When living cells are exposed to non-lethal heat shock, they acquire a transient resistance to an otherwise lethal heat challenge as determined by the increase in cell survival. This phenomenon is termed thermotolerance. The non-lethal heat shock is also known to induce a family of proteins, called heat-shock or stress proteins (hsps). Recently, some hsps (especially hsp70) have been shown to have molecular chaperoning activity and play a role in protection of proteins from heat denaturation and in repair of heat-denatured proteins. From a general conceptual view, the mechanism of thermotolerance may involve protection from initial damage or better repair of similar levels of initial damage or some combination of both. Heat-induced “damage” seems to be protein denaturation, since protein denaturation (conformational change) could be observed above 38.7°C using differential scanning calorimetry. Several parameters of cellular functions and structures such as protein synthesis, RNA synthesis, and cytoskeletons are known to become transiently thermotolerant by prior mild non-lethal heat shock. This is considered to be due to protective effect of heat-shock proteins. These types of thermotolerance, however, decay by 24 hours after conditioning heating. Clonogenic thermotolerance is still near maximum at this time and decays more slowly. On the other hand, recovery of protein synthesis and RNA synthesis after challenge heating is faster in thermotolerant cells than in non-tolerant cells. Also, the extent of clonogenic thermotolerance is well correlated with the recovery rate of protein and RNA synthesis. Therefore, it seems that thermotolerant cells which contain elevated level of heat-shock proteins have higher protective activity and better repair function than non-tolerant cells. Thus, the phenomenon of thermotolerance can be interpreted based on the molecular chaperoning activities of heat-shock proteins.

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[in Japanese]

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To study the vascular endothelial cell injury under hyperthermia, human umbilical vein endothelial cells (HUVEC) were incubated for 60 min between 0°C and 50°C. Then, their morphological change, cell injury and their production of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were examined. The results were as follows.
1. Morphological changes of HUVEC were observed by heating between 40°C and 43°C. Intercelluar space of HUVEC became wider and shape of HUVEC became round according to the increase of heating temperature.
2. From the experiment with fluorescent Fura-2, heat injury of HUVEC was deteced above 43°C.
3. Production of PAI-1 increased in HUVEC incubated at 40°C with significant difference and significantly decreased at 50°C. Production of tPA slightly increased in HUVEC incubated at 40°C and significantly decreased at 50°C.
4. The presence of PAI-1 in HUVEC was demonstrated by immunohistochemical blotting method against anti-human PAI-1 antibody.
In the present experiment the critical temperature of HUVEC was demonstrated to be 43°C, similarly in the previous data of clotting and fibrinolytic parameters. The fact that injury of HUVEC and increase of PAI-1 induced DIC, strongly supports our previous reports that whole body-heated rabbits show the symptoms of DIC.

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The combined effect of 5-FU, DP, and HT was investigated both in vitro and in vivo. When HeLa and B16 melanoma cells were exposed concomitantly ti heat (43' C, 40min) and DP (2.5 μg/ml), the cytotoxicity of 5-FU (0.1 μg/ml) was sugnificantly enhanced determined with colonergic assay. SDI test also revealed that this trimodality treatment was more cytotoxic to B16 melanoma cells and human cancer tissues than 5-FU alone.
Growth of B16 melanoma that had been implanted subcutaneously was inhibited by DP (100mg/kg), and 5-FU (13.2mg/kg), when compared with 5-FU alone.
Hyperthermia (HT) and dipyridamole (DP) augment the cytotoxicity of 5-fluorouracil (5-FU) in vitro and in vivo. The combination therapy of 5-FU, DP and HT is thought to be useful toward malignant diseases.

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The thermal damage to the normal tongue was studied. Fortyone hamsters were devided into single heating group (SH) at 42°C, 43°C and 44°C each for 20min. and 40 min., repeated heating group (RH) at 42°C for 40 min. 4 times for 2 weeks, and sham group (SG) with a sensor inserted into the tongue. The tongue was heated by the 13.56 MHz RF capasitive heating system with a pair of applicators 10 mm in diameter filled with jelly.
In SH at 42°C for 20 min., slight to moderate redness and/or swelling were observed and the reaction increased slightly after heating for 40 min. The occurence of moderate redness increased in SH at 43°C for 20min., and the 40 min. heating resulted in the formation of vesicle, erosion and deep ulcer. In SH at 44°C for 20 min., necrosis of more or less than 50% of the heated region was observed, the necrosis involved more than 50% or all of the heated region after 40 min heating.
In RH, slight to moderate redness of the first heating remained until the second heating, but erosion was the severest damage encountered after the successive procedures. In SG, slight redness was observed.
In conclusion, single heating at 42°C was tolerated by the tongue and a little damage and no cumulative effect were noted by repeated heating at 42°C.

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There are more and more devices around us which employ great electric current or magnet thus generate strong magnetic fields. In effect, there is a increasing tendency for people not only those exercise the special profession but also those spend ordinary life to be exposed to the magnetic field.
This paper is aimed at investigating the influence of strong magnetic fields through observing the heartbeat variations of the loaches. By laying loaches under stationary magnetic field with a maximum of 1.8 T for several hours, the heartbeat of the loaches decreases to about 21 beats/min., while that of the control is about 26 beats/min.. Moreover, the variation of heartbeat is independent from the strength of the magnetic field and the exposed time, while the time that the influence of magnetic field on the heartbeat remains is a function of the strength of the magnetic field and the exposed time. Such influence dosen't appear for weak magnetic field or short exposed time.
As a result, it is reasonable to say that when an organism is exposed to a strong stationary magnetic field, the circulatory system of which suffers some influence. Discussion on the reason of the influence is not carried out in the paper.

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[in Japanese]

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We evaluated the effect of induced whole-body hyperthermia on renal tissue blood flow in dogs by the hydrogen clearance technique. The heart rate increased significantly at 41°C and above, whereas blood pressure decreased significantly at 43°C. Cardiac output increased significantly at 41°C and above, whereas renal arterial blood flow tended to decrease above 41°C. Although renal cortical tissue blood flow significantly decreased at 42°C, renal medullary tissue blood flow showed no marked changes with increasing temperature. Redistribution of blood flow within the kidney was therefore apparent during hyperthermia. A significant decrease was observed in the partial pressure of oxygen in arterial blood, as well as in oxygen saturation of arterial, renal venous, and central venous blood, suggesting that hypoxia also may have occurred in the kidneys. Several animals showed an increase in the ratio of thromboxane B₂ to 6-keto-PGF₁ α in renal venous blood at 42°C. These data indicate that renal injury during hyperthermia may result from decreased tissue blood flow in the renal cortex and hypoxia in renal tissue. Furthermore, metabolites of arachidonic acid, such as thromboxanes, may help to mediate the changes in tissue blood flow.

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