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Biomedical subjects

K Kuriyama

Publications and source records attributed to K Kuriyama.

At least 37 records · Page 2Linked to original sources
PubMed2001

Analysis of prognostic factors in newly diagnosed patients with acute promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group (JALSG).

All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the JALSG APL92 study), and analyzed prognostic factors to increase the cure rate in our subsequent trial. From 1992 to 1997, adult patients with newly diagnosed APL received oral ATRA 45 mg/m2 daily alone until complete remission (CR) if initial leukocyte counts were < 3.0x10(9)/l, and ATRA daily plus daunorubicin (DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if leukocyte counts were > or =3.0 x 10(9)/l. If peripheral blasts exceeded 1.0x10(9)/l during therapy, DNRx3 days plus BHACx5 days was added. After CR was achieved, three courses of consolidation and six courses of maintenance/intensification chemotherapy were administered. Of 376 patients enrolled, 369 were evaluable (median age 46 years, range 15-86 years; median leukocyte counts 2.0x10(9)/l), and 333 (90%) achieved CR (94% of patients treated with ATRA alone, 88% with ATRA plus later chemotherapy, 89% with ATRA plus initial chemotherapy, and 86% with ATRA plus initial and later chemotherapy). At a median follow-up of 45 months, the predicted 6-year overall and event-free survival (EFS) rates for all patients were 65% and 52%, respectively. Favorable prognostic factors for CR were younger age, no or mild purpura, high serum total protein level, low lactate dehydrogenase level, and no or mild disseminated intravascular coagulation (DIC). Favorable prognostic factors for EFS were leukocyte counts < 10.0x10(9)/l, mild DIC, and no sepsis during induction therapy. In the JALSG APL97 study, we intensified chemotherapy for patients with leukocyte counts > or =3.0x10(9)/l, and are randomly testing whether further chemotherapy is required for APL patients with negative PCR for PML/retinoic acid receptor alpha in the maintenance phase.

Adolescent↗
PubMed2001

Immunohistochemical detection of parathyroid hormone-related peptide, Indian hedgehog, and patched in the process of endochondral ossification in the human.

Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (Ihh), and patched (Ptc; a receptor for Ihh) were immunolocalized in tissue undergoing endochondral ossification in the human. PTHrP, Ihh, and Ptc were immunolocalized in prehypertrophic and hypertrophic chondrocytes in mature cartilage matrix. PTHrP and Ptc were immunostained in proliferating chondrocytes and perichondrial cells, whereas Ihh was not. PTHrP, Ihh, and Ptc showed positive immunostaining in osteoblasts in the bone-forming area. In the bone resorption site, PTHrP was immunolocalized in osteoclasts, whereas Ihh and Ptc were not. The present findings indicated that PTHrP, Ihh, and Ptc were associated with the process of endochondral ossification, and suggested the possible involvement of Ihh and PTHrP signaling in the regulation of proliferation and hypertrophy of chondrocytes in human chondrogenesis.

Bone Neoplasms↗
PubMed2001

De novo acute myeloid leukemia in the elderly; a consistent fraction of long-term survivors by standard-dose chemotherapy.

To clarify the characteristics of de novo acute myeloid leukemia (AML) among the elderly, we reviewed 112 patients over 60 years old (median age 72 years) who were treated at hospitals in Nagasaki Prefecture with a population of 1.5 million between 1987 and 1994. Reclassification of morphological diagnosis revealed that the proportion of M3 was lower but that of M6 and the incidence of cases with trilineage dysplasia (TLD), known as poor prognostic features, were higher in the elderly than in patients less than 60 years old. Similarly, chromosomal data showed a lower frequency of favorable karyotypes such as t(8;21) and t(15;17) in the elderly. The overall survival of all 112 patients was 10.3% at 5 years. Multivariate analysis indicated that good performance status (PS), low WBC at diagnosis, standard dose multi-drug chemotherapy and all-trans retinoic acid (ATRA) treatment for M3 patients, and morphological findings without TLD were significantly correlated with longer survival. Most of the long-term survivors were found among those who received standard dose therapy in this series, although no consensus has been established how to treat elderly AML patients. We propose that a prospective controlled trial is necessary to confirm the role of standard dose chemotherapy for elderly patients with de novo AML.

Acute Disease↗
PubMed2001

Prognostic value of ground-glass opacity found in small lung adenocarcinoma on high-resolution CT scanning.

