Biomedical subjects

S Iwase

Publications and source records attributed to S Iwase.

At least 19 recordsLinked to original sources

PubMed1999

UDP-GlcNAc:Galbeta1-->3GalNAc (GlcNAc to GalNAc) beta1-->6N-acetylglucosaminyltransferase holds a key role on the control of CD15s expression in human pre-B lymphoid cell lines.

Expression mechanism of CD15s (sialyl-Lex, sLex) antigen has been investigated using human B lymphoid cell lines. sLexstructures were not expressed in mature B lymphoids but highly expressed in pre-B leukemia and pre-B lymphoma cell lines. The expression site was mainly on the O -linked oligosaccharide chains and E-selectin mediated-cell adhesion capability of sLex-positive cells were significantly suppressed by benzyl-alpha-GalNAc treatment. Subsequently, the bases of the sLexexpression control mechanism were examined at the levels of enzymatic activities and transcripts of glycosyltransferases. (1) The activities of alpha1-->3fucosyltransferase, alpha2-->3sialyltransferase, beta1-->4Gal-transferase, and elongation beta1-->3GlcNAc-transferase, did not correlate with sLexexpression levels. (2) The transcripts of Fuc-TVII were not parallel with sLexexpression, and those of ST3Gal IV and beta1-->4Gal-transferase were constitutively detected in all cell lines tested. (3) There was no detectable enzyme activity for core 3 and 4 backbone structure synthesis in human B cell lines. (4) By contrast, the enzyme activities and transcripts of UDP-GlcNAc:Galbeta1-->3GalNAc (GlcNAc to GalNAc) beta1-->6 N -acetylglucosaminyltransferase (Core2GnT) had significant correlation with the cell surface expression of sLexantigen. (5) Moreover, Western blot analysis revealed the presence of a major approximately 150 kDa glycoprotein that carries O -linked oligosaccharides recognized by anti-sLexmonoclonal antibody in sLex-positive pre-B leukemia cell lines. This correlation of Core2GnT with CD15s expression suggests that Core2GnT is a regulator of the cell surface expression of sLexin human pre-B lymphoid cells.

Antigens, CD↗

PubMed1999

Responses of sympathetic outflow to skin during caloric stimulation in humans.

We previously showed that caloric vestibular stimulation elicits increases in sympathetic outflow to muscle (MSNA) in humans. The present study was conducted to determine the effect of this stimulation on sympathetic outflow to skin (SSNA). The SSNA in the tibial and peroneal nerves and nystagmus was recorded in nine subjects when the external meatus was irrigated with 50 ml of cold (10 degrees C) or warm (44 degrees C) water. During nystagmus, the SSNA in tibial and peroneal nerves decreased to 50 +/- 4% (with baseline value set as 100%) and 61 +/- 4%, respectively. The degree of SSNA suppression in both nerves was proportional to the maximum slow-phase velocity of nystagmus. After nystagmus, the SSNA increased to 166 +/- 7 and 168 +/- 6%, respectively, and the degree of motion sickness symptoms was correlated with this SSNA increase. These results suggest that the SSNA response differs from the MSNA response during caloric vestibular stimulation and that the SSNA response elicited in the initial period of caloric vestibular stimulation is different from that observed during the period of motion sickness symptoms.

Adult↗

PubMed1999

[A case of aggressive myeloma with abnormal plasmocytes in pleural effusion and cerebrospinal fluid].

Extramedullary involvement of myelomas is common but invasion of myeloma cells into the pleural cavity and cerebrospinal fluid (CSF) is rare. We report an aggressive case of multiple myelomas (Bence Jones lambda type) with pleural and meningeal infiltration. A 66-year-old man was referred to our hospital because of anemia, thrombocytopenia, and dyspnea. His peripheral blood contained 2% bizarre plasma cells. Bone marrow biopsy specimens and immunoelectrophoresis confirmed the diagnosis. A chest radiograph disclosed pleural effusion in both lungs containing M-protein and numerous abnormal cells. The patient also suffered from disorientation, speech disorder, and muscle weakness. A lumbar puncture revealed atypical plasma cells in CSF. Four courses of chemotherapy (cyclophosphamide, doxorubicin, and prednisolone) and the intrathecal administration of methotrexate and cytarabine at 3-week intervals were effective in decreasing the pleural effusions and eliminating plasma cells from CSF. Nonetheless a chest wall tumor, pelvic mass, and pneumonia developed, and the patient died 5 months after initial presentation. Pleural infiltration of myeloma cells and multiple lesions with plasma cell involvement were discovered at autopsy.

