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Biomedical subjects

H Nose

Publications and source records attributed to H Nose.

At least 19 recordsLinked to original sources

Thermoregulatory and aerobic changes after endurance training in a hypobaric hypoxic and warm environment.

Plasma volume (PV) expansion by endurance training and/or heat acclimatization is known to increase aerobic and thermoregulatory capacities in humans. Also, higher erythrocyte volume (EV) fractions in blood are known to improve these capacities. We tested the hypothesis that training in a hypobaric hypoxic and warm environment would increase peak aerobic power (VO(2)(peak)) and forearm skin vascular conductance (FVC) response to increased esophageal temperature (T(es)) more than training in either environment alone, by increasing both PV and EV. Twenty men were divided into four training regimens (n = 5 each): low-altitude cool (610-m altitude, 20 degrees C ambient temperature, 50% relative humidity), high-altitude cool (2,000 m, 20 degrees C), low-altitude warm (610 m, 30 degrees C), and high-altitude warm (HW; 2,000 m, 30 degrees C). They exercised on a cycle ergometer at 60% VO(2)(peak) for 1 h/day for 10 days in a climate chamber. After training, PV increased in all trials, but EV increased in only high-altitude trials (both P < 0.05). VO(2)(peak) increased in all trials (P < 0.05) but without any significant differences among trials. FVC response to increased T(es) was measured during exercise at 60% of the pretraining VO(2)(peak) at 610 m and 30 degrees C. After the training, T(es) threshold for increasing FVC decreased in warm trials (P < 0.05) but not in cool trials and was significantly lower in HW than in cool trials (P < 0.05). The slope of FVC increase/T(es) increase increased in all trials (P < 0.05) except for high-altitude cool (P > 0.4) and was significantly higher in HW than in cool trials (P < 0.05). Thus, against our hypothesis, the VO(2)(peak) for HW did not increase more than in other trials. Moreover, slope of FVC increase/T(es) increase in HW increased most, despite the similar increase in blood volume, suggesting that factors other than blood volume were involved in the highest FVC response in HW.

Adult↗

Effect of acute hypoxia on vasopressin release and intravascular fluid during dynamic exercise in humans.

To test the hypothesis that acute hypoxia does not modify the relationship between plasma vasopressin concentration ([AVP](p)) and plasma osmolality (P(osmol)) during exercise and that the increase in [AVP](p) during exercise is due mainly to the exercise intensity-dependent increase in P(osmol), we examined [AVP](p) during a graded exercise in a hypoxic condition (13% O(2), N(2) balance) in seven healthy male subjects. A graded exercise in a normoxic condition on a separate day served as the control. Hypoxia reduced peak aerobic power (VO(2 peak)) by 32.4 +/- 2.7%. Blood samples obtained during rest and at around 25, 45, 65, 80, and 100% of VO(2 peak) of each of the respective conditions were used for analyses of intravascular water and electrolyte balance. The pattern of the changes in fluid and electrolyte balance in response to percent VO(2 peak) was similar between the two conditions. Plasma volume decreased linearly as percent VO(2 peak) increased while P(osmol) increased in a curvilinear fashion with a steep increase occurring at above approximately 66% VO(2 peak). Above this relative exercise intensity, plasma sodium, potassium, and lactate concentrations also increased, whereas plasma bicarbonate concentration decreased. Thus transvascular fluid movement at above approximately 66% VO(2 peak) was due to the net efflux of hypotonic fluid out of the vascular space in both conditions. The relationship between [AVP](p) and P(osmol) during exercise in response to relative exercise intensity was similar between the two conditions. The results indicate that acute mild hypoxia itself has no direct effect on vasopressin release, and it does not modify the relationship between [AVP](p) and P(osmol) during exercise. The results also support the hypothesis that exercise-induced vasopressin release is primarily stimulated by increased P(osmol) produced by hypotonic fluid movement out of the vascular space in a relative exercise intensity-dependent manner.

