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C Mukai

Publications and source records attributed to C Mukai.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sympathetic outflow to muscle in humans during short periods of microgravity produced by parabolic flight.

We have investigated the changes in muscle sympathetic nerve activity (MSNA) from the tibial nerve during brief periods of microgravity (microG) for approximately 20 s produced by parabolic flight. MSNA was recorded microneurographically from 13 quietly seated human subjects with their knee joints extended in a jet aircraft simultaneously with the electrocardiogram, the blood pressure wave (measured with a Finapres), the respiration curve, and the thoracic fluid volume (measured by impedance plethysmography). During quiet and seated parabolic flight, MSNA was activated in hypergravity and was suppressed in microG phasically. At the entry to hypergravity at 2 G just before microG, the thoracic fluid volume was reduced by 3.2 +/- 3%, and the arterial blood pressure was lowered transiently and then gradually elevated from 89.5 +/- 1.7 to 100.2 +/- 1.7 mmHg, which caused the enhancement of MSNA by 91.4 +/- 14.2%. At the entry to microG, the thoracic fluid volume was increased by 3.4%, which lowered the mean blood pressure to 77.9 +/- 2.3 mmHg and suppressed the MSNA by 17.2%. However, this suppression lasted only approximately 10 s, followed by an enhancement of MSNA that continued for several seconds. We conclude that MSNA is suppressed and then enhanced during microG produced by parabolic flight. These changes in MSNA are in response not only to intrathoracic fluid volume changes but also to arterial blood pressure changes, both of which are caused by body fluid shifts induced by parabolic flight, and these changes are quite phasic and transient.

Adult↗
PubMed1999

Sensitivity of shuttle vector plasmid pZ189 DNA to carbon ion beams.

The sensitivity of shuttle vector plasmid pZ189 DNA to carbon ion beams was studied under dry conditions. This plasmid contains the supF gene that can be used in mutagenesis analysis. The survival curve of the plasmid had both a shoulder and exponential parts, and showed a D10 value of about 17 kGy for both Escherichia coli wild-type and DNA repair-deficient mutant (UV-sensitive) strains. Therefore, it was assumed that the excision repair system was not effective for repairing DNA lesions induced by irradiation with carbon ion beams.

Carbon↗
PubMed1999

Space flight modulates signal transduction pathway of growth factor receptors in rat osteoblasts.

Bone metabolism is regulated by the balance of bone formation and resorption. Osteoblasts serves primarily for bone formation. Microgravity deteriorates osteoblastic function and inhibit bone formation. Growth factors regulate osteoblast function via receptors. Binding of EGF and PDGF to the receptors activates receptor tyrosine kinase and rapid association of adapter proteins Shc and Grb2, and evokes the Ras/MAP kinase cascade. Signals from various chemical and physical stimuli are transmitted to the nucleus, and induce c-fos and c-jun gene expression. However, effects of microgravity on the molecular events in osteoblasts remain unknown. The purpose of this study is to investigate the mRNA levels for PDGF-beta receptor, EGF receptor, Shc, and c-fos in rat osteoblasts during space flight.

Animals↗
PubMed1999

Frequency distribution of axon diameters in the left aortic nerve of the rat raised in space--Neurolab Program.

INTRODUCTION: To study development of the aortic baroreflex mechanisms under conditions of microgravity, we carried out the various experiments in the neonate rats aged 25 days raised in microgravity for 16 days (flight: FLT group) in Neurolab program (STS-90, space shuttle Columbia, launch date: Apr 17, '98. Some results of the experiments were already reported. The results of histological examination of the aortic nerve which is the afferent of the aortic baroreflex showed that the number of unmyelinated fibers in FLT was significantly less in than those in two control groups and there was no difference between FLT and each control group in the analysis of myelin. In the present paper, the frequency distribution of axon diameters of the left aortic nerves in FLT was compared to that in two ground control groups to examine the growth of the aortic nerve fibers in space. METHODS: After breeding Sprague-Dawley rats for 16 days in the shuttle in space and in the animal center in the Kennedy space center, a total of 43 deeply anesthetized rats were perfused with 1% parahormaldehyde and 1% glutaraldehyde or 4% parahormaldehyde solution buffered at pH7.4 with 0.12 M phosphate solution. Concerning the control groups, one group was the asynchronous ground control (AGC) group in which the rats were housed in the same cages as those on the shuttle, and the other was the vivarium ground control (VIV) group in which the rats were housed in commercial cages. The cervical region of the left aortic nerve which is a branch of the vagus was cut off and stored in the same fixative as that used for perfusion, and postfixed in the solution of 1% OsO4, for 2 hours within 24 hours after the perfusion. The fixed specimens were embedded in epoxy resin blocks by the usual method for electron microscopy following dehydration. Electron microscopic montages of transverse sections of these nerve trunks were made from the five left aortic nerves in each group. The magnification of the montages was approximately 13400 times. The long and short axes (a and b) of the nerve fibers and the myelin thickness (T) were measured with a caliper and the axon diameters (R were calculated by following formula: R2=[(a-2T)2+(b-2T)2]/2.

