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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 91 records · Page 5Linked to original sources

Antagonism of saikosaponin-induced prostaglandin E2 release by baicalein in C6 rat glioma cells.

There are several Kampo medicines (Chinese herbal medicines) containing both Bupleuri Radix and Scutellariae Radix, which are used for the treatment of inflammation. Saikosaponins are derived from Bupleuri Radix, and baicalein is from Scutellariae Radix. The present study was undertaken to investigate the pharmacological interaction of saikosaponin b1 and baicalein in prostaglandin E2 (PGE2) release from C6 rat glioma cells in vitro. Saikosaponin a, b1 and d potently stimulated PGE2 release, while saikosaponin b2 and c moderately stimulated PGE2 release. Saikosaponin b1 caused an irreversible elevation of intracellular Ca2+ concentration, which was eliminated by removing extracellular Ca2+. On the other hand, baicalein inhibited saikosaponin b1-induced PGE2 release in a concentration-dependent manner. These results suggest that saikosaponins are activators of PGE2 release, and baicalein is one of the functional inhibitors of PGE2 release by saikosaponins.

Animals↗

[A study of air pollution in the smoking hall].

We investigated the air pollution in the student smoking hall from February 1st in the winter season, and during 8 days in the middle of April in the spring season. The student smoking hall was in an open, draught location. Moreover, the concentration of pollutants were measured in three time periods: break, lecture and lunch times. The pollutants measured were nitrogen monoxide (NO), nitrogen dioxide (NO2), carbon monoxide (CO), carbon dioxide (CO2), suspended particulate matter (SPM) and polynuclear aromatic hydrocarbon (PAH). The concentrations of pollutants measured during the break times were of a relatively higher level than those during the lecture and lunch times. However, the concentration of pollutants were not influenced by ventilation operation in the smoking hall, which is not a closed place. SPM and CO2 concentrations during the break time were instantaneously investigated above Building Sanitation Standards Management, Japan (SPM: 0.15 mg/m3, CO2: 1,000 ppm). Especially, the SPM concentration was recognized to be strongly influenced by tobacco smoke.

Air Pollution, Indoor↗

High incidence of meningioma among Hiroshima atomic bomb survivors.

Since the atomic bomb explosions in Hiroshima and Nagasaki, high incidences of leukemia, thyroid cancer and other tumors have been reported as atomic bomb-induced tumors. We investigated the incidence of meningioma among Hiroshima atomic bomb survivors. Sixty-eight patients surgically treated for meningioma who had been within 2.0 km of the hypocenter of the explosion were identified. Six hundred and seven non-exposed patients with meningioma were also studied. Treatment dates were from 1975 to 1992. The incidences of meningioma among 68 subjects within 2.0 km and 607 non-exposed patients were 8.7 and 3.0 cases per 10(5) persons per year, respectively. The incidences of meningioma among the survivors of Hiroshima in 5-year intervals since 1975 were 5.3, 7.4, 10.1, and 14.9, respectively. The incidences of meningioma classified by distances from the hypocenter of 1.5-2.0 km, 1.0-1.5 km and less than 1.0 km were 6.3, 7.6 and 20.0, respectively. The incidences of meningioma classified by doses to the brain of 0-0.099 Sv, 0.1-0.99 Sv and more than 1.0 Sv were 7.7, 9.2 and 18.2, respectively. The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975. There was a significant correlation between the incidence and the dose of radiation to the brain. The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima.

Brain↗

Osteoclast formation in bone marrow cultures from two inbred strains of mice with different bone densities.

