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Biomedical subjects

A Nishida

Publications and source records attributed to A Nishida.

At least 19 recordsLinked to original sources
PubMed2002

Differences of three-dimensional trabecular microstructure in osteopenic rat models caused by ovariectomy and neurectomy.

We investigated the differences in three-dimensional microstructure of bone in cases of osteopenia caused by two different procedures: ovariectomy (ovx) and sciatic neurectomy (nx). Thirty-nine 8-week-old female Lewis rats were divided into two groups: (1) ovx and sham operation; and (2) nx and sham operation. At 12 weeks of age these rats were killed to sample the right tibiae. The samples were scanned using microcomputed tomography to obtain metric parameters such as bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp), and nonmetric parameters such as structure model index (SMI), trabecular bone pattern factor (TBPf), and degree of anisotropy (DA). The changes in all microstructural parameters were significant in both the ovx and nx groups, with those of BV/TV, Tb.Th, Tb.Sp, and SMI more significant in the ovx group than in the nx group, in comparison to their respective controls. The significantly higher coefficient of variance for Tb.Th across the entire analyzed area of the individual samples indicated that the trabecular thinning occurred heterogenously and that the microstructural deterioration induced by ovx and nx appeared to be locally accelerated, so as to induce perforation and disappearance of trabeculae. The DA increased significantly in the ovx rats, whereas it decreased in the nx rats. The appearance of microstructural deterioration differed between the two osteopenic models. The three-dimensional (3D) images from the nx rats showed flake-like trabeculae, whereas the ovx rats exhibited a diffuse disappearance of trabeculae, especially in the central part of the tibia, but with a preservation of shape for those trabeculae that were retained. The reduction in cortical area was more significant in the nx group. nx and ovx resulted in significant changes in bone microstructure, showing perforation and removal of trabeculae due to locally accelerated bone resorption. The 3D microcomputed tomography images demonstrated the different microstructural changes that occurred in the ovx and nx groups. Loading during bone resorption increased the anisotropy, whereas immobilization increased the isotropy. In addition, immobilization had a more significant effect on the cortical area.

Animals↗
PubMed2002

Contribution of trabecular and cortical components to the mechanical properties of bone and their regulating parameters.

To evaluate the mechanical contributions of the spongiosa and cortex to the whole rat vertebra, we developed a finite element analysis (FEA) system linked to three-dimensional data from microcomputed tomography (micro-CT). Twenty-eight fifth lumbar vertebrae (L-5) were obtained from 10-month-old female rats, comprised of ovariectomized (ovx, n = 6), sham operated (n = 7), and alfacalcidol-treated after ovx (0.1 microg/kg [n = 8] and 0.2 microg/kg [n = 7]) groups. The trabecular microstructure of L-5 was measured by micro-CT. Yield strength at the tissue level (YS), defined as the value at which 0.034% of all elements reached yield stress, was calculated by the FEA. Then, the ultimate compressive load of each specimen was measured by mechanical testing. The YS of the whole bone (YSw) showed a significant correlation with ultimate load (r = 0.91, p < 0.0001). The YS values of the isolated spongiosa (YSs) and cortex (YSc) were calculated in models with varying amounts of trabecular or cortical bone mass. The mechanical contribution of the spongiosa showed a nonlinear relationship with bone mass, and ovx reduced the mean mechanical contribution of the spongiosa to the whole bone by 13% in comparison to the sham group. YSs had a strong relationship with trabecular microstructure, especially with trabecular bone pattern factor (TBPf) and structure model index (SMI), and YSc had a strong relationship with cortical bone volume. The structural parameters most strongly related to YSw were BV/TV and TBPf. Our micro-FEA system was validated to assess the mechanical properties of bone, including the individual properties of the spongiosa and cortex, in the osteoporotic rat model. We found that the mechanical property of each component had a significant relationship with the respective bone mass, volume, or structure. Although trabecular microstructure has a significant relationship with bone strength, in ovx bone with deteriorated trabecular microstructure, the strength depended mainly on the cortical component.

Animals↗
PubMed2001

Synthesis and antibacterial activity of acylides (3-O-acyl-erythromycin derivatives): a novel class of macrolide antibiotics.

