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Biomedical subjects

S Sakaguchi

Publications and source records attributed to S Sakaguchi.

At least 235 records · Page 13Linked to original sources

[Immunological study of beryllium workers].

Immunological health surveys of Beryllium (Be) workers in a copper-beryllium casting factory were made 10 times during the 5-year period from 1981 to 1985. The total number of Be workers was 150. 1) Macrophage migration inhibition test was performed by an agarose plate method using Be as antigen with peritoneal cells from guinea pigs and small amounts of Be worker's blood. We found that 1 out of 22 healthy Be workers (4.5%) that migration index (MI) was below 80% after 24 h and 5 (22.7%) after 48 h. The mean of MI in Be workers showed significant low value as compared with that of the control group (p less than 0.01). 2) It was found that the serum complement titer tended to be lower in Be workers than in the control group. The serum complement titer of 3 to 6 subjects showed to be less than 30 U/ml every survey. 3) Although a few showed the abnormal levels in serum immunoglobin (IgG, IgA and IgE), the means of these immunoglobin levels were not markedly changed and they were in the normal ranges, respectively. 4) MI values significantly correlated with IgE level in Be workers, that is y= -8.9 x + 997.8 (r = -0.473, p less than 0.05). These results suggest that macrophage migration inhibition test and serum complement titer were of value for assaying of sensitivity to Be and immune responses in Be workers.

Beryllium↗

[Intrahepatic cholangio-jejunostomy in patients with unresectable carcinoma of the biliary tract and pancreas].

We have experienced 59 jaundiced patients with unresectable carcinoma of the biliary tract or pancreas in our institute for 7 years and 6 months. A side-to-side anastomosis between a bile duct in the segment III of the liver and jejunum by Roux-en Y manner was preferred as a palliative internal drainage operation in 13 cases out of them. The operative procedure was described in details. There was no operative death. The postoperative complications occurred in 4 cases, 2 at early and 2 at late phase, respectively. However, they were all recovered within a short period. Mean survival time after the surgery was 8.9 months. The longest survivor died of primary lesion at 25.5 months. In 6 out of 7 patients who survived more than 6 months, performance status was improved after surgery. Indication of this surgery was discussed based on our experiences. It should be emphasized that good palliation may be expected by this procedure for unresectable carcinoma of the biliary tract or pancreas.

Adult↗

[An experimental study on the pathophysiology of stenosis and occlusion in portal vein reconstruction in resection of cancer of the hepatic hilus].

An experimental study using mature mongrel dogs was performed to clarify the pathophysiology of stenosis and occlusion of portal vein reconstruction accompanied with hepatectomy. All the animals underwent partial (53%) hepatectomy. They were arbitrarily divided into three groups: Non-stenosis Group I with hepatectomy only, Stenosis Group II with partial '70%) stenosis of the portal vein, and Occlusion Group III with ligation of the portal vein. All cases of Group III died within about 122 minutes. The blood flow and pressure of the portal vein, portography, ICG Rmax and the residual liver weight were serially examined until the fourth week following the operation in Group I and Group II. Two principal results were derived: 1) In Group I, portal circulation was sufficiently restored and the residual liver showed adequate regeneration. 2) In Group II, hepatofugal collateral vessels developed. However, the portal pressure remained significantly high (p less than 0.002) and, the portal blood flow and liver tissue blood flow were markedly reduced (p less than 0.001) for 1 week after operation. The residual liver weight and liver function (ICG Rmax) were significantly decreased even in the fourth week. Recently, portal vein resection accompanied with hepatectomy has been accepted as a procedure for advanced carcinoma of the hepatic hilus. This study suggests that stenosis or occlusion of the portal vein should be avoided in the procedure.

Animals↗

Surgery of the portal vein in resection of cancer of the hepatic hilus.

Resectability of cancer that has invaded the hepatic hilus is still very low, mainly because of the invasion of the cancer to the confluence of the portal veins. Resection of the tumor with right hepatic trisegmentectomy accompanied by resection of the portal vein invaded by the tumor was performed on three patients suffering from cancer of the intrahepatic bile duct, two with cancer of the upper bile duct and three with cancer of the gallbladder. Reconstruction of the portal vein was achieved by end-to-end anastomosis between the left hepatic branch and the trunk, except in one patient in whom an autovein was grafted. There was one postoperative death. There were no unpleasant symptoms caused by portal vein reconstruction in the remaining patients and there was one case of long survival (55 months). Although the significance of this surgery for patient survival is not yet clear, the procedure may elevate the rate of resectability of advanced cancer invading the hepatic hilus. The indication and special technical points of the procedure are described.

Adult↗

Fibrinogenolysis and fibrinolysis in normal volunteers and patients with thrombosis after infusion of urokinase.

