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Biomedical subjects

K Nakaya

Publications and source records attributed to K Nakaya.

At least 55 records · Page 3Linked to original sources
PubMed1999

beta-hydroxyisovalerylshikonin inhibits the cell growth of various cancer cell lines and induces apoptosis in leukemia HL-60 cells through a mechanism different from those of Fas and etoposide.

beta-Hydroxyisovalerylshikonin (beta-HIVS), which was isolated from the plant, Lithospermium radix, inhibited the growth of various lines of cancer cells derived from human solid tumors at low concentrations between 10(-8) and 10(-6) M. When HL-60 cells were treated with 10(-6) M beta-HIVS for 3 h, characteristic features of apoptosis, such as DNA fragmentation, nuclear fragmentation, and activation of caspase-3-like activity, were observed. The most characteristic features of the effect of beta-HIVS were the remarkable morphological changes induced upon treatment of HL-60 cells with beta-HIVS, as visualized on the staining of actin filaments with phalloidin labeled with tetramethylrhodamine B isothiocyanate. Moreover, activation of MAP kinases, such as ERK2, JNK and p38, was detected after treatment with 10(-6) M beta-HIVS preceding the appearance of the characteristics of apoptosis, and the features of the activation of these MAP kinases were quite different from those of Fas and anticancer drug-induced apoptosis. The activation of JNK by beta-HIVS was not inhibited by inhibitors of caspases, suggesting that JNK is located either upstream or independent of the caspase signaling pathway. beta-HIVS did not inhibit the activity of topoisomerase II. These results indicate that beta-HIVS induces apoptosis in HL-60 cells through a mechanism unlike those reported for anti-Fas antibodies and etoposide.

Antineoplastic Agents↗
PubMed1999

Induction of apoptosis by bufalin in human tumor cells is associated with a change of intracellular concentration of Na+ ions.

In an attempt to characterize the mechanisms that are operative at the early stages of the induction of apoptosis by bufalin, a component of the traditional Chinese medicine chan'su, we examined the effects of bufalin on plasma membrane potential, as determined by monitoring the uptake by cells of rhodamine 123. Bufalin induced apoptosis in human monocytic leukemia THP-1 cells, in human lymphoblastic leukemia MOLT-3 cells, and in human colon adenocarcinoma COLO320DM cells but not in normal human leukocytes, for example, polymorphonuclear cells and lymphocytes, and not in murine leukemia P388D1 and M1 cells. Treatment for 3 h with bufalin at 10(-6) M caused a decrease in the plasma membrane potential in several lines of human tumor cells but not in murine leukemia cells. No changes in mitochondrial membrane potential, as monitored with the fluorescent dye JC-1, and no release of cytochrome c were observed within at least 6 h after the start of treatment with bufalin. Moreover, overexpression of bcl-2 in human leukemia HL60 cells that had been transfected with cDNA for bcl-2 prevented bufalin-induced apoptosis but had no significant effect on the change in plasma membrane potential induced by bufalin. Since bufalin specifically inhibits the Na+,K(+)-ATPase of human but not murine tumor cells, and since this inhibition leads to a change in intracellular concentration of Na+ ions, our findings suggest that bufalin induces apoptosis in human tumor cells selectively via inhibition of the Na+,K(+)-ATPase, which acts upstream of the bcl-2 protein.

Animals↗
PubMed1999

Angles between A1 and A2 segments of the anterior cerebral artery visualized by three-dimensional computed tomographic angiography and association of anterior communicating artery aneurysms.

