Interleukin-1 up-regulates transcription of its own receptor in a human fibroblast cell line TIG-1: role of endogenous PGE2 and cAMP.

The regulation of interleukin-1 receptor (IL-1R) mRNA expression by IL-1 in a human lung fibroblast cell line (TIG-1) was investigated. After 2 h of stimulation with human recombinant IL-1 alpha or IL-1 beta, the levels of T cell/fibroblast-type IL-1R mRNA increased, and the elevation was sustained for at least 72 h. IL-1 also stimulated synthesis of prostaglandin E2 (PGE2) and secondary cAMP accumulation. Exogenously added PGE2 increased the levels of both IL-1R mRNA and intracellular cAMP. Forskolin, cholera toxin and 8-Bromo adenosine (8-Br-cAMP) all increased IL-1R mRNA levels. Indomethacin blocked IL-1 stimulation of IL-1R mRNA expression, PGE2 production and cAMP. 125I-labeled IL-1 alpha-binding studies showed that this cell line expresses 2.6 x 10(4) IL-1R per cell with a Kd of 5.1 x 10(-10) M. After treatment of the cells with IL-1, the level of IL-1R increased over that of control cells. PGE2 also increased IL-1R without alteration in its affinity. Cross-linking experiments indicate that this cell line expresses the 80-kDa receptor molecule before and after treatment with PGE2; the molecular mass corresponds to the T cell/fibroblast type I IL-1R. These results indicate that IL-1 does not directly stimulate expression of IL-1R mRNA or cell surface IL-1R, but only indirectly by stimulation of endogenous PGE2.     

NASOGALLBLADDER DRAINAGE FOR MIRIZZI’S SYNDROME

The authors experienced a case of Mirizzi’s syndrome successfully treated with endoscopic nasogallbladder drainage (ENGBD). The patient was a 63‐year‐old man. He was admitted with abdominal pain and jaundice. Laboratory data indicated leukocytosis and elevation of serum bilirubin level. Abdominal ultrasound showed marked swelling of gallbladder and debris in the gallbladder, therefore, the authors strongly suspected Mirizzi’s syndrome. He had past history of acute myocardial infarction and treated with anticoagulation therapy. Then, the authors couldn’t perform surgical removal or percutaneous transhepatic drainage, and tried endoscopic transpapillary drainage. Endoscopic retrograde cholangiopancreatography revealed smooth stricture in the superior portion of common bile duct and occlusion of the cystic duct, and ENGBD was then performed. After ENGBD, his complaints, laboratory data, swelling of gallbladder and stricture of common bile duct were all remarkably improved.     

DIURNAL RHYTHM OF SERUM gM-SEMINOPROTEIN IN PATIENTS WITH UNTREATED PROSTATE CANCER: COMPARISON OF THE ORIGINAL AND REVISED ASSAY KITS

To compare levels of y-seminoprotein (gM-Sm) assayed by original and revised assay systems, blood was obtained every 4 h over a 32-h period from 8 untreated prostate cancer patients. Serum levels of prostate specific antigen (PSA) were also examined. In 6 patients, the coefficient of variation (CV) of the serum levels assayed by the revised assay was significantly different from that of the intra-assay samples. In contrast, the CV of the gM-Sm serum levels assayed by the original assay differed significantly from that of the intra-assay samples in only 2 patients. The fluctuations in gM-Sm assayed by the revised assay were, at least in part, similar to those of the PSA serum levels in all patients. The mean CV of the gM-Sm serum levels assayed by the revised assay was significantly larger than that for levels measured by the original assay. After treatment, the rate of decrease in gM-Sm serum levels determined by the original assay differed from that in the serum levels of PSA and prostatic acid phosphatase. These results indicate that the original assay for gM-Sm do not detect diurnal differences in serum gM-Sm levels, even at levels below 20 ng/ml. These observations indicate that the analysis of data obtained using the original gM-Sm kit should be interpreted with caution.     

Increase in the proportion of granulated CD56+ T cells in patients with malignancy.

Evidence is presented for the existence of a unique T cell population which expressed one of the natural killer (NK) markers, CD56 antigen, in humans. Although such CD56+ T cells were a minor population in the peripheral blood (< 10%), they were abundant in the liver (up to 50%), which was recently demonstrated to be a major organ for extrathymic T cell differentiation in mice. As in the case of extrathymic T cells in mice, these CD56+ T cells in humans contained a higher proportion of gamma delta T cells than did CD56- T cells, contained double-negative CD4-8- cells, and had the morphology of large granular lymphocytes. This unique population of CD56+ T cells tended to be elevated in the blood and among tumour-infiltrating lymphocytes in patients with colorectal cancer, especially in advanced cases. These results raise the possibility that, as in mice, CD56+ T cells with extrathymic T cell properties may also be associated with tumour immunity in humans.     

Simple method for the identification of oxidative fibers in skeletal muscle

Skeletal muscle is composed of several different types of myofiber: slow oxidative (SO), fast glycolytic oxidative and fast glycolytic. However, the classification is usually determined by myosin heavy chain typing rather than by metabolic index. In this study, the oxidative metabolic index was investigated as a possible method of myofiber typing. Myoglobin, which is involved in oxygen transport and storage in myofibers, and mitochondria, which are the central organelles for oxidative metabolism, were studied. High levels of myoglobin and mitochondria are believed to exist in SO fibers, but the current study showed that they are considerably richer in some fast type fibers. As myofiber typing using the oxidative metabolic index is important physiologically, an attempt was made to find a simple method for this purpose. Some mitochondrial proteins have been observed to auto-fluoresce but until now this effect was too faint to detect easily. Owing to the recent advances in cooling charge-coupled device technology, such auto-fluorescence can now be used for myofiber typing, and the simple and rapid method for doing so is reported here.     

