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Biomedical subjects

H Arakawa

Publications and source records attributed to H Arakawa.

At least 19 recordsLinked to original sources
PubMed1999

Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I.

J-107088 [6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carb azo le-5,7(6H)-dione] is a new derivative of NB-506, an indolocarbazole antitumor agent. J-107088 induced single-strand DNA cleavage only in the presence of topoisomerase I (top1) more effectively than NB-506 or camptothecin. The preferable sequences of the DNA cleaved by J-107088 were C/T / G as in the case of NB-506. This base-preference of J-107088 in top1-mediated cleavage was different from that of camptothecin, which was T / G/A. top1 poisons stabilize the complex between DNA and top1 (cleavable complex). This cleavable complex is released on addition of a high concentration of monovalent cation or removal of top1 poisons. The complex induced by J-107088 was quite stable; it was scarcely released on the addition of NaCl or dilution of J-107088, contrary to the case with camptothecin and NB-506. J-107088-inducing complexes were also stable in cultured cells, when the compound was added to the culture medium. These unique in vitro activities of J-107088 on top1 that differed from those of camptothecin and NB-506 may be relevant to its more potent in vivo antitumor efficacy in a human tumor xenographted nude mouse model.

Animals↗
PubMed1999

Astrocyte differentiation mediated by LIF in cooperation with BMP2.

Leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP) 2 signal via different receptor systems. We have recently demonstrated that simultaneous stimulation of fetal mouse neuroepithelial cells with these distinct types of cytokines synergistically induces astrocyte differentiation in a 2-day culture. Here we show that astrocytes spontaneously emerge in vitro without exogenously added LIF and BMP2 in the culture of neuroepithelial cells for a much longer period. This spontaneous astrocyte differentiation is completely impaired when neuroepithelial cells deficient for gp130, a signal transducing receptor component for LIF, are used. We also show that LIF and BMP2 as well as related cytokines and respective receptor molecules are expressed in fetal mouse brain and cultured neuroepithelial cells. Taken together with our previous finding that prenatal mouse brain deficient for gp130 exhibits a severe reduction of astrocytes, it is suggested that LIF acts cooperatively with BMP2 in vivo to induce astrocyte differentiation in mouse developing brain.

Animals↗
PubMed1999

Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation.

gp130 is a signal-transducing receptor component used in common by the interleukin-6 (IL-6) family of hematopoietic and neurotrophic cytokines, including IL-6, IL-11, leukemia-inhibitory factor, ciliary neurotrophic factor, oncostatin-M, and cardiotrophin-1. We have examined in this study a role of gp130 in the nervous system by analyzing developmental cell death of several neuronal populations and the differentiation of astrocytes in gp130-deficient mice. A significant reduction was observed in the number of sensory neurons in L5 dorsal root ganglia and motoneurons in the facial nucleus, the nucleus ambiguus, and the lumbar spinal cord in gp130 -/- mice on embryonic day 18.5. On the other hand, no significant neuronal loss was detectable on day 14.5, suggesting a physiological role of gp130 in supporting newly generated neurons during the late phase of development when naturally occurring cell death takes place. Moreover, expression of an astrocyte marker, GFAP, was severely reduced in the brain of gp130 -/- mice. Our data demonstrate that gp130 expression is essential for survival of subgroups of differentiated motor and sensory neurons and for the differentiation of major populations of astrocytes in vivo.

Animals↗
PubMed1999

Synthesis of taxoids 5. Synthesis and evaluation of novel water-soluble prodrugs of a 3'-desphenyl-3'-cyclopropyl analogue of docetaxel.

A novel 3'-desphenyl-3'-cyclopropyl analogue of docetaxel was synthesized from 10-deacetyl-baccatin III. The cytotoxicity of the new taxoid was evaluated against several human tumor cell lines, and it had ca. 20 times stronger activity against human colon cancer cell lines (WiDr and Colon 320) than that of docetaxel. This taxoid was converted to its water-soluble prodrugs that have 2'-substituted amino acid derivatives with spacer. The prodrugs had good solubility in saline and showed more potent antitumor activity against B 16 melanoma in mice than that of docetaxel.

Animals↗
PubMed1999

Synthesis and biological activities of topoisomerase I inhibitors, 6-N-amino analogues of NB-506.

