PubMed Health⌕ Search

Biomedical subjects

K Hiruma

Publications and source records attributed to K Hiruma.

At least 37 records · Page 2Linked to original sources
PubMed1999

Molecular remission in adult T cell leukemia after autologous CD34+ peripheral blood stem cell transplantation.

This report describes a patient with acute-type adult T cell leukemia/lymphoma (ATLL) successfully treated by autologous CD34+ peripheral blood stem cell transplantation after fractionated total body irradiation and high-dose cytarabine and cyclophosphamide. A newly established inverse polymerase chain reaction method was used to demonstrate the disappearance of ATLL clonal cells. The patient achieved a sustained molecular remission after transplantation, but died from opportunistic infection 4 months after transplantation. Thus, autologous CD34+ peripheral blood stem cell transplantation is promising for this type of malignancy. However, a prudent clinical attitude toward immunological fragility after transplantation is needed for better outcome.

Antigens, CD34↗
PubMed1999

Diesel exhaust particulates upregulate histamine receptor mRNA and increase histamine-induced IL-8 and GM-CSF production in nasal epithelial cells and endothelial cells.

BACKGROUND: Histamine is the most important chemical mediator in the pathogenesis of nasal allergy. Diesel exhaust particulates (DEPs) are common air pollutants from diesel engine-powered car exhaust and cause chronic airway diseases. Recently we observed that the nasal reactivity to histamine was enhanced in diesel exhaust-exposed guinea-pigs. It was also revealed that epithelial cells and endothelial cells in the airway produce certain cytokines in response to histamine. OBJECTIVE: We examined the effects of DEP extract on the expression of histamine H1 receptor (H1R) mRNA in human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs), and on the production of IL-8 and GM-CSF induced by histamine. METHODS: HNECs and HMMECs were isolated from human nasal mucosa specimens. HNEC and HMMEC monolayers were cultured in the presence or absence of DEP extract. The change in the expression of H1R mRNA was then evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and the Southern blot analysis. To investigate the effects of DEP extract on the histamine-induced cytokine production, HNEC and HMMEC monolayers were cultured in the presence or absence of DEP extract for 3-24 h. After three washes with PBS, they were then incubated with 10(-6) mol/L histamine for 24 h. The amounts of IL-8 and GM-CSF in the culture media were measured by enzyme-linked immunoabsorbent assay. RESULTS: DEP extract increased the expression of H1R mRNA in both HNECs and HMMECs. The amount of IL-8 and GM-CSF, induced by histamine, was significantly higher in DEP extract pretreated HNECs and HMMECs than nontreated HNECs and HMMECs. CONCLUSION: These results strongly suggest that DEP accelerates the inflammatory change by not only directly upregulating H1R expression but also increasing histamine-induced IL-8 and GM-CSF production.

Cell Survival↗
PubMed1999

Activation of a delayed-early gene encoding MHR3 by the ecdysone receptor heterodimer EcR-B1-USP-1 but not by EcR-B1-USP-2.

MHR3, a homolog of the retinoid orphan receptor (ROR), is a transcription factor in the nuclear hormone receptor family that is induced by 20-hydroxyecdysone (20E) in the epidermis of the tobacco hornworm, Manduca sexta. Its 2.7-kb 5' flanking region was found to contain four putative ecdysone receptor response elements (EcREs) and a monomeric (GGGTCA) nuclear receptor binding site. Activation of this promoter fused to a chloramphenicol acetyltransferase (CAT) reporter by 2 micrograms of 20E per ml in Manduca GV1 cells was similar to that of endogenous MHR3, with detectable CAT by 3 h. When the ecdysone receptor B1 (EcR-B1) and Ultraspiracle 1 (USP-1) were expressed at high levels under the control of a constitutive promoter, CAT levels after a 3-h exposure to 20E increased two- to sixfold. In contrast, high expression of EcR-B1 and USP-2 caused little increase in CAT levels in response to 20E. Moreover, expression of USP-2 prevented activation by EcR-B1-USP-1. Deletion experiments showed that the upstream region, including the three most proximal putative EcREs, was responsible for most of the 20E activation, with the EcRE3 at -671 and the adjacent GGGTCA being most critical. The EcRE1 at -342 was necessary but not sufficient for the activational response but was the only one of the three putative EcREs to bind the EcR-B1-USP-1 complex in gel mobility shift assays and was responsible for the silencing action of EcR-B1-USP-1 in the absence of hormone. EcRE2 and EcRE3 each specifically bound other protein(s) in the cell extract, but not EcR and USP, and so are not EcREs in this cellular context. When cell extracts were used, the EcR-B1-USP-2 heterodimer showed no binding to EcRE1, and the presence of excess USP-2 prevented the binding of EcR-B1-USP-1 to this element. In contrast, in vitro-transcribed-translated USP-1 and USP-2 both formed heterodimeric complexes with EcR-B1 that bound ponasterone A with the same Kd (7 x 10(-10) M) and bound to both EcRE1 and heat shock protein 27 EcRE. Thus, factors present in the cell extract appear to modulate the differential actions of the two USP isoforms.