Animals↗
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↗
PubMed1998

Room temperature-induced apoptosis of Jurkat cells sensitive to both caspase-1 and caspase-3 inhibitors.

We recently reported that HL-60 cells underwent apoptosis when exposed to room temperature (RT) (21 degrees C). RT-induced apoptosis of HL-60 cells is inhibited by the caspase-1 inhibitor (YVAD-CMK), but not by the caspase-3 inhibitor (DEVD-CHO). In this study, we studied RT-induced apoptosis in 15 human cell lines of hematopoietic lineage and found that the Jurkat cell line also responded to RT by a different apoptotic process. RT-induced apoptosis of Jurkat cells was attenuated by YVAD-CMK as well as DEVD-CHO. Increased caspase activity on DEVD-AMC, which was inhibited by both YVAD-CMK and DEVD-CHO added to the cell culture, was also detected. The involvement of caspase-3 itself, however, was not recognized by Western blot analysis. In contrast, the processing of caspase-3 was observed in the apoptotic HL-60 cells. These data implicate the presence of the redundant processes of apoptosis induced by RT treatment.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Medical baseline data collection on bone and muscle change with space flight.

It has been documented that astronauts suffer from a progressive and continuous negative calcium balance in space flight. The National Space Development Agency of Japan (NASDA) discussed the experimental protocols with the National Aeronautics and Space Agency's (NASA's) Johnson Space Center (JSC) and has started a medical baseline collection on bone and calcium metabolism, and muscle changes with space flight. The subjects were two astronauts, a 42-year-old female and a 32-year-old male, who experienced real space flights. Fractional excretion of calcium (FECa) increased in both subjects just after the space flight. There was a negative calcium balance with urinary calcium leak even after a short flight. We also noticed a decrease (-3.0%) of bone mineral density (BMD) of the lumbar spine (L2-4), a weight bearing bone. These bone changes may be due to a negative calcium balance. However, the BMD of the skull, a nonweight bearing bone, increased after the flight. This indicates that the effect of weightlessness on bone is different in respective bones, depending on the weight loading. Our data of the bone metabolic marker clearly indicate that bone resorption is stimulated, shown by an elevation of urinary pyridinolinks and plasma tartrate-resistant acid phosphate (TRACP) activity. Bone specific alkaline phosphatase, a bone formation marker, was elevated in both subjects, but not intact osteocalcin. Whether this pathophysiological phenomenon is due to an accelerated bone resorption or suppressed bone formation is still obscure. In addition, the physiological cross-sectional area (PCSA) of muscle in the legs greatly decreased (from - 10% to -15%) after the flight, and it took over a month to be recovered in both subjects. However, the muscle volume loss in the legs seemed to be reversible. To examine bone and muscle metabolism with space flight, further investigations and international standardization of experimental protocols are necessary.

Adult↗
PubMed1998

Spaceflight modulates insulin-like growth factor binding proteins and glucocorticoid receptor in osteoblasts.

Rat osteoblasts were cultured for 4 or 5 days during a Space Shuttle mission. After 20-h treatment with 1alpha,25-dihydroxyvitamin D3, conditioned media were harvested and cellular DNA and/or RNA were fixed on board. The insulin-like growth factor binding protein (IGF BP)-3 levels in the media were three- and tenfold higher than in ground controls on the fourth and fifth flight days, as quantitated by Western ligand blotting and radioimmunoassay, respectively. The increased IGF BP-3 protein levels correlated with two- to threefold elevation of IGF BP-3 mRNA levels, obtained by reverse transcription-polymerase chain reaction. The IGF BP-5 mRNA levels in flight cultures were 33-69% lower than in ground controls. The IGF BP-4 mRNA levels in flight cultures were 75% lower than in ground controls on the fifth day but were not different on the fourth day. The glucocorticoid receptor mRNA levels in flight cultures were increased by three- to eightfold on the fourth and fifth days compared with levels in ground controls. These data suggest potential mechanisms underlying spaceflight-induced osteopenia.

Animals↗
PubMed1998

Histological analysis of the aortic nerve in the rat raised in space (Rapid communication on Neurolab Project).