OBJECTIVE: This study was undertaken to investigate the value of the ground-glass opacity (GGO) area found on high-resolution computed tomography (HRCT) scanning as a preoperative prognostic indicator. PATIENTS AND METHODS: We studied 104 patients with small-sized lung adenocarcinoma, 20 mm or less in diameter, between 1995 and 1999. Three independent radiologists semi-quantitatively scored the extent of GGO on HRCT as greater than or less than 50%. Three independent pathologists semi-quantitatively scored the extent of the bronchioloalveolar carcinoma (BAC) component of the tumor on histologic examination as greater than or less than 50%. As no relapse occurred in patients with GGO greater than 50%, multivariate analysis of this prognostic factor was not possible. RESULTS: Fifty patients were scored as having both BAC and GGO greater than 50%, 36 as both BAC and GGO less than 50%, and 16 as BAC greater than 50% and GGO less than 50%. In only two patients (1.9%), BAC less than 50% was overestimated on HRCT as GGO greater than 50%. The sensitivity and specificity of GGO to BAC were 76 and 95%, respectively. The 3 year-relapse-free survival rates in each group of 52 patients with GGO greater than and less than 50% were 100 and 72%, respectively, after a median follow-up of 24 months. Univariate analysis indicated that both GGO and BAC areas were significantly correlated with cancer relapse (P=0.005 and P=0.002). The multivariate analysis revealed an independent prognostic influence of the BAC area on relapse-free survival (P=0.015, relative risk=0.07). CONCLUSIONS: To date there has been no relapse among the 52 patients with GGO greater than 50%. This novel classification based on the semiquantitative analysis of GGO area on HRCT should become an useful independent preoperative indicator when deciding on operative procedure, and to predict the potential of relapse in patients with small adenocarcinoma arising from the peripheral lung.

Adenocarcinoma↗
PubMed2001

The differential expression patterns of messenger RNAs encoding K-Cl cotransporters (KCC1,2) and Na-K-2Cl cotransporter (NKCC1) in the rat nervous system.

Cation-chloride cotransporters have been considered to play pivotal roles in controlling intracellular and extracellular ionic environments of neurons and hence controlling neuronal function. We investigated the total distributions of K-Cl cotransporter 1 (KCC1), KCC2 (KCC2), and Na-K-2Cl cotransporter 1 (NKCC1) messenger RNAs in the adult rat nervous system using in situ hybridization histochemistry. KCC2 messenger RNA was abundantly expressed in most neurons throughout the nervous system. However, we could not detect KCC2 messenger RNA expression in the dorsal root ganglion and mesencephalic trigeminal nucleus, where primary sensory neurons show depolarizing responses to GABA, suggesting that the absence of KCC2 is necessary for this phenomenon. Furthermore, KCC2 messenger RNA was also not detected in the dorsolateral part of the paraventricular nucleus, dorsomedial part of the suprachiasmatic nucleus, and ventromedial part of the supraoptic nucleus where vasopressin neurons exist, and in the reticular thalamic nucleus. As vasopressin neurons in the suprachiasmatic nucleus and neurons in the reticular thalamic nucleus produce their intrinsic rhythmicity, the lack of KCC2 messenger RNA expression in these regions might be involved in the genesis of rhythmicity through the control of intracellular chloride concentration. The expression levels of KCC1 and NKCC1 messenger RNAs were relatively low, however, positive neurons were observed in several regions, including the olfactory bulb, hippocampus, and in the granular layer of the cerebellum. In addition, positive signals were seen in the non-neuronal cells, such as choroid plexus epithelial cells, glial cells, and ependymal cells, suggesting that KCC1 and NKCC1 messenger RNAs were widely expressed in both neuronal and non-neuronal cells in the nervous system. These results clearly indicate a wide area- and cell-specific variation of cation chloride cotransporters, emphasizing the central role of anionic homeostasis in neuronal function and communication.

Animals↗
PubMed2001

Involvement of BMP-2 signaling in a cartilage cap in osteochondroma.

This study describes the distributions of bone morphogenetic protein (BMP)-2 as well as mRNAs for BMP receptor type IB (BMPRIB). collagen types II (Col II) and III (Col III) in a growing "cartilage cap" of osteochondroma. In situ hybridization and immunohistochemical study were performed using histological sections obtained during surgery. BMP-2 was detected in mesenchymal cells in the outer fibrous layer and chondrocytes in the inner cartilaginous matrix, positive for Col III and Col II, respectively. BMPRIB mRNA was distributed in chondrocytes. This is the first study to provide observational evidence of the involvement of BMP-2 signaling in the pathogenesis of cartilage cap of osteochondroma. and suggests the role of BMP-2 in the growth of cartilage cap in osteochondroma.

