Biomedical subjects

S Iwase

Publications and source records attributed to S Iwase.

At least 73 records · Page 4Linked to original sources

PubMed1999

A comparison of the effects of lower body positive pressure and head-down tilt on cardiovascular responses in humans.

Both lower body positive pressure (LBPP) and head-down tilt (HDT) can induce fluid shifts from the lower body to the thorax and result in a loading of cardiopulmonary baroreceptors. The aim of this study was to compare the effects of LBPP and HDT on cardiovascular responses in humans. To accomplish this, a graded LBPP test of 10, 20 and 30 mmHg, as well as a 6 degrees HDT was applied. It has been suggested that <20 mmHg LBPP and <30 degrees HDT load the cardiopulmonary baroreceptors by translocation of blood volume from the lower body to the thorax, while >20 mmHg LBPP activates the intramuscular pressure-sensitive receptors.

Adult↗

PubMed1999

Vasomotor sympathetic nerve responses to static handgrip after simulated microgravity.

During the isometric exercise, the autonomic nervous system has a major role in the regulation of arterial blood pressure, blood flow, and perfusion to the active skeletal muscle in humans. An increase in cardiac sympathetic nerve activity and a withdrawal of vagal tone cause elevations of heart rate, cardiac contractility and cardiac output. An increase in vasomotor sympathetic nerve activity causes a vascular constriction to redirect the oxygen transport to the contracting muscle. It has been reported that the autonomic and cardiovascular systems are commonly affected by the exposure to the real (i.e. spaceflight) and simulated microgravitational environment( i.e. 6 degrees head-down bed rest (HDBR)). The alteration in the autonomic system includes a reduced vagal tone, and an attenuated carotid-cardiac baroreflex function. It may also include an altered control of peripheral vessels, a reduced sympathetic vasoconstriction, an attenuated release of norepinephrine from sympathetic nerve terminal, an impaired myogenic contractility, an up- or down regulation of alpha-adrenergic receptors, and an attenuated multiple vasodilatation. Therefore, there seems to be a possibility that HDBR alters the sympathetic and cardiovascular responses to isometric exercise in humans, however, this possibility has not been examined efficiently. We compared the vasomotor sympathetic and cardiovascular responses to sustained handgrip (HG) until fatigue followed by post-exercise muscle ischemia (PEMI) after 14 days of HDBR, to those before HDBR, in 16 healthy males.

Adult↗

PubMed1999

Sympathetic response to horizontally linear acceleration in humans.

There is considerable evidence that stimulation of the vestibular system has effects on the activities of sympathetic preganglionic neurons in animals and of postganglionic nerves in animals and humans. In previous studies, we showed that the muscle sympathetic nerve activity (MSNA) from the human tibial nerve is enhanced after caloric vestibular stimulation (Cui et al. 1997), whereas the skin sympathetic nerve activity is suppressed during the nystagmus evoked by the caloric vestibular stimulation (Cui et al. 1999). These results suggest that the stimulation of the horizontal semicircular canal has effects on sympathetic outflows to muscle and skin in humans. However, much less is known about the MSNA response to dynamic stimulation of otolith organs in humans. To clarify this issue, we used a linear accelerator to stimulate the vestibular organs, especially otolith organs, and observed the MSNA and hemodynamic responses during movement.

Acceleration↗

PubMed1999

Changes in muscle sympathetic nerve activity and effects of breathing maneuvers in humans during microgravity induced by parabolic flight.

The mechanism of cardiovascular deconditioning, such as an orthostatic intolerance after space flight, has not been well clarified. Several studies to investigate that mechanism have focused mainly on hemodynamic changes including heart rate, arterial blood pressure, cardiac output, etc., but no studies have yielded a direct insight into changes in the sympathetic nervous system. Among ground-based experiments, parabolic flight is the only maneuver to expose human subjects to actual microgravity although it lasts for only a short duration of approx. 20 sec. Using microneurography, the present study aimed to analyze the involvement of the sympathetic nervous system in regulating the acute effects of fluid shift induced by parabolic flight during the transitional changes from 1 G to hypergravity, hypergravity to microgravity, and microgravity to hypergravity by direct measurement of sympathetic outflow to the muscles. Some parts of the study were published elsewhere. We also investigated how the sympathetic outflow to muscle is modified during microgravity with elimination of the breathing effect by comparing the cardiovascular parameters under controlled and uncontrolled respiration.

Adult↗

PubMed1999

Muscle sympathetic nerve activity (MSNA) after 120 days of 6 degrees head-down bed rest (HDBR).

The alterations in the sympathetic nervous system are commonly seen after spaceflight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR). Several studies have examined the effect of HDBR for a few days or a weeks on the vasomotor sympathetic tone at rest. However, it remains unclear how a long-lasting (>50 days) HDBR affects resting vasomotor sympathetic nervous activity. Consequently, we measured muscle sympathetic nerve activity (MSNA) in six healthy male volunteers (range, 26-42 years) in a resting supine position before and after 60 and 120 days of HDBR. MSNA was measured directly from the tibial nerve using a microneurographic technique. Resting supine MSNA significantly increased after 60 (28.2 +/- 2.7 bursts/min) and 120 (29.4 +/- 4.2 bursts/min) days of HDBR compared with the pre-HDBR level (19.0 +/- 2.3 bursts/min). Heart rate was significantly higher after 60 (73 +/- 2 beats/min) and 120 (72 +/- 3 beats/min) days of HDBR than before (65 +/- 2 beats/min). In contrast, mean blood pressure remained unchanged during and after 120 days of HDBR. In conclusion, the resting vasomotor sympathetic tone increased after long-lasting simulated microgravity.