To study development of the aortic nerve baroreflex under conditions of microgravity, we examined the cross section of the left aortic nerve (LAN), which is the afferent of the baroreflex, in the neonate rats aged 25 days raised in microgravity on the space shuttle Columbia (flight:FLT group) for 16 days. In this paper, we report a part of the result obtained from the data of the myelinated fibers of LAN analyzed with an electron microscope. Two kind of ground control groups were compared to the FLT group; one was asynchronous ground control (AGC) group where the rats were housed in the same cage as that on the shuttle, and the other was vivarium(VIV) group where the rats were housed in a commercial cage. The LANs in each group were extirpated the from rats perfused with a fixative and embedded for histological analysis. We observed the transverse sections of LAN and took pictures of several areas (magnified to x 2K to x 200K). No irregular myelination was found in all fibers of FLT group when they were compared with two control groups. The thickness of myelin of the maximally myelinated fibers were 0.55 +/- 0.17 micrometer in FLT(n=5), 0.45 +/- 0.10 micrometer in AGC(n=5), and O.47 +/- 0.06 micrometer meter in VIV(n=5). There was no significant difference among three groups (unpared t-test). The results suggest that there is no effect of space environment on the myelin formation of each nerve fiber in the aortic nerve.

Animals↗
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↗
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

[Analysis of flushing response to alcohol and drinking behavior in Japanese male students].

The purpose of this study is to clarify the relationship between hereditary predisposition and social-psychological factors in terms of drinking behavior of Japanese male students. The subjects were 123 male students who belonged to athletic clubs of K university in 1993. Regular drinking was evaluated as "drinking at home or with intimate friends" and party drinking as "drinking at club parties". On the two drinking occasions, the frequency and amount of drinking, and social drinking behavior were evaluated. Problem drinking behavior was investigated by a modified version of Aoyama's questionnaire (1984). Low Km aldehyde dehydrogenase (ALDH2) activity was evaluated by the facial flushing response to alcohol and the ethanol patch test. Evaluable results of the ethanol test as well as replies of the questionnaire were obtained from 109 students. Twenty-three students positive for both the facial flushing response to alcohol and the ethanol patch test were considered to be flushers, and 42 negative for both to be non-flushers. The non-flushers consumed a higher amount of alcohol than the flushers did on drinking occasions at home or with intimate friends. The number of problem drinking behavior items in the non-flushers was significantly higher than that in the flushers and increased with the amount and frequency of drinking. The ratio of students who had inappropriate drinking motivations, began to drink by themselves, or continued to offer alcohol to drinkers showing flushing even when they declined it, was significantly higher in the non-flushers than in the flushers. In addition, non-flushers showing such social drinking behavior drank more than those not showing such behavior. The frequency of positive or inappropriate drinking behavior was significantly lower in the flushers than in the non-flushers. However, the amount and frequency of drinking and problem drinking behavior were similar in the flushers and non-flushers. These results indicate that social drinking behavior of non-flushers influences not only themselves but also other drinkers, and that drinking of flushers is strongly influenced by social factors.

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↗
PubMed1996

Feeding frequency affects cultured rat pituitary cells in low gravity.

In this report, we describe the results of a rat pituitary cell culture experiment done on STS-65 in which the effect of cell feeding on the release of the six anterior pituitary hormones was studied. We found complex microgravity-related interactions between the frequency of cell feeding and the quantity and quality (i.e. biological activity) of some of the six hormones released in flight. Analyses of growth hormone (GH) released from cells into culture media on different mission days using gel filtration and ion exchange chromatography yielded qualitatively similar results between ground and flight samples. Lack of cell feeding resulted in extensive cell clumping in flight (but not ground) cultures. Vigorous fibroblast growth occurred in both ground and flight cultures fed 4 times. These results are interpreted within the context of autocrine and/or paracrine feedback interactions. Finally, the payload specialist successfully prepared a fresh trypsin solution in microgravity, detached the cells from their surface and reinserted them back into the culture chamber. These cells reattached and continued to release hormone in microgravity. In summary, this experiment shows that pituitary cells are microgravity sensitive and that coupled operations routinely associated with laboratory cell culture can also be accomplished in low gravity.

Adrenocorticotropic Hormone↗
PubMed1996

An improved quantitative RT-PCR fluorescent method for analysis of gene transcripts in the STS-65 space shuttle experiment.

We describe a reverse transcription polymerase chain reaction (RT-PCR) technique using fluorescent dUTP to examine changes in mRNA level in samples. In this procedure, the amplified product is identified by the fluorescent detection system in an automated DNA sequencer, and if the MW of the DNA/RNA or the fluorescent dye is different, several samples can be analyzed in a single lane. The basis for this technique is similar to that of radiolabeled methods, and we applied this technique for the comparison of the expression level of the rat c-myc gene in osteoblasts exposed to microgravity and unit gravity conditions. Using the fluorescent- and radiolabeled methods, the level of rat c-myc mRNA were compared quantitatively and the results demonstrated that the c-myc expression level was not altered by microgravity. Therefore, this fluorescent RT-PCR technique is useful for gene expression analysis particularly when the samples are limited, such as in space flight experiments. The method also allows for rapid assessment of mRNA changes in many samples simultaneously.

Animals↗