Aged↗

PubMed1998

Attenuation of regional differentiation of sympathetic nerve activity during sleep in humans.

The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.

Adult↗

PubMed1998

Single glycosyltransferase, core 2 beta1-->6-N-acetylglucosaminyltransferase, regulates cell surface sialyl-Lex expression level in human pre-B lymphocytic leukemia cell line KM3 treated with phorbolester.

Sialyl-Lex (sLex) antigen expression recognized by KM93 monoclonal antibody was significantly down-regulated during differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human pre-B lymphocytic leukemia cell line KM3. The sLex determinants were almost exclusively expressed on O-linked oligosaccharide chains of an O-glycosylated 150-kDa glycoprotein (gp150). A low shear force cell adhesion assay showed that TPA treatment significantly inhibited E-selectin-mediated cell adhesion. Transcript and/or enzyme activity levels of alpha1-->3-fucosyltransferase, alpha2-->3-sialyltransferase, beta1-->4-galactosyltransferase, and elongation beta1-->3-N-acetylglucosaminyltransferase did not correlate with sLex expression levels. However, transcript and enzyme activity levels of core 2 GlcNAc-transferase (C2GnT) were significantly down-regulated during TPA treatment. Following transfection and constitutive expression of full-length exogenous C2GnT transcript, C2GnT enzyme activities were maintained at high levels even after TPA treatment and down-regulation of cell surface sLex antigen expression by TPA was completely abolished. Furthermore, in the transfected cells, the KM93 reactivity of gp150 was not reduced by TPA treatment, and the inhibition of cell adhesion by TPA was also blocked. These results suggest that sLex expression is critically regulated by a single glycosyltransferase, C2GnT, during differentiation of KM3 cells.

Animals↗

PubMed1998

A Janus kinase inhibitor, JAB, is an interferon-gamma-inducible gene and confers resistance to interferons.

It has been shown that interferons (IFNs) exert their signals through receptor-associated Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). However, molecular mechanism of regulation of IFN signaling has not been fully understood. We have reported novel cytokine-inducible SH2 protein (CIS) and JAK binding protein (JAB) family genes that can potentially modulate cytokine signaling. Here we report that JAB is strongly induced by IFN-gamma but not by IFN-beta in mouse myeloid leukemia M1 cells and NIH-3T3 fibroblasts. NIH-3T3 cells ectopically expressing JAB but not CIS3 lost responsiveness to the antiviral effect of IFN-beta and IFN-gamma. M1 leukemic cells stably expressing JAB were also resistant to IFN-gamma and IFN-beta-induced growth arrest. In both NIH-3T3 and M1 transformants expressing JAB, IFN-gamma did not induce tyrosine phosphorylation and DNA binding activity of STAT1. Moreover, IFN-gamma-induced activation of JAK1 and JAK2 and IFN-beta-induced JAK1 and Tyk2 activation were inhibited in NIH-3T3 JAB transformants. These results suggest that JAB inhibits IFN signaling by blocking JAK activity. We also found that IFN-resistant clones derived from LoVo cells and Daudi cells expressed high levels of JAB without stimulation. In IFN-resistant Daudi cells, IFN-induced STAT1 and JAK phosphorylation was partially reduced. Therefore, overexpression of JAB could be, at least in part, a mechanism of IFN resistance.

3T3 Cells↗

PubMed1998

Two types of anti-TL (thymus leukemia) CTL clones with distinct target specificities: differences in cytotoxic mechanisms and accessory molecule requirements.

