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K Hiruma

Publications and source records attributed to K Hiruma.

At least 55 records · Page 3Linked to original sources

A new decision rule for parameter delta in MAP EM (OSL) reconstruction with the Gibbs prior.

In MAP EM (OSL) reconstruction with the Gibbs prior, the parameter delta which appears in the prior is commonly treated as a fixed value. Because the quality of reconstructed images depends on this parameter, we have to select delta very carefully, and because the statistics of an image vary locally, we should not choose a single delta value for each image. We propose a new decision rule to select an appropriate local delta. In our proposed method, delta is determined as the median of the differences between a value of the pixel of interest and those of neighboring pixels. This selection yields an appropriate prior depending on the regional statistics. The prior therefore preserves the edge property without amplifying statistical noise and it is not necessary to know the appropriate delta value to obtain high quality images. We performed computer simulations to determine the effectiveness of the proposed method. The results showed that the quality of reconstructed images obtained with the proposed method was superior to those obtained with the prior with a fixed delta.

Algorithms↗

[The effect of histamine on the adhesion of endothelial cells to eosinophils].

Recent studies have revealed that eosinophils and eosinophil-derived mediators strongly contribute to the onset of nasal swelling and nasal hyperreactivity. The effect of histamine on the adhesion of endothelial cells to 35S-labeled eosinophils and on eosinophil transendothelial migration was investigated. Human microvascular endothelial cells were isolated and cultured from the mucosa of the inferior turbinates of patients with nasal allergy. Histamine caused dose-related enhancement of adhesiveness to eosinophils. Incubation of endothelial cells treated with 10(-5)M and 10(-4)M histamine increased adhesion to eosinophils by a mean of 56.4% (p < 0.05) and 66.0% (p < 0.05), respectively. When eosinophils were incubated with histamine, they did not induce any increase in adhesion to endothelial cells. Preincubation of endothelial cells with anti-ELAM-1 significantly inhibited histamine-induced adhesion, whereas anti-ICAM-1 and anti-VCAM-1 had no inhibitory effect. Histamine did not increase eosinophil transendothelial migration. Histamine is known to be vasoactive, mediating vasodilation and plasma extravasation. In addition, the results of this study raise the possibility that histamine promotes eosinophil adhesion to endothelial cells by increasing ELAM-1 molecules on endothelial cells and promotes nasal inflammatory and allergic reactions.

Adolescent↗

[Resolution of psoriasis vulgaris following allogeneic bone marrow transplantation for aplastic anemia].

A 36 year-old man had suffered from psoriasis vulgaris for about 25 years. He had received corticosteroids ointment and PUVA therapy with partial response. In 1987, he was diagnosed as having aplastic anemia (AA) and treated with various medications, but failed to respond. He received an allogeneic bone marrow transplantation (BMT) from his histocompatible sister in 1993. Conditioning regimen of BMT consisted of total lymphoid irradiation (7.5 Gy) and cyclophosphamide (200 mg/kg). Cyclosporin A and methotrexate were given for prophylaxis of graft-versus-host disease. On day 24, bone marrow examination disclosed normocellular marrow and karyotypic analysis completely confirmed the donor's origin. Before BMT, he had systemic psoriatic plaques with scales, together with nail involvement. After BMT, psoriatic plaques disappeared and nail deformity improved. He has remained in remission of his AA and completely free of psoriasis in the absence of immunosuppressive or other treatments. The cause of psoriasis is thought to be an immune-mediated disorder. Our case supports the observation that changing the host's immune system through allogeneic BMT can achieve remission of psoriasis. It is suggested that allogeneic BMT may be one strategy for the treatment of intractable immune-mediated disorders.

Adult↗

[The combination therapy with vinca-alkaloid slow infusion and cholchicine was effective to refractory idiopathic thrombocytopenic purpura. The patient could receive femoral head replacement in safety].

A 46-year-old man with idiopathic thrombocytopenic purpura (ITP) refractory to corticosteroid, splenectomy and other drugs was admitted to our hospital in August, 1994, because of aseptic necrosis of the right femoral head. Although high-dose intravenous gamma-globulin was ineffective, the platelet count was increased within two weeks by the combination therapy that consisted of 0.02 mg/kg vincristine alternating with 0.1 mg/kg vinblastine by slow infusion at a 1-week interval, and oral 1.5 mg/day colchicine. He subsequently underwent the femoral head replacement. This combination therapy seems to be useful for refractory ITP in preparation for surgery.