Acute Disease↗

Plasma lactate concentration and muscle blood flow during dynamic exercise with negative-pressure breathing.

This study assessed the hypothesis that increasing cardiac filling pressure (CFP) would enhance contracting muscle blood flow (MBF) by stretching cardiopulmonary baroreceptors and attenuate the increase in plasma lactate concentration ([Lac(-)](p)) during dynamic exercise. Continuous negative-pressure breathing (CNPB) (-15 cmH(2)O) was used to increase the CFP by accelerating the venous return to the heart. In the first series of experiments, 10 men performed a graded exercise seated on a cycle ergometer with (N1) and without CNPB (C1). The increase in [Lac(-)](p) for N1 was attenuated at 60%, 90%, and 100% of maximal exercise intensity compared with that in C1 (P < 0.001). Also, the increases in mean arterial pressure (MAP) and plasma catecholamine concentrations were attenuated in N1 compared with those in C1 throughout the graded exercise (P < 0.05). However, heart rate and pulse pressure were not significantly influenced by CNPB. Second, we studied the impact of CNPB on forearm MBF during a rhythmic handgrip exercise in 5 of the 10 subjects. Forearm MBF was measured immediately after cessation of the exercise by venous occlusion plethysmography at rest, 30%, 50%, and 70% of maximal work load (WL(max)) with (N2) and without CNPB (C2). Forearm MBF and vascular conductance for both trials increased with the increase in intensity, but forearm skin blood flow measured by laser-Doppler flowmetry remained unchanged. MBF and vascular conductance in N2, however, increased more than in C2 at every intensity (P < 0.01) except for MBF at 70% WL(max), whereas the increase in MAP for N2 was attenuated compared with that in C2 (P < 0.05). Thus augmented active muscle vasodilation occurred in N2 with a lower increase in MAP compared with that in C2. These findings suggest that the stretch of intrathoracic baroreceptors, such as cardiopulmonary mechanoreceptors, by CNPB increased MBF by suppressing sympathetic nerve activity. The attenuation of the increase in [Lac(-)](p) might be caused, at least partially, by the increased MBF.

Adult↗

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. I. Taxonomy of producing strain, fermentation, isolation and biological activities.

Two novel antifungal antibiotics, PF1163A and B, were isolated from the fermentation broth of Penicillium sp. They were purified from the solid cultures of rice media using ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies. PF1163A and B showed potent growth inhibitory activity against pathogenic fungal strain Candida albicans but did not show cytotoxic activity against mammalian cells. These compounds inhibited the ergosterol biosynthesis in Candida albicans.

Antifungal Agents↗

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. II. Physico-chemical properties and structure elucidation.

The structures of new antifungal antibiotics, PF1163A and B, were elucidated by spectroscopic analyses of the degradation products and by X-ray crystallography of the de-2-hydroxyethyl derivative of PF1163B. Both antibiotics consist of a 13-membered macrocyclic structure containing a derivative of N-methyl tyrosine and a hydroxy fatty acid. PF1163A differs from PF 1163B by having an additional hydroxyl group on the side chain.

Antifungal Agents↗

Comparison between tail skin blood flow measurements by ultrasonic Doppler flowmetry and plethysmography during heating in anesthetized rats.

Tail skin blood flow (TBFu) was directly measured in anesthetized and passively heated rats by ultrasonic Doppler flowmetry during heating, and the values were compared to those (TBFp) simultaneously measured by venous-occlusion plethysmography. TBFp was estimated from the values per unit tissue multiplied by the tail volume, the shape of which was assumed to be a cone. TBFp was highly correlated with TBFu, with a regression equation of TBFp = 0.7TBFu+0.1 (r2 = 0. 94, p<0.001). Although TBFp was slightly lower than TBFu, the equation is useful to estimate the absolute values of tail skin blood flow from the values of plethysmography in awake rats.