For the purpose of identifying genes that affect bone volume, we previously identified two inbred mouse strains (C57BL/6J and C3H/HeJ) with large differences in femoral bone density and medullary cavity volume. The lower density and larger medullary cavity volume in C57BL/6J mice could result from either decreased formation or increased resorption or both. We recently reported evidence suggesting that bone formation was increased in vivo and that osteoblast progenitor cells are more numerous in the bone marrow of C3H/HeJ compared with C57BL/6J mice. In the present study, we determined whether osteoclast numbers in vivo and osteoclast formation from bone marrow cells in vitro might also differ between the two mouse strains. We have found that the number of osteoclasts on bone surfaces of distal humerus secondary spongiosa was 2-fold higher in 5.5-week-old C57BL/6J mice than in C3H/HeJ mice of the same age (p < 0.001). Bone marrow cells of C57BL/6J mice cocultured with Swiss/Webster mouse osteoblasts consistently produced more osteoclasts than did C3H/HeJ bone marrow cells at all ages tested from 3.5-14 weeks of age (p < 0.001). Osteoclast formation was also greater from spleen cells of 3.5-week-old C57BL/6J mice than C3H/HeJ mice. The distribution of nuclei per osteoclast and the 1, 25-dihydroxyvitamin D3 dose dependence of osteoclast production from bone marrow cells were similar. Osteoclasts that developed from both C57BL/6J and C3H/HeJ marrow cells formed pits in dentin slices. Cultures from C57BL/6J marrow cells formed 2.5-fold more pits than cultures from C3H/HeJ marrow cells (p < 0.02). We compared the abilities of C57BL/6J and C3H/HeJ osteoblasts to support osteoclast formation. When bone marrow cells from either C57BL/6J or C3H/HeJ mice were cocultured with osteoblasts from either C57BL/6J or C3H/HeJ newborn calvaria, the strain from which osteoblasts were derived did not affect the number of osteoclasts formed from marrow cells of either strain. Together, these observations suggest that genes affecting the bone marrow osteoclast precursor population may contribute to the relative differences in bone density that occur between C3H/HeJ and C57BL/6J mouse strains.

Animals↗

Effects of feed restriction and cold exposure on glucose metabolism in response to feeding and insulin in sheep.

The effects of feed restriction, cold exposure, and the initiation of feeding on blood glucose metabolism, other blood metabolites, hormones, and tissue responsiveness and sensitivity to insulin were measured in sheep. The sheep consumed orchardgrass hay ad libitum (AL) or were restricted to 82% of the ME requirement for maintenance (RE) and were exposed to a thermoneutral (20 degrees C) or a cold environment (2 degrees C). An isotope dilution method and a glucose clamp approach were applied to determine blood glucose metabolism and insulin action, respectively. Plasma NEFA and insulin concentrations were influenced by feed restriction. Concentrations of plasma glucose, NEFA, insulin, and glucagon were influenced by cold exposure. Plasma NEFA concentration for RE decreased after the initiation of feeding and plasma insulin concentration increased transiently for all treatments. [U-13C]Glucose was continuously infused for 8 or 7 h after a priming injection starting 3 h before the initiation of either feeding or insulin infusion, respectively. When responses to feeding were studied, blood glucose turnover rate was less (P < .001) for RE than for AL, and it was greater (P < .001) during cold exposure than in the thermoneutral environment. The rate changed little after the initiation of feeding. For the glucose clamp approach, insulin was infused over four sequential 1-h periods at rates from .64 to 10 mU x kg BW(-1) x min(-1), with concomitant glucose infusion to maintain preinfusion plasma glucose concentrations. The rates of glucose infusion and blood glucose turnover increased (P < .001) dose-dependently with insulin infusion rate. The maximal glucose infusion rate was greater (P < .05) for RE than for AL and was greater (P < .001) during cold exposure than in the thermoneutral environment. The plasma insulin concentration at half-maximal glucose infusion rate was lower (P < .1) during cold exposure. Blood glucose turnover rate tended to be greater (P = .10) for RE than for AL, and it was greater (P < .001) during cold exposure than in the thermoneutral environment. The ratio of endogenous production to utilization of glucose was suppressed by insulin infusion. In sheep fed a roughage diet, blood glucose turnover rate seems to be influenced by both intake level and environmental temperature, but not by the act of feeding. Moreover, the action of insulin on glucose metabolism is enhanced during cold exposure, and the effect of feed restriction is somewhat enhanced.

Animals↗

The absolute configuration of belactin A, a beta-lactone-containing serine carboxypeptidase inhibitor: importance of the beta-lactone structure for serine carboxypeptidase inhibition.

The absolute configuration of belactin A, a beta-lactone-containing serine carboxypeptidase inhibitor was studied by a crystal X-ray diffraction analysis and its absolute structure was determined to be (2R,3S)-2-¿(3S)-3-[(2-amino-5-chlorophenyl)carboxamido]-1,1-dimethyl-2-o xobutyl¿-3-methyl-4-oxooxetane. The importance of the beta-lactone structure for inhibitory activity was found by preparing several derivatives of belactin A.