Colchicine↗

Recent advances in radioimmunoassay technology for the juvenile hormones.

Recent refinements in juvenile hormone radioimmunoassay technology now make this method significantly more sensitive and easier to use. Rabbit polyclonal antisera against (10R) JH III and racemic JH II have been developed to determine hemolymph hormone titers in the low picogram range. The antisera display minimal cross-reactivity with JH metabolites, JH analogs, and hemolymph lipids. One antiserum recognizes racemic JH I, II, and (10R) III almost equivalently, exhibiting 50% displacement between 100 and 130 pg per tube. Another antiserum is JH II-specific and exhibits 50% displacement at 35 pg per tube. Assay sensitivity has been enhanced by using (10R,11S) [methyl-3H]-JH II of very high specific activity (> 80 Ci/mmol) generated with Hyalophora cecropia accessory gland S-adenosylmethionine transferase and S-[methyl-3H]-adenosyl-L-methionine. Preparation of biological samples has been simplified with overall recoveries of JH from hemolymph ranging between 60 and 75%.

Animals↗

Characterization of the dopa decarboxylase gene of Manduca sexta and its suppression by 20-hydroxyecdysone.

Manduca dopa decarboxylase (DDC) cDNA was isolated, sequenced, and found to be most closely related to Drosophila DDC (72% amino acid identity). Culture of Day 2 fourth instar larval epidermis with 20-hydroxyecdysone (20E) showed that 20E was necessary to determine the later expression of the gene, but its removal was required for this expression to occur. Experiments with the protein synthesis inhibitors, cycloheximide and anisomycin, and the mRNA synthesis inhibitor, alpha-amanitin, showed that 20E induced a protein(s) which suppressed transcription of the DDC gene. Gel mobility shift assays using epidermal extracts and various fragments of the first 1.1 kb of the 5' flanking region of the DDC gene showed only one DNA fragment 87 to 167 bp upstream of the 5' initiation site that bound a nuclear protein(s) with the expected developmental specificity. The protein was abundant at the time of high ecdysteroid titer when no DDC mRNA was present, but low both before the rise (no DDC mRNA) and after the decline of ecdysteroid titer (maximal DDC mRNA). Thus, this protein(s) is a candidate for an ecdysteroid-induced transcription factor which acts to suppress DDC transcription. DNase I footprinting assays confirmed by use of a specific oligonucleotide showed that this protein(s) bound to the sequence 5'-GGCTTATGCGCTGCA-3'.

Amino Acid Sequence↗

Cloning of an ecdysone receptor homolog from Manduca sexta and the developmental profile of its mRNA in wings.

Using the Drosophila melanogaster ecdysone receptor (DmEcR) B1 cDNA clone, we isolated three genomic clones for EcR from the tobacco hornworm, Manduca sexta. Subsequent isolation and sequencing of several cDNAs yielded a homolog of the B1 isoform with 50, 95 and 70% amino acid identities with DmEcR in the N-terminal A/B, the DNA binding and the ligand binding domains respectively. Unlike Drosophila, an intron occurs between the exons encoding the two zinc fingers of Manduca EcR (MsEcR). A 6.0 kb mRNA encoding MsEcR was found in both larval wing discs and prothoracic glands and in pupal wings. During the final larval instar, the mRNA was maximal in the wing discs at one day after wandering (W1), whereas in the prothoracic gland EcR mRNA increased rapidly to high levels on day 2 and remained high thereafter. During the onset of adult development, two peaks of EcR mRNA were observed in wings from day 3 to 5 and on day 8 after pupal ecdysis. These two peaks correlated with the time of increasing titers of ecdysone (E) and 20-hydroxyecdysone (20E), respectively. The EcR mRNA peaks always preceded the large ecdysteroid peak, suggesting that the transcription of the EcR gene is induced by a low concentration of ecdysteroid in vivo.

Amino Acid Sequence↗

A nuclear juvenile hormone-binding protein from larvae of Manduca sexta: a putative receptor for the metamorphic action of juvenile hormone.

