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Biomedical subjects

S Iwase

Publications and source records attributed to S Iwase.

At least 91 records · Page 5Linked to original sources
PubMed1998

Sympathetic nerve response to muscle during anteroposterior acceleration in humans.

This study aimed to elucidate the effects of linear acceleration on muscle sympathetic nerve activity (MSNA) in humans. Eight healthy young male volunteers were seated in a linear accelerator (sled) during the recording of their electrocardiogram, blood pressure with the Finapres, thoracic impedance and respiration curve. MSNA was recorded from the tibial nerve by microneurography. At a fixed distance of sled movements in an anteroposterior direction, eight modes of stimulation with peak accelerations at 0.05, 0.10, 0.15, and 0.20 G (gravity) in sinusoidal or step mode were applied to each subject. Each movement was repeated for 5 cycles. Both the total activity and the burst rate of MSNA decreased during acceleration, and the level of the decrease was proportional to the level of the acceleration, whereas the average heart rate, thoracic impedance and mean arterial pressure did not change significantly. These results suggests that moderate linear acceleration may suppress MSNA in humans.

Acceleration↗
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↗
PubMed1997

Skin sympathetic nerve activity in Guillain-Barré syndrome: a microneurographic study.

To assess autonomic dysfunction, skin sympathetic nerve activity (SSNA) of four patients with Guillain-Barré syndrome was microneurographically studied in the acute and remission phase. Autonomic symptoms such as sinus tachycardia, palmar hyperhidrosis, hypertension, and orthostatic hypotension were present in the acute phase, but all subsided during remission. Basal resting SSNA and the responses to various physical and mental stimuli were all increased in the acute phase and returned almost to normal during remission. Rate of response in sweat rate and blood flow against SSNA were kept proportionally constant during both the acute and remission phases. These findings suggest that some autonomic nerve symptoms of Guillain-Barré syndrome, particularly during the acute phase, are due to increased SSNA.

Acute Disease↗
PubMed1997

Effects of three days of dry immersion on heart rate and blood pressure variabilities during head-up tilting in humans.

In this study we examined the effects of 3 days of dry immersion on heart rate variability (HRV) and blood pressure variability (BPV) in response to head-up tilting in 4 healthy young subjects aged 21 to 36 years. Resting value of the high-frequency (HF) power of BPV and HRV decreased, while the low-frequency (LF)/HF ratio of HRV and blood pressure increased after the dry immersion. The HF power of HRV decreased, while the LF/HF ratio of HRV and heart rate increased during head-up tilting before and after dry immersion. All powers of BPV and BP were unchanged during head-up tilting. The values of the decrease in the HF power of HRV and the increase in the LF/HF ratio during head-up tilting after dry immersion were larger than those before. These results suggest that 3 days of dry immersion altered the autonomic balance toward the sympathetic dominant at rest, and that cardiac function may play a crucial role in BP maintenance during head-up tilting compared with vasoconstrictor function.

Adult↗
PubMed1997

Sympathetic nerve response to microgravity induced by parabolic flight.

The aim of this study was 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 conditions. Subjects were seated in a jet aircraft with their legs extended. MSNA was recorded microneurographically from the tibial nerve of the sitting subjects with simultaneous monitoring of electrocardiogram, blood pressure, respiration, and intrathoracic blood volume during parabolic flights. In the Air Force training area, the aircraft made parabolas up to 10 times. At the entry to microgravity, intrathoracic blood volume increased, systemic blood pressure was elevated, and MSNA was suppressed. However, this MSNA suppression lasted only 10-15 sec, and then followed by an enhancement to the end of the parabolas. We conclude that MSNA is suppressed at the onset of microgravity during parabolic flight in response to loading of the cardiopulmonary volume receptor due to a cephalad body fluid shift. However, this MSNA suppression is transient during such dynamic gravitational changes as those induced by parabolic flight, probably modulated by arterial baroreceptors.

Adult↗
PubMed1997

Sympathetic control of hemodynamics during moderate head-up tilt in human subjects.