TCRalphabeta CTL clones recognizing mouse thymus leukemia (TL) Ags were established and categorized into two groups: those killing any TL+ target cells (type I) and those killing only TL+ Con A blasts (type II). Cold target inhibition assays showed that the antigenic determinant(s) recognized by type II clones are expressed not only on TL+ Con A blasts but also on other TL+ target cells. The relation of the target specificity to the killing machinery and the accessory molecules involved in cytotoxicity were therefore analyzed using four representative clones selected from each type. Of the target cells tested, Fas was only expressed on Con A blasts, indicating that Fas ligand (FasL)-dependent cytotoxicity is limited to such cells. All four type II and one of four type I clones expressed FasL on the surface, while both types contained perforin in the cytoplasm. Blocking studies using neutralizing anti-FasL mAbs and concanamycin A (CMA), a selective inhibitor of the perforin pathway, suggested that type I clones kill target cells by way of perforin, while type II clones kill TL+ Con A blasts through FasL together with perforin. For their cytotoxicity, type I CTLs require a signal through CD8, while type II require LFA-1/ICAM-1 interactions. Type II clones also need a co-stimulatory signal through an unknown molecule for perforin-dependent cytotoxicity. These results taken together suggest that the difference in the target specificity of anti-TL CTL clones is due to variation in the killing machineries and the dependence on accessory molecules.

Animals↗

PubMed1998

Vasodilator component in sympathetic nerve activity destined for the skin of the dorsal foot of mildly heated humans.

1. Skin sympathetic nerve activity (SSNA) was recorded in seven male subjects from the peroneal nerve by microneurography, and the temporal correspondence of spontaneously occurring SSNA bursts with vasodilatation and sweating responses on the dorsal foot was studied during a mild body heating at rest. 2. Some SSNA bursts were followed by a sweat expulsion with a latency of 2.4 +/- 0.4 s, and some bursts by a transient vasodilatation with a latency of 2.2 +/- 0.4 s (means +/- S.D.). SSNA bursts followed both by a sweat expulsion and by a vasodilatation response (Type 1), those followed only by a sweat expulsion (Type 2) and those followed only by a vasodilatation, response (Type 3) were 70%, 10% and 1% of the total bursts examined, respectively. 3. For Type 1 bursts, there was a significant, but weak linear relationship among the burst amplitude, the amplitude of the corresponding vasodilatation and the amplitude of the corresponding sweat expulsion. 4. It was concluded that SSNA contains vasodilatory activity which is synchronous with sudomotor nerve activity. The results suggest that such vasodilatory activity contributes to sustaining the sweat gland function by supplying sufficient blood.

Adult↗

PubMed1998

A novel variant of acute myelomonocytic leukemia carrying t(3;12)(q26;p13) with characteristics of 3q21q26 syndrome.

Chromosomal translocation often results in aberrant activation of the genes with oncogenic potential and, thus, plays an important role in leukemogenesis. We report a unique case of acute myelomonocytic leukemia carrying a rare reciprocal translocation, t(3;12)(q26;p13). This patient displayed typical clinical features of 3q21q26 syndrome such as abnormal thrombopoiesis and rapid disease progression. Blastic cells from the patient strongly expressed the EVI1 gene, which is located on 3q26 and is normally suppressed in bone marrow cells. Expression of the TEL gene, located on 12p13, was also observed, but fusion transcript between two genes was not found. No structural alterations of the EVI1 and TEL genes were detected by Southern blot and PCR analyses. We reviewed previous literature and found 10 other cases with t(3;12)(q26;p13). These patients comprise a unique disease group with features including dyshematopoiesis and poor prognosis. However, characteristics related to 3q21q26 syndrome were observed only in the present case. Further investigation is required to elucidate the molecular basis of this particular entity.

Chromosomes, Human, Pair 12↗

PubMed1998

Hemolysis caused by CMV infection in a pregnant woman with silent elliptocytosis.