Benzamides↗

The F value for chromosome aberrations in atomic bomb survivors does not provide evidence for a primary contribution of neutrons to the dose in Hiroshima.

Brenner and Sachs (Radiat. Res. 140, 134-142, 1994) proposed that the ratio of interchromosomal to intrachromosomal exchanges, termed the F value, can be a cytogenetic fingerprint of exposure to radiations of different linear energy transfer (LET). Using published data, they suggested that F values are over 10 for low-LET radiations and approximately 6 for high-LET radiations. Subsequently, as F values for atomic bomb survivors were reported to be around 6, Brenner suggested that the biological effects of atomic bomb radiation in Hiroshima are due primarily to neutrons. However, the F values used for the survivors were means from individuals exposed to various doses. As the F-value hypothesis predicts a radiation fingerprint at low doses, we analyzed our own data for the survivors in relation to dose. G-banding data for the survivors showed F values varying from 5 to 8 at DS86 doses of 0.2 to 5 Gy in Hiroshima and around 6 in Nagasaki with no evidence of a difference between the two cities. The results are consistent with our in vitro data that the F values are invariably around 6 for X and gamma rays at doses of 0.5 to 2 Gy as well as two types of fission-spectrum neutrons at doses of about 0.2 to 1 Gy. Thus, apart from a possible effect at even lower doses, current data do not provide evidence to support the proposition that the biological effects of atomic bomb radiation in Hiroshima are caused mainly by neutrons.

Chromosome Aberrations↗

[A case of chordoid meningioma].

Chordoid meningioma is a very rare variant, especially in adults. We report an adult case of chordoid meningioma. A 52-year-old man was admitted to our hospital due to right hemiparesis. MRI revealed a left temporal convexity mass that showed two structures; the cerebral layer was shown as an isointensity area on T1WI and T2WI, and the dural layer seemed relatively hypointense on T1WI and hyperintense on T2WI. The tumor was well enhanced with gadolinium, especially on the dural side. A left external carotid arteriogram showed tumor stains with feeding vessels from the left middle meningeal artery. The tumor was totally removed via fronto-temporal craniotomy. Histological examination of the surgical specimen revealed two different structural components, meningothelial meningioma on the cerebral side, and chordoid meningioma on the dural side, consisting of clustering spindled cells and partly vacuolated ones in the mucoid stroma. In immunohistochemical examination, tumor cells showed positive staining for vimentin and epithelial membrane antigen (EMA), and negative for cytokeratin. From the above findings, this case was diagnosed as chordoid meningioma in an adult, a very rare variant of meningioma.

Chordoma↗

Attenuation of regional differentiation of sympathetic nerve activity during sleep in humans.

The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.

Adult↗

Zinc transport from the striatum and substantia nigra.

65Zn was unilaterally injected into the striatum or substantia nigra of rats to see the transport of intracerebral zinc (Zn). In the case of intrastriatal injection, 65Zn was densely distributed in the ipsilateral medial forebrain bundle (MFB) and the substantia nigra. On unilateral colchicine injection into the MFB, 65Zn distribution in the ipsilateral substantia nigra decreased significantly compared to that of the contralateral one after 65Zn injection into the bilateral striata. These results suggest the presence of axonal transport of 65Zn taken up by striatonigral gamma-aminobutyric acid (GABA)-ergic and/or nigrostriatal dopaminergic neurons. On the other hand, in the case of intranigral injection, 65Zn was distributed in the ipsilateral MFB, striatum, globus pallidus, pontine reticular nuclei, and pontine nuclei. 65Zn distribution in the pons 1 day after intranigral injection was very similar to that 6 days after intrastriatal injection, suggesting that, in the case of intrastriatal injection of 65Zn, nigral 65Zn, which was transported anterogradely and/or retrogradely from the striatum, was transported to the postsynaptic neurons through the synapse and then transported to the pons.

Animals↗

Affinity purification of Helicobacter pylori urease. Relevance to gastric mucin adherence by urease protein.