OBJECTIVE: The angle of arteries at bifurcations, as well as the blood flow, are factors of hemodynamic stress on the apical region, where aneurysms often develop. Using images obtained with three-dimensional computed tomographic angiography, we sought to determine the angles between the A1 and A2 segments of the anterior cerebral artery of the anterior communicating artery (ACoA) complex associated with aneurysms. These angles cannot be detected by conventional cerebral angiography. METHODS: The course of the anterior cerebral artery was studied using three-dimensional computed tomographic angiography in 42 consecutive patients with ACoA aneurysms. Twenty-one other subjects, randomly chosen from patients without aneurysms, served as controls. Bilateral A1-A2 angles of the contrast-opacified anterior cerebral artery were measured by three-dimensional computed tomographic angiography in patients with normoplastic A1 segments, and the relationship between the angle and the association of aneurysms was analyzed using cerebral angiography. RESULTS: Of the 42 patients with ACoA aneurysms, 19 patients showed hypo- or aplastic A1 segments, as did only 2 of the 21 patients without ACoA aneurysms. The average A1-A2 angle was determined to be 116+/-24 degrees (mean+/-standard deviation) in 18 patients having ACoA complexes with normoplastic A1 segments with aneurysms; 17 patients without aneurysms had A1-A2 angles measuring 143+/-14 degrees (P < 0.0001). The A1-A2 angle associated with ACoA aneurysms was 103+/-20 degrees, which was much smaller than that of the non-aneurysm side in the former group (128+/-20 degrees) (P = 0.0036). CONCLUSION: ACoA aneurysms are associated with the smaller A1-A2 angle junction of the ACoA complex, where higher hemodynamic stress may occur in patients with normoplastic A1 segments.

Adult↗
PubMed1999

Elasticity effects on domain coarsening of the lamellar-gyroid transition observed in a nonionic surfactant system.

The coarsening process of the gyroid phase of a nonionic surfactant system is investigated by time resolved small angle neutron scattering (SANS) and small angle neutron Laue diffraction techniques. The time evolution of SANS patterns shows anomalous coarsening of the gyroid domains. The observed Laue spot from a gyroid domain becomes elongated along the radial direction with the elapse of time and at a certain time the elongated spot is split into two spots. The results can be interpreted as follows. During the coarsening process, mismatch of the lattice orientation at the domain boundary brings strong stress to the gyroid domain, resulting in the distortion of the domain. The stored stress in the domain finally brings splitting of the gyroid domain. The elastic and fragile nature of the gyroid domains composed of the "soft matter" is responsible for the anomalous coarsening.

Journal Article↗
PubMed1999

Insufficient resistance of trehalose-6,6-dimycolate-treated T-cell receptor delta gene mutant (TCR delta-/-) mice against influenza virus infection.

Normal mice inoculated intravenously with 50 microg trehalose-6,6'-dimycolate, a glycolipid component of the cell wall of Mycobacterium, in an oil-in-water emulsion (TDM emulsion) acquired a high resistance to intranasal lethal infection of an influenza virus. In contrast, TDM emulsion-treated T-cell receptor delta gene mutant (TCR delta-/-) mice acquired insufficient resistance against the lethal influenza virus infection. The patterns of insufficient resistance were identical to the results obtained previously with mice which were depleted of T-lymphocytes bearing gammadelta T-cell receptors (gammadelta T-cells) by in vivo administration of anti-gammadelta T-cell receptor monoclonal antibody (Hoq et al, J. Gen. Virol. 78: 1597-1603, 1997). These results strongly suggest that the gammadelta T-cells play an important non-specific role in resistance against influenza virus infection.

Animals↗
PubMed1999

Low-dose radiosurgery for meningiomas.

Gamma Knife radiosurgery is an effective treatment for meningiomas. However, it may be difficult to deliver what is currently considered an optimal dose, especially if the tumor is large or adjacent to critical structures. Eleven cases are presented with a follow-up of more than 12 months where the margin dose did not exceed 10 Gy. The mean age was 48.8 years. The mean follow-up period was 35.7 months (range 21 to 57 months). The mean volume of the tumors was 9.4 cm3 (range 1.6 to 28.9 cm3). The margin dose was less than 10 Gy in all 11 cases, due to a large volume in two cases. Four tumors were close to the visual pathways. Five tumors were close to the brain stem. Imaging follow-up showed that four tumors had shrunk after radiosurgery. The remaining seven cases remained unchanged. There was no tumor growth after radiosurgery. A transient oculomotor palsy was observed in two cases after radiosurgery. It is suggested that Gamma Knife radiosurgery using lower dosage than usual is one of the options for the treatment of meningioma.

