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Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 145 records · Page 8Linked to original sources

Neutrophilic cell production by combination of stem cell factor and thrombopoietin from CD34(+) cord blood cells in long-term serum-deprived liquid culture.

In the present study, we investigated the effects of stem cell factor (SCF) and/or thrombopoietin (TPO) on the cell production by cord blood CD34(+) cells using a serum-deprived liquid culture system. Although SCF alone supported a modest production of neutrophilic cells and a remarkable generation of mast cells, the addition of TPO to the culture containing SCF caused an apparent generation of neutrophilic cells, identified by immunocytochemical staining and flow cytometric analysis. The significant production of neutrophilic cells by SCF and TPO was persistently observed from 2 weeks to 2 to 3 months of culture. The interaction between SCF and TPO on the neutrophilic cell generation was greater than the combined effects of SCF with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). The addition of neutralizing antibody against G-CSF or GM-CSF did not influence the SCF + TPO-dependent neutrophilic cell production. A single-cell culture study showed that not only CD34(+)CD38(+) c-kit+ cells but also CD34(+)CD38(-)c-kit+ cells were responsible for the neutrophilic cell generation. In clonal cell cultures, GM progenitors as well as erythroid progenitors and multipotential progenitors expanded in the cultures supplemented with SCF and TPO. The neutrophilic cells grown by SCF + TPO were at myeloblast to band cell stages, and scarcely matured to segmented neutrophils. In addition, the cells generated by SCF + TPO were stained with monoclonal antibodies against myeloperoxidase, elastase, lactoferrin, and CD11b, but they had negligible levels of alkaline phosphatase (ALP) and CD35. The replating of the CD34(-)c-kit-/low CD15(+) cells grown by SCF + TPO into a culture containing SCF + G-CSF permitted both the terminal maturation into segmented cells and the appearance of ALP and CD35. These results indicate the existence of a G-CSF/GM-CSF-independent system of neutrophilic cell production.

ADP-ribosyl Cyclase↗

Persistence and clinical outcome of hepatitis G virus infection in pediatric bone marrow transplant recipients and children treated for hematological malignancy.

The natural course and the clinical significance of hepatitis G virus (HGV) infection were investigated in 106 pediatric patients who received chemotherapy for hematological malignancy or underwent bone marrow transplantation (BMT) using HGV-RNA and antibodies to the HGV-E2 protein (anti-E2). HGV markers were detected in 21 patients (19.8%; HGV-RNA in 19 and anti-E2 in 2). Longitudinal analysis of these HGV-infected patients showed that 1 had anti-E2 before the initial blood transfusion, 14 had persistent viremia, and 6 became clear of circulating HGV-RNA after completion of therapy, although 5 of the 6 HGV-cleared patients never developed anti-E2. Reactivation of HGV infection during chemotherapy was observed in two anti-E2-positive, HGV-RNA-negative patients; the reappearance of the same HGV strain was confirmed by phylogenetic analysis. Among BMT survivors without other known causes of liver dysfunction, HGV-RNA-positive patients had a higher peak serum alanine amino transferase (ALT) value than negative patients. Contrary to previous reports, immunosuppressed patients can apparently recover from HGV infection without detectable anti-E2 and some patients who supposedly recovered from HGV infection can nonetheless suffer exacerbation when subsequently immunosuppressed.

Adolescent↗

Membrane-type matrix metalloproteinase-1 expression and activation of gelatinase A as prognostic markers in advanced pediatric neuroblastoma.

BACKGROUND: Recently a novel membrane-type matrix metalloproteinase-1 (MT-MMP-1) was discovered to be a specific activator of progelatinase A, and was correlated with tumor invasion. To the authors' knowledge, no information regarding the expression of MT-MMP-1 has been reported in childhood malignancies. In this study, the authors attempted to elucidate the specific mechanisms that underlay the invasive behavior of neuroblastoma (NB) cells with respect to the expression of MT-MMP-1 and its determined prognostic value, especially in pediatric patients with advanced Evans' Stage IV NB. METHODS: Thirty specimens from surgically excised NB (mainly Stage IV) were collected retrospectively. The total levels of progelatinase A (68 kilodaltons [kD]) and its activated form (62 kD) in the tumor lysates were quantified by gelatin zymography. The expression of MT-MMP-1 was estimated by immunostaining with a monoclonal antibody (113-5B7). RESULTS: Progelatinase A and the activated form were detected in each of the 30 specimens. The gelatinase A activation ratio, 62 kD/(62 kD + 68 kD), strongly correlated with the high levels of MT-MMP-1 expression found in specimens of advanced tumor stage. In the patients with advanced Stage IV NB, the activation ratio was strongly associated with unfavorable clinical outcome; the 5-year survival was 88.9% in the patients with a low activation ratio (< or = 26%) versus only 21.2% in the patients with a high activation ratio (>26%). CONCLUSIONS: Gelatinase A activation correlates with high expression of MT-MMP-1 on NB cells and is associated strongly with advanced stage and poor clinical outcome. These results are consistent with the notion that MT-MMP-1 expression is an important prognostic determinant of the biologic behavior of NB.

