Effect of a novel immunosuppressive agent, FK506, on mitogen-induced inositol phospholipid degradation in rat thymocytes.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Y Fujii.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To elucidate the effect of combined therapy of glucagon and insulin on the hepatectomized remnant liver of rats, postoperative changes of liver nuclear poly (ADP-ribose) polymerase activity were measured. The maximal value of poly (ADP-ribose) polymerase activity without glucagon and insulin was revealed as 354 +/- 44pmole/mg/min at the stage of 5 days after partial hepatectomy. In contrast, the enzyme activity with glucagon and insulin reached to peak value as 242 +/- 46pmole/mg/min at the stage of 2 days after hepatectomy. Liver weight regeneration rate of the group with glucagon and insulin showed higher values than that of the group without glucagon and insulin in the period from 5 to 21 days after hepatectomy. The amounts of DNA showed similar changes to poly (ADP-ribose) polymerase activity after hepatectomy. Thus it is suggested that the combined therapy of glucagon and insulin may act to promote liver regeneration through the changes of poly (ADP-ribose) polymerase activity.
A new murine monoclonal antibody (2C-8) was prepared by immunizing mice ip with CEA producing human pancreatic cancer cell line, AsPC-1.SDS-PAGE and Western blot analysis showed that 2C-8 monoclonal antibody recognized CEA and NCA. This anti-CEA monoclonal antibody was conjugated with large multilamellar liposomes incorporated 10B compound (Cs2 10B12H11SH). This immunoliposomes applicated to boron neutron capture therapy. AsPC-1 cells were incubated with the 10B-Lip-MoAb(CEA) for 8 hours. After the irradiation with thermal neutron (1 x 10(11)-1 x 10(13) n/cm2), boronated AsPC-1 cells were showed decreasing uptake of 3H-TdR compared with control group. The numbers of 10B atoms in liposomes bound to an antibody were in proportion to the dose of 10B compounds added and maximum number of 10B atoms was approximatory 1.2 x 10(4)/Ab. These data indicated that the immunoliposomes could deliver highly amount of 10B atoms to the tumor cells and exert cytotoxic effect by thermal neutron. BNCT with immunoliposome may be useful to the non resectable malignant tumors in clinical application.
Explore the source record for details and available documents.
The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.
Human oral isolates of Streptococcus intermedius, which were biochemically identified, have been classified into 5-Serogroups (I-V). Selecting some representive stock cultures together with the type strain ATCC 27335, comparisons were carried out between them in terms of cell extractable proteins, G + C mol% values, DNA-DNA homology and DNA restriction fragments. Since the taxon of S. intermedius has not been clarified, comparison was also made between the above strains and the type strains of the "Streptococcus anginosus-milleri Group", Streptococcus anginosus, "Streptococcus milleri" and Streptococcus constellatus, which were thought to be related to S. intermedius. 1. G + C mol% of S. intermedius ATCC 27335 was 38.0 +/- 0.28. The values of all the isolates tested ranged from 37.0 to 38.8. On the other hand, the values of the type strains of the "S. anginosus-milleri Group" were 38.0-38.8. 2. Under stringent conditions of DNA-DNA hybridization, all the isolates showed more than 66.7% homology with S. intermedius ATCC 27335, demonstrating that these strains belonged to the same species. On the other hand, S. anginosus ATCC 33397, "S. milleri" NCTC 11169 and S. constellatus ATCC 27823 hybridized at levels of 50%, 53% and 28%, respectively. Consequently, it was impossible to classify these strains as being the same species as S. intermedius. 3. When the DNA restriction fragments were compared by PAGE, the strains of Serogroups I and V showed the same pattern, respectively. The strains of Serogroups II and III, however, showed two different patterns, and these of Serogroup IV showed five different patterns. DNA fragments specific to S. intermedius could not be identified. 4. When cell extractable groups were compared by SDS-PAGE, the strains of Serogroups I and V showed identical patterns. The strains of Serogroup III showed 2 different patterns and those of Serogroup IV showed 5 patterns. These results reflected those of the DNA restriction analysis. However, the strains of Serogroup II showed the same protein pattern, although 2 different patterns were observed in DNA restriction fragments. Unique proteins, which were not detected in the proteins extracted from the type strains of the "S. anginosus-milleri Group", were observed in the cell proteins of S. intermedius strains. 5. The results of DNA-DNA hybridization and the existence of unique extractable proteins together with the chondroitinase productivity suggest that the strains of S. intermedius might represent a particular taxon among the strains of the "S. anginosus-milleri Group".(ABSTRACT TRUNCATED AT 400 WORDS)
Explore the source record for details and available documents.