Bone Morphogenetic Protein 2↗
PubMed2001

Effect of a selective Abl tyrosine kinase inhibitor, STI571, on in vitro growth of BCR-ABL-positive acute lymphoblastic leukemia cells.

By employing a new semi-quantitative assay system that includes co-culturing leukemia cells with the mouse bone marrow-derived stromal cell line MS-5, we examined the suppressive effect of a selective inhibitor of ABL tyrosine kinase, STI571, on acute lymphoblastic leukemia (ALL) cells with BCR-ABL fusion. Leukemic blast cells from eight patients with B-precursor ALL, including three patients with BCR-ABL-positive ALL, were cultured on monolayers of MS-5 cells for 3 weeks with or without addition of variable amounts of STI571. In all cases, cobblestone areas (CAs) were formed, showing clear linear cell dose-dependent curves, allowing quantitative assessment of blast cell growth. The progenitor frequencies obtained by this direct CA-forming cell (CAFC) assay were equivalent to ALL progenitor frequencies assessed by the standard limiting dilution assay. The number of CAFCs ranged from 12.3 to 140.3/10(4) cells. In BCR-ABL-positive ALL patients, CA-containing cells were examined by FISH, and all contained BCR-ABL fusion genes. STI571 inhibited CA formation of BCR-ABL-positive ALL cells virtually 100% at 0.1-1.0 micromol/l. None of the five BCR-ABL-negative ALL patients showed this growth inhibition by STI571 at 0.1-1.0 micromol/l. Our results indicate that STI571 selectively inhibits in vitro growth of BCR-ABL-positive ALL cells.

Adolescent↗
PubMed2001

Neuroreceptors and ion channels as targets of alcohol.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Kinya Kuriyama. The presentations were (1) Modulation of neuroreceptors and ion channels by alcohol, by T. Narahashi; (2) Inhibition by ethanol of NMDA and AMPA receptor-channels, by P. Illes, K. Wirkner, W. Fischer, K. Mühlberg, P. Scheibler, and C. Allgaier; (3) Effects of ethanol on metabotropic glutamate receptors, by K. Minami; (4) Acute alcohol actions on the 5-HT3 ligand-gated ion channel, by D. Lovinger; (5) Inhibition of NMDA receptors by MK801 attenuates ethanol-induced taurine release from the hippocampus, by F. Lallemand, R.J. Ward, and P. DeWitte; and (6) Effect of ethanol on voltage-operated Ca2+ channels in hepatic stellate cells, by T. Itatsu, Y. Takei, H. Oide, M. Hirose, X. E. Wang, S. Watanabe, M. Tateyama, R. Ochi, and N. Sato.

Animals↗
PubMed2001

[Acute myeloid leukemia].

Acute myeloid leukemia (AML) has been treated with combination chemotherapy, hematopoietic stem cell transplantation (HSCT) and differentiation induction therapy. Intensive induction and consolidation therapy including high dose cytarabine (HDAC) is a widely used combination in chemotherapy in the USA and European countries. In Japan, the efficacy of HDAC needs to be evaluated under a good clinical trial. Stem cell source for HSCT has been expanded, and the number of peripheral blood stem cell transplantations is greater than that of bone marrow transplantation, especially for auto-transplantation. Despite some randomized clinical trials, we still do not know whether HSCT provides longer survival than chemotherapy for patients with AML when performed during their first remission. Differentiation therapy for acute promyelocytic leukemia (APL) using ATRA showed clear success in the treatment for AML. APL is stratified with its specific karyotype and morphology, and this stratification leads to the improvement of overall survival of patients with APL. Several clinical study groups in the world have studied prognostic factors and it has been shown that the chromosomal abnormality of AML cells is closely related to the response to the chemotherapy. The stratification of AML using these prognostic factors is incorporated in some clinical trials to determine whether this approach actually leads to better survival for patients with AML.

Acute Disease↗
PubMed2000

Wound healing acceleration of a novel transforming growth factor-beta inducer, SEK-1005.

