Yuko Agishi

Characteristics of pulmonary function in patients with diabetes mellitus

The incidence of pulmonary diseases among diabetics in Japan has been found to be more than 50% at death. This suggests the existence of some pulmonary risk factors. We analyzed pulmonary functions in 50 diabetics (31 males and 19 females) without overt lung disease, compared to 21 healthy male subjects of the same age (around 50 years old). Forced vital capacity and timed vital capacity were lower in diabetics (P less than 0.005). Diffusing capacity was also decreased in male diabetics (P less than 0.05). Among diabetics, a decrease in the diffusing capacity was dominant in patients with diabetic retinopathy, which correlated with an increasing duration of their diabetes. Analysis by the partial correlation method which accounts for the smoking index showed that standardized indices for peripheral airflow in male diabetics decreased significantly as the patients age increased (P less than 0.005); the rate of decrement was greater than that of the control subjects. Diabetic patients showed abnormal lung function in the peripheral airways which increased with age and gas transfer was also affected by diabetic microangiopathy as well as the duration of diabetes. These changes seemed to deteriorate progressively, possibly combining and contributing to respiratory insufficiency in critical pathological conditions.

Effect of thermal stress on glutathione metabolism in human erythrocytes.

This is the first experiment to investigate the effect of heat and cold stress on glutathione metabolism in human erythrocytes. We immersed men at three different water temperatures for 10 min. At 39°C, no remarkable changes were observed. Levels of glutathione (GSH) decreased from 2.44 (0.14) to 1.80 (0.10) μmol·ml red blood cells−1 [μmol·ml RBC−1; mean (SEM);P<0.0005] and those of lipid peroxides increased from 1.87 (0.03) to 2.06 (0.04) nmol · ml RBC−1 (P<0.01) after the immersion at 42°C. In contrast, levels of GSH increased from 2.46 (0.17) to 2.91 (0.17) μmol · ml RBC−1 (P<0.05) and those of lipid peroxides did not change after the immersion at 25°C. The activities of glutathione peroxidase decreased from 35.90 (1.83) to 34.33 (1.66) IU · g Hb−1 (P < 0.01) after the immersion at 42°C; however, these activities did not change after the immersion at 25°C. The activities of glutathione reductase (both active and inactive forms) showed no changes at any temperatures. These changes indicate that heat stress causes oxidative stress in the human body; however, cold stress is thought to augment the activity of the antioxidative defence system. It is suggested that body exposure to hot environmental conditions should not be recommended for patients suffering from a damaged antioxidative defence system.

Elevated levels of heat-shock protein 70 (HSP70) in the mononuclear cells of patients with non-insulin-dependent diabetes mellitus

Increased free radicals and reduced levels of antioxidants have been reported in diabetes mellitus. Since heat-shock protein 70 (HSP70) is a stress-induced protein and is suggested to play a protective role against oxidative stress, we have investigated whether HSP7O acts as one of the defense systems against this stress. We separated mononuclear cells from diabetic patients (N=12) and age- and sex-matched healthy controls (N =12), and detected HSP70 by western blot analysis. The results were expressed by the ratio of the density determined by laser densitometry, to that of 10 mu g of purified HSP70. HSP70 levels in the mononuclear cells of diabetic patients (0.78 + or- 0.56) were significantly high, compared with healthy subjects (0.43 + or - 0.23) (P < 0.05). No correlation was found between HSP7O and hemoglobin A1c, fasting plasma glucose, duration of diabetes or diabetic complications except age. A negative correlation was found between HSP70 and age (r = -0.658, P < 0.05). These results suggest that HSP70 levels in the mononuclear cells are elevated reflecting increased oxidative stress in patients with diabetes.

Balneotherapy and platelet glutathione metabolism in type II diabetic patients

Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG;r=0.692,P<0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG <150 mg/dl), the level increased (P<0.01) and in poorly controlled patients (FPG >150 mg/dl), the value decreased (P<0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG (r=−0.430,P<0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

INVOLVEMENT OF RAS IN THE EXPRESSION OF GLYCOLIPID SULFOTRANSFERASE IN HUMAN RENAL CANCER CELLS

Glycolipid sulfotransferase activity in a human renal cell carcinoma cell line, SMKT‐R3, is enhanced by epidermal growth factor (EGF); tyrosine kinase inhibitors suppress this enhancement. To investigate the involvement of Ras in the signal transduction pathway from the EGF receptor to the expression of glycolipid sulfotransferase, we introduced v‐H‐ras into SMKT‐R3 cells. In a quiescent state, the percent GTP bound to Ras in v‐H‐ras‐expressing cells increased about 2.5‐fold compared with control cells, suggesting that v‐Ras introduced into the renal cancer cells is in an active form without EGF stimulation. Glycolipid sulfotransferase activity in v‐H‐ras‐expressing cells was higher than in control cells. The sulfotransferase activity was affected neither by EGF nor by genistein, a tyrosine kinase inhibitor, in v‐H‐ras‐expressing cells, whereas it was enhanced by EGF and reduced by genistein in control cells. Our observations suggest that Ras mediates the regulation pathway of glycolipid sulfotransferase activity in SMKT‐R3 cells. Int. J. Cancer 71:620‐623, 1997.

