[Autoimmune basophilopenia].
Explore the source record for details and available documents.
Agranulocytosis↗
Biomedical subjects
J Nishimura
Publications and source records attributed to J Nishimura.
A long-term stress exposure impairs maze learning performance in rats.
To elucidate hippocampal dysfunctions following chronic stress exposure, we evaluated the effect of chronic stress on maze learning performance, as assessed by a radial eight-arm maze task. In the 12-week stress sessions, male rats in the stress group were exposed to the stress of a 15-min immersion in cold water once a day and, rats in the control group were slightly handled. Rats in the stress group performed significantly poorly during the acquisition period (P < 0.01) and required more trials to attain at least seven correct choices in the first eight choices for five consecutive trials (P < 0.05). Together with our previous findings that chronic stress exposure damages the hippocampus histologically, we concluded that chronic stress exposure resulted in an impairment of maze learning performance, probably due to hippocampal damages.
Animals↗
Troglitazone inhibits the capacitative Ca2+ entry in endothelial cells.
To investigate the effects of troglitazone on the capacitative Ca2+ entry, we monitored changes in cytosolic Ca2+ concentrations ([Ca2+]i) induced by thapsigargin in fura-2-loaded porcine endothelial cells in situ and in primary culture. In aortic valve endothelial cells in situ, thapsigargin induced sustained elevation of [Ca2+]i. Both troglitazone and SKF 96365 inhibited the steady state increase in [Ca2+]i in a concentration-dependent manner. At 30 microM, troglitazone and SKF 96365 inhibited the [Ca2+]i elevation to 19.4 +/- 3.6% and 43.9 +/- 4.5%, respectively. In aortic endothelial cells in primary culture, both troglitazone (10 microM) and SKF 96365 (100 microM) completely inhibited the thapsigargin-induced [Ca2+]i increase. The EC50 value of troglitazone (1.4 +/- 0.1 microM) was lower than that of SKF 96365 (10.0 +/- 3.3 microM). We suggest that troglitazone would be a useful tool to investigate the capacitative Ca2+ entry.
Adenosine Triphosphate↗
NH2-terminal fragments of the 130 kDa subunit of myosin phosphatase increase the Ca2+ sensitivity of porcine renal artery.
1. The effects of the NH2-terminal fragments of M130, a 130 kDa regulatory subunit of smooth muscle myosin phosphatase, on contraction and myosin light chain phosphorylation were investigated in Triton X-100-permeabilized porcine renal artery. 2. Incubation of the permeabilized fibres with M1301-633 (a fragment containing amino acid residues 1-633) or M13044-633 enhanced the Ca2+-induced contraction and shifted the [Ca2+]i-force relationship to the left (EC50 of Ca2+: 330 nM, control, without fragment; 145 nM, M1301-633; 163 nM, M13044-633). Pre-incubation for 1-3 h was needed for these long constructs. 3. M1301-374, M130304-511 and M130297-374, i.e. relatively short constructs compared with M1301-633 and M13044-633, also induced leftward shifts of the [Ca2+]i-force relationship (EC50 of Ca2+: 65 nM, 72 nM and 180 nM, respectively). However, these required no pre-incubation. 4. Deletion of residues 304-374 from the most potent construct, M1301-374, abolished the Ca2+-sensitizing effect. 5. Wortmannin inhibited the enhancement of contraction induced by M130 fragments when added before contraction was initiated and partially inhibited the effects when added after steady-state contraction. 6. M1301-374 slowed the rate of relaxation in Ca2+-free medium. The time for 50 % relaxation with this fragment was 510 +/- 51 s, compared with 274 +/- 14 s for control. 7. The levels of myosin light chain phosphorylation (22.4 %) and force (34. 5 %) obtained with 300 nM Ca2+ were increased by 3 microM M1301-374 to 35.7 and 92.2 %, respectively. However, M1301-374 had no effect on the phosphorylation-force relationship. 8. In conclusion, the NH2-terminal M130 fragments containing residues 304-374 inhibited myosin phosphatase, increased myosin light chain phosphorylation and increased the Ca2+ sensitivity of the contractile apparatus in permeabilized porcine renal artery.