Adolescent↗

Steatosis and intrahepatic hepatitis C virus in chronic hepatitis.

Hepatic steatosis has been reported as one of the characteristics which discriminates hepatitis C from other forms of hepatitis, besides lymphoid follicles and bile duct damage. However, it is unclear whether or not the presence of hepatitis C virus (HCV) itself is associated with the development of steatosis. The possibility that the HCV itself is directly related to the development of steatosis was examined. The intrahepatic core protein levels, as a marker of the HCV load, were correlated with the presence of steatosis in 43 patients with chronic hepatitis C. Among 43 patients studied by Western blotting, the core protein was detected in the liver in 27 (62.8%). On the other hand, hepatic steatosis was observed in 21 (48.8%) of the 43 patients. Importantly, the core protein was detectable in 19 (90.4%) of the 21 patients with steatosis, while it was detected in only 8 (36.4%) of the 22 patients without steatosis (P = 0.008). However, serum HCV-RNA levels as determined by the Amplicor monitor were not significantly different between patients with and without steatosis. Multivariate analysis showed that the serum alanine aminotransferase level (P = 0. 013), body mass index (P = 0.038), and intrahepatic HCV core protein positivity (P = 0.038) were the independent parameters best predictive of steatosis. These results indicate a close relationship between intrahepatic HCV and the development of steatosis, and suggest a possible role of the HCV itself or core protein in the pathogenesis of steatosis in human chronic hepatitis C.

Aged↗

Apoptosis of erythroid precursors under stimulation with thrombopoietin: contribution to megakaryocytic lineage choice.

Although the effect of thrombopoietin (TPO) on megakaryocyte production is well established, its role in the commitment of multipotential hematopoietic progenitors to the megakaryocytic lineage remains to be determined. In the present study, we attempted to clarify the determination process of megakaryocytic lineage as a terminal differentiation pathway under stimulation with TPO. Day 7 cultured cells grown by TPO derived from cord blood CD34+ cells were divided into four subpopulations on the basis of CD34 and CD41 expression. The CD34-/CD41- cells showed the labeling pattern of anti-CD42b and anti-CD9 antibodies closer to that of the CD34+/CD41- cells than the CD34+/CD41+ cells. Replating experiments revealed that approximately 40% of the CD34-/CD41- cells proliferated in response to a combination of growth factors, and more than 80% of them were pure erythroid precursors. However, this subpopulation failed to grow/survive and fell into apoptosis in the presence of TPO alone. In contrast, the CD34+/CD41+ cells, which predominantly contained megakaryocytic precursors, exerted a low but significant proliferative potential in the presence of TPO. The insufficient response to TPO of the CD34-/CD41- cells may result from the apparently low expression of c-MpI, as determined by flow cytometric analysis and reverse transcription-polymerase chain reaction analysis. Therefore, these results suggest that the apoptosis of hematopoietic precursors other than megakaryocytic precursors is related to the determination of the terminal differentiation under the influence of TPO.

Antigens, CD↗

Chemokine production by human megakaryocytes derived from CD34-positive cord blood cells.