A 29-kDa nuclear juvenile hormone (JH)-binding protein from the epidermis of Manduca sexta larvae was purified by using the photoaffinity analog for JH II ([3H]epoxyhomofarnesyldiazoacetate) and partially sequenced. A 1.1-kb cDNA was isolated by using degenerate oligonucleotide primers for PCR based on these sequences. The cDNA encoded a 262-amino acid protein that showed no similarity with other known proteins, except for short stretches of the interphotoreceptor retinoid-binding protein, rhodopsin, and human nuclear protein p68. Recombinant baculovirus containing this cDNA made a 29-kDa protein that was covalently modified by [3H]epoxyhomofarnesyldiazoacetate and specifically bound the natural enantiomer of JH I (Kd = 10.7 nM). This binding was inhibited by the natural JHs but not by methoprene. Immunocytochemical analysis showed localization of this 29-kDa protein to epidermal nuclei. Both mRNA and protein are present during the intermolt periods; during the larval molt, the mRNA disappears but the protein persists. Later when cells become pupally committed, both the mRNA and protein disappear with a transient reappearance near pupal ecdysis. The properties of this protein are consistent with its being the receptor necessary for the antimetamorphic effects of JH.

Amino Acid Sequence↗

Evidence of a stimulatory effect of cyclic AMP on corpus allatum activity in Manduca sexta.

Injection of dibutyryl-cAMP prevents cuticular melanization of black Manduca sexta larvae, whose pigmentation is related to a defect in the control of the corpus allatum. The cAMP analog has no effect in allatectomized black larvae. Significant stimulation of corpus allatum activity was obtained in vitro with compounds which elicit or mimic elevated intracellular cAMP levels (dibutyryl-, 8-bromo-, N6 benzoyl-, and 8-thiomethyl-cAMP, 3-isobutyl-1-methylxanthine), but not with dibutyryl-cGMP. Relatively inactive glands, such as those on day 4 of last larval stadium or from black mutant larvae, were more sensitive to these compounds than glands actively synthesizing JH/JH acid. JH acid synthesis by corpora allata taken after pupal commitment in the last larval stadium (days 6 and 8) was not stimulated by either dibutyryl-cAMP or 3-isobutyl-1-methylxanthine, but day 8 glands appeared to be inhibited by dibutyryl--cAMP. The results indicate that a cAMP second messenger system is involved in the transduction of signals which stimulate JH/JH acid synthesis by Manduca corpora allata prior to pupal commitment and suggest that it may be involved in the inhibition of JH acid synthesis after commitment. They also imply that the proposed hemolymph factor to which the black mutant corpora allata are differentially sensitive interfaces with the cAMP system.

1-Methyl-3-isobutylxanthine↗

[Hematologic abnormalities in a patient with chronic myelogenous leukemia with advanced myelofibrosis were improved by G-CSF].

A 56-year-old woman was admitted with pyrexia, cough, and dyspnea on August 21, 1991. Physical examination revealed anemia in the palpebral conjunctivas and moist rales at the right lower lung field. Neither the Liver nor spleen was enlarged. Examination of the peripheral blood showed a hemoglobin level of 8.1 g/dl, a platelet count of 14.8 x 10(4)/microliters, and a white blood cell count of 2,800/microliters, with 7% blasts and 8% megakaryocytes. Tear drop-like erythrocytes, agranular neutrophils, and erythroblasts were also seen in the peripheral blood. Examination of the bone marrow showed 15% peroxidase positive blasts, and many micromegakaryocytes. Cytogenetic studies for bone marrow cells revealed the existence of the Philadelphia (Ph1) chromosome. Bone marrow biopsy showed normal cellularity with increase of megakaryocytes and advanced myelofibrosis. Breakpoint cluster region (bcr) rearrangement analysis using the peripheral blood mononuclear cells revealed M-bcr rearrangement. According to the Hannover classification for myeloproliferative disease, she was diagnosed as having CML with advanced myelofibrosis followed by CML with megakaryocytic increase. Since she had neutrocytopenia and severe infectious disease, she received a subcutaneous injection of 125 micrograms of G-CSF. Not only increase of the white blood cell count, but also disappearance of blasts, improvement of anemia, increase of the platelet count, and improvement of myelofibrosis were observed.