Elliptocytosis is reported to occur in at least 1 per 5000 individuals, but most cases are heterozygous and do not show clinical hemolysis. Healthy individuals with silent elliptocytosis, however, may suddenly have an episode of hemolysis [1]. Here we report a woman in the third trimester of pregnancy who suffered from cytomegalovirus (CMV) infection with hemolysis. Scanning electron microscopy showed that half of her red blood cells were oval, and protein analysis revealed a 50% reduction of protein 4.1. We discuss the role of CMV infection and pregnancy in the onset of hemolysis in a patient with otherwise silent elliptocytosis.

Adult↗

PubMed1998

Biological effects of a relatively low concentration of 1-beta-D-arabinofuranosylcytosine in K562 cells: alterations of the cell cycle, erythroid-differentiation, and apoptosis.

Therapeutic strategies for leukemia are directed to induction of differentiation and apoptosis as well as growth inhibition. One of the key antileukemic agents, 1-beta-D-arabinofuranosylcytosine (ara C), is clinically applied according to these therapeutic aims. However, the molecular effects of 0.1 microg/ml of ara C, a concentration that corresponds to the serum level in leukemic patients on a conventional dose of ara C, have not been well disclosed. Here, we addressed these issues using K562 cells which derived from a blastic crisis of chronic myeloid leukemia. DNA synthesis of treated cells was suppressed from 1-6 h. But, it recovered at 12 h and no further inhibition was observed. The number of cells was not decreased but DNA fragmentation was observed at 72 h. The number of erythroid-differentiated cells also increased to 30% at 72 h. Along with treatment, no marked alteration of mRNAs for cell cycle-regulating genes was found and the retinoblastoma gene product remained hyperphosphorylated throughout treatment. The expression of mRNAs for apoptosis-regulating genes also remained unchanged, except for slight down-regulation of Bax. c-myc protein was not found later than 48 h, and Max mRNA was downregulated. c-jun was immediately induced, followed by the fluctuated expression level along with treatment. These findings suggest that the 0.1 microg/ml ara C changed the proliferation, differentiation and death of K562 cells in a biphasic manner. In the early phase, DNA synthesis was inhibited without altering the expression of cell cycle regulating-genes. In the latter phase, cell death and erythroid- differentiation occurred in accordance with the down-regulation of c-myc.

Apoptosis↗

PubMed1998

Band 3 Tokyo: Thr837-->Ala837 substitution in erythrocyte band 3 protein associated with spherocytic hemolysis.

We report a case of spherocytosis associated with erythrocyte band 3 deficiency. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of erythrocyte membrane proteins showed that the patient's band 3 was reduced to about 80% of the control level. Molecular analysis revealed that this quantitative alteration was accompanied by a novel base change at codon 837 (ACG-->GCG) of the AE1 gene, resulting in substitution of alanine for threonine. In bone marrow mononuclear cells, both mutant and wild-type mRNA were comparably detected, suggesting that this mutation interfered with band 3 processing or assembly, leading to impaired accumulation of mutant band 3 in the plasma membrane.

Adult↗

PubMed1998

Bcl-x is a regulatory factor of apoptosis and differentiation in megakaryocytic lineage cells.

Differentiation- and lineage-related differences in the expression of two anti-apoptotic molecules, bcl-x and bcl-2, were examined using various human hematopoietic cell lines. Bcl-x was strongly expressed in cell lines with erythroid and megakaryocytic properties (K562, HEL, CMK, and Mo7E), and was moderately expressed in immature myeloid cell lines (KG-1 and KCL-22). Bcl-2 expression was relatively weak in these cells. On the other hand, bcl-x was not expressed in more mature myeloid cell lines (HL-60 and PL-21), but bcl-2 was strongly expressed in these cells and in monocytoid cell lines (U937, THP-1, and JOSK-I). We investigated the biological significance of high levels of bcl-x expression in erythroid and megakaryocytic lineage cells. When K562 cells were specifically differentiated into megakaryocytic lineage by phorbol ester, the amounts of bcl-x increased by 10-fold. In contrast, bcl-x was gradually downregulated during erythroid differentiation induced by cytosine arabinoside. Apoptosis was observed following erythroid differentiation of K562 cells, but it was not associated with megakaryocytic differentiation in consistent with the increase in bcl-x. Moreover, phorbol ester-induced megakaryocytic differentiation was facilitated by the overexpression of bcl-x in K562 cells. Finally, in situ hybridization revealed that bcl-x mRNA expression was strongest in megakaryocytes among normal bone marrow cells. These results suggest that bcl-x is a regulatory factor in the apoptosis and differentiation of megakaryocytes.

