Naoki Nishimura

Bio: Naoki Nishimura is an academic researcher from Aichi Medical University. The author has contributed to research in topics: Bathing & Sympathetic nervous system. The author has an hindex of 13, co-authored 47 publications receiving 527 citations. Previous affiliations of Naoki Nishimura include Nihon Fukushi University.

Adaptation to microgravity, deconditioning, and countermeasures.

Abstract: Humans are generally in standing or sitting positions on Earth during the day. The musculoskeletal system supports these positions and also allows motion. Gravity acting in the longitudinal direction of the body generates a hydrostatic pressure difference and induces footward fluid shift. The vestibular system senses the gravity of the body and reflexively controls the organs. During spaceflight or exposure to microgravity, the load on the musculoskeletal system and hydrostatic pressure difference is diminished. Thus, the skeletal muscle, particularly in the lower limbs, is atrophied, and bone minerals are lost via urinary excretion. In addition, the heart is atrophied, and the plasma volume is decreased, which may induce orthostatic intolerance. Vestibular-related control also declines; in particular, the otolith organs are more susceptible to exposure to microgravity than the semicircular canals. Using an advanced resistive exercise device with administration of bisphosphonate is an effective countermeasure against bone deconditioning. However, atrophy of skeletal muscle and the heart has not been completely prevented. Further ingenuity is needed in designing countermeasures for muscular, cardiovascular, and vestibular dysfunctions.

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

Abstract: 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.

Effects of repeated carbon dioxide-rich water bathing on core temperature, cutaneous blood flow and thermal sensation.

Abstract: We examined the effects of repeated artificial CO2 (1,000 ppm) bathing on tympanic temperature (Tty), cutaneous blood flow, and thermal sensation in six healthy males. Each subject was immersed in CO2-rich water at a temperature of 34°C up to the level of the diaphragm for 20 min. The CO2-rich water was prepared using a multi-layered composite hollow-fiber membrane. The CO2 bathing was performed consecutively for 5 days. As a control study, subjects bathed in fresh water at 34°C under the same conditions. Tty was significantly lowered during CO2 bathing (P<0.05). Cutaneous blood flow in the immersed skin (right forearm) was significantly increased during CO2 bathing compared with that during fresh-water bathing (P<0.05), whereas cutaneous blood flow in the non-immersed skin (chest) was not different between CO2 and fresh-water bathing. Subjects reported a "warm" sensation during the CO2 bathing, whereas they reported a "neutral" sensation during the fresh-water bathing. The effects of the repeated CO2 bathing were not obvious for core temperature and cutaneous blood flow, but the thermal sensation score during the CO2 bathing was reduced sequentially by repeated CO2 bathing (P<0.05). These thermal effects of CO2 bathing could be ascribed largely to the direct action of CO2 on vascular smooth muscles and to the activity of thermoreceptors in the skin. Serial CO2 bathing may influence the activity of thermoreceptors in the skin.

The effects of facial fanning on thermal comfort sensation during hyperthermia.

Abstract: We studied how facial fanning during hyperthermia improves the thermal comfort sensation. Experiments were carried out on ten male subjects. They were immersed in hot water at 40°C for 45 min. At 20 min and 35 min, fanning (1 m·s–1) was applied to their faces for 5 min. Core temperature (Tc) measured as esophageal temperature (Tes) and tympanic temperature (Tty) continued to rise during the immersion, but temporarily decreased during fanning with a delay of 2 or 3 min. Skin temperatures (Ts) on the forehead and cheek continued to increase slightly during immersion, but decreased immediately after the start of fanning. During immersion before face fanning, the time trend of thermal sensation towards the warm level was similar to that of skin temperature on the face, whereas the time trend of thermal comfort ratings towards the uncomfortable level was similar to that of Tc. The scores of both thermal sensation and thermal comfort were reduced significantly immediately after the start of fanning, and their time courses were different to those of Ts and Tty. These results support previous reports that thermal sensation depends on skin temperature, and that thermal comfort depends on both the skin and core temperatures. Moreover, they indicate that both thermal sensation and comfort ratings are affected by the dynamic responses of the cutaneous thermoreceptors when fanning is applied to the face during hyperthermia.