Blood Cell Count↗

[Autologous bone marrow transplantation following high-dose busulfan and etoposide for a patient with non-Hodgkin's lymphoma].

A 26-year-old man was admitted to our hospital with cervical tumor and facial edema on July 8, 1991. Examination of chest X-ray and chest CT showed a bulky tumor in the mediastinum and pleural effusion. A pathological diagnosis of non-Hodgkin's lymphoma (diffuse large cell, immunoblastic type) was made by biopsy of the cervical lymph node. MACOP-B chemotherapy or other combination chemotherapy did not achieve complete remission. The man was given a preparative regimen consisting of busulfan at 16 mg/kg orally and 60 mg/kg of etoposide (Bu-Et); 30 mg/kg of etoposide was administered by continuous intravenous infusion for 12 hours on day-5 and day-4, before he received autologous bone marrow on February 20. He was then given 300 micrograms of G-CSF was given to him to accelerate recovery of hematopoiesis from one day after BMT. The neutrophil count to 500/microliters recovered on day 28, and residual tumors disappeared. Although moderate-grade stomatitis and nasal bleeding developed, these toxicities were controllable and no veno-occlusive disease resulted. Regimen-related toxicities of Bu-Et preparatory regimen have been generally considered to be severe, but continuous and separate administration of etoposide as reported in this case may be useful to reduce side effects of this preparatory regimen.

Adult↗

Cyclosporine A and peripheral tolerance. Inhibition of veto cell-mediated clonal deletion of postthymic precursor cytotoxic T lymphocytes.

Veto cell-mediated suppression of CTL responses has been proposed as one mechanism by which self tolerance is maintained in mature T cell populations. We have reported that murine bone marrow cells cultured in the presence of high-dose IL-2 (activated bone marrow cells) mediate strong veto suppressor function in vitro and in vivo, and that such veto activity is effected through clonal deletion of cytotoxic T cell precursors. In our studies, we have determined that bone marrow cell populations from athymic NCr-nu mice (H-2d) mediate strong veto cell activity without exposure to exogenous IL-2 in vitro. To examine mechanisms by which these naturally occurring veto cell populations in BM suppress precursor CTL (pCTL) responses, we used as a responding cell population in MLC, spleen cells of transgenic mice expressing at high frequency TCR specific for H-2 Ld encoded Ag with stimulation by H-2d-expressing cells in culture. Flow cytometric analysis was performed by staining the responding MLC cell population with the mAb 1B2 specific for the transgene-encoded TCR and determined changes of 1B2+ T cells. Such experiments demonstrated that the anti-H-2d cytotoxic response by these cell populations was specifically suppressed by NCr-nu (H-2d) bone marrow, and that 1B2+ pCTL were in fact specifically deleted from the responding cell population by incubation with such naturally occurring veto cell populations expressing the appropriate target Ag. In addition, to further understand the interactions of pCTL and veto cells and possible contributions by the latter to peripheral tolerance, we evaluated the effect of cyclosporine A (CsA) on veto cell-mediated suppression of pCTL of the transgenic mice. CsA inhibited veto cell-mediated suppression of cytotoxic T cell responses, and this inhibition correlated with a lack of clonal deletion of pCTL by veto cells in the presence of CsA. Furthermore, CsA exerted its effect through pCTL and not through veto cells, indicating that pCTL may play an active role in their own deletion by veto cells.

Animals↗

Effects of anti-CD3 monoclonal antibody on engraftment of T-cell-depleted bone marrow allografts in mice: host T-cell suppression, growth factors, and space.

To investigate the role of CD3-positive T cells in allogeneic marrow rejection in mice and to examine the effects of anti-CD3 monoclonal antibody (MoAb) on allogeneic marrow engraftment, a hamster MoAb, 145-2C11, with specificity for the CD3 epsilon portion of the murine T-cell receptor complex was administered to B6 (H-2b) mice that had been sublethally irradiated with 626 cGy and injected with 10 x 10(6) T-cell-depleted B6C3F1 (H-2b/k) bone marrow cells. Lymphoid chimerism status was assessed by flow cytometric analysis of peripheral blood lymphocytes using H-2k-specific MoAb 5 to 6 weeks after bone marrow transplantation. When hosts were treated with 400 micrograms of anti-CD3 MoAb at the time of marrow injection, the percentage of donor-type cells was 75.2% +/- 15.0%, while it was 1.9% +/- 1.2% in untreated mice. It was demonstrated that anti-CD3 MoAb not only suppressed T-cell function but also induced colony-stimulating factors in host mice, and that enhancement of marrow engraftment in anti-CD3 MoAb-treated mice was associated with factor release as well as suppression of host T-cell function. Results were consistent with engraftment being enhanced by a differential response of donor (rather than host) marrow to serum factors in association with host T-cell immunocompromise.