Adult↗

PubMed1999

Effects of aging on leg vein filling and venous compliance during low levels of lower body negative pressure in humans.

To evaluate the fluid shift and leg venous compliance during orthostatic stress with advancing age, 12 aged and 5 young healthy males were subjected to graded lower body negative pressures (LBNP) of -5, -10, and -15 mmHg. Cardiovascular variables were monitored continuously, and leg venous compliance was determined by venous occlusion plethysmography. Neither heart rate nor mean arterial pressure changed significantly in any subject during LBNP. A progressive decrease in the thoracic fluid volume index and a gradual increase in the leg fluid volume index, indicating a fluid shift towards the lower body were observed significantly in the young group (p<0.05), while these changes were not significant in the aged group. A linear reduction in peripheral venous pressure could be seen during graded LBNP in all subjects, but the reduction rate was smaller in the aged group. Baseline leg venous compliance was reduced in the elderly (p<0.05). During LBNP, venous compliance decreased in all subjects, but the decrease was significantly smaller in the aged group (p<0.05). It is suggested that the smaller fluid shift and smaller decreased leg venous compliance in aged people during gravitational stress were mainly due to the vascular and ventricular stiffness induced by an age-related reduction in visco-elasticity of the peripheral venous and ventricular walls.

Adult↗

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

Sympathetic nerve responses in humans to short and long term simulation of microgravity.

The present paper aimed to review findings obtained by our researches to elucidate sympathetic nerve mechanisms of cardiovascular deconditioning in humans exposed to short and long term simulation of microgravity. Sympathetic nerve activity in humans has been so far investigated using indirect methods by analyzing the activities of effector organs, such as heart rate, blood flow, blood pressure, sweating etc. or by measuring the plasma nor-adrenaline level. Now we have a technique called microneurography which has enabled us to measure directly the sympathetic nerve activity form human peripheral nerves. The microneurography technique was used for the first time before, during and after the Space Shuttle "Neurolab" mission launched in April 1998 to elucidate how sympathetic nerve activity in astronauts is modified by exposure to microgravity in space. In this paper, we would like to present our recent findings concerning sympathetic nerve responses to short and long term microgravity simulated by different methods.

Bed Rest↗

PubMed1998

Changes in muscle sympathetic nerve activity and effect of breathing maneuvers during microgravity induced by parabolic flight in humans.

UNLABELLED: This study aimed to clarify how muscle sympathetic nerve activity (MSNA) in humans, which plays an important role in blood pressure control against gravity, is altered under microgravity (microG) conditions, and how the MSNA change is modified by breathing maneuvers. Ten subjects seated themselves in a jet aircraft with their knees extended. MSNA was recorded microneurographically from the left tibial nerve with simultaneous monitoring of ECG, blood pressure, respiration, and intrathoracic blood volume estimated by the impedance method during parabolic flight in a jet aircraft. In half of the parabolas, their respiration was controlled at 0.25 Hz by a metronome. RESULTS: MSNA was enhanced under hypergravity just before microG entry, and immediately suppressed by microG induced by parabolic flight. The suppression was more marked with controlled than with uncontrolled respiration (51.6 +/- 7.2 vs 82.8 +/- 2.5%, mean +/- SE, 1G=100%). MSNA changes during microG correlated significantly to changes in blood pressure and intrathoracic blood volume. The blood pressure fall 10 to 15 sec after microG entry was less prominent with controlled than with uncontrolled respiration. We conclude that changes in arterial blood pressure and intrathoracic blood volume modulate MSNA during microG induced by parabolic flight, depending largely on breathing maneuvers.

Adult↗

PubMed1998

Muscle sympathetic nerve activity and plasma norepinephrine during 6 degrees head-down bed rest.

Alterations in autonomic function are evident during spaceflight. These conditions are also simulated by ground-based experimental models of a microgravity environment such as 6 degrees head-down bed rest (BR). They include a reduction in baroreflex function, a decrease in vagal tone and a loss of circulatory blood volume during weightlessness. However, it is not clear whether vasomotor sympathetic outflow, which controls peripheral vascular tone neurally, and plasma norepinephrine concentration will change or not during weightlessness. The purpose of the present study is to examine changes in vasomotor sympathetic nerve activity during six days of 6 degrees head-down BR. Vasomotor sympathetic nervous activity was evaluated by the direct recording of muscle sympathetic nerve activity (MSNA) by a use of microneurographic technique. MSNA on the sixth day during BR was the same as that in a horizontally supine position before BR (before BR; 15.4 +/- 1.6 bursts/min, during BR; 16.7 +/- 3.5 bursts/min), though plasma norepinephrine concentrations during BR were reduced by 25% compared with those before BR (before BR; 263 +/- 33 pg/ml, during BR; 193 +/- 79 pg/ml, p < 0.05). This dissociation cannot be determined precisely, but it suggests the possibility of peripheral changes in terminal sympathetic nerve endings, etc.

Adult↗