The studies were carried out to elucidate the effect of a novel cyclic peptide, SEK-1005 (C(45)H(70)N(8)O(13)), on wound healing. SEK-1005 (4-10 microg/wound) applied topically significantly accelerated the healing of a full-thickness wound on the dorsal skin of a rat. In a healing-impaired mouse, the peptide (2-10 microg/wound) had more potent activity, exerting an effect comparable to that of basic fibroblast growth factor (FGF). However, SEK-1005 (0.1-100 ng/ml) scarcely promoted the proliferation of cultured fibroblasts (NIH3T3 cells) while basic FGF (0.2-5 ng/ml) showed marked mitogenic activity. SEK-1005 (2-10 microg/wound) significantly increased the topical production of transforming growth factor (TGF)-beta1, a cytokine that is known to accelerate wound healing. This activity was closely correlated with the wound-repairing effect. From the above, SEK-1005 can be considered as a new type of wound healing agent with potent TGF-beta1-inducing activity.

3T3 Cells↗
PubMed2000

Identification of a novel cytokine response element in the human IFN regulatory factor-1 gene promoter.

The present study investigates the regulatory mechanisms involved in the cooperation between IFN-gamma and TNF-alpha to promote transcription from IFN regulatory factor-1 (IRF-1). A transient transfection analysis revealed that the region between -218 and -144, where +1 is the transcription start site, as well as previously reported downstream elements, ppkappaB and IFN-gamma activation site/kappaB, were required for the optimal response to the two cytokines. A subsequent DNase I footprint analysis showed that the region between -171 and -144 was inducibly protected with stimulation by TNF-alpha, and this protection was significantly enhanced with the combination of IFN-gamma and TNF-alpha. In an EMSA with the protected region as a probe, a TNF-alpha-inducible complex (C1) and an IFN-gamma-inducible complex (C2), but no synergy-specific DNA-protein complexes, were recognized. The C1 complex consisted of a pre-existing factor (p65/p50), whereas the C2 complex consisted of a newly synthesized IRF-1-related factor. A methylation interference assay revealed the critical G residues (from -167 to -151) for the DNA-protein complex formation specific to the cytokine response, and within this region the novel kappaB sequence, the promoter distal kappaB (pdkappaB) element (5'-GGGGAAG TAC-3'), was identified. Because the base substitutions over the pdkappaB region (from -171 to -144) affected not only the TNF-alpha-response but also that of IFN-gamma, this region might contribute to the cooperative action of the NF-kappaB subunits with the IRF-1-related factor. Finally, we demonstrated that none of the cis-acting elements, ppkappaB, pdkappaB, or IFN-gamma activation site/kappaB, is dispensable for the optimal synergism in response to IFN-gamma and TNF-alpha.

Adjuvants, Immunologic↗
PubMed2000

Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of infants and children with B-cell precursor acute lymphoblastic leukemia.

An attractive hypothesis is that in utero exposure of hematopoietic cells to oncogenic agents can induce molecular changes leading to overt acute lymphoblastic leukemia (ALL) in infants and perhaps older children as well. Although supported by studies of identical infant twins with concordant leukemia, and of nontwined patients with MLL gene rearrangements, this concept has not been extended to the larger population of B-lineage ALL patients who lack unique nonconstitutive mutations or abnormally rearranged genes. We therefore sought to demonstrate a prenatal origin for 7 cases of B-cell precursor ALL (either CD10(+) or CD10(-)) that had been diagnosed in infants and children 14 days to 9 years of age. Using a polymerase chain reaction-based assay, we identified the same clonotypic immunoglobulin heavy-chain complementarity determining region or T-cell receptor V(D)2-D(D)3 sequences in the neonatal blood spots (Guthrie card) and leukemic cell DNAs of 2 infants with CD10(-) ALL and 2 of the 5 older patients with CD10(+) ALL. Nucleotide sequencing showed a paucity of N or P regions and shortened D germ line and conserved J sequences, indicative of cells arising from fetal hematopoiesis. Our findings strongly suggest a prenatal origin for some cases of B-cell precursor ALL lacking specific clonotypic abnormalities.

Base Sequence↗
PubMed2000

Anti-inflammatory action of a novel peptide, SEK-1005, isolated from a Streptomyces.