To clarify the roles of megakaryocytes and platelets in the responses associated with infection and inflammation, we examined the effects of interleukin (IL) 1, the common mediator of the inflammatory process, on the development and secretory functions of megakaryocytes generated from CD34(+)cord blood cells under stimulation with thrombopoietin (TPO). The addition of IL-1alpha did not influence the generation, endomitosis or expression of surface makers of megakaryocytes, compared with TPO alone. However, IL-1alphaenhanced the ability of megakaryocytes to produce IL-8 and growth-regulating oncogene-alpha(GRO-alpha) in the presence of TPO. In contrast, the production of regulated on activation with normal T cell expressed and secreted (RANTES), platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were not potentiated. A flow cytometric analysis and a reverse transcription-polymerase chain reaction analysis revealed IL-1 receptor type I (IL-1RI) expression of megakaryocytes generated by TPO. Moreover, the addition of an anti-IL-1RI monoclonal antibody significantly decreased the TPO plus IL-1alpha-induced secretion of IL-8 by the cultured megakaryocytes to the level attained by TPO alone. These results suggest that the production of IL-8 and GRO-alpha (but not RANTES), PF4 and beta-TG, by megakaryocytes is potentiated by signalling through IL-1RI with the aid of TPO. Thus, megakaryocytes and platelets may play an important role in the development of inflammation via chemokine release.

Antigens, CD34↗

Correlation of anatomic and hemodynamic features with aortic valve leaflet deformity in doubly committed subarterial ventricular septal defect.

The records of 153 patients with doubly committed subarterial ventricular septal defect (DCVSD) who underwent intracardiac repair were analyzed to evaluate factors responsible for aortic valve leaflet deformity. The patients were divided into two groups according to their echocardiographic and angiographic features as well as anatomic findings at operation: DCVSD without (17/153, 11.1%) and with arterial valve offsetting (136/153, 88.9%). Aortic regurgitation (AR) was much more prevalent in the patients with (50.0%) than in those without leaflet deformity (2.2%, P < 0.01). Arterial valve offsetting is one of the major contributing factors to the development of leaflet deformity, accounting for 5.9% in the patients without offsetting and 46.3% in those with offsetting (P < 0.01). Among the patients with arterial valve offsetting, the pulmonary-to-systemic pressure ratio was significantly higher (P < 0.01) in the patients without (0.76 +/- 0.14) than in those with leaflet deformity (0.36 +/- 0.12), suggesting that pulmonary hypertension might prevent the aortic valve leaflet from prolapsing in DCVSD. In addition, increased severity of aortic valve leaflet deformity and subsequent AR were observed with increasing age. These results suggest that aging and the presence of arterial valve offsetting as well as the absence of pulmonary hypertension might be factors responsible for aortic valve leaflet deformity and subsequent AR in DCVSD. The anatomic and hemodynamic features in DCVSD have a great impact on the development of aortic valve leaflet deformity and subsequent AR.

Adolescent↗

A magnetic resonance abnormality correlating with permeability of the blood-brain barrier in a child with chemical meningitis during central nervous system prophylaxis for acute leukemia.

Chemical meningitis developed in a boy with acute lymphoblastic leukemia during central nervous system (CNS) prophylaxis. Cerebrospinal fluid examination showed pleocytosis and a high protein level. There were no malignant cytological findings. Calculated permeability of albumin across the blood-brain barrier (BBB) was more elevated than that of immunoglobulin or alfa2-macroglobulin. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement without any intracerebral lesion. Subsequent CNS prophylaxis was postponed. CSF findings and BBB permeability returned to normal, correlating well with the decrease of MRI abnormality.

Albumins↗

Acyclic and incompletely cyclized triterpene alcohols in the seed oils of theaceae and gramineae.

The triterpene alcohol constituents of the non-saponifiable lipids of two Theaceae seed oils, sasanqua and camellia oils, and two Gramineae seed oils, wheat germ and rice bran oils, were investigated. This led to the isolation and characterization of one acyclic and eight incompletely cyclized triterpene alcohols. They are camelliol A, camelliol B, camelliol C, achilleol A, helianol, isohelianol, sasanquol, graminol A [(13R, 14R)-3,4-seco-25(10->9)abeo-8alpha,9beta,10al phapodioda-4,17,21 -trien-3-ol], and (2Z,6Z,10Z,14E,18E)-farnesyl-farnesol. Two other compounds isolated were characterized as (2Z,6Z,10E,14E)-geranylfarnesol, a sesterterpene alcohol, and phytol, a diterpene alcohol. Graminol A and (2Z,6Z,10E,14E)-geranylfarnesol are considered to be new natural products.

Alcohols↗

Triterpenoidal saponins from Gleditsia sinensis.