A simple, reproducible and high yield method of Helicobacter pylori urease enzyme purification was developed using a heparinoid (Cellufine sulfate) affinity gel. The purification method involved two sequential steps using the same gel that takes advantage of the differential affinity of urease to the heparinoid at two levels of hydrogen ion concentration. SDS-polyacrylamide gel electrophoresis analysis of affinity-purified urease revealed two major protein bands with about 62- and 30-kDa molecular mass. When whole cell lysates of clinical and laboratory strains of H. pylori were probed by Western blot, anti-urease hyperimmune serum produced by affinity-purified urease in rabbit recognized only the two bands corresponding to the urease A and B subunits. To probe the molecular relevance of affinity gel adherence to mucin adherence, the purified urease was derivatized with N-hydroxysuccinimidobiotin and used in adherence assays. Competitive inhibition tests revealed commonality of urease receptors among gastric mucin, heparin, and heparinoid. Composite data on adherence kinetics modulated by pH, salt, incubation time, and concentration of urease or mucin were indicative of conformation-dependent ligand-receptor interaction.

Animals↗

Specificity of pyridinium inhibitors of the ubiquinone reduction sites in mitochondrial complex I.

Dual binding sites for pyridinium-type inhibitors in bovine heart mitochondrial complex I have been proposed (Gluck, M. R., Krueger, M. J., Ramsay, R. R., Sablin, S. O., Singer, T. P., and Nicklas, W. J. (1994) J. Biol. Chem. 269, 3167-3174). The marked biphasic nature of the dose-response curve for inhibition of the enzyme by MP-6(N-methyl-4-[2-(p-tert-butylbenzyl)propyl]pyridinium) makes this compound the first selective inhibitor of the two sites (Miyoshi, H., Inoue, M., Okamoto, S., Ohshima, M., Sakamoto, K., and Iwamura, H. (1997) J. Biol. Chem. 272, 16176-16183). Modifications of the structure of MP-6 show that a tert-butyl group on the benzene ring, a methyl group attached to the pyridine nitrogen atom, para-substitution pattern in the pyridine ring, and the presence of a branched structure in the spacer moiety are important for the selective inhibition. On the basis of the structural specificity, we synthesized a selective inhibitor, MP-24 (N-methyl-4-[2-methyl-2-(p-tert-butylbenzyl)propyl]pyridinium), which elicits greater selectivity. Characterization of the inhibitory behavior of MP-24 provided further strong evidence for the dual binding sites model.

Animals↗

Effect of chronic amitriptyline administration on serotonergic receptors in rats with methylazoxymethanol-induced microencephaly.

Methylazoxymethanol (MAM)-induced cortical hypoplasia resulted in a 20% decrease in the Bmax of 5-HT2A receptors in the frontal cortex with no change in the Bmax of 5-HT1A receptors. Chronic treatment with amitriptyline did not further decrease the Bmax of 5-HT2A receptors in the MAM-lesioned cortex, suggesting that the persistent down-regulation of cortical 5-HT2A receptors in MAM-lesioned rats was induced by serotonergic hyperinnervation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effects of prenatal methylazoxymethanol treatment on striatal dopaminergic systems in rat brain.

To further examine the effects of prenatal methylazoxymethanol (MAM) treatment on striatal dopaminergic systems, the status of presynaptic dopamine transporters was examined by quantitative autoradiography of [3H]GBR 12935 binding. Significantly higher [3H]GBR 12935 binding was seen in MAM-lesioned striatum in comparison to the controls, indicating relative dopaminergic hyperinnervation in MAM-induced hypoplastic striatum. The effect of prenatal MAM treatment on extracellular levels of dopamine and its metabolites in the striatum was also examined using in vivo microdialysis. As measured in conscious freely-moving rats, prenatal MAM treatment significantly increased basal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) release in the striatum in comparison with control rats. These data suggest that in accordance with morphological dopaminergic hyperinnervation, dopaminergic functions are significantly augmented in MAM-lesioned brains. Thus, it is suggested that MAM-induced microencephalic rats should serve as a good animal model for the study of augmented dopaminergic functions in the striatum.

3,4-Dihydroxyphenylacetic Acid↗

Oral passive immunization against experimental salmonellosis in mice using chicken egg yolk antibodies specific for Salmonella enteritidis and S. typhimurium.