Introduction of an acyl group to the 3-O-position of erythromycin A derivatives instead of L-cladinose led to a novel class of macrolide antibiotics that we named "acylides". The 3-O-nitrophenylacetyl derivative TEA0777 showed significantly potent activity against not only erythromycin-susceptible Gram-positive pathogens but also inducibly macrolides-lincosamides-streptogramin B (MLS(B))-resistant Staphylococcus aureus and efflux-resistant Streptococcus pneumoniae. These results indicated that acylides have potential as next-generation macrolide antibiotics.

Animals↗
PubMed2001

Structural requirements of sphingosine molecules for inhibition of DNA primase: biochemical and computational analyses.

Using 28 chemically well-defined compounds containing D-erythro-sphingosine and its analogues, we analyzed structure-activity relationships for DNA primase inhibition. Biochemical studies demonstrated a positively charged amino group at C2 and a long aliphatic chain to be absolutely required for inhibition. Whereas C2-amino group is intact, sphingosine 1-phosphate was totally inactive. This result could be due to cancellation of positive charge of the amino group by the interaction with negatively charged C1-phosphate, since simulations with the software INSIGHT II showed these two groups to be close enough to interact. The hydroxyl group at C3 and trans-double bond at C4-C5 were also found to be important for the inhibition. Dehydroxylation of C3, as well as saturation or cis-conversion of the trans-double bond led to decrease of inhibitory activity. Despite saturation of the double bond, introduction of a hydroxyl group into C4 of dihydrosphingosine resulted in restoration of inhibition. Conversion of the double bond into a triple bond did not abolish but rather enhanced the inhibitory activity. Among sphingosine stereoisomers, the naturally occurring D-erythro-sphingosine proved to be the strongest inhibitor. To ascertain the contribution of the total conformation to the inhibition, especially of the long aliphatic chain, we constructed a 3D-quantitative structure-activity relationship model using the computer program Catalyst/HipHop on the basis of information described above. Analysis of the hypothesis model for active compounds revealed that the orientation of aliphatic chain, represented by the dihedral angle of C2-3-4-5, correlated well with the inhibition. Modifications such as deletion of the hydroxyl group at C3 or saturation of the C4-C5 double bond caused shifts in the dihedral angle of C2-3-4-5, with concomitant decrease in inhibitory activity.

Animals↗
PubMed2001

Lysyl oxidase-catalyzed cross-linking and insolubilization reactions of Lys-containing polypeptides and synthetic adhesive proteins.

The lysyl oxidase- (LO-) mediated insolubilization reactions of the Lys-containing polypeptides have been examined using poly(L-Lys) with degrees of polymerization (Dps) ranging 1 from 2300, copoly(LysxAlay) (x:y = 1:4, 1:3; 1:1, 2:1, and 3:1), copoly(LysxGlyy) (x:y = 1:1 and 2:1), and synthetic adhesive proteins with sequential repetitive units enriched in the Lys residues, poly(Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-Tyr-Lys), poly(Ala-Gly-Tyr-Gly-Gly-Ala-Lys), and poly(Gly-Gly-Gly-Tyr-Gly-Gly-Tyr-Gly-Lys). All of the substrates were insolubilized by the LO-catalyzed oxidation of the epsilon-amino group in the Lys residues. The Dps of the polypeptide substrates did not affect the kinetic constants, the Km and Vmax values. The Km and Vmax values and the insolubilization rates varied depending on the Lys contents in the substrate polypeptides, which were enriched in Gly and Ala residues. As the Lys content increased, the Km and Vmax values became lower and higher, respectively. The insolubilization rates decreased with increase of the Lys content. The time-dependent changes in the LO-catalyzed aldehyde production, the insolubilization, and remaining LO activity demonstrated that the cross-linking and the insolubilization steps occurred along with LO deactivation, indicating that the enzymatic and chemical processes in the LO-mediated insolubilization occur in order.

Adhesives↗
PubMed2001

Induction of photoreceptor-specific phenotypes in adult mammalian iris tissue.