Animals↗

Clonal deletion of postthymic T cells: veto cells kill precursor cytotoxic T lymphocytes.

Veto cell-mediated suppression of cytotoxic T lymphocyte (CTL) responses has been proposed as one mechanism by which self-tolerance is maintained in mature T cell populations. We have previously reported that murine bone marrow cells cultured in the presence of high-dose interleukin 2 (IL-2) (activated bone marrow cells [ABM]) mediate strong veto suppressor function. To examine mechanisms by which ABM may suppress precursor CTL (p-CTL) responses, we used p-CTL generated from spleen cells of transgenic mice expressing a T cell receptor specific for H-2 Ld. It was demonstrated that the cytotoxic response by these p-CTL after stimulation with irradiated H-2d/k spleen cells was suppressed by DBA/2 (H-2d) ABM, but not by B10.BR (H-2k) ABM or dm1 (Dd, Ld mutant) ABM. Flow cytometry analysis with propidium iodide staining revealed that these p-CTL were specifically deleted by incubation with H-2d ABM, but not with H-2k ABM. These data indicate that ABM veto cells kill p-CTL with specificity for antigens expressed on the surface of the ABM, and that the mechanism for veto cell activity of ABM is clonal deletion of p-CTL.

Animals↗

An ecdysteroid-inducible Manduca gene similar to the Drosophila DHR3 gene, a member of the steroid hormone receptor superfamily.

Using cDNAs for the human retinoic acid receptor alpha (hRAR alpha) and Drosophila hormone receptor 3 (DHR3), we isolated a cDNA encoding a member of the steroid hormone receptor superfamily from the tobacco hornworm, Manduca sexta. Sequencing showed that this cDNA is most closely related to DHR3 (97 and 68% amino acid identity in the DNA and ligand binding regions, respectively) followed by hRAR alpha (65 and 20% identity, respectively) and therefore is named MHR3. The cDNA hybridized to two mRNAs (3.8 and 4.5 kb) found in the epidermis during the ecdysteroid rises for the embryonic, larval, and pupal molts. Culture of fourth instar larval epidermis with 4 microM 20-hydroxyecdysone (2 micrograms/ml 20HE) caused the appearance of MHR3 mRNA within 3 hr and maximal expression by 6 hr; after 12 hr continuous exposure to 20HE, the mRNA level declined. The 4.5-kb mRNA appeared first, both were present in equal amounts by 12 hr, and by 20 hr the predominant transcript was 3.8 kb. Similar 20HE-induced expression was seen in epidermis explanted 1 day after the onset of wandering, although with a slower time course. The induction was largely independent of protein synthesis, but the subsequent decline required protein synthesis as is typical of the "early" puffs in Drosophila. Continuous exposure to 20HE was necessary for MHR3 expression; in its absence, the mRNA declined with a half-life of 2 hr. Thus, MHR3 is an ecdysteroid-inducible DNA binding protein that likely is a transcription factor involved in the cascade of gene activation and inactivation caused by ecdysteroids during the insect molt.

Adipose Tissue↗

Hormonal regulation of epidermal metamorphosis in vitro: control of expression of a larval-specific cuticle gene.