We have studied the effects of urokinase (UK) on concentration changes of alpha 2 antiplasmin (alpha 2 AP) and on fibrino(geno)lysis. Medium dose (480,000 u) or large dose (960,000 u) of UK was given to each of seven normal volunteers by intravenous drip infusion within six hours, and then blood and urine analyses were carried out. Total alpha 2 AP, which includes free alpha 2 AP and alpha 2 AP-plasmin complex, decreased to about 50% of the original value with large dose of UK. alpha 2 AP-plasmin complex appeared in the plasma one hr after UK infusion and increased up to 50% of total alpha 2 AP at the end of UK infusion. B beta peptides, which are liberated from fibrin(ogen) at the very early stage of fibrino(geno)lysis, increased significantly with UK infusion, and was 65 times as much as the normal range at the end of UK infusion. Urinary B beta peptides increased as well as plasma B beta peptides. On the other hand, fibrin(ogen) degradation products (FDP) measured with enzyme immunoassay (EIA) increased only slightly, and moreover, urinary FDP was not detectable at any time. Plasma fibrinogen levels did not decrease and changed within the normal range in both groups. We then gave 960,000 u of UK to four patients with deep vein thrombosis and blood analyses were carried out as with normal volunteers. The most significant observation different from that of normal volunteers was shown in FDP levels. Serum FDP levels of four patients increased significantly in comparison with normal volunteers. Urinary FDP increased as significantly as plasma FDP. In conclusion, the infusion of 960,000 u of UK caused only very early stage of fibrinogenolysis without advanced fibrinogenolysis in normal volunteers, but in thrombotic patients, advanced fibrinolysis was observed.

Fibrinogen↗

Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease.

Organ-specific autoimmune diseases such as oophoritis, gastritis, thyroiditis, and orchitis were induced in female or male nude (nu/nu) mice by the transfer of nu/+spleen cells from which particular Lyt T cell subset(s) had been removed: nu/+spleen cells treated with anti-Lyt-1 plus complement (C) caused disease in recipient nude mice; anti-Lyt-2 plus C-treated spleen cells, in contrast, did not. The cells responsible for disease induction are believed to be Thy-1+, Lyt-1-, 2,3- (Thy-1, Lyt-1, 2,3), since spleen cells treated with mixed antisera, including anti-Lyt-1 and anti-Lyt-2, plus C, could induce the disease with almost the same incidence as anti-Lyt-1 plus C-treated cells (oophoritis 50%, gastritis 25%, thyroiditis 10-20%, and orchitis 40%). Cells treated with mixed antisera of anti-Thy-1, anti-Lyt-1, and anti-Lyt-2, plus C, could not induce autoimmune disease. Each induced autoimmune disease could be adoptively transferred to other nude mice via spleen cells, with resulting histological lesion of corresponding organs and development of specific circulating autoantibodies. Since anti-Thy-1 plus C treatment of donor spleen cells abrogated the capacity to transfer the disease, we conclude that T cells are required as effector cells, and that these may develop from Lyt-1-, 2,3- cells. Lyt-1+, 2,3- cells were demonstrated to have suppressive activity upon the development of the diseases; induction of autoimmunity was completely inhibited by the cotransfer of Lyt-1+, 2,3- cells with Lyt-1-, 2,3- cells. When anti-Lyt-2 plus C-treated cells (i.e., Lyt-1+, 2,3- and Lyt-1-, 2,3- cells) were mixed with anti-Lyt-1 and anti-Lyt-2 plus C-treated cells (i.e., Lyt-1-, 2,3- cells) in various ratios, then transferred to nude mice, the development of each autoimmune disease was clearly inhibited, even by small doses of Lyt-1+, 2,3- cells. The autoimmune disease we were able to induce was quite similar to human organ-specific autoimmune disease in terms of the spectrum of organs involved, histopathological features, and the development of autoantibodies to corresponding organ components (oocytes, parietal cells, thyroid colloid, including thyroglobulin, and sperm).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effector mechanisms of syngeneic anti-tumour responses in mice. I. Establishment and characterization of an exogenous IL-2-independent cytotoxic T-lymphocyte line specific for radiation-induced leukaemia RL male 1.