Androstadienes↗
Expression, subcellular localization, and cloning of the 130-kDa regulatory subunit of myosin phosphatase in porcine aortic endothelial cells.
In endothelial cells in situ and in primary culture, immunoblot analysis revealed an expression of the 130-kDa subunit of myosin phosphatase, similar to the myosin phosphatase targeting subunit (MYPT) of smooth muscle. Screening of an endothelial cell cDNA library yielded a clone encoding an NH2-terminal fragment of 89.6 kDa, closely related to smooth muscle MYPT1. Two isoforms differing by a central insert of 56 residues were detected. In growing cells, MYPT1 was localized on stress fiber, but at confluence the localization pattern changed and MYPT1 was distributed close to the cell membrane and at cell-cell contacts. The membrane localization of MYPT1 suggested a target other than myosin and raised the possibility that MYPT1 may be involved in dephosphorylation of alternative substrate(s). These distinct mechanisms would also be dependent on the growth state of the endothelial cells, i.e., regulation of actin-myosin interactions in growing cells and an unknown function in cells at confluence.
Amino Acid Sequence↗
The exogenously added small subunit of smooth muscle myosin phosphatase increases the Ca2+ sensitivity of the contractile apparatus in the permeabilized porcine renal artery.
The effects of the small noncatalytic subunit of myosin light chain phosphatase (MLCPsr) on the Ca2+-induced contraction of smooth muscle were investigated in the Triton X-100-permeabilized porcine renal artery. The full-length recombinant chicken MLCPsr obtained by the bacterial expression system induced an additional contraction at a constant [Ca2+]i and shifted the [Ca2+]i-force relation curve to the left. A deletion mutant containing the N-terminal 78 amino acids of MLCPsr retained the full action, compared with the full-length MLCPsr, while the deletion of this region completely abolished its effect. The process of relaxation was also delayed by the fragment containing the N-terminal 78 amino acids. These results indicated that MLCPsr increases the Ca2+ sensitivity of the contractile apparatus while the N-terminal 78 amino acids are responsible for this effect in vascular smooth muscle.
Amino Acid Sequence↗
Clonal identities and multiple isotype transcripts in hematological diseases revealed by a single-strand conformation polymorphism analysis of the immunoglobulin heavy chain messenger signals.
A single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified products of immunoglobulin (Ig) heavy chain rearrangements can be used to analyze B cell clonalities and clonal identities of B cells from different samples. However, the usefulness of the PCR-SSCP analysis is not fully assessed in B cell malignancies. For example, we did not know whether the PCR-SSCP method can be used to detect tumor-related clones in peripheral blood of patients with multiple myeloma and Waldenström's macroglobulinemia. In addition, because genomic DNA is used in the PCR-SSCP method, we could obtain no information about the isotype of the expanded B cell clone. In this study, we combined the reverse transcriptase (RT)-PCR of immunoglobulin heavy chain transcripts with an SSCP analysis and thus analyzed eight healthy individuals, five patients with B chronic lymphocytic leukemia, four patients with multiple myeloma and three patients with Waldenström's macroglobulinemia. Clonal B cell populations were detected as discrete bands in the RT-PCR-SSCP analysis that can be readily detected over the background of polyclonal rearrangements. Circulating tumor-related clones were detected in all but one peripheral blood sample from multiple myeloma and Waldenström's macroglobulinemia patients and B cell clones in peripheral blood and bone marrow from these patients showed a similar mobility on SSCP gel. Because the transcripts of different isotypes were separately analyzed, we could thus determine the isotype of B cell clones as well. When monoclonal Igs of different isotypes were detected in the individual samples, we analyzed the relationship of each monoclonal band by excising the band and then further analyzing it by a PCR-SSCP analysis. RT-PCR amplification in conjunction with the SSCP analysis is thus considered to be a useful method to detect and characterize the B cell clones in hematological diseases.
