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Biomedical subjects

O Nakamura

Publications and source records attributed to O Nakamura.

At least 55 records · Page 3Linked to original sources
PubMed1994

Three new furostanol saponins from the bulbs of Ipheion uniflorum.

Phytochemical screening of the bulbs of Ipheion uniflorum (Liliaceae) has led to the isolation of three new furostanol saponins (2-4) along with a known phytoecdysteroid, ecdysterone (1). The structures of the new compounds were determined by two-dimensional NMR techniques, 1H-1H correlation spectroscopy (COSY), homonuclear Hartmann-Hahn (HOHAHA), phase-sensitive nuclear Overhauser effect spectroscopy (NOESY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple-bond correlation (HMBC) spectra, and hydrolysis to be 3 beta-hydroxy-22 alpha-methoxy-26-O-beta-D- glucopyranosyloxy-5 alpha-furost-25(27)-en-2-one 3-O-[O-alpha-L-rhamnopyranosyl-(1-->2)-O-[O-alpha-L-arabinopyranosyl+ ++- (1-->2)-O-[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucopyranosyl-(1-->4)]- beta-D-galactopyranoside) (2) and its 25(27)-dihydro derivatives (3: 25S; 4: 25R). The inhibitory activity exhibited by compounds 1-4 and the corresponding spirostanol saponins (2a and 3a) of 2 and 3 on cAMP phosphodiesterase was assayed as a primary screening test to identify new compounds with medicinal potential.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

[Differential diagnosis between recurrence of gliomas and radiation necrosis by 201TlCl SPECT].

We studied the value of quantitative 201Thallium Chloride brain SPECT (Tl SPECT) in the differentiation between glioma recurrence and radiation necrosis. A total of 44 patients--26 patients with recurrent malignant glioma, 10 patients with low grade glioma and 8 patients with radiation necrosis--underwent Tl SPECT. The patients had early SPECT images taken 15 minutes after intravenous injection of 3mCi of 201TlCl and also had delayed SPECT images taken 4 hours after injection. Count ratios of a lesion to normal brain (L/N) were calculated from the rectangular ROI for the quantitative analysis. Count ratios of the lesion seen on the delayed image to that on the early image (D/E) were also calculated. In 26 patients with recurrent malignant gliomas, L/N ratio ranged from 2.6 to 12.6 with a mean of 4.4 +/- 2.3 on early images. All patients had L/N ratios greater than 2.5. However, in 8 patients with cerebral radiation necrosis, L/N ratios ranged from 1.5 to 2.4 with a mean of 2.0 +/- 0.3 on early image. L/N ratios were always 2.5 or less. In 8 patients with cerebral radiation necrosis, there were little differences between the L/N ratios for early and delayed images. D/E ratios ranged from 1.0 to 1.3 with a mean of 1.2 +/- 0.1. These results confirmed the validity of Tl SPECT in differentiating cerebral radiation necrosis from recurrent malignant gliomas. In 10 patients with low grade astrocytoma there was a subtle uptake or no uptake of Tl and the ratios of these patients were rated at 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Expression of hepatocyte growth factor in normal and carbon tetrachloride-treated monkeys.

We examined hepatocyte growth factor-producing organs in normal and carbon tetrachloride-treated Japanese monkeys, a species more related to human beings than rats, by measuring hepatocyte growth factor protein and hepatocyte growth factor mRNA in various tissues. Hepatocyte growth factor protein and hepatocyte growth factor mRNA levels were determined by use of an enzyme-linked immunosorbent assay for human hepatocyte growth factor and Northern-blot analysis using human hepatocyte growth factor cDNA as a probe, respectively. Although very slight amounts of hepatocyte growth factor protein were found in various organs of normal monkeys, the hepatocyte growth factor protein levels were remarkably increased only in the livers and spleens of carbon tetrachloride-treated monkeys. Hepatocyte growth factor mRNA was distinctly detected in the livers, spleens, lungs, intestinal tracts, adrenal glands and aortas of normal monkeys. After the administration of carbon tetrachloride, the hepatocyte growth factor mRNA levels in the liver, spleen and gastrointestinal tract were markedly increased; the level in the lung was unchanged, differing from the findings in rats; and the levels in adrenal gland and aorta were unaltered. These results indicate that the liver is an important hepatocyte growth factor-producing organ in monkeys during liver regeneration and that hepatocyte growth factor induced in the liver may stimulate hepatocyte proliferation by way of a paracrine mode.

Animals↗
PubMed1993

Molecular cloning and sequence analysis of cDNA for a 59 kD bone sialoprotein of the rat: demonstration that it is a counterpart of human alpha 2-HS glycoprotein and bovine fetuin.