Apoptosis↗

PubMed1997

Response to vestibular stimulation of sympathetic outflow to muscle in humans.

The objective of the present study was to determine the effect of vestibular stimulation on the sympathetic outflow to muscle in humans. Fourteen healthy volunteers were studied while in the supine position with electrocardiography, blood pressure monitoring and electro-oculography. The muscle sympathetic nerve activity (MSNA) was recorded directly from the bilateral tibial nerves by using microneurographic double recording technique. Caloric vestibular stimulation was loaded by alternate irrigation with 50 ml of cold (10 degrees C) water and 50 ml of hot (44 degrees C) water into the left and right external meatus. After cold water irrigation, two MSNA response peaks were elicited, respectively, before and after the maximum slow phase velocity (SPV) of nystagmus. The first peak of the MSNA enhancement was caused by non-specific factors because its time course coincided with that in cold pressor test with immersion of the subject's hand in ice/water (4 degrees C). Transient suppression of MSNA after cold water irrigation in the period of maximum SPV of nystagmus was observed by cross correlogram analysis between the SPV of the nystagmus and MSNA. After hot water irrigation, only one MSNA response peak was elicited after the period of strong nystagmus. The second peak of MSNA enhancement evoked by cold irrigation (379.4 +/- 221.8%, with the control value set as 100%, mean +/- SE) was significantly higher than that evoked by hot irrigation (243.0 +/- 14.5%). The degree of MSNA enhancement by either cold (the second peak) or hot stimulation was proportional to the maximum SPV of the nystagmus. There was no significant difference between the MSNA responses ipsilateral to and contralateral to the irrigated side. In conclusion, the caloric vestibular stimulation can influence the bilateral sympathetic outflow to muscle in humans. The degree of MSNA enhancement is proportional to the magnitude of vestibular excitement indicated by maximum slow phase velocity of the nystagmus.

Adult↗

PubMed1997

Regulatory effects of aggregated LDL on apoptosis during foam cell formation of human peripheral blood monocytes.

In order to investigate the mechanisms how modified lipoproteins enhance foam cell formation, we cultured peripheral blood monocytes with various stimulants and examined the effects of aggregated low-density lipoprotein (agLDL) on cell viability and lipid metabolism. AgLDL could completely inhibit phorbol ester-induced apoptosis, which was accompanied by intracellular cholesterol accumulation. Suppression of apoptosis-promoting proteases, ICE and CPP32, was observed in agLDL-treated cells. This indicates that agLDL accelerates foam cell formation through inhibition of apoptosis and enhancement of lipid accumulation in activated monocytes. By contrast, apoptosis was enhanced when monocytes were cultured with agLDL and M-CSF. Intracellular cholesterol accumulation was not significant in M-CSF treated cells. This suggests that M-CSF may act anti-atherogenic through apoptotic elimination of lipid-baring macrophages and enhanced lipid turnover. Our observation supports the novel hypothesis that regulation of apoptosis may play an important role in the development of atherosclerosis.

Apoptosis↗

PubMed1997

Altered response in cutaneous sympathetic outflow to mental and thermal stimuli in primary palmoplantar hyperhidrosis.