Highly purified S-antigen was isolated from bovine retinas by high performance liquid chromatography (HPLC), and was used to induce experimental autoimmune uveoretinitis (EAU) in various rat strains. Studies were then made of the genetic control of EAU, the effects of cyclophosphamide or irradiation on EAU, and the correlation between the EAU incidence and the serum levels of antibody to S-antigen. Lewis rats were the most susceptible to EAU followed by Wistar rats. F344 rats and BN rats were resistant to EAU. (Lewis X BN)F1 rats and (LBNF1 X Lewis) rats were susceptible to EAU, while (LBNF1 X BN) rats were resistant. These results indicate that susceptibility to EAU was inherited as an autosomal dominant trait. Treatment of rats with cyclophosphamide or irradiation (200 rad/rat) on the day before immunization markedly suppressed EAU development. On the other hand, the same dose of irradiation 7 days after the immunization did not affect the disease induction, yet the antibody levels to S-antigen were very high in the rats. In addition, BN rats resistant to EAU exhibited very high levels of antibody to S-antigen. Therefore, the antibody to S-antigen seems to play a minor role, if any, in the immunopathogenic mechanisms of EAU.
We made an attempt to treat with cefmetazole (CMZ) 25 patients who developed severe infectious diseases while suffering with granulocytopenia associated with the treatment of malignant hematological disorders. 1. Determination of bacteriological efficacy While 20 strains were isolated and identified from 15 patients, no significant bacteria were detected in 9 patients. Isolates obtained were: 5 strains of Enterococcus faecalis, 3 strains of Haemophilus influenzae, 2 strains of Staphylococcus epidermidis, 2 strains of Klebsiella oxytoca, 2 strains of Staphylococcus aureus, and 1 strain each of Neisseria sp., Pseudomonas maltophilia, Enterobacter sp., alpha-Streptococcus, beta-Streptococcus and Gram-positive cocci. Causative organisms were eradicated or markedly in 7 of the 15 patients from whom bacteria were isolated. Clinical findings, including fever, revealed that none of the patients, in whom bacteriological efficacy was determined to be poor, exhibited sufficient clinical response. E. faecalis was isolated from 4 of 6 patients bacteriologically determined to have no response. 2. As for 23 patients, who were found to be evaluable among the 25 patients, 8 (34.8%), 4 (17.4%), 4 (17.4%), and 7 (30.4%) demonstrated excellent, good, fair and poor responses, respectively, showing a 69.6% efficacy rate which indicates a sum of percentages of patients with excellent, good and fair responses. 3. While an efficacy rate of 100% was obtained for 3 patients with number of peripheral neutrophils less than 500/mm3 before the beginning of CMZ administration, only an efficacy rate of 66.7% was obtained for 15 patients with neutrophils more than 500/mm3.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Some Chinese medicines in Japan have been reported to have not only antitumour effects, but also to offer protection from the adverse effects of anti-tumour agents. However, there is controversy regarding the protective effects of such Chinese medicines against the adverse effects of anti-tumour agents, in this study, we examined the effects of Tsumura Juzentaiho-to (TJ-48) on the toxicity of mitomycin C (MMC) and cisplatin (CDDP). Both the pre-administration of TJ-48 a single time and for seven days shifted the dose response curve and LD50S of MMC and CDDP to the right. Seven days of treatment using TJ-48 delayed deaths due to lethal dose of MMC or CDDP and markedly changed their survival curves. Also, TJ-48 reduced the atrophy of the testis, thymus and spleen caused by MMC. TJ-48 also had beneficial effects on leukopenia, anemia and body weight loss caused by MMC, and increase of BUN and creatinine caused by CDDP. These results indicate that the combined use of TJ-48 may be a new way to in prevent or minimize the toxicity of MMC or CDDP.