A complementary DNA (cDNA) for the 59 kD bone sialoprotein, which is supposed to be the rat counterpart of human alpha 2-HS glycoprotein (alpha 2-HSG) and is synthesized by both hepatocytes and osteoblasts, has been cloned from a rat liver cDNA library. Polyclonal rabbit antibodies to rat 59 kD bone sialoprotein were used to identify and isolate the cDNA. The amino acid sequence of 59 kD bone sialoprotein deduced from the cDNA revealed that the entire protein consisted of 352 amino acid residues, including a signal peptide of 18 amino acid residues, and contained three possible N-glycosylation sites. On Northern blot analysis of rat liver, an mRNA of about 1.5 kilobases was detected. An mRNA of 59 kD bone sialoprotein was also detectable in rat bone but not in other tissues, such as kidney, brain, and lung. A computer search of protein and nucleic acid data bases revealed that 68.2, 63.2, and 97.4% amino acid residues of 59 kD bone sialoprotein were identical with those of human alpha 2-HSG, bovine fetuin, and rat phosphorylated N-glycoprotein (pp63), respectively. The positions of cysteine residues in 59 kD bone sialoprotein also completely matched those in human alpha 2-HSG and bovine fetuin, indicating that the sialoprotein is the rat counterpart of human alpha 2-HSG and bovine fetuin. In addition, comparison of the nucleotide sequence of cDNA for rat fetuin/alpha 2-HSG with that for pp63 recently corrected showed only two differences in nucleotides in the entire protein coding regions of the two proteins, and immunoreactive rat fetuin/alpha 2-HSG in the conditioned medium of adult rat hepatocytes in primary culture was found to be phosphorylated. Thus, because rat fetuin/alpha 2-HSG isolated from bone and synthesized by osteoblasts in culture does not contain phosphorus, it seems to be pp63 dephosphorylated during circulation or in the bone matrix.

Amino Acid Sequence↗
PubMed1993

Reassessment of quantitative thallium-201 brain SPECT for miscellaneous brain tumors.

In order to reassess the value of quantitative thallium-201 brain SPECT in the differentiation of miscellaneous brain tumors, we studied a total of 89 patients--35 pre-operative patients suspected of having a brain tumor and 54 post-operative patients with a brain tumor. We came to the conclusion that quantitative Tl-201 brain SPECT was very useful in discriminating cerebral radiation necrosis from recurrent tumor, estimating residual tumor burden, and detecting tumor regrowth earlier in postoperative patients. In preoperative patients, however, Tl-201 SPECT cannot be used effectively to differentiate glioma from other intracranial tumors, although intense uptake of Tl-201 may provide evidence of glioblastoma or a hypervascular lesion.

Adolescent↗
PubMed1993

Steroidal saponins from the bulbs of Lilium regale and L. henryi.

Two new and three known steroidal saponins were isolated from the fresh bulbs of Lilium regale and two known saponins from those of L. henryi. The structures of the new saponins were established by extensive spectral data, hydrolysis and chemical correlation as (25R)-27-O-[(S)-3-hydroxy-3-methylglutaroyl]-spirost-5 -ene-3 beta,27-diol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->3)]- beta-D-glucopyranoside and (25S)-spirost-5-ene-3 beta,17 alpha,27-triol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->2)-O- beta-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside. Inhibitory activity of the saponins on cyclic AMP phosphodiesterase was evaluated.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Effect of centrifugal force on growth of mouse osteoblastic MC3T3-E1 cells in vitro.

The effect of biomechanical force on growth of skeletal tissue was studied in monolayer cultures of mouse osteoblastic MC3T3-E1 cells which were centrifuged at 320 g for 15 min to 72 h in a CO2 incubator. Centrifugation of the cells for 30 min in low concentrations (0.3 or 1%) of fetal bovine serum (FBS) caused a two-fold increase of [3H]thymidine incorporation at 20 h from the start of centrifugation. However, centrifugation under 10% FBS caused no increase in [3H]thymidine incorporation into DNA. Under 0.3% FBS, [3H]thymidine incorporation increased in a manner dependent on the period of centrifugation and reached a maximum when the cells were centrifuged for 3 h. Stimulation of DNA synthesis by centrifugation was abolished in the presence of H-7, an inhibitor of protein kinase C. Moreover, conditioned medium collected from the centrifuged cultures increased [3H]thymidine incorporation by two-fold over the basal when added to a quiescent culture of MC3T3-E1 cells. These results suggest that centrifugal force stimulates growth of osteoblastic cells through autocrine secretion of some diffusible growth-promoting activity. On the other hand, centrifugation of the cells inhibited induction by FBS of alkaline phosphatase activity and calcium-uptake, two indices of the differentiated phenotype of osteoblasts.