The pharmacological activity of a novel cyclic peptide (SEK-1005: C(45)H(70)N(8)0(13)) isolated from Streptomyces nobilis was studied in rats during the development of inflammation. SEK-1005 (0.1-0.5 mg/kg, i.p.) suppressed the passive Arthus reaction and the carrageenin-induced oedema. A steroidal anti-inflammatory drug, prednisolone (10 mg/kg, i.p.), also was effective on both inflammations. However, indomethacin (5 mg/kg, i.p.), a cyclooxygenase inhibitor, was less effective on the passive Arthus reaction. Also interesting was that the SEK-1005 effect showed its maximum level after a 24-h lag period and that its effect, as well as the prednisolone effect, was reduced by the treatment with a protein synthesis inhibitor, cycloheximide. SEK-1005 and prednisolone also showed marked protection against the adjuvant-induced arthritis, but failed to prevent the tuberculin response. These findings indicate that SEK-1005 is a new type of non-steroidal anti-inflammatory agent with an action similar to that of prednisolone.

Animals↗
PubMed2000

Low-cost soft-copy display accuracy in the detection of pulmonary nodules by single-exposure dual-energy subtraction: comparison with hard-copy viewing.

This study endeavored to clarify the usefulness of single-exposure dual-energy subtraction computed radiography (CR) of the chest and the ability of soft-copy images to detect low-contrast simulated pulmonary nodules. Conventional and bone-subtracted CR images of 25 chest phantom image sets with a low-contrast nylon nodule and 25 without a nodule were interpreted by 12 observers (6 radiologists, 6 chest physicians) who rated each on a continuous confidence scale and marked the position of the nodule if one was present. Hard-copy images were 7 x 7-inch laser-printed CR films, and soft-copy images were displayed on a 21-inch noninterlaced color CRT monitor with an optimized dynamic range. Soft-copy images were adjusted to the same size as hard-copy images and were viewed under darkened illumination in the reading room. No significant differences were found between hard- and soft-copy images. In conclusion, the soft-copy images were found to be useful in detecting low-contrast simulated pulmonary nodules.

Humans↗
PubMed2000

Minimally differentiated acute myeloid leukemia (AML-M0) with extensive erythrophagocytosis and del(20)(q11) chromosome abnormality.

We describe an 84-year-old woman who presented severe pancytopenia and 36.6% of blasts accompanied with erythrophagocytosis in the bone marrow. According to cytochemical and immunological findings, a diagnosis of minimally differentiated acute myeloid leukemia (AML-M0) was established. Cytogenetic analysis revealed del(20)(q11) which were previously reported for one case each of ALL and MDS associated with cytophagocytosis by blasts, leading us to speculate a disease entity. Interestingly, a high expression of mRNA of TNF-alpha was detected by RT-PCR on the bone marrow mononuclear cells.

Acute Disease↗
PubMed2000

Absolute number of circulating CD34+ cells is abnormally low in refractory anemias and extremely high in RAEB and RAEB-t; novel pathologic features of myelodysplastic syndromes identified by highly sensitive flow cytometry.

We scored absolute numbers of circulating CD34+ cells by a highly sensitive triple-color flow cytometric analysis using CD45 monoclonal antibody, CD34 monoclonal antibody and propidium iodide. Forty-one patients with MDS (RA: 27, RARS: 1, RAEB: 6, RAEB-t: 3,CMML: 4), 12 patients with aplastic anemia (AA) and 36 age-adjusted normal subjects were studied. RA had significantly decreased numbers of cells expressing CD34 (0.21 +/- 0.29 x 10(6)/l) compared with normal subjects (0.81 +/- 0.36 x 10(6)/l)(P < 0.001). This low number of CD34+ cells in RA resembles the case of AA (0.39 +/- 0.73 x 10(6)/l). In light-scatter analysis, the CD34+ cells of RA patients were distributed mainly in low forward scatter (FSC) (lymphocyte region). In contrast, the CD34+ cell counts were extremely high in patients with RAEB (46.54 +/- 71.37 x 10(6)/l) and RAEB-t (57.00 +/- 52.36 x 10(6)/l) (P < 0.001) and the CD34+ cells were observed in high FSC (blast region).CMML patients showed moderately increased numbers of CD34+ cells (3.69 +/- 4.64 x 10(6)/l). Thus, there was a distinct difference in cell size and number of circulating CD34+ cells between RA and RAEB/RAEB-t. In univariate and multivariate analysis, a high CD34+ cell count (> or = 1.0 x 10(6)/l) was a poor prognostic factor. This method allows one to distinguish RA from other MDS subtypes more reliably than by morphology alone and provides early signs of progression to acute leukemia.

Adult↗