Anesthesia↗

Role of plasma osmolality in the delayed onset of thermal cutaneous vasodilation during exercise in humans.

To elucidate the role of increased plasma osmolality (Posmol), which occurs during exercise in the regulation of cutaneous vasodilation (CVD) during exercise, we determined the relationship between the change in esophageal temperature (DeltaTes) required to elicit CVD (DeltaTes threshold for CVD) and Posmol during light and moderate exercise (30 and 55% of peak oxygen consumption, respectively) and passive body heating. Then we compared the relationship with the data obtained in our previous study [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto. Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R197-R204, 1997], in which we determined the relationships during passive body heating following isotonic (0.9% NaCl) or hypertonic (2 or 3% NaCl) saline infusions in the same subjects. Posmol values at 5 min after the onset of exercise were 287.5 +/- 0.9 mosmol/kgH2O during light exercise and 293.0 +/- 1.2 mosmol/kgH2O during moderate exercise. Posmol just before passive body heating was 289.9 +/- 1.4 mosmol/kgH2O. The DeltaTes threshold for CVD was 0.09 +/- 0.05 degrees C during light exercise, 0.31 +/- 0. 09 degrees C during moderate exercise, and 0.10 +/- 0.05 degrees C during passive body heating. The relationship between the DeltaTes threshold for CVD and Posmol was shown to be on the same regression line both during exercise and during passive body heating with or without infusions [A. Takamata, K. Nagashima, H. Nose, and T. Morimoto. Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R197-R204, 1997]. Our data suggest that the elevated body core temperature threshold for CVD during exercise could be the result of increased Posmol induced by exercise and is not due to reduced plasma volume or the intensity of the exercise itself.

Adult↗

Plasma hyperosmolality and arterial pressure regulation during heating in dehydrated and awake rats.

To gain better insights into the effect of dehydration on thermal and cardiovascular regulation during hyperthermia, we examined these regulatory responses during body heating in rats under isosmotic hypovolemia and hyperosmotic hypovolemia. Rats were divided into four groups: normovolemic and isosmotic (C), hypovolemic and isosmotic [L, plasma volume loss (DeltaPV) = -20% of control], hypovolemic and less hyperosmotic [HL1, increase in plasma osmolality (DeltaPosm) = 23 mosmol/kgH2O, DeltaPV = -16%], and hypovolemic and more hyperosmotic (HL2, DeltaPosm = 52 mosmol/kgH2O, DeltaPV = -17%). Hyperosmolality was attained by subcutaneous injection of hypertonic saline and hypovolemia by intra-arterial injection of furosemide before heating. Then rats were placed in a thermocontrolled box (35 degreesC air temperature, approximately 20% relative humidity) for 1-2 h until rectal temperatures (Tre) reached 40.0 degreesC. Mean arterial pressure in L decreased with rise in Tre (P < 0.001), whereas mean arterial pressure remained constant in the other groups. Maximal tail skin blood flow in L, HL1, and HL2 was decreased to approximately 30% of that in C (P < 0. 001). Tre threshold for tail skin vasodilation (TVD) was not changed in L, whereas the threshold shifted higher in the HL groups. Tre threshold for TVD was highly correlated with Posm (r = 0.94, P < 0. 001). Heart rate in the HL groups increased with rise in Tre (P < 0. 001), whereas it remained unchanged in C and L. Cardiovascular responses to heating were not influenced by V1 antagonist in C, L, and HL2. Thus isotonic hypovolemia attenuates maximal tail skin blood flow, whereas hypertonic hypovolemia causes an upward shift of Tre threshold for TVD and an increase in heart rate during hyperthermia. These results suggest that plasma hyperosmolality stimulates pressor responses in the hypovolemic condition that subsequently contribute to arterial pressure regulation during heat stress.

Animals↗

Effect of continuous negative-pressure breathing on skin blood flow during exercise in a hot environment.