Aged↗
Paroxysmal nocturnal hemoglobinuria: An acquired genetic disease.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterized by an intravascular hemolytic anemia. Abnormal blood cells lack a series of glycosylphosphatidylinositol (GPI)-anchored proteins. The lack of GPI-anchored complement regulatory proteins, such as decay-accelerating factor (DAF) and CD59, results in complement-mediated hemolysis and hemoglobinuria. In the affected hematopoietic cells from patients with PNH, the first step in biosynthesis of the GPI anchor is defective. At least four genes are involved in this reaction step, and one of them, an X-linked gene termed PIG-A, is mutated in affected cells. The PIG-A gene is mutated in all patients with PNH reported to date. Here, we review recent advances in the understanding of the molecular pathogenesis of PNH.
Glycosylphosphatidylinositols↗
Macrophage inflammatory protein 1alpha enhances in a different manner adhesion of hematopoietic progenitor cells from bone marrow, cord blood, and mobilized peripheral blood.
Regulatory mechanisms governing adhesion of hematopoietic progenitor cells to the stromal nische are poorly understood. Growth factors such as stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, and thrombopoietin were reported to upregulate the adhesion of hematopoietic progenitors to immobilized fibronectin through activation of integrin alpha4beta1 and alpha5beta1. Macrophage inflammatory protein (MIP)-1alpha is a C-C chemokine that suppresses colony formation by stem/progenitor cells in vitro. We asked if MIP-1alpha would modulate the adhesive phenotype of colony-forming cells (CFCs) obtained from healthy donor bone marrow (BM), cord blood (CB), and mobilized peripheral blood (mPB) CD34+ cells, in comparison with SCF, using immobilized fibronectin. SCF significantly increased the level of adhesion of CFCs from BM, CB, and mPB. On the other hand, MIP-1alpha significantly increased the level of adhesion of CFCs from BM and CB, but less so from mPB. The effects of MIP-1alpha were inhibited by blocking antibodies to integrin alpha4, alpha5, or beta1, and polymerization plus rearrangement of F-actin were observed in affected cells by labeling with rhodamine-conjugated phalloidine. These data indicate that the effect of MIP-1alpha on the adhesive phenotype of CFCs is mediated by modulation of the organization of integrin. The amount of MIP-1alpha receptor on mPB was less than for BM or CB, which may explain the distinct characteristics in the adhesive response induced by MIP-1alpha. We suggest that hematopoietic progenitor cells from different sources may be heterogeneous with respect to maturation, integrin affinity, MIP-1alpha receptor expression, and regulation of MIP-1alpha signaling. Our data indicate that MIP-1alpha may affect migration, homing, and mobilization of hematopoietic progenitors by modulating the adhesive phenotype of these cells.
Actins↗
Vasorelaxation and inhibition of the voltage-operated Ca2+ channels by FK506 in the porcine coronary artery.
Using fura-2 fluorometry, the effects of FK506, an immunosuppressant, on changes in cytosolic Ca2+ concentrations ([Ca2+]i) and tension were investigated in porcine coronary arterial strips. The effects of FK506 on the activity of voltage-operated Ca2+ channels were examined by applying a whole cell patch clamp to the isolated smooth muscle cells of porcine coronary artery. FK506 inhibited the sustained increases in both [Ca2+]i and tension induced by 118 mM K+ depolarization and 100 nM U46619 in a concentration-dependent manner (1-30 microM). The extent of inhibition of the K+-induced contraction was greater than that of the U46619-induced contraction. The increases in [Ca2+]i and tension induced by histamine and endothelin- in the presence of extracellular Ca2+ were also inhibited by 10 microM FK506. FK506 (10 microM) had no effect on Ca2+ release induced by caffeine or by histamine in the Ca2+-free solution. FK506 (10 microM) had no effect on the [Ca2+]i-tension relationships of the contractions induced by cumulative increases of extracellular Ca2+ during K+ depolarization or stimulation with U46619. In the patch clamp experiments, FK506 (30 microM) partially inhibited the inward current induced by depolarization pulse from -80 mV to 0 mV. In conclusion, FK506 induces arterial relaxation by decreasing [Ca2+]i mainly due to the inhibition of the L-type Ca2+ channels, with no effect on the Ca2+ sensitivity of the contractile apparatus.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Thapsigargin-induced endothelium-dependent triphasic regulation of vascular tone in the porcine renal artery.