3T3 Cells↗
PubMed1993

Successful treatment of recurrent malignant germ cell tumors: report of two cases.

We report two patients with recurrent malignant germ cell tumors who were successfully treated with radiation therapy and cisplatin combination chemotherapy. Patient 1, who had a suprasellar mixed yolk sac tumor, had been free of tumor for 3.5 years after cisplatin/vinblastine/bleomycin combination chemotherapy alone but showed a recurrent tumor in the pineal region. In Patient 2, who had a pineal alpha-fetoprotein-producing tumor, recurrent tumors appeared in the lateral ventricle 3 years after the tumor was controlled by radiation and cisplatin/vinblastine/bleomycin therapy. They were treated successfully again by radiation therapy, followed by cisplatin and etoposide combination therapy, and they have been free of tumor for 5.5 and 7 years after recurrence, respectively. The total dose of cisplatin in both patients exceeded 1,000 mg/m2, which would have contributed to the control of the recurrent tumors. Anterior pituitary dysfunction observed in Patient 1 did not improve, even after tumor disappearance by chemotherapy, suggesting severe damage to the neurohypophysis by direct invasion of the tumor.

Adolescent↗
PubMed1993

Agapanthussaponins A-D, new potent cAMP phosphodiesterase inhibitors from the underground parts of Agapanthus inapertus.

The saponin fraction prepared from the methanolic extract of the underground parts of Agapanthus inapertus was found to exhibit inhibitory activity on cAMP phosphodiesterase (55.2%) at a concentration of 100 micrograms/ml. From this fraction, four new steroidal saponins, designated as agapanthussaponin A (1), B (2), C (3) and D (4), were isolated as the active principles, along with an inactive new furostanol saponin (5). The structures of 1-5 were determined by spectroscopic data and hydrolysis. The IC50 of 1-4 on cAMP phosphodiesterase were 0.7, 1.2, 1.1 and 2.0 (x 10(-5) M), respectively, which are more potent than that of papaverine (IC50 3.0 x 10(-5) M).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

[Brain SPECT by intraarterial infusion of 99mTc-HMPAO for assessing the cerebral distribution of carotid artery infusions in patients with brain tumor].

In order to assess the cerebral distribution of intracarotid chemotherapy, 17 postoperative patients with brain tumor underwent brain SPECT obtained by intraarterial infusion of 18.5 MBq of 99mTc-HMPAO. Injection methods were continuous (5.0 ml/min) or pulsatile infusion with supraor infraophthalmic catheterization. The findings obtained by brain SPECT were frequently different from those of angiography and/or DSA. In supraophthalmic catheterization with continuous infusion, only 2 of 10 studies (20%) had homogeneous distribution and 5 of them (50%) had maldistribution of 99mTc-HMPAO which appears in association with laminar flow effect. The remaining 3 studies showed localized distribution (two: tumor localization, one: healthy brain localization). On the other hand, all of 5 studies with pulsatile infusion had homogeneous distribution of 99mTc-HMPAO. In infraophthalmic catheterization, all but one of 5 studies had homogeneous distribution with continuous infusion. These results suggest that pulsatile infusion may be effective in eliminating maldistribution of 99mTc-HMPAO in supraophthalmic catheterization. In conclusion, we are convinced that 99mTc-HMPAO is a useful intraarterial agent for assessing cerebral distribution of intracarotid chemotherapy.

Adolescent↗
PubMed1992

Antibody responses to ganglio-series gangliosides in different strains of inbred mice.

We studied antibody responses after immunization with ganglio-series gangliosides against 10 strains of inbred mice, including Balb/c, C57BL/6, A/J, C3H/HeN, C3H/HeJ, CBA/N, AKR/N, NZB/N, DBA/2 and nu/nu Balb/c. Twelve gangliosides having NeuAc as their sialic acid moiety (GM4, GM3, GM2, GM1, GD3, O-Ac-GD3, GD2, GD1a, GD1b, GT1a, GT1b and GQ1b), four gangliosides having NeuGc (GM3, GM2, GM1 and GD3) and four asialo-gangliosides (GA4, GA3, GA2 and GA1) were injected intravenously adsorbed to Salmonella minnesota. The antibody titers of the mice sera were determined by an enzyme-linked immunosorbent assay and an immune adherence assay. Antibody responses were found to depend not only on the ganglioside used as an immunogen but also on the mouse strain. Gangliosides having a trisaccharide sequence (NeuAc alpha 2----8NeuAc alpha 2----3Gal-) such as GD3, GD2, GD1b, GT1a and GQ1b, in particular O-Ac-GD3, induced high-titer antibody responses, whereas those having a disaccharide sequence (NeuAc alpha 2----3Gal-) such as GM4, GM3, GM2, GM1, GD1a and GT1b induced low-titer antibody responses. On the other hand, gangliosides with NeuGc developed minimum titers. In contrast, asialogangliosides induced much higher responses than the corresponding gangliosides. The differences in ceramide portions of these gangliosides did not appear to be involved in inducing antibody responses. Mice could be divided into three groups according to the magnitude of their antibody responses: Group 1, those that produce the highest antibody responses (C3H/HeN and A/J); Group 2, those that demonstrate moderate antibody titers (Balb/c, C57BL/6, DBA/2 and nu/nu Balb/c); and Group 3, those that make minimum responses (AKR/N, C3H/HeJ, CBA/N and NZB/N). The pattern of reactivity to the various gangliosides was similar in all the strains tested.