Animals↗
PubMed1999

Effect of diesel exhaust on guinea pig nasal mucosa.

In this study using guinea pigs, we investigated the effects of diesel exhaust (DE) containing diesel exhaust particulate (DEP) on 1) vascular permeability induced by histamine, 2) nasal mucosal permeability to horseradish peroxidase (HRP), and 3) eosinophilic epithelial infiltration. The vascular permeability induced by histamine was enhanced significantly and dose-dependently in DE-exposed guinea pigs. The HRP reaction products in epithelial cells and intercellular spaces were significantly and dose-dependently increased in those guinea pigs. Eosinophil infiltration into the epithelial layer was significantly increased in guinea pigs exposed to DE containing 3.2 mg/m3 DEP, and the reactivity of the nasal mucosa to histamine solution applied on the nasal mucosa was significantly enhanced in those guinea pigs. These findings suggest that DE may play an important role not only in promoting nasal hyperreactivity induced by the enhancement of absorption of antigen through the nasal epithelium, but also in inducing eosinophil infiltration in nasal mucosa and enhancing nasal mucosal reactivity.

Animals↗
PubMed1998

Juvenile hormone prevents ecdysteroid-induced expression of broad complex RNAs in the epidermis of the tobacco hornworm, Manduca sexta.

A cDNA homolog of the Drosophila melanogaster Broad Complex (BRC) gene was isolated from the tobacco hornworm, Manduca sexta, which shows a predicted 88% amino acid identity with Drosophila BRC in the N-terminal BTB domain. Three zinc finger domains encoding homologs of the Drosophila Z2, Z3, and Z4 domains (93, 100, and 85% identity, respectively) were obtained by RT-PCR. In Manduca dorsal abdominal epidermis, BRC RNAs were not observed during the larval molt. Three BRC transcripts-6.0, 7.0, and 9.0 kb-first appeared at the end of the feeding stage of the fifth (final) instar when the epidermis is exposed to ecdysteroids in the absence of juvenile hormone (JH) and becomes committed to pupal differentiation. These RNAs were induced in day 2 fifth larval epidermis in vitro by 20-hydroxyecdysone (20E) in the absence of JH with dose-response and time courses similar to the induction of pupal commitment. This induction by 20E in vitro was prevented by the presence of JH I at levels seen in vivo during the larval molt. In the wing discs, the BRC RNAs appeared shortly after ecdysis to the fifth instar and coincided with the onset of metamorphic competence of these discs. Application of a JH analogue pyriproxifen during the fourth instar molt delayed and reduced the levels of BRC mRNAs seen in the wing discs in the early fifth instar, but did not completely prevent their appearance in this tissue that first differentiates at metamorphosis. The expression of the BRC transcription factors thus appears to be one of the first molecular indications of the genetic reprogramming of the epidermis necessary for insect metamorphosis. How JH prevents BRC expression in this epidermis may provide the key to understanding how this hormone controls metamorphosis.

Amino Acid Sequence↗
PubMed1998

Regulation of the transcription factor E75 by 20-hydroxyecdysone and juvenile hormone in the epidermis of the tobacco hornworm, Manduca sexta, during larval molting and metamorphosis.