Six bisdesmosidic triterpenoidal saponins, gleditsiosides H-K and gleditsia saponins C' and E', were isolated from the anomalous fruits of Gleditsia sinensis. Their structures were established by a combination of extensive NMR (DEPT, DQF-COSY, HETCOR, HOHAHA, HMBC and ROESY) studies and chemical degradation.

Carbohydrate Conformation↗

Confirmation of domoic acid production of Pseudo-nitzschia multiseries isolated from Ofunato Bay, Japan.

Production of domoic acid (DA), the responsible toxin for amnesic shellfish poisoning, was examined for 44 strains of Pseudo-nitzschia spp. isolated from Ofunato Bay, Japan. Only one strain which was identified as Pseudo-nitzschia multiseries produced DA in a level comparable to Canadian strains. No significant DA was detected in the rest of the strains, indicating that toxic P. multiseries does not bloom in a high density in the bay.

Canada↗

Effect of bupranolol for BRL37344 and noradrenaline-induced relaxations mediating atypical beta/beta3-adrenoceptor in rat oesophageal muscularis mucosae.

We previously suggested that the existence of atypical beta/beta3-adrenoceptor with pA2-values for bupranolol, a non-selective beta-adrenoceptor antagonist, against BRL37344 and noradrenaline were 5.79 and 5.53 in guinea pig taenia caecum, respectively. We furthermore determined the affinity of bupranolol to subclassify atypical beta/beta3-adrenoceptor in rat oesophageal muscularis mucosae, because it is rich in atypical beta/beta3-adrenoceptor. BRL37344 and noradrenaline produced a concentration-dependent relaxation of rat oesophageal muscularis mucosae. The responses to BRL37344 and noradrenaline were resistant to 3x10(-6) M propranolol, 10(-4) M atenolol, and 10(-4) M butoxamine. However, bupranolol antagonized the responses to BRL37344 and noradrenaline in a concentration-dependent manner. Schild plot analyses of bupranolol against BRL37344 and noradrenaline gave pA2-values of 7.06 and 6.96, respectively. These results suggest that bupranolol can distinguish the difference in affinity between atypical beta/beta3-adrenoceptors in rat oesophageal muscularis mucosae and guinea pig taenia caecum. The difference in behavior of bupranolol confirms the existence of some atypical beta/beta3-adrenoceptors subtypes.

Adrenergic alpha-Agonists↗

Two diterpenoids from the roots of gaultheria yunnanensis

Two new diterpenoids, gaultheric acid (1) and gaultheronoterpene (2), were isolated from the roots ofGaultheria yunnanensis. Their structures were elucidated as 12-hydroxy-13-acetyl-8,11, 13-podocarpatrien-18-oic acid (1) and 3beta, 12-dihydroxy-13-acetyl-4(18),8,11,13-podocarpatetraene (2) on the basis of spectral analysis.

Journal Article↗

New triterpenoid saponins from Maesa japonica.

New triterpenoid saponins, maejaposides A, B, C, D, and E, were isolated from the roots of Maesa japonica and were, respectively, defined to be 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->2)-bet a-D-galactopyranosyl-(1-->3)] [beta-D-galactopyranosyl-(1-->2)]beta-D-glucuronopyranosides of 22alpha-[(Z)-2-hexenoyloxy]-13beta,28-oxido-olean++ +-16alpha, 28alpha-diol (1); 22alpha-[2'-methylbutanoyl]-13beta, 28-oxido-olean-16alpha,28alpha-diol (2a) and 22alpha-angeloyloxy-13beta,28-oxido-olean-16a lpha,28alpha-diol (2b); 21beta,22alpha-diangeloyloxy-13beta,28-oxido- olean-16alpha, 28alpha-diol (3); 21beta-angeloyloxy, 22alpha-(2'-methylbutanoyl)-13beta,28-oxido-olean++ +-16alpha, 28alpha-diol (4), and 21beta-angeloyloxy, 22alpha-[(Z)-2'-hexenoyl]-13beta,28-oxido-olean- 16alpha,28alpha-diol (5). Their structures were established on the basis of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC, and NOESY) and ESIMS/MS studies, along with chemical degradation.

Carbohydrate Sequence↗

Camelliols A-C, three novel incompletely cyclized triterpene alcohols from sasanqua oil (Camellia sasanqua)

Three novel triterpene alcohols, camelliols A (1), B (3), and C (5), possessing a mono-, bi-, and tricyclic ring system, respectively, have been isolated, along with achilleol A, a known monocyclic triterpene alcohol, from the nonsaponifiable lipids of sasanqua oil (Camellia sasanqua). The structures of these new alcohols were determined on the basis of spectroscopic methods.