To assess the impact of continuous negative-pressure breathing (CNPB) on the regulation of skin blood flow, we measured forearm blood flow (FBF) by venous-occlusion plethysmography and laser-Doppler flow (LDF) at the anterior chest during exercise in a hot environment (ambient temperature = 30 degreesC, relative humidity = approximately 30%). Seven male subjects exercised in the upright position at an intensity of 60% peak oxygen consumption rate for 40 min with and without CNPB after 20 min of exercise. The esophageal temperature (Tes) in both conditions increased to 38.1 degreesC by the end of exercise, without any significant differences between the two trials. Mean arterial pressure (MAP) increased by approximately 15 mmHg by 8 min of exercise, without any significant difference between the two trials before CNPB. However, CNPB reduced MAP by approximately 10 mmHg after 24 min of exercise (P < 0.05). The increase in FBF and LDF in the control condition leveled off after 18 min of exercise above a Tes of 37.7 degreesC, whereas in the CNPB trial the increase continued, with a rise in Tes despite the decrease in MAP. These results suggest that CNPB enhances vasodilation of skin above a Tes of approximately 38 degrees C by stretching intrathoracic baroreceptors such as cardiopulmonary baroreceptors.

Adult↗

Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma.

BACKGROUND: Radiotherapy plus bolus 5-fluorouracil (5-FU) is generally accepted as the standard treatment for locally advanced pancreatic carcinoma. To intensify the antitumor effect of chemotherapy, the authors administered protracted 5-FU infusion with concurrent radiotherapy. The aim of this study was to determine the feasibility and effectiveness of this combined therapy. METHODS: Twenty patients, all of whom had histologically confirmed exocrine pancreatic carcinoma that was nonresectable but confined to the pancreatic region, were enrolled in a Phase II trial of protracted 5-fluorouracil infusion (200 mg/m2/day) with concurrent radiotherapy (50.4 gray in 28 fractions over 5.5 weeks). Chemotherapy began on the first day of radiation and continued through the entire radiation course. Thereafter, weekly infusions (500 mg/m2) were administered until disease progression. RESULTS: Of the 20 patients, 17 (85%) completed the scheduled course of chemoradiotherapy. Grade 3 or worse toxicity, graded according to World Health Organization criteria, was observed in 4 patients (20%). Two patients (10%) achieved partial response, and disease remained stable in 16 patients (80%). After the completion of combined therapy, serum CA 19-9 levels were reduced by more than 50% in 10 of 12 patients (83%) who had pretreatment CA 19-9 levels of 100 U/mL or greater. The median progression free survival and 1-year progression free survival rate were 4.9 months and 29.5%, respectively. The median overall survival and 1-year overall survival rate were 10.3 months and 41.8%, respectively. CONCLUSIONS: This treatment showed moderate activity against locally advanced pancreatic carcinoma and was accompanied by an acceptable toxicity level.

Adenocarcinoma↗

Negative pressure breathing and the control of skin blood flow during exercise in a hot environment.

Factors which modify the relationship between body temperature and skin blood flow during exercise in heat were studied. Direct measurement of right atrial pressure during exercise in heat showed that the leveling off of forearm blood flow took place when blood temperature exceeded 38 degrees C and central venous pressure was lower than 6.3 mm Hg. Continuous negative pressure breathing increased the forearm and chest blood flow and the esophageal temperature at which leveling off was observed shifted from 37.7 degrees C to 38.0 degrees C. When the leveling off temperature was compared between subjects with high and low blood volume, the subject with low blood volume showed the leveling off of forearm blood flow at a temperature of 37.6 degrees C, while it was 38.0 degrees C in the subject with high blood volume. All these results suggest the involvement of cardiopulmonary mechanoreceptors, while further studies are required to clarify the mechanism which the leveling off of skin blood flow is observed at 38 degrees C of body temperature.

Adult↗

Evidence for increased somatic cell mutations in patients with hepatocellular carcinoma.