1. To elucidate the role of thapsigargin-induced Ca2+ entry in endothelial cells in the regulation of vascular tone, changes in Ca2+ and force of smooth muscle were simultaneously monitored in fura-2-loaded strips of porcine renal artery. 2. During phenylephrine-induced sustained contraction, thapsigargin caused an endothelium-dependent triphasic response; an initial relaxation, a subsequent transient contraction, and a sustained relaxation. The initial relaxation and the contraction were associated with a decrease and an increase in [Ca2+]i, respectively. There was no apparent [Ca2+]i decrease during the sustained relaxation. Thapsigargin-induced responses were observed at 10-8 M and higher concentrations, with the maximum response observed at 10-6 M. 3. The transient contraction was inhibited by a cyclo-oxygenase inhibitor (10-5 M indomethacin), a thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10-5 M ONO-3708), and a TXA2 synthase inhibitor (10-5 M OKY-046). 4. During the phenylephrine-induced contraction in the presence of indomethacin, thapsigargin caused an initial, but not a sustained relaxation, in the presence of Nomega-nitro-L-arginine methylester (L-NAME). During the contraction induced by phenylephrine plus 40 mM K+-depolarization in the presence of indomethacin, thapsigargin induced both a transient and a sustained relaxation. However, these relaxations were completely abolished in the presence of L-NAME. 5. Thapsigargin caused a large Ca2+ elevation in cultured endothelial cells of the renal artery. The concentration-response relation was thus similar to that for force development in the arterial strips. 6. In conclusion, thapsigargin-induced Ca2+ entry in endothelial cells led to triphasic changes in the tone of the porcine renal artery. The endothelium-dependent contraction was mediated mainly by TXA2. Nitric oxide and hyperpolarizing factor are both involved in the initial relaxation. However, a sustained relaxation was observed which mainly depended on nitric oxide.
Animals↗
CD59-deficient blood cells and PIG-A gene abnormalities in Japanese patients with aplastic anaemia.
Patients with aplastic anaemia (AA) frequently develop paroxysmal nocturnal haemoglobinuria (PNH) as a late complication. We investigated the frequency of the development of PNH features including a glycosyl phosphatidylinositol (GPI) anchoring defect in 73 Japanese patients with AA. A deficient expression of CD59 was found on erythrocytes and/or granulocytes in 21/73 (28.8%) of the patients. A Ham/sugar water test was positive in 13/21 patients. We also examined mutations of the PIG-A gene in 11 patients with CD59 deficiency. A heteroduplex analysis detected PIG-A gene abnormality in 10/11 patients tested. Nucleotide sequencing was performed in six patients and identified eight mutations including three mutations in one patient. The mutations of the PIG-A gene were all different and included two single-base insertions, one single-base deletion, two two-base deletions, and one each of eight-base insertion and nine- and ten-base deletions. All mutations but one caused frameshifts. Our findings indicate that a high proportion of Japanese patients with severe AA have a GPI-anchoring defect and that the PIG-A gene is mutated in the AA patients who had a GPI deficiency. We found no significant difference in the pattern of the PIG-A gene mutation between the AA patients with a GPI deficiency and those with de novo PNH.
Adolescent↗
Mucosa-associated lymphoid tissue type lymphoma of the gallbladder associated with acute myeloid leukemia.