We show that iris tissue in the adult rat eye, which is embryonically related to the neural retina, can generate cells expressing differentiated neuronal antigens. In addition, the Crx gene transfer induced the specific antigens for rod photoreceptors in the iris-derived cells, which was not seen in the adult hippocampus-derived neural stem cells. Our findings demonstrate a remarkable plasticity of adult iris tissue with potential clinical applications, as autologous iris tissue can be feasibly obtained with peripheral iridectomy.

Aging↗
PubMed2001

Antidepressant drug treatments induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells.

Modulation of neurotrophic factors to protect neurons from damage is proposed as a novel mechanism for the action of antidepressants. However, the effect of antidepressants on modulation of glial cell line-derived neurotrophic factor (GDNF), which has potent and widespread effects, remains unknown. Here, we demonstrated that long-term use of antidepressant treatment significantly increased GDNF mRNA expression and GDNF release in time- and concentration-dependent manners in rat C6 glioblastoma cells. Amitriptyline treatment also increased GDNF mRNA expression in rat astrocytes. GDNF release continued for 24 h following withdrawal of amitriptyline. Furthermore, following treatment with antidepressants belonging to several different classes (amitriptyline, clomipramine, mianserin, fluoxetine and paroxetine) significantly increased GDNF release, but which did not occur after treatment with non-antidepressant psychotropic drugs (haloperidol, diazepam and diphenhydramine). Amitriptyline-induced GDNF release was inhibited by U0126 (10 microM), a mitogen-activated protein kinase (MAPK)-extracellular signal-related kinase (ERK) kinase (MEK) inhibitor, but was not inhibited by H-89 (1 microM), a protein kinase A inhibitor, calphostin C (100 nM), a protein kinase C inhibitor and PD 169316 (10 microM), a p38 mitogen-activated protein kinase inhibitor. These results suggested that amitriptyline-induced GDNF synthesis and release occurred at the transcriptional level, and may be regulated by MEK/MAPK signalling. The enhanced and prolonged induction of GDNF by antidepressants could promote neuronal survival, and protect neurons from the damaging effects of stress. This may contribute to explain therapeutic action of antidepressants and suggest new strategies of pharmacological intervention.

Amitriptyline↗
PubMed2001

Osteoporosis in the Japanese population.

The characteristic of osteoporosis in the Japanese population is different from that in the Caucasian population. The different incidence of vertebral and hip fracture may be related to both genetic and lifestyle factors. In the aspect of genetics, approximately 77% of the Japanese have the bb genotype of the vitamin D receptor gene, which is considered to be associated with higher bone mass and lower bone turnover than the Bb genotype. The incidence of vertebral fracture is significantly lower in the younger birth cohorts in both genders. However, the total number of hip fractures rapidly grows as the elderly population increases in Japan. It may be explained by some epidemiological studies that the traditional Japanese lifestyle may prevent hip fractures in the Japanese elderly. The knowledge of the differences of osteoporosis between Caucasian and Japanese people must contribute to the prevention of osteoporosis and its complications.

Accidental Falls↗
PubMed2001

[Extraaxial primary malignant lymphoma associated with calcified chronic subdural hematoma: a case report].

The authors report the case of a 54-year-old male with extraaxial primary malignant lymphoma associated with calcified chronic subdural hematoma. He slowly developed progressive headache accompanied by a bulge in the left forehead. Skull radiogram showed a large biconvex calcification in the left frontoparietal region, with concave change in the overlying bone. Computed tomograms and magnetic resonance images revealed a left frontoparietal chronic subdural hematoma surrounded by a calcified rim, with marginal enhancement in the frontal portion extending upward to the subcutaneous tissue through the underlying bone. The lesion was suspected to be an infectious calcified hematoma. The patient underwent a craniotomy for the removal of the hematoma. It was observed that the tumor was located mainly in the epidural and subdural space. The extent of the tumor corresponded with the enhanced area of the lesion in the preoperative neuroimages. The histological diagnosis was malignant lymphoma of B cell origin. General examination, which included bone marrow study and Ga scintigraphy, failed to prove systemic lymphoma. Extraaxial primary malignant lymphoma is extremely rare, and this is the first report of a lymphoma associated with calcified chronic subdural hematoma. The authors review the literature and discuss the clinical features and the pathogenesis of the lesion.