Adult↗
PubMed1999

Gamma Knife radiosurgery for pituitary adenomas.

Ninety-two patients with pituitary adenomas have been treated during the last 5 years. Sixty-three of these patients had more than 6 months follow-up, and they form the basis of this report. Eighteen had non-functioning adenomas (NFA), and 36 had functioning adenomas (FA). The mean marginal dose was 22.5 Gy (NFA 19.5 Gy, FA 23.9 Gy). Control of tumor growth was achieved in 92%. A significant decrease of excessive hormone production was seen in 75.6%, and the endocrinopathy normalization rate was 26.7%. Post-radiosurgical complications were seen in 4.7%.

Acromegaly↗
PubMed1998

Vasopressin neuron activation and Fos expression by stimulation of the caudal ventrolateral medulla.

The present study demonstrates that projections ascending from the caudal ventrolateral medulla have direct effects on the expression of the immediate early gene c-fos and of the arginine-vasopressin gene in neurosecretory cells of the hypothalamic supraoptic nucleus. Intense Fos-like immunoreactivity (Fos-LI) was observed in many magnocellular neurons of the supraoptic nucleus after electrical stimulation of the caudal ventrolateral medulla. In sham-operated rats, Fos-LI was absent or present in very few magnocellular neurons in the supraoptic nucleus. Fos-LI was visible in neurons expressing arginine-vasopressin, and was seen rarely in oxytocin neurons by double-immunostaining method. This study showed that 76% of all Fos-positive cells were arginine-vasopressin immunoreactive, whereas only 4% of them showed oxytocin immunoreactivity in the supraoptic nucleus. With in situ hybridization, a high level of arginine-vasopressin mRNA was noted in the supraoptic nucleus 3 h after stimulation of the caudal ventrolateral medulla; the expression was highest 6 h after the stimulation compared with the same region in sham-operated animals. These findings suggest that noradrenaline, released from the axon terminals originating from the caudal ventrolateral medulla, may participate in the regulation of gene transcription of arginine-vasopressin in response to physiological stimuli.

Afferent Pathways↗
PubMed1998

Activation of AP-1 is required for bufalin-induced apoptosis in human leukemia U937 cells.

In a previous study, we demonstrated that bufalin caused apoptosis in human leukemia U937 cells by the anomalous activation of mitogen-activated protein kinase (MAPK) via a signaling pathway that included Ras, Raf-1 and MAPK kinase-1. We report here the effect of bufalin on c-Jun N-terminal protein kinase (JNK), a member of the MAPK family, and on the signaling pathway downstream of MAPKs in U937 cells. When U937 cells were treated with 10(-8) M bufalin, the activity of JNK1 was markedly elevated 3 h after the start of treatment and remained so for 9 h. This activation of JNK and the induction of apoptosis by bufalin were suppressed by expression of antisense mRNA for MAPK kinase-1. c-Jun was translocated from the cytoplasm to the nucleus after treatment of U937 cells with bufalin. The transcriptional activity of AP-1 was transiently enhanced by the treatment with bufalin and this activation was suppressed by the expression of antisense mRNA for MAPK kinase-1. Both curcumin (1,7-bis[4-hydroxy-3-methoxy-phenyl]-1,6-heptadiene-3,5-dione), an inhibitor of the biosynthesis of AP-1, and the expression of dominant negative c-Jun inhibited the activation of AP-1 and the induction of apoptosis by bufalin. Expression of a constitutively active mutant form of MAPK kinase-1 induced the activation of AP-1 and subsequent apoptosis in U937 cells. These results suggest that the activation of AP-1 via a MAPK cascade that includes JNK is required for the induction of apoptosis by bufalin in U937 cells.

Antineoplastic Agents↗
PubMed1998

Distribution of PNP 14 (beta-synuclein) in neuroendocrine tissues: localization in Sertoli cells.

