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Biomedical subjects

N Nishiyama

Publications and source records attributed to N Nishiyama.

At least 19 recordsLinked to original sources
PubMed2003

Accidentally induced periodontitis in primary dentition: longitudinal examinations of periodontal bacteria and clinical conditions.

Periodontitis is very rare in the primary dentition although it can be accidentally induced in young children. The purpose of this study was to describe a case of periodontitis in a 4-year-old child, which was accidentally induced by insertion of small plastic tubes into the dental cervix of the primary incisors during play, and to discuss the clinical, radiographic, and microbiological findings. Removal of the plastic tubes resulted in resolution of the periodontal condition. Prevotella nigrescens and Campylobacter rectus were detected in subgingival plaque samples from the affected teeth at every examination, whereas Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, and Bacteroides forsythus were never found during the two-year observation period. The clinical and microbiological results suggest that the type of periodontitis caused by such an incidence is not progressive, unlike other periodontal diseases such as prepubertal and juvenile periodontitis.

Accidents↗
PubMed2003

Dissociation states of collagen functional groups and their effects on the priming efficacy of HEMA bonded to collagen.

Applying 2-hydroxyethylmethacrylate (HEMA) solution to etched dentin enhances the bonding of resin to dentin. However, the principal adhesion mechanisms have not yet been identified. In this study, we examined the dissociation states of the collagen functional groups of the side-chain amino acid residues and their effects on the bond strength of resin to etched dentin primed by the HEMA solution. The bond strength was strongly dependent upon the dissociation state of the collagen functional groups. Inhibiting the dissociation of the carboxylic acid or the amine of a collagen functional group resulted in increased bond strength of resin to collagen. By understanding the significance of inhibiting the dissociation state, we can better design and develop more effective and efficient primer and bonding agents.

Adhesiveness↗
PubMed2002

Down-regulation of Lsm1 is involved in human prostate cancer progression.

Elucidation of genetic alterations is an approach to understanding the underlying molecular mechanisms of progression of human prostate cancers. We have searched for genes differentially expressed in advanced prostate cancers using cDNA-representational difference analysis, and thereby isolated the Lsm1 as one of down-regulated gene. An Lsm1 expression vector was transfected into PC3 cells, normally featuring down-regulated Lsm1, and four transfectants were established. No differences in morphology or cell proliferation were evident in comparison with parent PC3 or PC3/mock-transfectants. In contrast, significant suppression of invasive potential or metastatic ability of Lsm1 transfectants was observed in the Matrigel chemoinvasion assay and in nude mice, respectively. With human prostate cancers, almost all of informative prostatectomised cases without neoadjuvant therapy showed allelic retention in the Lsm1 region, whereas refractory cancers frequently showed allelic loss in this region. No critical gene mutations were found in open reading frame of Lsm1 in prostate cancers examined by PCR-SSCP analysis, including localised and refractory cancers. These results suggest that Lsm1 is deeply involved in prostate cancer progression through its down-regulation, independent of any gene mutation.

Animals↗
PubMed2002

A 13C NMR study on the adsorption characteristics of HEMA to dentinal collagen.

To develop a more effective primer, we must understand how 2-hydroxyethylmethacrylate, the HEMA primer, enhances bonding at the resin-dentin interface. In this study, to obtain an insight into the adhesion mechanisms of adhesive resin to etched dentin through HEMA, we examined the adsorption characteristics of HEMA to dentinal collagen by using the 13C NMR technique. The addition of dentinal collagen to the HEMA solution resulted in a decrease in T(1) values of carbons attributed to the HEMA, thus reflecting an interaction between HEMA and collagen. Specifically, a reduction in the T(1) value in the ester carbonyl carbon attributed to HEMA greater than that in the other carbons suggested the formation of a hydrogen bond between the ester carbonyl group in HEMA and the dentinal collagen.

Acid Etching, Dental↗
PubMed2001

Organization and expression of the Paramecium caudatum gene encoding nucleosome assembly protein 1.

The complete genomic and partial complementary DNAs encoding the ciliate Paramecium caudatum nucleosome assembly protein 1 (NAP1) have been sequenced. The nap1 gene is situated 1.2 kbp from the hemoglobin (hb) gene, with the 3' end of both genes facing each other. The nap1 gene contains no introns, and encodes a protein of 369 amino acid residues with a calculated molecular weight of 42,627. The P. caudatum NAP1 amino acid sequence shares only 23-27% identity with NAP1 amino acid sequences from other eukaryotes. Although the nap1 transcript was detected in the P. caudatum cells at both the logarithmic and stationary phases, its level increased during the stationary phase. Southern blot analysis and polymerase chain reaction amplification revealed that the P. caudatum macronucleus has a heterogeneous composition at genomic regions around the nap1 gene. The present studies indicate the nap1 and hb genes are closely arranged in the macronucleus with the intergenic region between their sequences heterogeneously composed.