6-N-Amino analogues of NB-506 [6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosyl) -5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione] (3b) were synthesized and tested with respect to topoisomerase inhibition, cytotoxicity and anticancer effects. Among them, a 1,3-dihydroxypropane analogue (J-109,404, 5t) showed more than ten times more potent anticancer activity in MKN-45 human stomach cancer cells implanted in mice than NB-506.

Animals↗
PubMed1999

Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.

The cytokines LIF (leukemia inhibitory factor) and BMP2 (bone morphogenetic protein-2) signal through different receptors and transcription factors, namely STATs (signal transducers and activators of transcription) and Smads. LIF and BMP2 were found to act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacts physically with STAT3 at its amino terminus in a cytokine stimulation-independent manner, and with Smad1 at its carboxyl terminus in a cytokine stimulation-dependent manner. The formation of a complex between STAT3 and Smad1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neural progenitors.

Animals↗
PubMed1999

Effective control of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis with immunochemotherapy. Histiocyte Society.

The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder. Although the prognosis for Epstein-Barr virus-associated HLH (EBV-HLH) remains uncertain, numerous reports indicate that it can also be fatal in a substantial proportion of cases. We therefore assessed the potential of immunochemotherapy with a core combination of steroids and etoposide to control EBV-HLH in 17 infants and children who met stringent diagnostic criteria for this reactive disorder of the mononuclear phagocyte system. Treatment of life-threatening emergencies was left to the discretion of participating investigators and typically included either intravenous Ig or cyclosporin A (CSA). Five patients (29%) entered complete remission during the induction phase (1 to 2 months), whereas 10 others (57%) required additional treatment to achieve this status. In 2 cases, immunochemotherapy was ineffective, prompting allogeneic bone marrow transplantation. Severe but reversible myelosuppression was a common finding; adverse late sequelae were limited to epileptic activity in one child and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with immunochemotherapy have maintained their complete responses for 4+ to 39+ months (median, 15+ months), suggesting a low probability of disease recurrence. These results provide a new perspective on EBV-HLH, showing effective control (and perhaps cure) of the majority of EBV-HLH cases without bone marrow transplantation, using steroids and etoposide, with or without immunomodulatory agents.

Child↗
PubMed1999

CMAP: a novel cystatin-like gene involved in liver metastasis.

A novel metastasis-associated gene was identified with a differential display system in murine carcinoma cells showing a high rate of metastasis to the liver. A human homologue was also identified using a PCR-based strategy. The protein coded by this gene was named cystatin-like metastasis-associated protein (CMAP) and showed 22.1-28.1% homology to human family 2 cystatins. CMAP mRNA was selectively overexpressed in all murine liver metastatic tumors but not in any pulmonary metastatic tumors examined. Transfection of CMAP antisense DNA into highly metastatic liver cells greatly decreased their metastatic potential and CMAP expression, indicating that CMAP is involved in liver metastatic ability after intravasation of malignant cells. The human homologue of CMAP was found to be expressed in various human cancer cell lines established from malignant tumors. Our discovery of this novel liver metastasis-related gene indicates a new approach to the diagnosis and/or prevention of liver metastasis of human cancer.

Amino Acid Sequence↗
PubMed1999

Quality of life assessment of bone-anchored fixed partial denture patients with unilateral mandibular distal-extension edentulism.

STATEMENT OF PROBLEM: Dental implants are expanding their use among partially edentulous patients. However, whether implants can promote the quality of life (QOL) of these patients has not been sufficiently examined. PURPOSE: This study compared the QOL level among implant denture, removable partial denture, and no restoration patients with distal extension type unilateral mandibular edentulism. MATERIAL AND METHODS: Three groups (n = 12 each) of subjects with unilateral mandibular distal-extension edentulism who were matched for age, sex, and missing teeth were studied. The groups were (1) implant denture, (2) removable partial denture, and (3) no restoration. QOL levels of these 3 groups were compared using a self-administered questionnaire with 3 major subscales: oral condition, general condition, and dental treatment. RESULTS: The implant denture group showed higher oral condition related QOL score than the other groups. There was no significant difference in oral condition-related QOL scores between the removable partial denture and no restoration groups. There was no significant difference in the general condition related QOL score and dental treatment-related score among the 3 groups. CONCLUSION: In unilateral mandibular distal extension edentulous patients, oral-condition-related QOL levels for dental implant patients were higher than those of removable partial denture or no restoration patients. The QOL levels of the removable partial denture patients were almost identical to those of no restoration patients.