A CTL line (CTLL-D4) mediating specific cytolytic activity against radiation-induced leukaemia RL male 1 has been established and maintained on a long-term basis without the addition of exogeneous TCGF. This line was originally selected by the limiting dilution of MLTC cells from RL male 1-immune (BALB/c X C57BL/6) F1-nu/+(CB6F1-nu/+) spleen cells (500 cells/well) in the presence of 5% rat TCGF, 2000 rads-irradiated normal CB6F1-nu/+ spleen cells as the feeder cells, and 10,000 rads-irradiated RL male 1 tumour cells as the stimulator. After expansion only with the feeder and tumour cells, CTLL-D4 shows highly specific cytotoxic activity against RL male 1 by in vitro CMC assay, since cells such as RL male 6, RL female 8, RL female 9, P815, MOPC-315 (H-2d), EL-4 (H-2b) and YAC (H-2a) are not killed. Microcytoxicity assay of this line has revealed that CTLL-D4 comprises three subsets of T lymphocytes (100% Thy-1.2+): 15-25% Lyt-1+23-, 60-75% Lyt-1+23+ and 10-15% Lyt-1-23+. The proliferation of this line seems to depend largely upon the syngeneic MLR-like responsiveness of the Lyt-1+23- subsets of CTLL-D4 to the Ia-positive cells in CB6F1-nu/+ splenic feeder cells, and has been restricted to the H-2d-haplotype of the feeder cells. In spite of the vigorous cell proliferation by coculturing with the feeder cells alone, the cytolytic activity of this line begins to decrease after some 7 days of culture in the absence of the stimulator RL male 1 cells which have no capacity to stimulate by themselves. Thus, by long-term culture of CTLL-D4 with the syngeneic feeder cells alone, a new non-cytolytic line (D4f) was established. Mechanisms enabling the long-term maintenance of CTL activity and subset composition have been discussed in terms of cellular cooperation between the subsets of this line.

Animals↗

Effector mechanisms of syngeneic anti-tumour responses in mice. II. Cytotoxic T lymphocytes mediate neutralization and rejection of radiation-induced leukaemia RL male 1 in the nude mouse system.

We demonstrated the efficacy of a long-term cultured cytotoxic T-lymphocyte line, CTLL-D4, on tumour growth inhibition using athymic nude mice as recipients. CTLL-D4, specific for a unique surface determinant on a radiation-induced leukaemia RL male 1 of BALB/c origin, was obtained from the limiting dilution culture of MLTC cells performed between spleen cells of a CB6F1-nu/+ mouse immunized in vivo and RL male 1 stimulator cells, and cultured for several months in the absence of added TCGF as described in our preceding paper (Kuribayashi, 1985). The specific inhibition of tumour growth by CTLL-D4 was demonstrated both in Winn-type neutralization assay and in systemic transfer experiments. A subcutaneous inoculation of the mixture of CTLL-D4 and RL male 1 cells resulted in the complete inhibition of tumour growth, even at the effector to tumour cell ratio of 1:1, whereas non-cytolytic D4f, which was self-Ia antigen(s)-reactive, composed entirely of Lyt-1+23- T cells and derived originally from CTLL-D4 but completely lost its cytotoxic activity during culture with the irradiated syngeneic feeder cells alone, had no inhibitory effect at all. In the adoptive transfer studies, the subcutaneously established tumours were rejected by the single i.v. transfer of 2 X 10(7) CTLL-D4 cells into CB6F1-nu/nu mice. However, D4f was ineffective again in this systemic transfer system. When the effect of CTLL-D4 cells on tumour rejection in vivo was compared to that of non-cultured spleen cells hyperimmunized with RL male 1 cells, the former exhibited more rapid rejection in nude mice after i.v. transfer than the latter did, suggesting that CTLL-D4 cells also attack the tumour cells much more effectively as effectors in vivo. Thus, it is conceivable that CTLs are mainly involved in tumour rejection in this adoptive transfer system using RL male 1 tumour cells and athymic nude mice.

Animals↗

[Focal nodular hyperplasia-like lesion of the liver associated with thorotrast liver disease--report of a case].

A 66-year-old man with Thorotrast liver disease underwent a partial hepatectomy for a small tumor of the liver, which was demonstrated by digital subtraction angiography. The resected specimen was grossly a sharply circumscribed, gray-yellow nodule, 7.5 mm in diameter. Microscopically, the nodule was an ill-defined hepatic cell mass, which was divided by fine fibrous septa irregularly and incompletely. Central veins and Glisson's capsules were not observed inside the nodule. Bile duct proliferation and infiltration of lymphocytes were found in the fibrous septa. There were Thorotrast depositions within the fibrous tissues around the nodule. Because a typical fibrous boundary and central scar were not found, we have termed this condition a focal nodular hyperplasia-like lesion. A relationship between focal nodular, hyperplasia as a precancerous state and Thorotrast liver disease was suggested.

Aged↗

Hemodynamic effects of the antithrombotic drug cilostazol in chronic arterial occlusion in the extremities.

An open clinical trial was performed to determine whether or not the antithrombotic drug cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-qui nolinone, OPC-13013) at 150 mg/day would increase ankle blood flow in 13 lower extremities in 9 patients with chronic arterial occlusion. After 2 weeks of treatment, ankle blood flow in the lower extremities increased by a mean of 16.16 +/- 7.08% (p less than 0.05, t-test) over the initial level. From these results, it was concluded that cilostazol has a significant beneficial hemodynamic effect on chronic arterial occlusion in the extremities.

Aged↗