Amino Acid Sequence↗
PubMed2001

Systemic administration of lentinan, a branched beta-glucan, enhances long-term potentiation in the rat dentate gyrus in vivo.

We investigated the effects of oral and intravenous application of lentinan, a branched beta-glucan, on the induction of long-term potentiation (LTP) in the rat dentate gyrus in vivo. Oral administration of lentinan (200 mg/kg) enhanced the induction of LTP evoked by sub-threshold tetanic stimulation (20 pulses at 60 Hz) of the perforant pathway without affecting normal synaptic potentials. Intravenous injection of the compound (0.2-10.0 mg/kg) also enhanced the induction of LTP in a bell-shaped manner, whereas it had no effect on LTP evoked by supra-threshold tetanic stimulation (100 pulses at 100 Hz). Structurally related beta-glucans did not mimic the lentinan-triggered enhancement of LTP. These results suggest that peripherally applied lentinan facilitates the synaptic efficacy of the dentate gyrus neurons in vivo.

Adjuvants, Immunologic↗
PubMed2001

Use of marginal organs from non-heart-beating cadaveric kidney donors.

BACKGROUND: The severe shortage of cadaver donor kidneys for transplantation has prompted many centers to utilize older donor kidneys, which have been associated with lower graft survival rates. The aim of the present study was to examine the availability and feasibility of considering kidneys from donors over the age of 60. METHOD: We studied 252 cadaveric renal transplant recipients (156 males, 96 females) who received kidneys from uncontrolled non-heart-beating donors between 1987 and 1997. We performed in situ cooling with especially designed double-balloon catheters to minimize warm ischemic kidney damage. Recipients were classified according to donor age ( age 60), and we examined graft survival rates. All patients were followed for a minimum of 1 year after transplantation. RESULTS: Graft survival rates for recipients of kidneys from the older donor group at 1, 5, and 10 years after transplantation were 77%, 37%, and 30%, respectively. Corresponding values for the younger donor kidney recipients were 87%, 64%, and 47%, respectively (P=0.0011). Improved survival rates were noted when older kidneys were used for lighter weight recipients (<54 kg). No other significant factors impacted on older donor graft survival rates. CONCLUSION: Older donor kidneys are associated with poorer graft survival rates. However, kidney transplants from older donors can be quite effective in lighter weight recipients (<54 kg).

Adult↗
PubMed2001

Germinal center-associated nuclear protein (GANP) has a phosphorylation-dependent DNA-primase activity that is up-regulated in germinal center regions.

Antigen stimulation induces a rapid proliferation of B cells for expansion of specific B cell clones and their further differentiation into antibody-producing cells in germinal centers of T-dependent antigen-immunized mice. Previously, we identified a 210-kDa germinal center-associated nuclear protein (GANP) that is up-regulated selectively in germinal centers and carries an MCM-binding domain in the carboxyl-terminal side. In addition, here, we found a region (from 414 to 550 aa) in GANP molecule that is slightly similar to the known DNA-primase component p49. The recombinant GANP fragment covering this region synthesizes RNA primers for extension by DNA polymerase I with single-stranded DNA templates in vitro. GANP DNA-primase activity is controlled by phosphorylation at Ser(502) that is induced by CD40-mediated signaling in vitro and in the germinal center B cells stimulated with antigen in vivo. Overexpression of ganp cDNA in Daudi B cells caused the increased DNA synthesis more than the levels of the mock-transfectants. These evidences suggested that the novel DNA-primase GANP is involved in regulation of cell proliferation of antigen-driven B cells in germinal centers.

Acetyltransferases↗
PubMed2001

Cyclic nucleotide-mediated regulation of hippocampal mossy fiber development: a target-specific guidance.