Skin sympathetic nerve activities (SSNAs) were recorded simultaneously from the tibial and peroneal nerves by microneurography at an ambient temperature of 25 degrees C in five subjects with primary palmoplantar hyperhidrosis. The resting of the tibial SSNA innervating the sole (glabrous skin) increased moderately (36.5 +/- 1.5 bursts/min), while mental arithmetic provoked marked responses (1,003.3 +/- 457.4% compared with the resting level) in the hyperhidrosis group compared with the control normohidrosis group (n = 5, 25.3 +/ 4.2 bursts/min and 142.2 +/- 58.4%, respectively). Differentiation of the tibial SSNA into sudomotor (innervating sweat glands) and vasoconstrictor (innervating presphincter of skin vessels) revealed that this SSNA enhancement was attributable to not only sudomotor but also vasoconstrictor components during mental arithmetic. In contrast, the responses in the peroneal SSNA (innervating the dorsum pedis, hairy skin) of the hyperhidrosis group were only slightly changed, exhibiting no significant difference from those in the normohidrosis group. Reflex bursts elicited by sound and electric stimulation were normal in amplitude and latency. When the ambient temperature was elevated to 30 degrees C, the tibial SSNAs became more enhanced than did the peroneal SSNAs. The tibial SSNA was markedly enhanced in the hyperhidrosis group (290.0 +/- 78.5%) compared with the normohidrosis group (78.3 +/- 25.4%). We conclude that the excessive responses in SSNA to the plantar glabrous skin to both mental and thermal stimuli may be responsible for the profuse sweating in subjects with primary palmoplantar hyperhidrosis.

Acoustic Stimulation↗

PubMed1997

Polyploidization and functional maturation are two distinct processes during megakaryocytic differentiation: involvement of cyclin-dependent kinase inhibitor p21 in polyploidization.

The mechanism of megakaryocytic differentiation was investigated using human megakaryocytic leukemia cell line UT-7. Polyploidization of UT-7 cells was induced by the microtubule-depolymerizing agent, nocodazole, and 12-O-tetradecanoylphorbol-13-acetate (TPA), but the effect was much more striking with nocodazole. By contrast, induction of cytoplasmic maturation, as judged by beta-thromboglobulin production and platelet factor 4 expression, was more prominent in TPA-treated cells than in nocodazole-treated cells. Nocodazole and TPA could act synergistically to increase ploidy and to enhance the expression of mature phenotypes. Human thrombopoietin induced functional maturation but not polyploidization in UT-7 cells and also acts synergistically with nocodazole. Cyclin-dependent kinase inhibitor p21 was upregulated at the early stage of megakaryocytic differentiation, and overexpression of p21 resulted in an increase in ploidy of UT-7 cells. This suggests that p21 is implicated in polyploidization via suppression of CDC2 activity at mitosis. UT-7 but not HL-60 cells could incorporate [3H]thymidine in the presence of TPA, indicating the presence of megakaryocyte-specific licensing factor to allow DNA replication during differentiation. Taking these data together, we propose that megakaryocytic differentiation consists of two distinct processes, polyploidization and functional maturation, and that these two processes are independently regulated.

Carcinogens↗

PubMed1997

Modulation of E2F activity is linked to interferon-induced growth suppression of hematopoietic cells.

E2F is a heterodimeric transcription factor that controls transcription of several growth-regulatory genes including cdc2. To investigate the mechanism of interferon-alpha (IFN-alpha)-mediated growth suppression of hematopoietic cells, we examined the effect of IFN-alpha on the expression and function of E2F using IFN-sensitive Daudi cells. Down-regulation of E2F-1, a subunit of E2F, was observed after 8 h of culture with IFN-alpha; expression of E2F-4, another subunit of E2F, and DP-1, a heterodimeric partner of E2F, was unaffected. Gel shift assays revealed that the DNA binding activity of free E2F, which is composed of E2F-1 and E2F-4, was inhibited by IFN-alpha. In contrast, IFN-alpha did not affect the DNA binding ability of E2F-1 and E2F-4 in a complex with retinoblastoma (RB) susceptibility gene family proteins including pRB, p107, and p130. IFN-alpha could induce dephosphorylation of pRB, thereby turning active E2F-pRB complexes into transcriptional repressors. Transient chloramphenicol acetyltransferase assays revealed that the activity of the E2F-dependent cdc2 promoter was suppressed by IFN-alpha. These results suggest that the antiproliferative action of IFN-alpha is mediated through the modulation of E2F activity in two different ways: down-regulation of transcriptionally active free E2F and conversion of E2F-pRB complexes into transcriptional repressors.

Antiviral Agents↗