The measurement of somatic cell mutation may assist in the assessment of human cancer risk. The glycophorin A (GPA) assay, which measures the frequency of variant erythrocytes in persons with blood type MN, was used to directly assess in vivo mutability in 30 patients with hepatocellular carcinoma (HCC). HCC patients showed significantly increased frequencies of both hemizygous (MO) and homozygous (MM) variants, due to somatic loss of expression of the N allele, when compared with 27 patients with chronic liver disease and 21 healthy controls. The mean elevations of the MO and MM variant frequencies (VF) in HCC patients were 2-3-fold greater than the comparable VF in the control groups. The mean MO and MM VF in the patients with chronic liver disease was slightly elevated compared to that in healthy controls, but the difference was not significant. In the 19 anti-hepatitis C virus (HCV)-positive patients with a history of blood transfusion, significant linear relations between VF and the duration of HCV infection were observed for MO and MM. These data indicate a high background frequency of somatic mutations in HCC patients. The GPA assay may prove to be a useful estimation of the individual's risk of development of HCC.

Carcinoma, Hepatocellular↗

Relationship between aerobic power, blood volume, and thermoregulatory responses to exercise-heat stress.

To clarify the relationship between aerobic power (VO2max), blood volume (BV), and thermoregulatory responses to exercise-heat stress, we analyzed the cross-sectional relationship between the resting BV, plasma volume (PV), erythrocyte volume (EV), VO2max, forearm blood flow (FBF), and sweating responses during exercise in a hot environment (31 degrees C, 50% relative humidity). Twelve college-aged male subjects with a mean maximal oxygen uptake of 48 (range 42-59) mL.kg-1.min-1, a mean PV of 54 (range 42-72) mL.kg-1, a mean EV of 31 (range 23-43) mL.kg-1, and a mean BV of 85 (range 67-115) mL.kg-1 (measured by the Evans Blue dye dilution method) performed three sessions of 20-min cycle exercise at two levels of intensity (40% and 60% VO2max). The BV, PV and EV correlated positively with peak FBF (r = 0.596-0.711, P < 0.05), the increase of FBF in response to a unit rise in esophageal temperature (Tes; peak delta FBF/peak delta Tes) (r = 0.592-0.656, P < 0.05) and with total sweat loss (TSL) (r = 0.599-0.634, P < 0.05) during the exercise. The VO2max correlated with TSL during exercise at 40% VO2max (r = 0.578, P < 0.05), but not with peak FBF and peak delta FBF/peak delta Tes. The VO2max per lean body mass also showed a significant positive correlation with BV (r = 0.769, P < 0.01), PV (r = 0.706, P < 0.05), and with EV (r = 0.841, P < 0.001). The peak delta FBF/peak delta Tes was correlated positively with peak FBF (r = 0.597-0.830, P < 0.05-0.01) and negatively with peak Tes (r = 0.641-0.769, P < 0.05-0.01) during the exercise at the two levels. However, the chest sweat rate (CSR), TSL, and the increase of CSR in response to a unit rise in Tes (peak delta CSR/peak delta Tes) showed no correlation with peak Tes during the exercise at the two levels. These findings suggest that 1) heat dissipation responses during exercise were related more to blood volume than aerobic power and 2) skin blood flow was related more to body temperature than sweating responses during exercise under mild heat stress.

Adolescent↗

Osmoregulatory inhibition of thermally induced cutaneous vasodilation in passively heated humans.