Brain Neoplasms↗
PubMed2000

Targeted disruption of Na+/Ca2+ exchanger gene leads to cardiomyocyte apoptosis and defects in heartbeat.

Ca(2+), which enters cardiac myocytes through voltage-dependent Ca(2+) channels during excitation, is extruded from myocytes primarily by the Na(+)/Ca(2+) exchanger (NCX1) during relaxation. The increase in intracellular Ca(2+) concentration in myocytes by digitalis treatment and after ischemia/reperfusion is also thought to result from the reverse mode of the Na(+)/Ca(2+) exchange mechanism. However, the precise roles of the NCX1 are still unclear because of the lack of its specific inhibitors. We generated Ncx1-deficient mice by gene targeting to determine the in vivo function of the exchanger. Homozygous Ncx1-deficient mice died between embryonic days 9 and 10. Their hearts did not beat, and cardiac myocytes showed apoptosis. No forward mode or reverse mode of the Na(+)/Ca(2+) exchange activity was detected in null mutant hearts. The Na(+)-dependent Ca(2+) exchange activity as well as protein content of NCX1 were decreased by approximately 50% in the heart, kidney, aorta, and smooth muscle cells of the heterozygous mice, and tension development of the aortic ring in Na(+)-free solution was markedly impaired in heterozygous mice. These findings suggest that NCX1 is required for heartbeats and survival of cardiac myocytes in embryos and plays critical roles in Na(+)-dependent Ca(2+) handling in the heart and aorta.

Animals↗
PubMed2000

Application of Carbopol to controlled release preparations I. Carbopol as a novel coating material.

We investigated the application of Carbopol(R) (CP) as a novel coating material prepared with various grades of CP having different degrees of cross-linking and molecular weights. Viscosity and spray mist size of CP aqueous solutions at various concentrations of CP were measured. Core tablets containing theophylline (TP), as a model drug, were coated with CP at various coating ratios. The TP release profile from the CP-coated tablets was studied by the JP13 paddle method. CP tablets were prepared by compressing CP powder, and the swelling behavior of the CP tablets in JP 1st fluid, purified water, and JP 2nd fluid was observed. The spray mist size of all CP aqueous solutions was small at a concentration of 1% and below, and drastically increased over a concentration of 1%. This result suggests that the appropriate concentration of the CP solution for coating is 1% or below. Sustained release of TP from the CP-coated tablets at a coating ratio of only 3% was observed in the JP 1st fluid and purified water, although fast release was observed in the JP 2nd fluid. The fast release in the latter fluid may be due to the fact that CP is an acid material. These results suggest that it is feasible to control the drug release by use of an extremely small amount of CP coating and that CP is useful as a novel coating material.

Acrylic Resins↗
PubMed2000

Ytterbium(III) triflate/TMSCI: efficient catalyst for imino ene reaction

[reaction: see text] Ytterbium trifluoromethanesulfonate [Yb(OTf)3] catalyzed the imino ene reaction of N-tosyl aldimine with alpha-methylstyrene to give a homoallylamine in moderate yield. Furthermore, addition of a catalytic amount of chlorotrimethylsilane (TMSCI) dramatically enhanced the imino ene reaction.

Journal Article↗
PubMed2000

Effect of heat stress on serotonin-2A receptor-mediated intracellular calcium mobilization in rat C6 glioma cells.

This study was conducted to investigate an effect of heat stress at 44 degrees C for 30 min on intracellular Ca2+ signaling system and on heat shock protein (HSP)-70 expression. 5-HT-induced Ca2+ mobilization was reduced 1, 3 and 6 hrs after heat stress, and recovered to the control level 12 and 24 hrs after heat stress. One hr after heat stress, Ca2+ rise was significantly decreased when the cells were stimulated by any concentration of 5-HT. Thrombin-induced Ca2+ increase was also markedly reduced 1 hr after heat stress. HSP-70 level was increased 6 and 9 hr after heat stress. In HSP synthesis inhibitor quercetin-treated cells, HSP-70 expression was not enhanced after heat stress, and Ca2+ rise in response to 5-HT did not return to the control level. However, the Ca2+ rise induced by 5-HT was not restored to the control level after stress in Ac-Asp-Glu-Val-Asp-H (DEVD)-exposed cells while DEVD had little effect on heat stress-induced synthesis of HSP-70. Dexamethasone did not alter the change in HSP-70 expression or Ca2+ response after heat stress. These results indicate that heat stress attenuated 5-HT-induced Ca2+ mobilization and that HSP-70 expression played an important role in recovery from Ca2+ impairment, possibly via protease activity in C6 cells.