Phosphoneuroprotein (PNP 14) is abundant in the central nervous system and is localized at nerve endings but not in synaptic vesicles. In this study, we examined the presence of PNP 14 in various endocrine tissues of the rat. PNP 14 was not detected in the endocrine cells of the intestine, testes, or adrenal gland, but it was present in axon terminals in both the medulla of the adrenal gland and the anterior pituitary gland. When testes were stained with PNP 14-specific antibodies by an indirect immunofluorescence method, PNP 14 was found in Sertoli cells of the testes, associated with fibrillar structures. PNP 14 was also detected in cultured Sertoli cells with a fibrillar pattern in the cytoplasm and around the nuclei. The fibrillar structure did not resemble actin stress fibers, microtubules, or intermediate filaments. The amount of PNP 14 in the testis changed with development. It increased markedly during the first 4 weeks after birth and then decreased. During the first 4 weeks after birth, spermatogonia undergo two rounds of meiosis. It is possible, therefore, that PNP 14 might be a factor related to meiosis.

Animals↗
PubMed1998

Experimental infection of larval Echinococcus multilocularis in the rodent brain as a model for cerebral alveolar echinococcosis.

Experimental infection of larval Echinococcus multilocularis in the rodent brain was attempted to establish a murine model for cerebral alveolar echinococcosis. Balb/c mice and jirds were injected intracranially with 10% of a homogenated hydatid cyst mass. Small cystic larvae were observed macroscopically in the cranial cavity 1, 2 and 5 months post-infection in both mice and jirds. Some larval cysts from both rodents contained mature or immature protoscoleces. In mice, the laminated layer was found in the lateral ventricle 2 months post-infection but without protoscoleces. At five months post-infection, larger larval cysts were found in the cranial cavity of a mouse, which also demonstrated partial palsy of the legs. A laminated layer with mature protoscoleces was observed in the third ventricle and the mouse also harboured, in the left lung, a larval cyst containing protoscoleces surrounded by lymphocytes. Jirds were also found to be infected with metacestodes in the cranial cavity, but neither unusual behaviour nor establishment of cysts inside the brain was observed in jirds during the course of infection.

Animals↗
PubMed1998

Morphological changes of larval Echinococcus multilocularis in mice treated with albendazole or mebendazole.

Using DBA/2J mice, tissue homogenates of larval Echinococcus multilocularis were injected into the mesenteric veins to generate the liver infection. Mice were treated with either albendazole or mebendazole for prolonged periods to examine the morphological changes of the metacestode. Albendazole induced disorganization of both laminated and germinal layers and suppressed the maturation of vesicles. Amorphous but loosely laminated PAS-positive material was observed inside the damaged vesicles, although new vesicles slightly developed inside or outside of the damaged ones. Active proliferation of vesicles occurred after treatment with albendazole was terminated. Hydatid cysts were more severely damaged in mice treated with mebendazole and new vesicles did not develop around the damaged ones. Also, hydatid cysts reappeared after treatment with mebendazole was terminated. These results indicate that these drugs do not eliminate larval E. multilocularis in the long-term, but mebendazole has a higher suppressive effect on multivesiculation than albendazole.

Albendazole↗
PubMed1998

Zinc ions prevent processing of caspase-3 during apoptosis induced by geranylgeraniol in HL-60 cells.

Geranylgeraniol (GGO) at 50 microM induces apoptosis in HL-60 cells. We examined the effects of Zn2+ ions on this process. Treatment of HL-60 cells with Zn2+ ions inhibited subsequent GGO-induced fragmentation of DNA. In a cell-free system that consisted of a specific substrate for caspase-3 and a lysate of HL-60 cells that had been treated with 50 microM GGO, Zn2+ ions at concentrations above 0.1 mM inhibited the activity of caspase-3. The effect of Zn2+ ions on the processing of caspase-3 during GGO-induced apoptosis was investigated by Western blotting, which revealed that an inactive 32-kDa precursor of caspase-3 was cleaved, in response to GGO, to yield an activated 17-kDa enzyme. Treatment of HL-60 cells with Zn2+ ions inhibited the cleavage of the precursor by a protease that was induced by treatment with GGO, and inhibition of this processing was well correlated with the inhibition by Zn2+ ions of caspase-3 activity in the cell-free system. In cell-extracted cytosols, Zn2+ ions inhibited the cleavage of the 32-kDa precursor by caspase-9 (Aapf-3) that was activated by addition of cytochrome c and dATP. These results indicate that inhibition of GGO-induced apoptosis in HL-60 cells by Zn2+ ions might be due to inhibition by Zn2+ ions of the processing of a precursor to caspase-3.