Case-Control Studies↗
PubMed1999

Identification and cloning of a novel isoform of mouse secretory leukocyte protease inhibitor, mSLPI-beta, overexpressed in murine leukemias and a highly liver metastatic tumor, IMC-HA1 cells.

Several genes showing transcriptional alteration in a highly liver metastatic murine carcinoma cell line, IMC-HA1, were identified by mRNA differential display system. Among them, a gene identical to mSLPI was isolated as mSLPI-alpha and -beta. They were produced through an alternative splicing. Their full-length cDNA sequences were determined, and their expression in various murine tumors and normal tissues was analysed. The deduced translation product of mSLPI-alpha showed 59% identity to hSLPI. Although mSLPI-beta had the same 103-amino-acid sequence from the carboxyl terminus, the amino terminus showed hydrophilicity opposite mSLPI-alpha or hSLPI. The mSLPI-alpha was expressed ubiquitously in various tumor cell lines. Interestingly, however, mSLPI-beta expression was only observed in P388 and L1210 leukemias and IMC-HA1 cells, and in lower amounts in three normal tissues (thymus, lung and spleen), suggesting that mSLPI, and in particular the unusual splicing product, mSLPI-beta, plays a specific role in these cells, including malignant processes of tumor cells.

Amino Acid Sequence↗
PubMed1999

Relationship between systemic blood pressure, airway blood flow and plasma exudation in guinea-pig.

Plasma exudation in the airways is mainly dependent on microvascular permeability of the tracheobronchial circulation and may be affected by local blood flow. Aortic blood pressure provides the major inflow pressure to tracheobronchial circulation. Therefore, systemically administered vasoconstrictors, in doses enough to increase systemic blood pressure, may theoretically increase the blood flow in the tracheobronchial circulation by enhancing inflow pressure. Consequently, this may influence plasma exudation induced by inflammatory mediators in the airways. To test this hypothesis, we used guinea-pigs to study: (1) the effects of i.v. vasoconstrictors (methoxamine and angiotensin II) on blood flow in the tracheal mucosa and in the leg skeletal muscle (Laser-Doppler flowmetry); (2) the effects of i.v. vasoconstrictors on plasma exudation induced by tracheal administration of the inflammatory mediator bradykinin (150 nmol). We found that i.v. methoxamine and angiotensin II significantly increase tracheal mucosa blood flow and systemic blood pressure. The increase in tracheal mucosa blood flow was, in the case of angiotensin II, found to be significantly related to the increase in systemic blood pressure. In separate experiments, pre-treatment with i.v. methoxamine and angiotensin II significantly potentiates Evan's Blue dye exudation induced by bradykinin in the trachea and main bronchi. We conclude that i.v. methoxamine and angiotensin II potentiate bradykinin-induced plasma exudation in the guinea-pig airways, possibly by increasing the local blood flow. The increase in the local blood flow is most likely induced by enhanced systemic blood pressure (inflow pressure), owing to a redistribution of the total body blood flow.

Angiotensin II↗
PubMed1999

The vertical displacement sign: a technique for differentiating between left and right ribs on the lateral chest radiograph.

AIM: To evaluate a new approach to the differentiation of the right and left ribs, the vertical displacement sign, and to compare its efficacy with the big rib sign. MATERIALS AND METHODS: One hundred and nine lateral chest radiographs that clearly showed both the gastric air bubble sign and the cardiac silhouette sign were retrospectively reviewed by two radiologists. Each study was evaluated by consensus. Each radiograph was assessed for suitability of reading with each technique. Suitable radiographs were then reviewed using both the big rib sign and vertical displacement sign independently. RESULTS: Applicability of the vertical displacement sign [107 of 109 (98%)] was greater than that of the big rib sign [95 of 109 (87%)] (P = 0.0017). The accuracy of the vertical displacement sign [105 of 107 (98%)] was higher than that of the big rib sign [74 of 95 (78%)] (P < 0.001). CONCLUSION: The vertical displacement sign seems to be a reliable technique for the differentiation of right and left ribs on the lateral chest radiograph and can be used as a complementary technique when the big rib sign is not applicable.

Adult↗
PubMed1999

The distribution of sugar chains on the vomeronasal epithelium observed with an atomic force microscope.