Animals↗
PubMed2000

Differential display of ethanol-induced gene in N18TG2 cells.

BACKGROUND: Recent advances in molecular biology, such as polymerase chain reaction (PCR) differential display, have enabled the screening of mRNAs transcriptionally regulated by chronic ethanol treatment. Screening of gene expression after ethanol exposure will be the most needed for new biological insights into alcoholism. METHODS: We used PCR differential display to detect differentially expressed RNAs in N18TG2 cells treated for 4 days with physiologic concentrations of ethanol (25 mM). RESULTS: We succeeded in identifying two differentially expressed RNAs in the ethanol-treated cells. The increase in the expression of the two RNAs was verified by Northern hybridization analysis. Sequence analyses and searches of the sequence databases revealed that one of the RNAs was that of the heat shock cognate protein 73 (HSC73) gene and that the other was the product of a novel gene. The increase in the level of HSC73 mRNA after ethanol administration was consistent with similar reports from other laboratories, and indicated that our assay system would be applicable to the screening of up-regulated gene expression during ethanol treatment. Rapid amplification of cDNA 5'-ends (5'-RACE) allowed us to determine the upstream sequence of the uncharacterized mRNA that would code for a protein of 113 amino acids. A homology search by MPsrch indicated very low homology to the calcium channel L-type alpha I subunit. CONCLUSIONS: The function of this new gene product is presently unknown, but our results indicate that an investigation of the pathophysiological significance of the gene in alcoholism would be worthwhile. Identification of genes that are influenced by chronic ethanol will certainly increase of the molecular mechanisms underlying physiologic dependence.

Animals↗
PubMed2000

Protective effect of bradykinin against glutamate neurotoxicity in cultured rat retinal neurons.

PURPOSE: To identify the localization and expression of bradykinin (BK)-B2 receptors in rat retina and examine the effects of BK on glutamate-induced neurotoxicity using cultured rat retinal neurons. METHODS: An immunohistochemical study using a specific antibody against BK-B2 receptor was performed with rat retina. Primary cultures were obtained from the retina of fetal rats (gestation day 17-19). Expression of BK-B2 receptor mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA obtained from cultured retinal neurons. Cultured cells were exposed to glutamate (1 mM) for 10 minutes and followed by incubation in glutamate-free medium for 1 hour. The effects of BK were assessed by simultaneous application of BK with glutamate. The neurotoxic effects on retinal cultures were quantitatively assessed by the trypan blue exclusion method. RESULTS: Immunohistochemical study demonstrated that BK-B2 receptors were expressed in the ganglion cell, inner nuclear layers, and outer nuclear layers. Furthermore, BK-B2 receptor mRNA expression was observed in cultured retinal neurons. Cell viability was markedly reduced by 10-minute exposure to 1 mM glutamate followed by a 1-hour incubation in glutamate-free medium. Simultaneous application of BK at concentrations of 0.001 to 1 microM with glutamate demonstrated dose-dependent protection against glutamate neurotoxicity. The protective action of BK (1 microM) was inhibited by simultaneous application of BK-B2 receptor antagonist, Hoe140 (1 microM). Furthermore, 1 microM BK had protective effects on neurotoxicity induced by 1 microM ionomycin, a calcium ionophore, and sodium nitroprusside (SNP, 500 microM), a nitric oxide (NO)-generating agent. However, BK did not inhibit neurotoxicity induced by 3-morpholinosydnonimine (SIN-1, 10 microM), an NO and oxygen radical donor. CONCLUSIONS: These results suggest that BK-B2 receptors were distributed in rat retinas and cultured retinal neurons and that BK had a protective action against glutamate neurotoxicity through BK-B2 receptors in cultured retinal neurons. It is suggested that BK-induced protection against glutamate neurotoxicity took place downstream to NO generation and upstream to oxygen radical generation.

Adrenergic beta-Antagonists↗