Treatment of patients with acquired idiopathic generalized anhidrosis.

Abstract: 1 Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417:949–54. 2 Long GV, Menzies AM, Nagrial A et al. Clinico-pathologic correlates of BRAF mutation status in 207 consecutive patients with metastatic melanoma. J Clin Oncol 2010; 28:15S (suppl.; abstr. 8548) presented at the ASCO Annual Meeting, 4–8 June 2010, Chicago, IL, U.S.A. 3 Jakob JA, Bassett RL, Ng CS et al. Clinical characteristics and outcomes associated with BRAF and NRAS mutations in metastatic melanoma. J Clin Oncol 2011; 29(suppl.; abstr. 8500) presented at the ASCO Annual Meeting, 3–7 June 2011, Chicago, IL, U.S.A. 4 Dienstmann R, Tabernero J. BRAF as a target for cancer therapy. Anticancer Agents Med Chem 2011; 11:285–95. 5 Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364:2507–16. 6 U.S. Food and Drug Administration News Release. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm268241.htm (last accessed 2 July 2012). 7 Infante JR, Falchook GS, Lawrence DP et al. Phase I ⁄ II study to assess safety, pharmacokinetics, and efficacy of the oral MEK 1 ⁄2 inhibitor GSK 1120212 (GSK212) dosed in combination with the oral BRAF inhibitor GSK 2118436 (GSK 436). J Clin Oncol 2011; 29 (suppl.; abstr. CRA8503) presented at the ASCO Annual Meeting, 3–7 June 2011, Chicago, IL, U.S.A. 8 Benlloch S, Paya A, Alenda C et al. Detection of BRAF V600E mutation in colorectal cancer. Comparison of automatic sequencing and real-time chemistry methodology. J Mol Diagn 2006; 8:540–3. 9 Pichler M, Balic M, Stadelmeyer E et al. Evaluation of high-resolution melting analysis as a diagnostic tool to detect the BRAF V600E mutation in colorectal tumors. J Mol Diagn 2009; 11:140–7. 10 Carbonell P, Turpin MC, Torres-Moreno D et al. Comparison of allelic discrimination by dHPLC, HRM, and TaqMan in the detection of BRAF mutation V600E. J Mol Diagn 2011; 13:467–73. 11 Fusi A, Berdel R, Havemann S et al. Enhanced detection of BRAFmutants by pre-PCR cleavage of wild-type sequences revealed circulating melanoma cells heterogeneity. Eur J Cancer 2011; 47:1971– 6. 12 Houben R, Becker JC, Kappel A et al. Constitutive activation of the Ras-Raf signalling pathway in metastatic melanoma is associated with poor prognosis. J Carcinog 2004; 3:6. 13 Yancovitz M, Litterman A, Yoon J et al. Intraand inter-tumor heterogeneity of BRAF (V600E) mutations in primary and metastatic melanoma. PLoS ONE 2012; 7:e29336.

How to assess sympathetic activity in humans.