The distribution of sugar chains on tissue sections of the rat vomeronasal epithelium, and the adhesive force between the sugar and its specific lectin were examined with an atomic force microscope (AFM). AFM tips were modified with a lectin, Vicia villosa agglutinin, which recognizes terminal N-acetyl-D-galactosamine (GalNAc). When a modified tip scanned the luminal surface of the sensory epithelium, adhesive interactions between the tip and the sample surface were observed. The final rupture force was calculated to be approximately 50 pN based on the spring constant of the AFM cantilever. Distribution patterns of sugar chains obtained from the force mapping image were very similar to those observed using fluorescence-labeled lectin staining. AFM also revealed distribution patterns of sugar chains at a higher resolution than those obtained with fluorescence microscopy. Most of the adhesive interactions disappeared when the scanning solution contained 1 mM GaINAc. The adhesive interactions were restored by removing the sugar from the solution. Findings suggest that the adhesion force observed are related to the binding force between the lectin and the sugars distributed across the vomeronasal epithelium.

Acetylgalactosamine↗
PubMed1999

Effect of ultrasonically nebulized distilled water on airway epithelial cell swelling in guinea pigs.

To investigate the pathogenesis of ultrasonically nebulized distilled water-induced airway narrowing, we studied the role of airway epithelial cells during a distilled water-inhalation challenge in an animal model of airway inflammation. Guinea pigs were divided into four groups: 1) a sham/saline (S/S) group: sham ozone followed by saline inhalation; 2) a sham/water (S/W) group: sham ozone followed by water inhalation; 3) an ozone/saline (O/S) group: ozone followed by saline inhalation; and 4) an ozone/water (O/W) group: ozone followed by water inhalation. After exposure to either 3.0 parts/million ozone or air at the same flow rate for 2 h, guinea pigs were anesthetized and tracheostomized, and then lung resistance (RL) was measured. For morphometric assessment, tissues were fixed with formaldehyde, stained with hematoxylin and eosin, and cut into transverse sections. Airway dimensions were either measured directly or calculated from the internal perimeter, the external perimeter, and airway wall area. There were no statistical differences in the values of RL before distilled water inhalation between the sham groups and the ozone groups. RL increased significantly after 10 min of distilled water inhalation in both the S/W group and the O/W group. In the S/W group, epithelial cells were swollen, and intercellular spaces were wider, resulting in significant increase in epithelial wall thickness, but there was no significant infiltration by inflammatory cells. In the O/S group, the epithelium showed infiltration by inflammatory cells without change in cell volume. In the O/W group, the epithelium showed both infiltration and a greater increase in epithelial wall thickness compared with the S/W group. These results suggest that airway epithelial cell swelling, induced by inhaled distilled water, increases with RL in guinea pigs and that this reaction may be accelerated by airway inflammation.

Administration, Inhalation↗
PubMed1999

Functional pulmonary surfactant deficiency and neonatal respiratory disorders.

The pathophysiology of functional deficiency of pulmonary surfactant in the neonatal respiratory disorders represented by MAS, hemorrhagic lung edema and ARDS was discussed. The removal of inhibitor(s) is the cardinal procedure for MAS and the lavage with surfactant solution seems to be promising. In case of replacement therapy, we should consider using a different dose compared to the one used in RDS due to lung immaturity, in order to optimize results.

Humans↗
PubMed1998

Analysis of polymerase chain reaction products by high-performance liquid chromatography with fluorimetric detection and its application to DNA diagnosis.

We describe the development of a sensitive high-performance liquid chromatographic (HPLC) method for polymerase chain reaction (PCR) products using bisbenzimide (Hoechst 33258 dye) based fluorimetric detection. The detection limit and specificity for double-strand DNA detection are improved in comparison with HPLC with UV absorbance detection. This HPLC, using a column packed with diethylaminoethyl-bonded non-porous resin particles, was applied to the detection of allele-specific PCR and restriction fragment length polymorphism analysis. We also developed a hybridization method analyzed by HPLC. DNA fragments (149 bp) containing the mutation site (C->A,G,T) in the N-ras gene were amplified by PCR. Fluorescein isothiocyanate (FITC)-labeled DNA probes were also prepared by PCR using FITC-labeled 5' primer. Analysis of mutation was performed by the separation of a hybrid and non-reactive DNA probe with HPLC with fluorimetric detection after the hybridization of target DNA (149 bp) and a FITC DNA probe. The effects of various factors on hybridization were examined to establish optimal assay conditions. Under the conditions determined, a point mutation in PCR products obtained from the N-ras gene could be detected specifically by this method. The analysis of PCR products by HPLC may potentially be useful for DNA diagnosis.

Alleles↗