Animals↗
PubMed1992

Primary malignant lymphoma of the central nervous system by Ga-67 and TI-201 brain SPECT.

Two patients with primary lymphoma of the central nervous system underwent both Ga-67 and TI-201 brain SPECT. Ga-67 scans showed remarkable accumulation of radiotracer corresponding to tumors detected by CT and MRI. More avid uptake was noted on the Ga-67 scans than on the TI-201 scans. In one patient, the intense tracer uptake had disappeared in the Ga-67 study performed after irradiation with 50 Gy. We are convinced that Ga-67 SPECT is useful for detecting and following the progress of primary lymphoma of the central nervous system.

Aged↗
PubMed1992

Leptomeningeal dissemination of cerebellar pilocytic astrocytoma. Case report.

A case of surgically treated pilocytic astrocytoma in the cerebellar vermis is reported in a patient who subsequently demonstrated multiple subarachnoid nodular masses in the cerebrum and spinal cord 6 years after the initial surgery. The nodular tumors did not indicate a growth tendency on computerized tomography or magnetic resonance imaging over a 2-year observation period. The histology of the nodular masses in the cerebrum and spinal cord was similar to that of the original tumor. The bromodeoxyuridine labeling index indicated low proliferative activity (0.5%). The peculiar pattern of dissemination of the pilocytic astrocytoma is described.

Astrocytoma↗
PubMed1992

Inhibition of angiogenesis by staurosporine, a potent protein kinase inhibitor.

The effect of staurosporine, a potent inhibitor of protein kinases, on embryonic angiogenesis was studied in an in vivo assay system involving chorioallantoic membranes of growing chick embryo. Staurosporine inhibited embryonic angiogenesis in a dose-related manner, the ID50 value being 71 pmol/egg. Staurosporine dose-dependently suppressed the proliferation of vascular endothelial cells, an important event involved in the angiogenesis process. The IC50 value was 0.88 nM. In contrast, staurosporine did not affect the migration of vascular endothelial cells. These results suggest that staurosporine affected embryonic angiogenesis probably by inhibiting endothelial cell proliferation. In addition, these results might support the notion that certain protein kinase(s) could be implicated in induction of angiogenesis and also that staurosporine would be a useful compound for studying a mode of action of angiogenesis occurring in various diseases, including tumor development.

Alkaloids↗
PubMed1992

[Inhibition of neovascularization and tumor growth by dexamethasone].

It has been proposed that angiogenesis inhibitors should be used for the treatment of diseases accompanied by an uncontrolled angiogenic response, particularly such disease occurring during progressive growth of solid tumors. In this study, the antiangiogenic effect of dexamethasone (DEX) was studied in a system using chorioallantoic membranes (CAM) of fertilized eggs and rabbit corneas. First, DEX was examined for its effect on embryonic angiogenesis using 4, 5 day old CAMs of chick embryos. After the shell and shell membrane was removed, an EV pellet with or without DEX was placed within a silicon ring. Two days later, the antiangiogenic response was evaluated by measuring the avascular zone of the CAM beneath the pellet. When the CAM showed an avascular zone of 3 mm or more in diameter, the response was scored as positive. DEX showed potent antiangiogenic activity and produced an avascular zone in 100% of CAMs at the highest dose tested. (250 ng/egg). Next, inhibitory effect of vascularization and tumor growth by local implant of DEX was observed in a rabbit cornea assay. An intra-corneal pocket extending to within 1 mm of the limbus was used to house a 1-mm3 piece of glioma. In the treatment group, DEX-containing EV pellet was inserted between the limbus and glioma. Ten days after the implantation of glioma and EV pellet, vascular response and tumor growth was evaluated. For morphologic studies, the excised corneas were fixed with formaldehyde fixative and sectioned for light microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