Structural mutations in the p53 gene are seen in virtually every form of human cancer. To determine whether such mutations are important for initiating tumorigenesis, we have been studying hepatocellular carcinoma, in which most cases are associated with chronic hepatitis B virus infections. Using a transgenic mouse model where expression of a single HBV gene product, the HBx protein, induces progressive changes in the liver, we show that tumour development correlates precisely with p53 binding to HBx in the cytoplasm and complete blockage of p53 entry into the nucleus. Analysis of tumour cell DNA shows no evidence for p53 mutation, except in advanced tumours where a small proportion of cells may have acquired specific base substitutions. Our results suggest that genetic changes in p53 are late events which may contribute to tumour progression.

To examine sex- and menstrual cycle-related differences in thermoregulatory responses to heat exposure, ten young women and six young men were heated passively by immersing their legs in water heated to 42 degrees C for 60 min (in ambient conditions of 30 degrees C and 45% relative humidity). The women underwent heat exposure during the mid-follicular (F) and mid-luteal (L) phases of the menstrual cycle, which were confirmed by assaying plasma female reproductive hormones. The rectal and mean body (T(b)) temperatures of women in the L phase were significantly greater than those of women in the F phase and of men during a pre-heating equilibration period (28 degrees C) and during heat exposure. During heat exposure, the local sweat rates (m(sw)) on the forehead, chest, back, and forearm of women in either phase were significantly lower than those of men, but the thigh (m(sw)) was similar to that of men. The m(sw) did not change at any site during the different phases of the menstrual cycle. The cutaneous blood flow (%LDF) was significantly greater on the thigh for women in either phase compared with men, but no difference was found at any other site (forehead, chest, back, and forearm). The %LDF on the back was significantly greater for women in the L phase than in the F phase, but those at other sites were similar in both phases. We conclude that, compared with men, heat loss from women depends more on cutaneous vasodilation (especially on the thigh) than on sweating, irrespective of the phase of the menstrual cycle. This phenomenon was due to peripheral mechanisms, as reflected in the greater slope of the relationship between %LDF and T(b) lower slope of the relationship between m(sw)) and frequency of sweat expulsion, and lower sweat output per gland. The menstrual cycle modified the T(b) threshold for vasodilation and sweat onset in women. Therefore, the sex difference in the T(b) threshold was more marked for women during the L phase than during the F phase. Moreover, the menstrual cycle modified the slope of the relationship between %LDF on the back and T(b).

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Eight older (60-65 years) and six younger (20-25 years) men were exposed to a standard heat stress for 60 min in summer, autumn, winter, and spring. The test consisted of placing the lower legs and feet in a 42 degrees C water bath while sitting in constant environmental conditions (30 degrees C and 45% relative humidity). The increase of rectal temperature (delta Tre) was significantly greater (P < 0.05) in autumn, winter, and spring than in summer for the older group, but significantly greater only in winter than in summer for the younger group (P < 0.05). The delta Tre was greater for the older group in all seasons, but of significance only in autumn and spring (P < 0.01). There were no significant season-related differences for metabolic heat production (M) and mean skin temperature (Tsk) during the heat test in the respective groups, although the M and Tsk were lower for the older group in all seasons (P < 0.01). In the older group total body sweating rate (msw) divided by delta Tre (total msw/delta Tre) decreased from summer to winter (P < 0.02) and did not differ between winter and spring, whereas total msw/delta Tre in the younger group increased in spring after decreasing from autumn to winter (P < 0.03). The variations of the value, local sweating rate on the back and thigh divided by delta Tre (back msw/delta Tre and thigh msw/delta Tre), were similar to those of the total msw/delta Tre in each group, except for back msw/delta Tre in the younger group, which did not increase from winter to spring.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose -The aim of this study is to explore the influence of the clothing ventilation in three body regions on the humidity of the local clothing microclimates under five work-shirts immediately after the onset of sweating in light exercise. Design/methodology/approach -The clothing microclimate ventilations were measured at chest, back and upper arm using a manikin. Separate wear trials were performed to determine the sweat production and the humidity of the clothing microclimate at the same locations as where the ventilation was measured during light exercise. Findings -Every shirt shows the greatest value of ventilation index (VI) for the chest and the smallest one for the upper arm. The values of VI differ remarkably at the chest among the five shirts. Comfort sensation became gradually worse as the time passed after starting exercise. There was no significant difference among the clothing conditions in mean values of rectal temperature, local skin temperatures, microclimate temperatures, microclimate relative humidities and local sweat rates at three regions over 10 min after the onset of sweating. A relationship was observed between the ratio of the mean moisture concentration in the clothing microclimate to the mean sweat rate at the chest and the back and the VI. Originality/value -The results suggest that clothing ventilation should be measured in different body regions in response to sweat rates in corresponding regions.