Validation of ECRHS Questionnaire in Japanese to use for nation-wide prevalence study of adult asthma]

PURPOSE: To enable international comparison of prevalence in asthma, we translated and evaluated ECRHS Questionnaire, which is introduced in GINA. Considering COPD prevalence in elder people, we added two questions to the ECRHS Questionnaire. METHOD: The Japanese edition of ECRHS Questionnaire was responded by 366 patients who were diagnosed asthma without COPD, 61 patients who were diagnosed COPD without asthma, and 137 healthy persons who were not diagnosed asthma or COPD. We analyzed the answers of the each group and evaluated the validity of the questionnaire to use for the nation-wide prevalence study of adult asthma in future. RESULTS: The question of 'Wheezing at any time in the last 12 months' had the highest Youden's index and validity to pick up asthma patients. The questions of 'Waking up with a feeling of tightness in chest at any time in the last 12 months' and 'Waking up by an attack of shortness of breath at any time in the last 12 month' had the highest specificity to pick up asthma patients. Most of the questions which were related asthma were able to be answered by asthma patients properly, but some questions were improperly answered by patients and healthy persons in elderly. The results in this study showed the less recognition of their diseases in elderly patients than younger patients and the limitation of the study with written questionnaire for elderly people. Not a few COPD patients complained wheezing or whistling in the chests as same as asthma patients in this study. CONCLUSION: We concluded that we had almost enough reliability in the Japanese edition of the ECRHS questionnaire for screening survey of asthma prevalence in Japan.     

Effects of aerobic exercise conditioning at intensities corresponding to lactate threshold in the elderly

Summary In this study we attempted to determine the effects of exercise training at the intensity corresponding to lactate threshold (Th_la ^–) on various health-related variables in sedentary but apparently healthy elderly subjects. Six men and five women volunteers [mean age 68.9 (SD 3.4) years] performed supervised endurance-type training on stationary cycle ergometers for 30 min and recreational activities for 30 min, 3 days a week for 12 weeks. Four men and four women served as the control group [68.8 (SD 4.4) years]. As a result of the training programme, statistically significant increases in maximal oxygen consumption (10%), oxygen consumption at Th_la ^–(18%), distance covered in 12-min walk, side step, and leg extensor power were found in the training group, while no changes occurred in the control group. The changes in serum cholesterol and triglyceride concentrations from the pre- to post-training period were statistically significant. High-density lipoprotein cholesterol remained unchanged, and low-density lipoprotein cholesterol tended to decrease following the training programme. These data would indicate that exercise training at the intensity corresponding to Th_la ^–may have favourable effects on overall physical fitness and some serum lipid variables in older individuals.     

Flow-Cytometric Analysis of Human Basophil Degranulation

Quantification of human basophils and their degranulation were performed using a flow-cytometric system. It was shown that the number of basophils among total leukocytes, before and after the effect of degranulating agents, can be obtained rapidly and reproducibly, following alcian blue, staining. Dose-response curves of degranulation by anti-IgE and anti-IgG₄ were studied, and it was shown that these antibodies can induce basophil degranulation in a Ca⁺⁺ dependent manner. It was also shown that degranulation is completed within 10 min.
Values obtained by flow-cytometry and microscopic evaluation, as well as comparison made between percent basophil degranulation and percent histamine release, agreed well with each other in our system. Flow-cytometric analysis of human basophil degranulation provides a new reliable method to assess in vitro the morphological basis of immediate hyper-sensitivity.     

Stimulation of tumour necrosis factor-alpha production by recombinant human erythropoietin may contribute to failure of therapy

Although the mechanism of unresponsiveness to recombinant human erythropoietin therapy in dialysis patients has been studied extensively in recent years, many aspects remain unclear. We previously found that administration of erythropoietin induces interleukin-1beta, a cytokine that inhibits erythropoiesis. The present study investigated the involvement of tumour necrosis factor-alpha, another cytokine which inhibits erythropoiesis. Peripheral blood mononuclear cells were obtained from 18 patients on continuous ambulatory peritoneal dialysis, who were being treated with erythropoietin for renal anaemia, and were cultured with various concentrations of erythropoietin (0, 1, 5, 10, and 50 U/ml). Then the tumour necrosis factor-alpha level in the culture supernatant was assayed. The 18 patients were divided into four groups on the basis of the haematocrit after treatment: group A (n = 3), <23.0%; group B (n = 5), 23.0-24.9%; group C (n = 7), 25.0-26.9%; and group D (n = 3), > or =27.0%. In group A, the tumour necrosis factor-alpha level in the culture supernatant was increased by incubation with erythropoietin, while it was not increased in other groups. The tumour necrosis factor-alpha level was significantly higher in group A than in the other groups at erythropoietin concentrations of 5 U/ml. These results suggested that induction of tumour necrosis factor-alpha is one of the reasons for unresponsiveness to recombinant human erythropoietin.