The mossy fibers (MFs) arising from dentate granule cells project primarily onto a narrow segment of the proximal dendrites of hippocampal CA3 pyramidal cells. The mechanisms underlying this specific MF target selection are not fully understood. To investigate the cellular basis for development of the stereotyped MF trajectories, we have arranged the fascia dentata and hippocampal Ammon's horn tissues in diverse topographical patterns in organotypic explant coculture systems. Here we show that cyclic nucleotide signaling pathways regulate the MF pathfinding. When the dentate gyrus explants were ectopically placed facing the CA3 stratum oriens of hippocampal slices, MFs crossed the border between cocultures and reached their appropriate target area in the Ammon's horn, as assessed by membrane tracer labeling, Timm staining, electrophysiological recording of synaptic responses, and optical analyses using a voltage-sensitive dye. This lamina-specific MF innervation was disrupted by pharmacological blockade of cGMP pathway. Similar apposition of the dentate grafts near the CA1 region of host slices rarely resulted in MF ingrowth into the Ammon's horn. Under blockade of cAMP pathway, however, the MFs were capable of making allopatric synapses with CA1 neurons. These data were further supported by the pharmacological data obtained from granule cells dispersed over hippocampal slice cultures. Thus, our findings suggest that the stereotyped MF extension is mediated by at least two distinct factors, i.e., an attractant derived from the CA3 region and a repellent from the CA1 region. These factors may be regulated differently by cAMP and cGMP signaling pathways.

Adenylyl Cyclase Inhibitors↗
PubMed2001

Spatial performance correlates with long-term potentiation of the dentate gyrus but not of the CA1 region in rats with fimbria-fornix lesions.

Although hippocampal long-term potentiation (LTP) is generally assumed to be a cellular mechanism of learning and memory, there has not been definitive evidence for this hypothesis. In the present study, therefore, we addressed the possible relationship between spatial learning ability and LTP by using rats with bilateral fimbria-fornix lesions. The animals were tested for spatial performance in spontaneous alternation behaviors with further in vivo investigation of LTP. The behavioral parameters of spatial memory showed a significant correlation with LTP in the dentate gyrus, but we found no evidence for a linkage with LTP in the CA1 region. Thus, LTP in the dentate gyrus may be important for spatial cognitive ability.

Animals↗
PubMed2001

Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiammineplatinum(II) in the core.

Polymeric micelles of varying size in the range of 20 to 100 nm entrapping an antitumor drug, cis-dichlorodiammineplatinum(II) (cisplatin, CDDP), were prepared through the polymer-metal complex formation of CDDP with a mixture of poly(ethylene glycol)-poly(alpha,beta-aspartic acid) block copolymer (PEG-P(Asp)) and poly(alpha,beta-aspartic acid) homopolymer (P(Asp)) with the different feed ratio in distilled water. An increased ratio of P(Asp) to PEG-P(Asp) led to an increase in the micellar size in a controllable manner as well as prolongation in the induction period of the micellar decay accompanied by a sustained release of CDDP in physiological saline at 37 degrees C. All of the CDDP-loaded micelles with a different incorporation ratio of P(Asp) exhibited appreciable in vitro cytotoxicity due to CDDP release from the micelles by prolonged incubation. These CDDP-loaded micelles are expected to have potential utility in tumor-directed delivery system of CDDP through the modulated in vivo biodisposition based on the EPR effect.

Algorithms↗
PubMed2001

Neuroprotective effects of lipoxygenase inhibitors against ischemic injury in rat hippocampal slice cultures.

Using organotypic cultures of rat hippocampal slices, we investigated the possible involvement of arachidonate cascades in neuronal death following ischemic insult. Oxygen/glucose deprivation-induced neuronal damage was efficiently attenuated by various inhibitors of lipoxygenase, whereas cyclooxygenase inhibitors were less effective. Interestingly, 5- and 12-lipoxygenases are likely to separately mediate ischemic injury in the hippocampus. The present study will provide novel therapeutic targets for the development of neuroprotective agents.

Animals↗
PubMed2001

Aberrant synaptic transmission in the hippocampal CA3 region and cognitive deterioration in protein-repair enzyme-deficient mice.