We describe a patient with mucosa-associated lymphoid tissue (MALT) type lymphoma of the gallbladder who developed concurrent acute myeloid leukemia (M2). She was admitted because of progressive jaundice and underwent cholecystectomy. Histologic examination of the gallbladder showed diffuse proliferation of atypical lymphoid cells and a formed lymphoepithelial lesion. Because of progressive thrombocytopenia, a bone marrow tap was performed 25 days after the operation. Bone marrow contained 65.5% blasts, and was positive for peroxidase, CD33 and HLA-DR, and negative for lymphoid markers. We discuss the rare association of these disorders.
Acute Disease↗
Telomerase activity in myeloma cells is closely related to cell cycle status, but not to apoptotic signals induced by interferon-alpha.
Telomeres, G-rich structures at the ends of chromosomes are essential for maintaining chromosomal integrity. Most tumor cells contain telomerase, a ribonucleoprotein that elongates telomeric repeats, and it plays an essential role in indefinite proliferation. To better understand regulatory mechanisms of telomerase, in relationship with apoptosis and the cell cycle, we examined telomerase activity in PCM6, an interleukin-6 (IL-6)-responsive, interferon-alpha (IFN-alpha)-sensitive multiple myeloma cell line, using a PCR-based assay. When PCM6 cells were cultured in serum-free media, the addition of IFN-alpha resulted in apoptosis of the cells, but with no influence on telomerase activity. When IFN-alpha was added to the culture with serum plus rIL-6 after serum deprivation, G1-S transition was inhibited and telomerase activity was lower compare to findings in culture with no IFN-alpha. Dose response experiments of rIL-6 and IFN-alpha, and the measurement of telomerase activity of sorted cells in S-phase using CD71, demonstrated a higher activity of telomerase in the samples which contained a larger proportion of cells in S-phase. These data indicate that regulation of telomerase activity is closely related to cell cycle status, in particular cells in S-phase have an high telomerase activity. While telomeres play an important role in cellular senescence, the regulation of telomerase is independent from apoptotic signals induced by IFN-alpha in myeloma cells.
Apoptosis↗
[Effectiveness of Nd: YAG laser therapy on Japanese cedar pollinosis].
Many have reported on the effectiveness of laser surgery therapy for perennial allergic rhinitis. However, the suppressive effects of laser irradiation on allergic rhinitis and its symptoms have not been reported in patients with pollinosis. This is because therapeutic effects on pollinosis are difficult to evaluate. The amount of pollen in the air varies during the year, and from year to year. Also, allergic symptoms develop due to exposure to the amount of pollen which is markedly influenced by the weather. In this study, the severity of allergic symptoms in the pollen season was compared between patients treated with early medication, non-treated patients and patients treated with preseasonal contact Nd: YAG laser surgery. Results suggests that laser surgery was effective in reducing the severity of symptoms in patients with cedar pollinosis. Symptoms were milder in the laser group than in the medication group and non-treated group for 3-4 weeks after the start of seasonal pollinosis, although no differences were noted in the early weeks. This may be explained by the fact that laser irradiation reduces the lamina propria of the nasal mucosa, the site of allergic reactions. This also suggests that allergic pollen can't penetrate the mucosal surface which shows squamous epithelization after laser irradiation.
Adult↗
Outcome study of bilateral lateral rectus recession for intermittent exotropia in children.