Apoptosis↗
PubMed1998

Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.

Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, a point mutation in the gene encoding the presynaptic alpha-synuclein protein was identified in some autosomal-dominantly inherited familial PD pedigrees, and light microscopic studies demonstrated alpha-synuclein immunoreactivity in LBs of sporadic PD and DLB. To characterize alpha-synuclein in LBs, we raised monoclonal antibodies (MAbs) to LBs purified from DLB brains and obtained a MAb specific for alpha-synuclein that intensely labeled LBs. Light and electron microscopic immunocytochemical studies performed with this MAb as well as other antibodies to alpha-and beta-synuclein showed that alpha-synuclein, but not beta-synuclein, is a component of LBs in sporadic PD and DLB. Western blot analyses of highly purified LBs from DLB brains showed that full-length as well as partially truncated and insoluble aggregates of alpha-synuclein are deposited in LBs. Thus, these data strongly implicate alpha-synuclein in the formation of LBs and the selective degeneration of neurons in sporadic PD and DLB.

Antibodies, Monoclonal↗
PubMed1997

Neuronal nicotinic acetylcholine receptor in the hypothalamus: morphological diversity and neuroendocrine regulations.

The subcellular localization and functional significance of neuronal nicotinic acetylcholine receptor alpha4-subunits were investigated in the rat hypothalamic supraoptic nucleus. A high level of alpha4 mRNA expression was found in the magnocellular neurons in the supraoptic nucleus. Strong immunoreactitivy for alpha4 in neurons of the supraoptic nucleus was detected in the rough endoplasmic reticulum and cytoplasmic matrix, although it was very weak in the Golgi apparatus, except for the transport vesicles. Immunoreactivity for alpha4 was detected in both the pre-synaptic axon terminals and post-synaptic axon terminals. A high level of signals for vasopressin mRNA was detected in the supraoptic nucleus after the animals were injected s.c. with nicotine. These findings suggest that alpha4-containing subtypes are synthesized in the rough endoplasmic reticulum and transported to the plasma membrane and serve as pre- and post-synaptic nicotinic acetylcholine receptors. Nicotine may up-regulate vasopressin gene expression in the supraoptic nucleus, acting through nicotinic acetylcholine receptors.

Animals↗
PubMed1997

Pituitary adenylate cyclase-activating polypeptide (PACAP): a novel regulator of vasopressin-containing neurons.

Pituitary adenylate cyclase-activating polypeptide (PACAP) was localized in nerve terminals that innervate arginine-vasopressin (AVP)-containing neurons in the rat hypothalamic supraoptic nucleus (SON). PACAP receptor (PACAPR) mRNA was expressed at high-levels in AVP-containing neurons in the SON, but at very low-levels in oxytocin-containing neurons. PACAPR-like immunoreactivity was found in SON and it was observed in the post-synaptic membranes as well as on the rough endoplasmic reticulum and cytoplasmic matrices in the magnocellular neurons. Doses of PACAP in the nanomolar range increased cytoplasmic Ca2+ concentrations ([Ca2+]i) in AVP-containing neurons; the increase in [Ca2+]i was inhibited by a protein kinase A blocker. These findings suggest that PACAP serves as a transmitter and/or modulator and the activation of PACAPR stimulates a cAMP-protein kinase A pathway which in turn evokes the Ca2+ signaling system. It is hypothesized that PACAP regulates the functions of AVP-containing neurons which participate in the control of plasma osmolarity and blood pressure.

Animals↗