Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages.

Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.     

Comparison of flow capacities of arterial and venous grafts for coronary artery bypass grafting: evaluation with exercise thallium-201 single-photon emission tomography

Stress thallium-201 tomography was performed to compare the flow capacities of arterial and saphenous vein grafts in patients with coronary artery bypass grafting (CABG). One hundred and seven consecutive patients (95 male and 12 female; mean age 58±9.1 years) underwent exercise-redistribution ²⁰¹Tl myocardial single-photon emission tomography 4–5 weeks after CABG. When a reversible perfusion defect was present in the area covered by a patent bypass graft, the flow capacity of the graft was defined as insufficient. Of all 285 grafts, 211 were considered as complete bypass. Reversible perfusion defects were present in 29 (27%) of 108 myocardial areas supplied by patent arterial grafts but in only 5 (5%) of 103 myocardial areas supplied by patent saphenous vein grafts (P<0.0001). In the LAD area reversible defects were observed in 22 of 82 areas covered by arterial grafts, in contrast to only 1 of 29 areas covered by venous grafts (P<0.01); in the RCA area reversible defects were observed in 7 of 17 and 4 of 41 areas respectively (P<0.01). There was no difference between the native coronary artery stenosis bypassed by patent arterial and venous grafts (88%±12% vs 86%±14% respectively, P=0.27). In conclusion, flow capacities during peak myocardial demand were more frequently insufficient in arterial bypass grafts than in saphenous vein grafts. Received 23 May and in revised form 7 August 1997     

Clinical statistics on inpatients admitted to the Department of Urology, Hyogo Prefectural Hospital Nishinomiya during 20 years from 1972 to 1991]

A statistic analysis was carried out on the 4,956 inpatients admitted to our Department of Urology from April 1972 to December 1991. The patients included 3,399 males and 1,557 females. A total of 4,105 operations including 255 renal allotransplantations were performed on 3,590 patients. Open surgery for upper urinary tract stones has been replaced by extracorporeal shock-wave lithotripsy (ESWL) in the last three years.     

Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.     

Calorie restriction increases serum parathyroid hormone and decreases serum calcitonin levels in patients with maturity onset diabetes mellitus

Calorie restriction is important in managing patients with maturity onset diabetes mellitus (NIDDM). The effect of such restriction on calcium metabolism is not known. The objective of this study was to determine whether patients on calorie restricted diets would show any modification of parathyroid hormone (PTH) and calcitonin (CTN). The serum levels of PTH and CTN were measured by radioimmunoassays in 269 patients with NIDDM. The patients were divided into two groups depending on the intake of calorie, and PTH and CTN were monitored for 2 years. Plasma levels of vitamin D were measured by competitive protein binding assays before and after each program. The level of PTH (520.8±266.0 pg/ml) (mean±S.D.) was significantly (P<0.01) higher in 109 diabetic patients whose calorie intake was restricted for 2 years (diet (D) group) as compared with that (256.6±103.8 pg/ml) of 160 diabetic patients whose calorie intake was not restricted (non-diet (ND) group). The daily oral calcium intake of the two groups did not differ significantly. We found no significant difference in the serum PTH level in the ND groupVS. normal control subjects (248.8±98.4, N=78). The serum calcium concentration and the amount of calcium excreted in urine were slightly but significantly (P<0.01) lower in the D than in the ND group. The rate of tubular reabsorption of phosphate (% TRP) was significantly lower in the D group than that in the ND group (P<0.01). The serum CTN level was significantly (P<0.01) lower in the D group (33.9±11.3 pg/ml) than in the ND group (64.9±21.2 pg/ml) 2 years after each treatment. The plasma 1,25-(OH)₂-vitamin D level was significantly (P<0.01) lower in the D group (22.2±6.6 pg/ml) than in the ND group (50.6±4.2 pg/ml). When the restriction of calorie intake in the D group was canceled, their PTH levels decreased, which was accompanied by increase in the 1,25-(OH)₂-vitamin D levels, whereas their CTN levels were unchanged. These observations suggested that a restricted calorie intake is a risk factor for secondary hyperparathyroidism as well as for a low serum level of CTN in patients with NIDDM.     

Optimization of self-reference thermometry using complex field estimation.

Referenceless, or self-reference, thermometry is a technique for mapping temperature differences in the region of interest (ROI) using the baseline phase estimated by extrapolating the field in the surrounding region for estimation (RFE) and subtracting the estimated baseline from the measured field. In the present work a self-reference technique based on complex field estimation using 2D polynomials comprising complex-valued coefficients was proposed and optimized. Numerical simulations with a Gaussian-profiled phase distribution demonstrated that the ROI radius had to be 2.3-2.5 times the standard deviation (SD) of the Gaussian function in order to keep the error below 8% of the peak phase change. The area ratio between the ROI and the RFE had to be larger than 2.0 to maintain the error level. Based on the simulations, and phantom and volunteer experiments, the complex-based method with independently optimized polynomial orders for the two spatial dimensions was compared with the phase-based method using the similar-order optimization strategy. The complex-based method appeared to be useful when phase unwrapping was not removed. Otherwise, the phase-based method yielded equivalent results with less polynomial orders.     

Effect of Cry-consensus peptide, a novel recombinant peptide for immunotherapy of Japanese cedar pollinosis, on an experimental allergic rhinitis model in B10.S mice.

BACKGROUND: We are developing an immunotherapeutic peptide, Cry-consensus peptide, for Japanese cedar pollinosis. Cry-consensus peptide is a recombinant polypeptide containing six major human T-cell epitopes derived from both Cry j 1 and Cry j 2, two major allergens of Japanese cedar pollen. We examined the effect of Cry-consensus peptide on an allergic rhinitis model in B10.S mice, which have one common T-cell epitope in the Cry-consensus peptide. METHODS: B10.S mice were sensitized with Cry j 1/alum, then the Cry-consensus peptide was administered subcutaneously once a week for 5 weeks from the last sensitization. Histamine was dropped in both nostrils (10 microL per nostril) of each mouse on the day before continuous intranasal instillation of Cry j 1. Soon after the final challenge with Cry j 1, the mice were observed for 5 minutes for the resulting number of sneezes. In addition, serum levels of Cry j 1-specific IgE and IgG2a antibody, eosinophil infiltration in nasal tissue, and Cry j 1-specific cytokine production from splenocytes were evaluated. RESULTS: Cry-consensus peptide markedly inhibited Cry j 1-induced sneezes, eosinophil infiltration, and eosinophil peroxidase (EPO) activity in nasal tissue. Cry-consensus peptide inhibited the production of anti-Cry j 1 IgE (Th2-mediated) and significantly enhanced anti-Cry j 1 IgG2a (Th1-mediated). In cytokine production from splenocytes, Cry-consensus peptide significantly decreased in IL-4/IFN-gamma and IL-5/IFN-gamma ratios. CONCLUSIONS: It was concluded that Cry-consensus peptide effectively controlled allergic responses, which results from shifting from a Th2-dominated to a Th1-dominated immune response.