The homolog of the ecdysteroid-induced transcription factor E75A in Drosophila melanogaster was cloned from the tobacco hornworm, Manduca sexta, and its developmental expression and hormonal regulation were analyzed. Both E75A and E75B mRNAs were found in the abdominal epidermis during both the larval and the pupal molts, with E75A appearing before E75B, coincident with the rise of ecdysteroid. Exposure of either fourth or fifth instar epidermis to 20E in vitro caused the rapid, transient induction of E75A RNA with a peak at 6 and 3 h, respectively, followed by maintenance at low levels until 24 h. Epidermis from fourth instar larvae with high endogenous juvenile hormone (JH) showed a 10-fold higher sensitivity to 20E (EC50 = 2 x 10(-8) M for fourth instar and 2 x 10(-7) M for fifth instar epidermis). The presence of the protein synthesis inhibitor anisomycin had no effect on the induction but prevented the decline, indicating that E75A RNA was directly induced by 20E, but its down-regulation depended on protein synthesis. Exposure of day 2 fifth instar epidermis to 20E in the presence of JH I, which prevents the 20E-induced pupal commitment, caused an increased accumulation of E75A RNA throughout the culture period although the temporal pattern was unaffected. These findings show for the first time that JH plays a role in 20E-induced early gene expression and suggest that the higher levels of E75A may be required for maintenance of larval commitment of this epidermis.

Amino Acid Sequence↗
PubMed1998

Characterization of the sulfated fucose-containing trisaccharides by fast atom bombardment tandem mass spectrometry in the study of the acrosome reaction-inducing substance of the starfish, Asterias amurensis.

Fast atom bombardment mass spectrometry (FABMS) and collision-induced dissociation tandem mass spectrometry (CID-MS/MS) were applied to the investigation of the anomeric isomerism of synthetic trisaccharides consisting of xylose, galactose and sulfated fucose {Xyl1-->3Gal alpha 1-->3(4-OSO3Na)Fuc} and {Xyl1-->3Gal alpha 1-->4(3-OSO3Na)Fuc} and the linkage position of the sulfate group. It was possible to differentiate between various glycosidic linkages in several synthetic trisaccharides. The position of a sulfate group in synthetic methyl O-sulfo-alpha-L-fucopyranoside isomers was elucidated from the fragmentation patterns. Comparing the data from the synthetic sulfated trisaccharides with the spectra from the natural compound derived from glycan chains of the acrosome reaction-inducing substance (ARIS) from starfish, the anomeric structure and the position of the sulfate group in the natural sample were determined without ambiguity as Xyl beta 1-->3Gal alpha 1-->3(4-OSO3-)Fuc, in agreement with the result from an independent study based on nuclear magnetic resonance.

Animals↗
PubMed1998

Metastasis of renal cell cancer to the ethmoid sinus.

The origin of metastatic tumors in the nasal or paranasal sinuses is often renal cancer, and metastasis to the nasal or paranasal sinuses sometimes takes a long time after nephrectomy. The present paper deals with one patient with metastasis of renal cancer to the ethmoid sinus 2 years after nephrectomy. Even though many metastatic tumors originating from renal cancer develop in multiples, most metastatic tumors in the nasal or paranasal sinuses are single and treated surgically. However, even if multiple tumors are found in the nasal and paranasal region and other organs, surgery will be effective in preventing epistaxis and subsequent anemia. Also, when removing a tumor it will be effective to identify the feeding arteries of the tumor, perform embolization therapy, and clip the necessary arteries.

Blood Loss, Surgical↗
PubMed1998

A comparative study of a new, fully automated procedure and the standard mononuclear cell program using the Cobe Spectra for peripheral blood stem cell collection.

Recently, a completely automated procedure, the AutoPBSC program for the COBE Spectra cell separator, has been developed for peripheral blood stem cell harvest (PBSCH). We compared the performance of the AutoPBSC program with the standard mononuclear cell (MNC) program in the same patients and in a donor. Peripheral blood stem cells (PBSC) were collected from 3 patients or a donor alternately using the MNC program and the AutoPBSC program in a course of PBSC mobilization. Equal blood volume was processed from each patient (200 ml/kg) and a donor (150 ml/kg). We used a harvest volume of 3 ml and a chase volume of 7 ml in all AutoPBSC procedures. The procedure duration was almost equivalent for both programs. The volume of products was significantly lower in the AutoPBSC program (71 +/- 13 ml) than in the MNC program (183 +/- 30 ml). MNC yields were fewer, and total nucleated cell (TNC) and MNC collection efficiency was less for the AutoPBSC program compared to the MNC program. The CD34+ cell collection efficiency was less for the AutoPBSC program (26.5 +/- 13.7%, compared with 77.7 +/- 60.6%; p > 0.05). The contamination of platelets and red cells was significantly less in the AutoPBSC program than in the MNC program. In conclusion, we consider that the collection efficiency in the new program should be improved by modification of parameters because there exist great advantages to automated procedures.