To examine the mechanisms underlying the age-related decrement in the ability to sweat, seven older (64-76 years) and seven younger (20-24 years) men participated in a 60-min sweating test. The test consisted of placing the subject's lower legs in a water bath at 42 degrees C while sitting in a controlled environment of 35 degrees C ambient temperature and 45% relative humidity. The rectal (Trc) and skin temperatures, local sweating rates (m(sw): on the forehead, chest, back, forearm and thigh) and the frequency of sweat expulsion (f(sw)) were measured during the test. No group difference was observed in the mean body temperature (Tb) throughout the passive heating, although the older men had a higher Tre and a lower mean skin temperature during the last half of the 60-min test. There were no group differences in the Tb threshold for sweating, although the time to the onset of sweating tended to be longer for the older men regardless of body site. The m(sw) increased gradually for approximately 35 min after the start of heat exposure in the older men and for 30 min in the younger men and then reached a steady state. During the first half of the test, the older men had a significantly lower m(sw) at all sites. During the last half of the test, only m(sw) on the thigh was significantly lower in the older men than in the younger men. There was no group difference in the slope of f(sw) versus Tb (an indicator of the change in the central sudomotor response to thermal input). The slope of m(sw) versus f(sw) (an indicator of the change in peripheral activity in response to central sudomotor changes) was significantly lower on the thigh in the older men, but there were no differences for the other sites. These results suggest that in older men the lower thigh m(sw) observed during the last half of the heat test was possibly due to age-related modifications of peripheral mechanisms involving the sweat glands and surrounding tissues. It was not due to a change in the central drive to sudomotor function. Furthermore, the sluggish m(sw) responses in the older men appear to have been related to age-related modifications of the sensitivity of thermoreceptors in various body regions to thermal stimuli. They may also involve lower sweat glands' sensitivity to cholinergic stimulus or sluggish vasodilatation, and do not reflect age-related changes in the central drive.

Nine young (20-25 years) and ten older (60-71 years) men, matched for body fatness and surface area:mass ratio, underwent cold tests in summer and winter. The cold tests consisted of a 60-min exposure, wearing only swimming trunks, to an air temperature of 17 degrees C (both seasons) and 12 degrees C (winter only). Rectal (Tre) and mean skin (Tsk) temperatures, metabolic heat production (M), systolic (BPs) and diastolic (BPd) blood pressures and heart rate (fc) were measured. During the equilibrium period (28 degrees C air temperature) there were no age-related differences in Tre, Tsk, BPs, BPd, or fc regardless of season, although M of the older men was significantly lower (P < 0.003). The decrease in Tre and Tsk (due to the marked decrease in six of the older men) and the increase in BPs and BPd were significantly greater (P < 0.004) for the older men during all the cold exposures. The rate of increase in M was significantly greater (P < 0.01) for the older group when exposed to 12 degrees C in winter and 17 degrees C in summer (due to the marked increase in four of the older men). This trend was not apparent during the 17 degrees C exposure in winter. There was no age-related difference in fc during the exposures. Significant decreases in Tre and Tsk and increases in M, BPs and BPd during the 12 degrees C exposure were observed for the older group (P < 0.003) compared to their responses during the 17 degrees C exposure in winter. In contrast, Tre, M, BPs in the young group were not affected as much by the colder environment. It was concluded that older men have more variable responses and some appear more or less responsive to mild and moderate cold air than young men.

PurposeThe present study examined sex differences in the sweat gland response to acetylcholine (ACh) in physically trained and untrained male and female subjects.MethodsSweating responses were induced on the forearm and thigh in resting subjects by ACh iontophoresis using a 10% solution at 2 mA for 5 min at 26°C and 50% relative humidity.ResultsThe ACh-induced sweating rate (SR) on the forearm and thigh was greater in physically trained male (P < 0.001 for the forearm and thigh, respectively) and female (P = 0.08 for the forearm, P < 0.001 for the thigh) subjects than in untrained subjects of both sexes. The SR was also significantly greater in physically trained males compared to females at both sites (P < 0.001) and in untrained males compared to females on the thigh (P < 0.02) only, although the degree of difference was greater in trained subjects than in untrained subjects. These sex differences can be attributed to the difference in sweat output per gland rather than the number of activated sweat glands.ConclusionWe conclude that physical training enhances the ACh-induced SR in both sexes but that the degree of enhancement is greater in male than in female subjects. The effects of physical training and sex on the SR may be due to changes in peripheral sensitivity to ACh and/or sweat gland size.