a hyperintense area reflecting the characteristics of oxyhemoglobin. MR angiography and cerebral angiography indicated occlusion of the left sigmoid sinus. After 4 days of conservative treatment, her symptoms subsided completely. Follow-up MR angiography and cerebral angiography showed recanalization of the sigmoid sinus. The MR images and MR angiograms were useful for both early diagnosis and follow-up. Treatment should reflect the severity of individual cases, and early diagnosis will help achieve a good outcome.

Acute Disease↗
PubMed2000

Surgical treatment for intractable epilepsy caused by cavernous angioma in the temporal lobe of the dominant hemisphere--three case reports.

The surgical treatment modality for intractable epilepsy with cavernous angioma in the dominant hemisphere is still unclear. Three patients with medically intractable seizures associated with cavernous angioma in the dominant hemispheric temporal lobe underwent tailored resection based on magnetic resonance (MR) imaging, single photon emission computed tomography (SPECT), electroencephalography monitoring (from scalp and sphenoidal electrodes), and neuropsychologic assessment. Epileptogenic zones were located in the area surrounding the angioma in all patients and mesial temporal dysfunction in two patients. The adjacent cortex and gliotic tissues containing hemosiderin were resected, in conjunction with either total or partial resection of the nidus. Intraoperative electrocorticography (ECoG) was then performed. Additional resection of the mesial temporal structures or multiple subpial transection was performed as indicated by the ECoG findings. All three patients have been seizure free and showed no language or cognitive deterioration for 30, 18, and 14 postoperative months, respectively, while receiving tapered antiepileptic medication. Tailored resection based on electrophysiological data, MR imaging, SPECT, and intraoperative ECoG is effective for the treatment of medically intractable seizure associated with cavernous angioma in the temporal lobe of the dominant hemisphere.

Adolescent↗
PubMed2000

Telomerase activity in primary and secondary glioblastomas multiforme as a novel molecular tumor marker.

OBJECT: Telomerase activity is responsible for cell immortality. To examine the role of telomerase in the carcinogenesis of human glioblastomas multiforme (GBMs), the authors studied telomerase activity, telomerase component expression, and telomere lengths in 42 GBM samples. METHODS: In all samples, EGFR and MDM2 amplifications and overexpressions were examined using Southern and Northern blot analyses. The p53 mutation was analyzed using polymerase chain reaction-single strand conformational polymorphism and by direct sequence analysis. Specimens of tissues were immunostained with p53, EGFR, and MDM2 antibodies. Allelic loss on chromosomes 17p and 10 was assessed by loss of heterozygosity (LOH) assays. Telomerase activity, expression of its components (human telomerase reverse transcriptase [hTERT], human telomerase RNA component [hTERC], and telomerase-associated protein [TEP1]), and telomere lengths were analyzed using the telomeric repeat amplification protocol (TRAP)-hybridization protection assay, reverse transcription-polymerase chain reaction, and Southern blot analysis. According to the results of assessments of EGFR and MDM2 amplifications, p53 mutation, LOHs in chromosomes 17p and 10, and the clinical course of the disease, the 42 samples were classified into 22 primary and 20 secondary glioblastomas. Twenty-six (61.9%) of all 42 samples demonstrated detectable telomerase activity during the TRAP assay. Secondary GBMs displayed significantly higher levels of telomerase activity and hTERT expression than primary GBMs. Tumors with a p53 gene mutation demonstrated significantly higher telomerase activity than those without a p53 mutation. Four samples with a codon 175 mutation demonstrated an exceptionally high amount of telomerase activity. In secondary GBMs, the increase in telomerase activity and the hTERT expression level correlated with the increased frequency of p53 mutations. There was no significant difference in telomere length between primary and secondary GBMs. CONCLUSIONS: These results suggest that telomerase activity and p53 mutations both play important roles in the multistep carcinogenesis of GBMs. Telomerase activity and hTERT expression may be considered as novel distinctive factors in human GBMs.

Aged↗
PubMed2000

NADPH/quinone oxidoreductase is a priority target of glioblastoma chemotherapy.