Adult↗
PubMed1997

Action of different ecdysteroids on the regulation of mRNAs for the ecdysone receptor, MHR3, dopa decarboxylase, and a larval cuticle protein in the larval epidermis of the tobacco hornworm, Manduca sexta.

To determine which ecdysteroids may be biologically active in the larval epidermis of the tobacco hornworm, Manduca sexta, we studied the action of several known ecdysteroids and metabolites on the expression of the genes encoding the ecdysone receptor (EcR), Manduca hormone receptor 3 (MHR3), dopa decarboxylase (DDC), and a larval cuticle protein (LCP-14). Both Day 2 fourth- and Day 2 fifth-instar larval epidermis contained significant 3 beta-reductase activity which metabolized 3-dehydroecdysone (3DE) and 3-dehydro-20-hydroxyecdysone (3D20E) to ecdysone (E) and 20-hydroxyecdysone (20E), respectively, but had only very low amounts of ecdysone oxidase activity (E to 3DE) and no detectable ecdysone 20-monooxygenase activity (E to 20E). When the expression of the various genes was studied in the epidermis in vitro, 20E and 3D20E had similar effects, whereas E, 3DE, 26-hydroxyecdysone and 20,26-dihydroxyecdysone were ineffective. Exposure of Day 2 fifth-instar epidermis to 500 ng/ml of either 20E or 3D20E for 24 hr caused a rapid, biphasic increase in EcR-B1 mRNA. By contrast, EcR-A mRNA showed a less rapid initial increase followed by a slow steady rise and was less responsive to 3D20E. Ecdysone in a 1:1 mixture with 20E effectively halved the concentration of 20E needed to induce EcR-B1 mRNA but showed no synergism in the induction of EcR-A mRNA. The induction of MHR3 mRNA and of DDC mRNA in Day 2 fourth-instar epidermis as well as the suppression of DDC and LCP-14 gene expression by 3D20E was indistinguishable from that of 20E. Therefore, for Manduca larval epidermis, only 20E and 3D20E are biologically active ecdysteroids. Since the 3D20E can be converted to 20E by the epidermis, its effects are likely mediated by 20E.

Animals↗
PubMed1997

Risk factors for hepatic veno-occlusive disease after bone marrow transplantation: retrospective analysis of 137 cases at a single institution.

One hundred and thirty-seven consecutive patients who received bone marrow or peripheral blood stem cell transplantation were studied retrospectively to identify the risk factors for hepatic veno-occlusive disease (VOD). Of the 137 recipients, twenty (14.6%) patients were diagnosed with VOD using the McDonald's criteria. In these 20 patients with VOD, we analyzed various clinical parameters, including age, sex, HLA status, conditioning regimen, irradiation, immunosuppressive agents, mode of transplantation, history of hepatic dysfunction, pre-transplant hepatic and renal function, infectious episodes, antibiotics use, and serum viral titers. A history of hepatic dysfunction and low levels of pseudocholinesterase before transplantation were found to be statistically significant (P = 0.04 and 0.04). Low levels of pseudocholinesterase were significant by multivariate analysis using the logistic regression model (P = 0.02). These results suggest that pseudocholinesterase levels before transplant are important markers of VOD in patients receiving BMT.

Adolescent↗
PubMed1997

Effects of cyclosporin A on hepatitis C virus infection in bone marrow transplant patients. Bone Marrow Transplantation Team.

The hepatitis C virus (HCV) infection has, in general, been considered not to affect liver function severely during the course of bone marrow transplantation (BMT) except for late hepatitis which coincided with a decrease in immunosuppressive therapy. We examined serial sera of two patients with positive HCV antibody who underwent allogeneic BMT and found that while the dose of cyclosporin A tapered off, the serum concentration of HCV core protein increased before the occurrence of hepatitis. This suggests that viral reactivation and growth might be one of the important mechanisms of hepatitis after BMT in patients with positive HCV antibody.

Adult↗
PubMed1997

Diesel exhaust particulates enhance eosinophil adhesion to nasal epithelial cells and cause degranulation.