Journal Article↗

Saponarioside C, the first alpha-D-galactose containing triterpenoid saponin, and five related compounds from Saponaria officinalis.

Six novel triterpenoid saponins, named saponariosides C-H, were isolated from the whole plants of Saponaria officinalis. Their structures were established as saponarioside C (1), 3-O-beta-D-xylopyranosyl-gypsogenic acid-28-O-alpha-D-galactopyranosyl-(1-->6)-beta-D-glucopyranosyl-(1-- >6)-[beta-D-glucopyranosyl-(1-->3)]-beta-D-glucopyranoside; saponarioside D (2), 3-O-beta-D-xylopyranosyl-gypsogenic acid-28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6) -[beta-D-glucopyranosyl-(1-->3)]-beta-D-glucopyranoside; saponarioside E (3), 3-O-beta-D-glucopyranosyl-gypsogenic acid-28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6) -[beta-D-glucopyranosyl-(1-->3)]-beta-D-glucopyranoside; saponarioside F (4), 3-O-beta-D-xylopyranosyl-16alpha-hydroxygypsogenic acid-28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6) -[beta-D-glucopyranosyl-(1-->3)]-beta-D-glucopyranoside; saponarioside G (5), 3-O-beta-D-xylopyranosyl-16alpha-hydroxygypsogenic acid-28-O-beta-D-glucopyranosyl-(1-->6)-[beta-D-glucopyranosyl-(1-->3 )]-beta-D-glucopyranoside; and saponarioside H (6), 3-O-beta-D-xylopyranosyl-gypsogenic acid-28-O-beta-D-glucopyranoside, by a combination of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC, and NOESY) studies and chemical degradation.

Carbohydrate Sequence↗

Four new triterpenoidal saponins acylated with one monoterpenic acid from Gleditsia sinensis.

Four new oleanane-type triterpenoidal glycosides, named gleditsiosides A-D (1-4), were isolated from the anomalous fruits of Gleditsia sinensis. Using modern NMR techniques, including DQF-COSY, HETCOR, HOHAHA, HMBC, and ROESY experiments and MS analysis as well as chemical methods, their structures were determined as 3-O-beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)- bet a-D-glucopyranosyl oleanolic acid 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha- L-rhamnopyranosyl-(1-->2)-[(6S,2E)-6-hydroxy-2,6-dimethyl-2, 7-octadienoyl-(1-->6)]-beta-D-glucopyranosyl ester (1); 3-O-beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)- bet a-D-glucopyranosyl oleanolic acid 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha- L-rhamnopyranosyl-(1-->2)-[(2E)-2-hydroxylmethyl-6-hydroxy-6-methy l-2 ,7-octadienoyl-(1-->6)]-beta-D-glucopyranosyl ester (2); 3-O-beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)- bet a-D-glucopyranosyl echinocystic acid 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta- D-galactopyranosyl-(1-->2)]-alpha-L-rhamnopyranosyl-(1-->2)-[(2E)-2-h ydroxylmethyl-6-hydroxy-6-methyl-2, 7-octadienoyl-(1-->6)]-beta-D-glucopyranosyl ester (3); and 3-O-beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)- bet a-D-glucopyranosyl echinocystic acid 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta- D-galactopyranosyl-(1-->2)]-alpha-L-rhamnopyranosyl-(1-->2)-[(6S, 2E)-6-hydroxy-2,6-dimethyl-2, 7-octadienoyl-(1-->6)]-beta-D-glucopyranosyl ester (4).

Carbohydrate Sequence↗

Gleditsiosides N-Q, new triterpenoid saponins from Gleditsia sinensis.

The structures of gleditsiosides N, O, P, and Q (1-4), isolated from anomalous fruits of Gleditsia sinensis, were characterized as novel complex bisdesmosidic triterpenoid glycosides acylated with monoterpenoid units, by means of extensive 1D and 2D NMR studies. The four compounds shared a common structural feature with a trisaccharide [(beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)-be ta- D-glucopyranoside)] affixed to C-3 and a tetrasaccharide [(beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-r hamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester)] attached to C-28. Gleditsioside P (3) is the first saponin of this type found to date bearing three monoterpenoid units.

Carbohydrate Sequence↗