Fourth (penultimate) instar larval epidermis of the tobacco hornworm, Manduca sexta, was used to develop an in vitro culture system to study the hormonal control of metamorphosis at both the cellular and the molecular level. Immediate exposure to 4 x 10(-6) M 20-hydroxyecdysone (20-HE) for more than 8 hr, followed by hormone-free medium for 24 hr, caused the formation of a new larval cuticle. By contrast, incubation in hormone-free medium for more than 24 hr prior to exposure to 20-HE allowed pupal cuticle synthesis. The cessation of expression of the larval-specific cuticular gene LCP-14 occurred rapidly in response to 20-HE during the larval molt in vitro (half-life: ca. 6 hr), even in the presence of 3 x 10(-8) M JH I. This suppression by 20-HE was prevented by cycloheximide, indicating that 20-HE does not act directly on this gene. Incubation with alpha-amanitin showed that the half-life of LCP-14 was more than 10 hr. Thus, 20-HE must both suppress gene transcription and destabilize the mRNA. LCP-14 mRNA subsequently reappeared 24 hr after exposure to hormone-free medium, indicating that suppression was temporary. By contrast, when JH and its effects were absent after preincubation in hormone-free medium for 48 hr, 20-HE caused permanent suppression of LCP-14 mRNA, since the mRNA did not reappear after removal of 20-HE. Exposure of Day 2 fifth instar larval epidermis to 3 x 10(-7) M 20-HE, which causes pupal commitment in the absence of JH I, also permanently suppressed LCP-14 gene expression.

Animals↗

Developmental expression, synthesis, and secretion of insecticyanin by the epidermis of the tobacco hornworm, Manduca sexta.

Insecticyanin was found to be synthesized in several isoelectric forms and stored in the pigment granules in the epidermis. Both major epidermal forms (INS-a, pl 5.5; INS-b, pl 5.7) were found in the cuticle, but only the most basic form, INS-b, was present in the hemolymph. In vitro the epidermis synthesized and secreted both forms into both the cuticle and the medium. Isolation of two cDNA clones for insecticyanin followed by hybridization to epidermal mRNA showed the presence of only one 1.1 kb mRNA, but transcription of the longer cDNA yielded a RNA which produced INS-a but no INS-b. Insecticyanin mRNA was present during the intermolt feeding stages of the 4th and 5th instars and absent during the larval molt and after the onset of metamorphosis. Exposure of either day 2 4th-instar or day 1 5th-instar larval epidermis to 20-hydroxyecdysone (20HE) in vitro caused a dose-dependent decline in this mRNA that was not prevented by simultaneous exposure to JH. When synthesis resumes just before ecdysis, INS-b appears before INS-a; then on the final day of feeding, synthesis of INS-a ceases before that of INS-b. Culture experiments showed that exposure of day 15th epidermis to a small pulse of 20HE followed by an ecdysteroid-free period was best to mimic the in vivo situation, indicating that the small rise of ecdysteroid in the absence of JH on day-2 was responsible for this differential cessation.

Animals↗

Regulation of dopa decarboxylase gene expression in the larval epidermis of the tobacco hornworm by 20-hydroxyecdysone and juvenile hormone.

Dopa decarboxylase (DDC) which converts dopa to dopamine is important for cuticular melanization and sclerotization in insects. An antibody to Drosophila DDC was found to precipitate both DDC activity and a 49-kDa polypeptide synthesized by the epidermis of molting Manduca larvae. Using the Drosophila DDC gene, we isolated the Manduca DDC gene which on hybrid selection produced a 49-kDa translation product precipitable by the Drosophila DDC antibody. The 3.1-kb DDC mRNA appeared 12 hr after head capsule slippage (HCS) and reached maximal levels 7 hr later. Peak expression was twofold higher in melanizing allatectomized larvae and could be depressed to normal levels by application of 0.1 micrograms juvenile hormone I at HCS. Infusion of 1 microgram/hr 20-hydroxyecdysone (20-HE) for 18 hr beginning 2 hr after HCS or addition of 1 microgram/ml 20-HE to the culture medium for 24 hr prevented the normal increase in DDC mRNA. When Day 2 fourth instar epidermis was explanted before the molting ecdysteroid rise and cultured with 1-3 micrograms/ml 20-HE for 17 hr and then for 24 hr in hormone-free medium, DDC expression was three- to fourfold higher than that in epidermis cultured in the absence of hormone. Twelve or more hours of incubation with 20-HE was required for an increase in DDC mRNA, but continuous exposure to 20-HE prevented the increase. In all cultures an initial rapid increase in DDC mRNA was observed which decayed with time in vitro and apparently was associated with the wound response. Thus, ecdysteroid during a larval molt is necessary to program the later expression of DDC, but the subsequent decline of the ecdysteroid is required for this expression to occur.

Animals↗