To confirm sympathetic control of hemodynamics during postural change, sympathetic nerve activity supplying the anterior tibial muscle (MSNA) was measured by microneurography and muscle blood flow (MBF) by the xenon washout method during graded head-up tilt from 0 degrees horizontal to 30 degrees in 5 degrees increments. MSNA was represented as the increase in burst rate with increased tilt angle. The increments of MSNA from 0 degree horizontal were statistically significant at all tilt angles. MBF decreased gradually with increasing tilt angle, with no difference noted from 5 to 15 degrees, but a significant decrease between 20 and 30 degrees. Mean blood pressure remained unchanged during graded tilt. The heart rate did not increase until a tilt angle of 10 degrees, with increments becoming significant beyond 15 degrees. These results demonstrated that MSNA plays an important role in hemodynamic regulation during incremental changes in posture, while tilt angle increased HR and other control mechanisms that may be involves.

Adult↗
PubMed1997

Effects of positive and negative pressure breathing on muscle sympathetic nerve activity in humans.

To clarify the dynamic effects of short-term continuous positive-pressure breathing (CPPB) and continuous negative-pressure breathing (CNPB) on sympathetic nerve activity, we measured muscle sympathetic nerve activity (MSNA) in the tibial nerve together with blood pressure, heart rate, and central venous pressure (CVP) during spontaneous breathing: 5, 10, and 15 mm Hg (CPPB), and -5, -10, and -15 mm Hg (CNPB) for 5 min, respectively, in six healthy male volunteers. Increasing levels of CPPB at 5, 10, and 15 mm Hg produced increasing levels of MSNA, however, during CNPB, MSNA was virtually constant. Mean blood pressure decreased and heart rate increased during CNPB, while neither factor changed significantly during CPPB. CVP increased during CPPB and decreased during CNPB. These results suggest that CPPB and CNPB do not have the inverse effects on MSNA.

Adult↗
PubMed1997

CMP-NeuAc:Gal beta 1-->4GlcNAc alpha 2-->6sialyltransferase catalyzes NeuAc transfer to glycolipids.

Using mammalian gene-overexpression system, in vitro catalytic activities of CMP-NeuAc:Gal beta 1-->4GlcNAc alpha 2-->6sialytransferase on glycosphinogolipid acceptors were analyzed. We transfected the mammalian expression vector containing the cDNA that was cloned from Daudi cells into COS-1 cells, and selected monoclonal transfectants in the presence of G418. Although the transfected alpha 2-->6sialytransferase can catalyze NeuAc transfer onto glycoprotein acceptors more than glycolipids based on kinetic analyses, the substantial synthesis of IV6NeuAc-nLcOse4Cer was observed and the activities were 7- to 9-times higher in the transfected cells than in the mock transfectants. In addition, the transfected COS-1 cells with alpha 2-->6sialytransferase cDNA were revealed to contain a higher amount of ganglioside that has the terminal NeuAc alpha 2-->6Gal sequence in the in situ situation than the mock transfectants. These results using transfectants, together with those using the purified enzyme protein, suggest that the alpha 2-->6sialytransferase enzyme from Daudi cells can also catalyze NeuAc transfer in alpha 2-->6 linkage onto glycosphingolipid acceptors.

Amino Acid Sequence↗
PubMed1997

Sympatho-vagal responses in humans to thermoneutral head-out water immersion.

To clarify the role of autonomic nervous functions in cardiovascular adaptation to microgravity, heart rate variability (HRV) and blood pressure variability (BPV) were evaluated during thermoneutral head-out water immersion (HOI) of eight healthy young subjects 23 to 31 yr of age. The very low-frequency (VLF; 0.00-0.04 Hz) component of BPV tended to increase during HOI, whereas the low-frequency (LF; 0.04-0.15 Hz) component of BPV and the ratio of LF power to high-frequency (HF; 0.15-0.40 Hz) component (LF/HF ratio) of HRV decreased. The HF component of HRV increased in all the subjects during immersion up to the shoulder. Concomitantly, we found a decrease in heart rate and increases in stroke volume and cardiac output with no significant changes in BP and respiration rate during HOI. These results suggest that both vasomotor and cardiac sympathetic activities are suppressed and that the parasympathetic (vagal) activity is enhanced during HOI.