Diesel exhaust particulates (DEP) are a common air pollutant from diesel-engine-powered car exhaust and are thought to cause chronic airway diseases. On the other hand, eosinophils are major components of allergic inflammatory disorders such as asthma, nasal allergy and atopic dermatitis. We examined the effects of DEP and DEP extract (extract of polyaromatic hydrocarbons) on eosinophil adhesion, survival rate and degranulation. Eosinophils, human mucosal microvascular endothelial cells (HMMECs) and human nasal epithelial cells (HNECs) were preincubated in the presence or absence of DEP and DEP extract. 35S-labeled eosinophils were allowed to adhere to monolayers of HMMECs and HNECs. After washing, 35S radioactivity was determined and numbers of adherent eosinophils were calculated using each standard curve. The effects of DEP and DEP extract on eosinophil survival rate and degranulation were also determined. Although neither DEP nor DEP extract affected the adhesiveness of HMMECs and HNECs to eosinophils, 5 ng/ml of DEP extract and 50 ng/ml of DEP extract each significancy increased eosinophil adhesiveness to HNECs (134+/-9 and 143+/-8%, respectively; p<0.01 vs. control), but neither effected eosinophil adhesiveness to HMMECs. DEP extract also induced eosinophil degranulation without changing the eosinophil survival rate. Given that eosinophil-derived lipid mediators and toxic proteins play important roles in the development of nasal allergy, the above findings strongly suggest that DEP plays an important role in promoting the nasal hypersensitivity induced by enhanced eosinophil infiltration of epithelium and eosinophil degranulation.

Adult↗
PubMed1997

[Relationship between the presence of side-holes in bone marrow aspiration needle and the number of harvested bone marrow mononuclear cells].

The aim of this study was to evaluate the yield of nucleated cells in bone marrow harvested by means of Downs' Islam aspiration needles with or without side-holes. Twenty marrow donors for HLA identical sibling transplants were studied. Bone marrow nucleated cells were harvested 50 ml in the right iliac bone with a Downs' Islam aspiration needle with or without side-holes and 50 ml in the left with another kind of needle by means of 5 ml aspirations in each donor. There were no significant difference between the number of nucleated cells by means of Downs' Islam aspiration needles with and without side-holes by cross-over analysis. All nucleated cell counts were 33.06 +/- 12.93 x 10(3)/microliter (mean +/- standard deviation) by means of the needle with side-holes and 32.90 +/- 15.25 x 10(3)/microliter by means of the needle without side-holes. The Downs' Islam aspiration needle without side-holes seems to be better in bone marrow harvest from normal volunteers than that with side-holes, because the former may be stronger than the latter.

Adolescent↗
PubMed1996

Developmental profiles and ecdysteroid regulation of the mRNAs for two ecdysone receptor isoforms in the epidermis and wings of the tobacco hornworm, Manduca sexta.

Ecdysteroids acting through multiple isoforms of the ecdysone receptor (EcR) initiate molting and metamorphosis of insects. Two isoforms of EcR, A (this paper) and B1 (Fujiwara et al., Insect Biochem. Mol. Biol. 25, 845-856, 1995), were isolated from the tobacco hornworm, Manduca sexta, and shown to be similar to the corresponding Drosophila EcR isoforms. The developmental profiles of both EcR-A and EcR-B1 (determined by both analysis of isoform-specific mRNAs and use of monoclonal antibodies that detect either EcR-B1 or all forms), however, were different in Manduca epidermis, which produces sequentially the larval, the pupal, and the adult cuticles. EcR-B1 predominated through the larval, pupal, and early developing adult stages with an upregulation early in each molt. By contrast, EcR-A was present only at the onset of new cuticle synthesis during the larval molt, but in the pupal and adult molts was upregulated slightly later than EcR-B1 during the commitment period and was present during the predifferentiative phase. Both isoforms appeared in the larval wing discs after pupal commitment and persisted through pupal differentiation. The mRNAs for both isoforms were directly induced in larval epidermis in vitro by 20-hydroxyecdysone, but EcR-B1 mRNA accumulated more rapidly, peaking at 3 hr. In the presence of a protein synthesis inhibitor, the accumulation of EcR-B1 mRNA was slower and its subsequent decline was prevented, but the accumulation of EcR-A mRNA was unaffected. Thus, in this polymorphic epidermis both isoforms appear in every molt, with EcR-B1 present during the commitment and predifferentiative phases and then at the onset of cuticle synthesis EcR-A prevails. Additionally, EcR-A is apparently associated with the switching and predifferentiative events necessary for a new synthetic program.

Amino Acid Sequence↗