The efficacy of chicken egg yolk homotypic antibodies specific for outer membrane proteins (OMP), lipopolysaccharide (LPS) or flagella (Fla) in controlling experimental salmonellosis in mice was investigated. Mice challenged orally with 2 x 10(9) c.f.u. of Salmonella enteritidis or 2 x 10(7) c.f.u. of S. typhimurium were orally treated with 0.2 ml anti-OMP, -LPS or -Fla yolk antibody three times a day for three consecutive days. In mice challenged with S. enteritidis, antibody treatment resulted in a survival rate of 80%, 47% and 60% using OMP, LPS or Fla specific antibodies respectively, in contrast to only 20% in control mice. In the S. typhimurium trial, survival rate was 40%, 30% and 20% using OMP, LPS or Fla specific antibodies respectively in contrast to 0% in control mice. In vitro adhesion of S. enteritidis and S. typhimurium to HeLa cells was significantly reduced by anti-OMP, -LPS, and -Fla homotypic antibodies. Results suggest that egg yolk antibodies specific for Salmonella OMP, LPS, and Fla may protect mice from experimental salmonellosis when passively administered orally. Of these antibodies, anti-OMP exhibited the highest level of protection in vivo and in vitro.

Animals↗

Manganese transport in the neural circuit of rat CNS.

To study manganese (Mn) transport in the neural circuit of rat CNS, brain isotope distribution after 54Mn injection into the brain was analyzed by autoradiography. One day after 54MnCl2 injection into the striatum, 54Mn was highly distributed in the ipsilateral thalamus, hypothalamus, and substantia nigra. When 54MnCl2 was bilaterally injected into the striata after unilateral treatment with colchicine or vehicle into the medial forebrain bundle, 54Mn was distributed in both sides of the substantia nigra of vehicle-treated rats. On the other hand, unilateral colchicine treatment caused a decrease of 54Mn distribution in the ipsilateral substantia nigra, suggesting that Mn is subjected to axonal transport in the striatonigra and/or nigrostriatal pathways. In the case of unilateral injection of 54MnCl2 into the olfactory bulb, 54Mn was distributed in the ipsilateral piriform, amygdaloid areas (the primary olfactory cortex), and entorhinal area (the secondary olfactory cortex). These results suggest that Mn is subject to widespread axonal transport in the neural circuits. Moreover, Mn may be taken up by the piriform neurons (the third olfactory neuron) after release from the secondary olfactory neuron terminals and transported to the entorhinal area.

Animals↗

Effect of mechanical unloading and reloading on periosteal bone formation and gene expression in tail-suspended rapidly growing rats.

In order to delineate the influence of mechanical unloading on the formation and resorption of trabecular and cortical bone, the effects of mechanical unloading on the volume, structure, and turnover of hindlimbs were examined using tail-suspended rapidly growing rats. In addition, to clarify the mechanism of how mechanical stimulation affects bone formation, the influence of reloading on the messenger ribonucleic acid (mRNA) expression of genes related to differentiation or proliferation of bone cells was examined. Tail suspension of 5-week-old rats for 14 days caused a suppression of the increase in the diameter, subperiosteal area, and bone mineral density (BMD) of the femur. The suppression of the increase in femoral BMD was composed of an early impairment in the gain of BMD at the femoral metaphysis, which is rich in trabecular bone, and a sustained reduction in the gain of BMD at the femoral diaphysis, which is rich in cortical bone. The early reduction in the increase of BMD at the metaphysis was due to an enhancement of bone resorption, whereas a sustained reduction of periosteal bone formation appeared to play an important role in the suppression of gain in cortical bone mass and size by mechanical unloading. Mechanical reloading of the hind limbs after 14 days of tail suspension caused a transient increase within 2 h of the expression of cyclooxygenase (COX)-2 in intraosseous cells, composed mainly of osteocytes, and in the expression of c-fos in periosteal cells. However, because the COX-2 expression in osteocytes was not enhanced after 20 min of reloading when the c-fos expression was already increased in periosteal cells, the enhancement of c-fos expression does not appear to be mediated by an increased production of prostaglandins in the osteocytes. It is suggested that mechanical unloading causes an impairment of periosteal bone formation by impairing the expression of c-fos in periosteal cells. The intercellular signaling cascade that mediates the enhancement of c-fos expression in periosteal cells in response to mechanical stimulation remains to be elucidated.

Alkaline Phosphatase↗