L-aspartate is the amino-acid residue most susceptible to spontaneous isomerization. This denaturation causes an alteration in the biological activity of the protein and is regarded as an aging process of the protein. Protein L-isoaspartyl methyltransferase (PIMT) repairs this post-translational modification and thus is implicated in retarding the aging process of proteins. PIMT is highly expressed in the brain, and its deficiency results in progressive epilepsy after 4 weeks of age, with a fatal seizure in mice. Here we report the pathophysiological role of this repair system in the hippocampal slice of PIMT-deficient mice. The hippocampal mossy fiber-CA3 synapses of PIMT-deficient mice showed hyperexcitation that was repressed by a gamma-aminobutyric acid (GABA)A receptor agonist muscimol. In addition, the mossy fiber-CA3 synapses failed to show long-term potentiation or paired-pulse facilitation. No abnormality, however, was observed in Schaffer collateral-CA1 synapses or in perforant path-dentate gyrus synapses. Electron microscopic study revealed aberrant distribution of synaptic vesicles in the mossy fiber terminals and vacuolar degeneration at the axon hillock of dentate granule cells in PIMT-deficient mice. Furthermore, the PIMT-deficient mice showed impaired spatial memory in Morris water maze test and exhibited fewer anxiety-related behaviors in the elevated-plus test. These results suggest that the mossy fiber-CA3 system is vulnerable to aspartate isomerization and that the PIMT-mediated repair system is essential for maintenance of normal functions of the hippocampus.

Aging↗
PubMed2001

Withdrawal from chronic morphine administration causes prolonged enhancement of immobility in rat forced swimming test.

RATIONALE: Opiate-dependent subjects experience severe depression as one of the subjective symptoms during withdrawal. No experimental work, however, has focused on the ability of opiate-withdrawal to produce depression-like behavior in dependent animal. OBJECTIVES. We therefore investigated whether withdrawal from chronic morphine treatment affects immobility in forced swimming test in rats. METHODS: Morphine was administered in a dose escalation fashion using doses ranging from 20 to 140 mg/kg twice daily for 14 days, followed by 1-6 days of withdrawal, and their duration of immobility was assessed. RESULTS: After the last morphine treatment. an increase in immobility occurred late on day 3 and persisted to at least day 6 of withdrawal without any change in ambulatory activity. CONCLUSIONS: The results suggest that the morphine withdrawal resulted in prolonged enhancement of depression-like behavior in drug-dependent laboratory animals.

Animals↗
PubMed2001

Cisplatin-loaded polymer-metal complex micelle with time-modulated decaying property as a novel drug delivery system.

PURPOSE: The pharmacological activity and pharmacokinetics of cisplatin (CDDP)-loaded polymeric micelles were examined to reveal their usefulness as a novel tumor-directed drug carrier system of CDDP. METHODS: In biodistribution assay, free CDDP or CDDP-loaded micelles were administered intravenously to Lewis lung carcinoma-bearing mice. Antitumor activity and nephrotoxicity were respectively evaluated by the measurement of tumor size and plasma blood urea nitrogen (BUN) after single bolus i.v. administration of each drug. RESULTS: The time profile of the plasma Pt level after the injection of the micelles exhibited a time-modulated disappearance as observed in saline in vitro. The micelles exhibited 5.2- and 4.6-fold higher AUC of Pt in the plasma and tumor, respectively, with minimal change in the kidney, in comparison with free CDDP, suggesting that prolonged circulation of Pt in circulation and specific accumulation in the tumor were achieved utilizing the micellar drug carrier system. Administration of the micelles at the dose exhibiting antitumor activity similar to free CDDP did not increase the plasma BUN, whereas free CDDP induced its remarkable increase. CONCLUSION: CDDP-loaded micelles restrained nephrotoxicity, which is the dose-limiting factor of CDDP, while exhibiting tumor-specific accumulation. Thus, CDDP-loaded micelles are expected to be a novel formulation of CDDP for clinical use.

Animals↗
PubMed2001

Docosahexaenoic acid improves long-term potentiation attenuated by phospholipase A(2) inhibitor in rat hippocampal slices.

1. We investigated the possible involvement of phospholipase A(2) (PLA(2)) and its products in long-term potentiation (LTP) in the CA1 neurotransmission of rat hippocampal slices. 2. Inhibitors of Ca(2+)-independent PLA(2) (iPLA(2)) prevented the induction of LTP without affecting the maintenance phase of LTP whereas Ca(2+)-dependent PLA(2) inhibitors were virtually ineffective, which suggests a pivotal role of iPLA(2) in the initiation of LTP. 3. We then investigated the effect of docosahexaenoic acid (DHA) and arachidonic acid (AA) on BEL (bromoenol lactone, an iPLA(2)-inhibitor) -impaired LTP, and found that either DHA or AA abolished the effect of BEL. However, DHA did not restore BEL-attenuated LTP when applied after the tetanus. DHA per se affected neither the induction nor maintenance of LTP. Linoleic acid had no effects, either. 4. These results suggest that DHA is crucial for the induction of LTP and that endogenously released DHA during tetanus is sufficient to trigger the formation of LTP.

Animals↗