We examined the effect of increased plasma osmolality (P(osm)) on cutaneous vasodilatory response to increased esophageal temperature (T(es)) in passively heated human subjects (n = 6). To modify P(osm), subjects were infused with 0.9, 2, or 3% NaCl infusions (Inf) for 90 min on separate days. Infusion rates were 0.2, 0.15, and 0.125 ml.min-1.kg body wt-1 for 0.9, 2, and 3% Inf, respectively, which produced relatively similar plasma volume expansion. Thirty minutes after the end of infusion, subjects immersed their lower legs in a water bath at 42 degrees C (room temperature 28 degrees C) for 60 min after 10 min of preheating control measurements. Passive heating without infusion (NI) served as time control to account for the effect of volume expansion. P(osm) (mosmol/kgH2O) values at the onset of passive heating were 289.9 +/- 1.4, 292.1 +/- 0.6, 298.7 +/- 0.7, and 305.6 +/- 0.6 after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively. The increases in T(es) (delta T(es)) at equilibrium during passive heating (mean delta T(es) during 55-60 min) were 0.47 +/- 0.08, 0.59 +/- 0.08, 0.85 +/- 0.13, and 1.09 +/- 0.12 degrees C after NI, 0.9% Inf, 2% Inf, and 3% Inf, respectively, which indicates that T(es) at equilibrium increased linearly as P(osm) increased. delta T(es) required to elicit cutaneous vasodilation (delta T(es) threshold for cutaneous vasodilation) also increased linearly as P(osm) increased as well as the delta T(es) threshold for sweating. The calculated increases in these thresholds per unit rise in P(osm) from regression analysis were 0.044 degree C for the cutaneous vasodilation and 0.034 degree C for sweating. Thus the delta T(es) thresholds for cutaneous vasodilation and sweating are shifted to higher delta T(es) along with the increase in P(osm), and these shifts resulted in the higher increase in T(es) during passive heating.

Adult↗

Segmental difference of water and electrolyte transport in rat colon in vivo.

The segmental difference of water and electrolyte transport in the rat colon was studied in vivo. The proximal and distal colon segments were perfused separately but simultaneously at a constant rate with physiological solution, and net movements of water, sodium and chloride were determined. The effects of osmolality and sodium concentration of perfusate were assessed. The effect of a sodium channel blocker on the net transport of water and electrolytes was also studied in each colon segment. The net absorption of water, sodium and chloride correlated with the sodium concentration and osmolality of the perfusion solution in both colon segments and were dominant in the distal colon segment in each condition, compared with that in the proximal colon segment. The concentrations of three electrolytes in the collected fluid were almost the same as those of the perfusion solutions in both segments and these results indicated that water was transported isotonically through the colon lumen. Benzamil, a specific sodium ion channel blocker, inhibited net water and sodium absorption by 58.8% and 63.1% in the proximal colon segment and by 52.0% and 43.6% in the distal colon segment, respectively. These results suggest the existence of an electrogenic sodium transport mechanism and a paracellular pathway in normal (i.e., not treated with corticosteroids or sodium-depleted food) rats which has not been detected in in vitro studies with both apical and basolateral membrane vesicles.

Amiloride↗

Local recurrence of hepatocellular carcinoma after percutaneous ethanol injection.

BACKGROUND: Percutaneous ethanol injection (PEI) therapy is now widely used for small hepatocellular carcinomas (HCC). However, only limited information is available regarding local tumor recurrence after PEI treatment. METHODS: We investigated the relationship of pretreatment clinicopathologic variables (tumor size, tumor cell differentiation and tumor staining) to local recurrence in 170 PEI-treated HCC nodules (measuring 5-39 mm in greatest dimension) in 84 patients. RESULTS: Local recurrence was observed in 17 of 170 PEI-treated nodules. Among these, 13 local recurrences were observed as the first event of progression after PEI. Local recurrence rates at 1, 2, and 4 years were 6.6%, 14.2%, and 14.2%, respectively, and all recurrences were observed within 2 years after PEI. Of the 3 variables investigated, large tumor size (31 mm or larger in greatest dimension) was significantly associated with a higher local recurrence rate. CONCLUSIONS: This study demonstrated that tumor size influences the local efficacy of PEI for small HCC. Therefore, we recommend that a reasonable indication for PEI therapy is HCC lesions measuring less than 30 mm in greatest dimension.

Antineoplastic Agents↗