Adult↗
PubMed1996

Positive selection of gamma delta CTL by TL antigen expressed in the thymus.

To elucidate the funciton of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tl alpha 2-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tla2-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg. Tla2-3-1, Tg. Tla2-3-2, and control C3H mice by skin grafts from H-2Kb/T3b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg. Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tla2-3-1 and Tg.Tla2-3-2, respectively, expressed TCR gamma delta, whereas almost all those from C3H expressed TCR alpha beta. The MLC from Tg. Tla2-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg. Tla2-3-1 had little or none. The generation of gamma delta CTL recognizing TL in Tg. Tla2-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 gamma delta CTL clones were established from Tg. Tla2-3-2, whereas none were obtained from C3H. Of the 14 gamma delta CTL clones, 8 were CD8+ and 6 were CD4-CD8- double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCR gamma delta and CD3, and also by antibodies to CD 8 alpha and CD8 beta in CD8+ clones, showing that the activity was mediated by TCR gamma delta and coreceptors. The thymic origin of these gamma delta CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8 alpha beta heterodimers in CD8+ clones on their surfaces and by the usage of TCR V gamma 4 chains in 12 of the 14 clones. Taken together, these results suggest that Tla2-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of gamma delta T cells.

Amino Acid Sequence↗
PubMed1996

Transcriptional activation of the cdc2 gene is associated with Fas-induced apoptosis of human hematopoietic cells.

Apoptosis has recently been hypothesized to be the result of aberrant cell cycle control. In this study, we have investigated the role of cell cycle-regulatory elements in Fas-induced apoptosis of hematopoietic cells. When HL-60 cells were treated with anti-Fas antibody, rapid activation of growth-associated histone H1 kinase was observed without any change in cell cycle distribution. This was accompanied by the increase in cdc2 mRNA expression and Cdc2 kinase activity. Up-regulation of cdc2 mRNA was similarly induced in BCL-2-overexpressing HL-60 subline by anti-Fas treatment independently of the appearance of apoptotic phenotypes. Fas-induced apoptosis was completely inhibited by butyrolactone I, a specific inhibitor of Cdc2 kinase. Moreover, the same phenomenon was observed during Fas-induced but not spontaneous apoptosis of postmitotic granulocytes. Finally, we have found that "Fas-responsive element" was located between nucleotides -730 and -552 of the cdc2 promoter and was responsive for transcriptional activation of the cdc2 gene during Fas-induced apoptosis. These results indicate that aberrant activation of Cdc2 is associated with Fas-induced apoptosis of hematopoietic cells, and that the mechanism of cdc2 transcription during Fas-induced apoptosis is different from that in normal cell cycle control.

Apoptosis↗
PubMed1996

Skin sympathetic nerve activity and event-related potentials during auditory oddball paradigms.

Skin sympathetic nerve activity (SSNA) from the tibial nerve and event-related brain potentials (ERPs) were recorded simultaneously during auditory oddball paradigms with a counting task in 10 healthy subjects to elucidate the relationships between the autonomic nervous system and the cognitive process. After the target tones. SSNA bursts were observed more frequently than after the non-target tones. Moreover, the amplitudes of SSNA bursts elicited after the target tones were higher than those elicited after the non-target tones. However, when subjects ignored the series of tones, there was no significant difference between the incidence of SSNA bursts after rare tones and frequent tones. The P300 latencies for the target trials with SSNA bursts were shorter than those for the target trials without SSNA bursts. The average ERP wave forms for the target trials with SSNA bursts showed larger positive deflection in the early part of the P300 component than those for the target trials without SSNA bursts. We conclude that SSNA is generated in relation to the conscious cognitive process, as well as to the reactive automatic process to changes in repeating stimuli. The early part of the P300 component, possibly P3a, may be related to the mechanisms that generate SSNA.

Adult↗