BACKGROUND AND OBJECTIVE: The purpose of this paper is to report a statistical analysis of the surgical results in a consecutive series of 52 children treated by bilateral lateral rectus recession for intermittent exotropia when the operating surgeon was confronted by an increase in manifestation of the strabismus. PATIENTS AND METHODS: The charts were abstracted for age at initial surgery, quantity of initial deviation, initial refraction, motor alignment at one week, six months, and at the end of the study. The incidence and result of secondary surgery and the incidence of the monofixation syndrome result was also determined. RESULTS: Thirty-two (62%) of the patients were successfully aligned at six months by the initial surgery performed for a mean of 25 prism diopters (PD) of preoperative deviation at a mean age of 4 years 8 months. Eleven patients (21%) were undercorrected and 9 patients (17%) were overcorrected at the six month exam. The patients were followed for a mean of 4 years, 4 months. Alignment at 6 months postoperatively was predictive of success by the end of the study, but the age at initial surgery, the size of the deviation, esotropia at 1 week, and initial refraction were not predictive of success. Secondary surgery was performed in 11 patients and the monofixation syndrome result was found in 5 patients. CONCLUSION: Successful alignment was achieved in the majority of children treated by an initial bilateral lateral rectus recession utilizing a currently popular surgical dosage table. Long term alignment success was not predicted by esotropia during the first postoperative week or the age at initial surgery but was correlated with the 6-month data. Secondary surgery was performed in 20% and the incidence of the monofixation syndrome was approximately 10% at the end of the study.
Adolescent↗
[Donor leukocyte transfusion in a patient with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation: analysis of natural killer cell activity and T-cell receptor repertoire in bone marrow T cells that exhibited graft-versus-leukemia activity].
Hematologic relapse of chronic myeloid leukemia developed in 37-year-old man 255 days after allogeneic bone marrow transplantation. The patient received a donor lymphocyte transfusion (DLT) twice at a dose of 5 x 10(6)/kg T cells. He achieved complete cytogenetic response (CCR) 14 weeks after DLT, and has remained in a CCR state for 17 months. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. Natural killer (NK) cell activity was elevated. Also, analysis of the T cell receptor (TCR) repertoire disclosed oligoclonal expansion of T cells of the TCR V beta and J beta subfamilies. These observations provide evidence for the clonal expansion of allogeneic T cells that are capable of mediating antileukemic activity without causing GVHD.
Adult↗
CD56+CD7+ stem cell leukemia/lymphoma with D2-Jdelta1 rearrangement.
OBJECT: We describe the characteristics of three patients with CD56+CD7+ stem cell leukemia/lymphoma. METHODS: These blasts were analyzed for morphologic, karyotypic, immunophenotypic, and immunogenotypic features using Southern blot and polymerase chain reaction analysis. MATERIALS: Peripheral blood, bone marrow aspirates, or biopsied mediastinal tumor specimens of three CD56+CD7+ stem cell leukemia/lymphoma patients were investigated. RESULTS: The bone marrow of all patients showed myeloperoxidase (MPO) negative blast cells with basophilic cytoplasm and distinct nucleoli with no azurophilic granules. The blasts of two patients were classified as acute lymphoblastic leukemia (L2). The liver, spleen, and lymph nodes were unaffected in all patients. All had an aggressive clinical course. The blasts were strongly positive for both CD7 and CD56 but negative for other T-lineage associated antigens, including CD1, CD2, surface membrane CD3, cytoplasmic CD3c (2/2), CD4, CD5 and CD8. The additional antigens were recognized as follows: CD19 (1/3 cases) as a B lineage, CD33 (1/3) as a myeloid marker, CD34 (2/3) as a stem cell, CD38 (1/1) and HLA-DR (2/3). When the patients relapsed, the phenotypes changed to blasts positive for CD5, CD10 and CD13 in patient 1, CD5 in patient 2, and CD33 in patient 3. MPO, however, remained negative. Cytogenetic analysis showed no common abnormal karyotype. All had a common D2-Jdelta1 induced by T-cell specific enhancer. Rearrangement of TCR beta and gamma genes occurred in patient 2, and IgH and TCR beta underwent rearrangement in patient 3. CONCLUSION: Although a more comprehensive case analysis is necessary, these data suggest the possibility that the blasts of the present cases come from a common lymphoid precursor (T, NK, and B cell) or from a NKT precursor as the fourth lymphoid lineage.
Acute Disease↗