Abstract: Sympathetic factors play a central role not only in cardiovascular homeostatic control but also in the pathogenesis and/or in the progression of several cardiovascular diseases, such as essential hypertension, myocardial infarction, cardiac arrhythmias and congestive heart failure. This explains why assessment of adrenergic neural function in humans has been, and certainly still remains, one of the major fields in cardiovascular research. The present paper will review in detail the haemodynamic, pharmacological, biochemical, neurophysiological, neurochemical and neural imaging techniques by which sympathetic activity is assessed in humans, highlighting the main advantages and limitations of each of them. Although plasma noradrenaline measurement represents a useful guide to assess sympathetic neural function, direct recording of sympathetic nerve traffic via microneurography and noradrenaline radiotracer methods have in recent years largely supplanted the plasma noradrenaline approach. This is because they allow (1) discrimination between the central or peripheral nature of increased plasma noradrenaline levels, and (2) precise estimation of the behaviour of regional sympathetic neural function both under physiological and pathological conditions. In contrast, the approach based on spectral analysis of heart rate and blood pressure signals has been shown to have important limitations which prevent the method from faithfully reflecting sympathetic cardiovascular drive. Neural imaging techniques, which require expensive technical support, allow direct visualization of sympathetic enervation of human organs, thus providing information on the 'in vivo' metabolism of noradrenaline in different cardiovascular districts. Although technical improvements have allowed a more precise assessment of human adrenergic function, no technique so far available can be viewed as a 'gold standard' with which the others might be compared. Limitations and disadvantages of the various techniques may be reduced if these methods are seen as being complementary and employed in combination, allowing more reliable information to be achieved on the sympathetic abnormalities characterizing cardiovascular diseases, and thus hopefully providing a stronger rationale for newer therapeutic approaches involving pharmacological modification of the sympathetic nervous system and adrenoreceptors.

In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges

Abstract: This review focuses on the neural and local mechanisms that have been demonstrated to effect cutaneous vasodilation and vasoconstriction in response to heat and cold stress in vivo in humans. First, our present understanding of the mechanisms by which sympathetic cholinergic nerves mediate cutaneous active vasodilation during reflex responses to whole body heating is discussed. These mechanisms include roles for cotransmission as well as nitric oxide (NO). Next, the mechanisms by which sympathetic noradrenergic nerves mediate cutaneous active vasoconstriction during whole body cooling are reviewed, including cotransmission by neuropeptide Y (NPY) acting through NPY Y1 receptors. Subsequently, current concepts for the mechanisms that effect local cutaneous vascular responses to direct skin warming are examined. These mechanisms include the roles of temperature-sensitive afferent neurons as well as NO in causing vasodilation during local heating of skin. This section is followed by a review of the mechanisms that cause local cutaneous vasoconstriction in response to direct cooling of the skin, including the dependence of these responses on intact sensory and sympathetic, noradrenergic innervation as well as roles for nonneural mechanisms. Finally, unresolved issues that warrant further research on mechanisms that control cutaneous vascular responses to heating and cooling are discussed.

Cutaneous vasodilator and vasoconstrictor mechanisms in temperature regulation.

Abstract: In this review, we focus on significant developments in our understanding of the mechanisms that control the cutaneous vasculature in humans, with emphasis on the literature of the last half-century To provide a background for subsequent sections, we review methods of measurement and techniques of importance in elucidating control mechanisms for studying skin blood flow In addition, the anatomy of the skin relevant to its thermoregulatory function is outlined The mechanisms by which sympathetic nerves mediate cutaneous active vasodilation during whole body heating and cutaneous vasoconstriction during whole body cooling are reviewed, including discussions of mechanisms involving cotransmission, NO, and other effectors Current concepts for the mechanisms that effect local cutaneous vascular responses to local skin warming and cooling are examined, including the roles of temperature sensitive afferent neurons as well as NO and other mediators Factors that can modulate control mechanisms of the cutaneous vasculature, such as gender, aging, and clinical conditions, are discussed, as are nonthermoregulatory reflex modifiers of thermoregulatory cutaneous vascular responses

Neural control and mechanisms of eccrine sweating during heat stress and exercise

Abstract: In humans, evaporative heat loss from eccrine sweat glands is critical for thermoregulation during exercise and/or exposure to hot environmental conditions, particularly when environmental temperature is greater than skin temperature. Since the time of the ancient Greeks, the significance of sweating has been recognized, whereas our understanding of the mechanisms and controllers of sweating has largely developed during the past century. This review initially focuses on the basic mechanisms of eccrine sweat secretion during heat stress and/or exercise along with a review of the primary controllers of thermoregulatory sweating (i.e., internal and skin temperatures). This is followed by a review of key nonthermal factors associated with prolonged heat stress and exercise that have been proposed to modulate the sweating response. Finally, mechanisms pertaining to the effects of heat acclimation and microgravity exposure are presented.