We attempted to determine a target of chemotherapy specific to glioblastoma cells to ensure a favorable response to anticancer drugs, through comparison in biologic nature related to drug resistance with other types of cancer cells. Using 13 human cancer cell lines including 3 glioblastoma lines, gene expression analysis and biochemical quantitative assay were performed for a total of 12 properties, which have been linked to drug action. Although most of genes related to drug resistance, such as MDR1, MRP, MGMT and GSTpi, were overexpressed in T98G, U-373MG, and U-251MG glioblastoma cells, Topo I (topoisomerase I) expression was relatively low and alpha- and beta-TUB (tubulin) expression was comparable to other types of 10 cell lines. The glioblastoma cell lines also showed an increased expression of NADPH/quinone oxidoreductase gene (NQO1), but the respective enzyme NQO activated MMC. Among the drugs targeting such properties, MMC was more active than Topo I inhibitors and docetaxel (TXT) due to the lack of other sensitivity (resistance) determinants. Differing from MMC, MGMT was shown to participate in the resistance of Topo I inhibitors (CPT-11, SN-38 and DX-8951f), while GSTpi and MDR1 were involved in docetaxel (TXT) resistance. MMC was also more active than ACNU and CDDP in the three glioblastoma cells. NQO may be a priority target of glioblastoma chemotherapy suitable for biochemical nature of the cells, and expression analysis of NQO1, alpha-TUB, beta-TUB, MGMT, MDR1 and GSTpi may help to seek a truly active drug against glioblastomas.

Antineoplastic Agents↗
PubMed1999

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↗
PubMed1999

Telomerase activity in central nervous system malignant lymphoma.

BACKGROUND: Primary central nervous system malignant lymphoma (PCNSL) has been regarded as a rare neoplasm. Recently, however, its incidence has been rapidly increasing. Despite active clinical trials, its clinical and biologic features remain unknown and there has been no effective treatment or prognostic factor. The current study attempted to elucidate telomerase activity and expression of the telomere-related RNA of PCNSL as novel prognostic factors. METHODS: The subjects were 12 patients with histologically diagnosed PCNSL. All patients were treated with chemoradiotherapy consisting of whole-brain radiation, vincristine, etoposide, and prednisolone. Telomerase activity in the resected tumor was analyzed both qualitatively and quantitatively using the TRAP (telomeric amplification assay protocol)/TRAP-HPA (hybridization protection assay) method. The expression of telomere-related RNA (hTERT, hTERC, and TEP1) was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: Telomerase activity was detected in 10 of 12 patients with PCNSL, with an average activity of 148.9 relative light units. The average telomere length was 5.55 kb. The expression of hTERT correlated with telomerase activity, and there was a statistically significant correlation between telomerase activity and both the duration of survival and the interval to tumor progression. CONCLUSIONS: Telomerase activity and the expression of hTERT may be novel prognostic factors in patients with PCNSL.

Adult↗
PubMed1999

Cholinergic and glutamatergic transmission in medial vestibular nucleus neurons responding to lateral roll tilt in rats.

The responses of the medial vestibular nucleus (MVN) neurons to lateral tilt and the neurotransmitters mediating otolith information to MVN neurons were investigated using rats. A computer-operated goniometer was tilted 20 degrees clockwise and counterclockwise at an angular speed of 5 degrees /s and paused in the inclined positions for 10 s to record neuronal responses in the static phase. The 185 MVN neurons recorded were classified into eight types according to their responses to tilt (alpha, beta, gamma, delta, epsilon, zeta, eta and theta). A majority showed increased firing in response to ipsilateral tilting and decreased firing in response to contralateral tilting (alpha type: 31.4%) or exhibited the reverse pattern (beta type: 36.8%). Further, other groups of neurons increased (gamma type) or decreased (delta type) firing rates to either side tilting and increased (epsilon and zeta type) or decreased (eta and theta type) firing only on one side. Atropine or L-glutamic acid diethyl ester hydrochloride (GDEE) applied microiontophoretically antagonized tilt-induced firing of alpha type neurons in 58.8% or 60.0%, respectively, and of beta type neurons in 66.7% or 58.3%, respectively. When the effects of atropine and GDEE were examined in the same neurons, antagonizing effects of both drugs on tilt-induced firing were obtained in 28.6% and 40.0% of alpha and beta type neurons, respectively. These results suggest that both acetylcholine and glutamate act as neurotransmitters in the transmission of otolith information to most MVN neurons.

Animals↗