Thermal stress and diabetic complications.

Activities of erythrocyte aldose reductase were compared in 34 normal subjects, 45 diabetic patients, and nine young men following immersion in water at 25, 39, and 42° C. Mean basal enzyme activity was 1.11 (SEM 0.12) U/g Hb and 2.07 (SEM 0.14) U/g Hb in normal controls and diabetic patients, respectively (P<0.0001). Activities of the enzyme showed a good correlation with hemaglobin A1 (HbA1) concentrations (P<0.01) but not with fasting plasma glucose concentrations. After immersion at 42° C for 10 min, enzyme activity was increased by 37.6% (P<0.01); however, the activity decreased by 52.2% (P<0.005) after immersion for 10 min at 39° C and by 47.0% (P<0.05) at 25° C. These changes suggest that heat stress might aggravate diabetic complications, and body exposure to hot environmental conditions is not recommended for diabetic patients.

Improvement of respiratory resistance by hot water immersing exercise in adult asthmatic patients

Acute effect of hot water immersing exercise on respiratory resistance (RR) was investigated in 12 adult asthmatics and six healthy males. They underwent mild exercise with comparable heart rates (HR = 120) in a hot water pool (water temp. 38°C) for 10 minutes. RRs were measured before and until 40 minutes after the exercise. Mean RRs of the patients before exercise (0.36 Kpa/l/s) reduced to less than 0.32 during 15 to 30 minutes after exercise (p<0.05). RRs of healthy subjects (0.19 Kpa/l/s) did not decrease significantly. Analysis of humoral factors relating to exercise metabolism and autonomic nervous system function of the patients suggested that the influence of sympathetic nervous activation persisted until 20 minutes after exercise. This physiotherapy had a specific feasibility for adult asthmatics in preventing exercise-induced wheezing.

Climatotherapy in Japan: a pilot study

Twenty-nine urban inhabitants participated in a half-day climatotherapy programme at the moderate mountain area and lowland area in the northwest part of the main island of Japan. The current study was aimed to investigate physically and mentally the objective and subjective influence of our short programme, which was a prospective pilot study of single intervention. Blood pressure was significantly descended during terrain cure at the uphill mountain path and returned after fresh-air rest cure, while there was no significant change throughout the programme at lowland flat path. Heart rate was significantly ascended and descended at both area, and more clearly changed at the mountain path. Profile of Mood Status brief form Japanese version administered before and after our half-day programme. Age adjusted T score of negative subscales, ‘tension-anxiety’, ‘depression’, ‘anger-hostility’, ‘fatigue’ and ‘confusion’ were significantly lower after climatotherapy at both sites. Whereas, there was no significant change concerning ‘vigour’ score. This short-version climatotherapy programme has been designed for people without enough time for long stay at health resort. It turned out our half-day climatotherapy programme contribute to mood status improvement. In addition, repeated practice of our short-version programme including endurance exercise with cool body shell using uphill path can be expected that blood pressure will go toward the normal range and heart rate will decrease both in usual time and during exercise. Therefore, health benefits can be expected of this climatotherapy programme.

Kältevasokonstriktion, Kältedilatation und reaktive Hyperämie der Haut, dargestellt anhand der Laser-Doppler-Flußmessung

Der Einsatz der Laser-Doppler-Flusmessung hat sich auch in der hydrotherapeutischen Forschung zur Frage der Objektivierung von thermisch ausgelosten Effekten im kutanen Gefassystem bewahrt. Die in der vorliegenden Arbeit dargestellten Versuchsergebnisse beruhen auf kleinflachigen lokalen Abkuhlungen mittels einer mit verschieden temperiertem Wasser perfundierten Thermode. Dabei wurden an definierten Messtellen periphere gefasregulatorische Vorgange, wie Kaltevasokonstriktion, -dilatation und reaktive Hyperamie, sowie Durchblutungsgrad und Vasomotion an 10 gesunden Versuchspersonen untersucht.