Antithrombin (AT), prekallikrein (PK), and fibronectin (FN) were measured in the plasma of 400 patients with a variety of disease states seen at Detroit Receiving Hospital from October 1983 through June 1987. The average lowest AT measured in these 400 patients was 69 +/- 19 per cent (SD) (Normal = 75-120%). The average lowest AT level in 152 septic patients (50 +/- 17%) was significantly lower than in the 248 patients without sepsis (79 +/- 22%) (P less than 0.001). The average lowest PK levels measured in 132 patients was 52 +/- 19 (Normal = 80-120%). The average PK level in 64 septic patients (34 +/- 17%) was significantly lower than in 68 who were not septic (69 +/- 21%) (P less than 0.001). The average lowest FN levels measured in 109 patients was 230 +/- 118 mcg/ml (Normal = 200-350 mcg/ml). The average FN level in 47 septic patients (162 +/- 88 mcg/ml) was significantly lower than in the 62 nonseptic patients (285 +/- 138) mcg/ml. AT or PK levels less than 50 per cent or FN levels less than 150 mcg/ml during the first 24 to 48 hours after severe trauma or burns were associated with a development of later sepsis in 90 per cent, 77 per cent, and 70 per cent, respectively. Thus, low or falling levels of AT, PK, and FN may be of great help in predicting sepsis or providing an early diagnosis in critically ill or injured patients.
The results of surgical treatment of pulmonary metastases from osteogenic sarcoma were analyzed. Total cases were 23 with mean age of 17.0 +/- 9.1. The number of operations were 46, and operative procedures consisted of pneumonectomy in 1, lobectomy in 3, partial resection in 37 and resection of adjacent organs in 5. The overall five-year survival rate from the first thoracotomy was 21%. This was significantly higher than prognosis of the previous cases with pulmonary metastases which were not resected (p less than 0.001). Three-year survival rate for the group with 5 or less metastases was 57%, whereas that for the group with 6 or more metastases was 0% (p less than 0.02). To assess both the number and the diameter of metastases, an index called number-size score (NS score) was introduced, which was the sum of the diameters of each metastatic lesion. The three-year survival rate for the group with NS score 6 or less was 73%, whereas that for the group with NS score 7 or more was 9% (p less than 0.001). Disease free interval, the time of operation and histological effect of chemotherapy were not significantly related with prognosis. There was no long-term survivor among the patients with resection of adjacent organs. In conclusion, an aggressive resection of pulmonary metastases from osteogenic sarcoma should be performed with intensive chemotherapy, but significance of the resection of multiple metastases more than 20 or tumors invading adjacent organs is doubtful.
The effect of pertussis toxin (PT) on experimental autoimmune uveoretinitis (EAU) induced by immunization with S-antigen was examined in rats. Intravenous administration of PT (2 micrograms/rat) initiated the development of EAU in rats that had been made resistant to the induction of EAU by immunization with S-antigen and complete Freund's adjuvant (CFA). The capacity of PT to promote EAU was also demonstrated by a marked augmentation of the inflammation in EAU eyes of rats susceptible to the induction of EAU. PT was most effective when it was given from the day before to the day after immunization with S-antigen. However the induction of EAU was promoted by the injection of PT even 7 days before and 14 days after immunization. The clinical and histopathological findings of the EAU produced by the additional PT treatment were described and the mechanisms by which PT augmented the induction of EAU were discussed.
Ten acetylcholine receptor (AChR)-specific T cell clones from Lewis rats were studied. These clones had various AChR subunit and peptide specificities, and proliferated in response to antigen on appropriate APC. All the T cell clones were CD4+CD8- and OX22-, helped anti-AChR antibody production by AChR-primed lymph node B cells, and could secrete IL-2. However, several lines of evidence suggested that IL-2 was not the lymphokine that mediated T cell help. B cells primed with native AChR and then exposed in culture to very low concentrations of native AChR effectively presented the Ag to the T cell lines, presumably due to uptake via Ag receptors, but primed B cells were no more effective than were non-specific APC at presenting a synthetic AChR peptide which is recognized by AChR-specific T cells but not by AChR-specific B cells. Increasing AChR doses produced an antibody production response that was bell shaped and low doses stimulated, whereas higher AChR concentrations suppressed the antibody production response. Evidence suggested that AChR exerted its inhibitory effect through the T cells, but not via IL-2.
A micro high-performance liquid chromatographic (micro-HPLC) method has been developed for the assay of beta-methyldigoxin and digoxin tablets. Quantitation of cardiac glycosides in tablets was carried out by the incorporation of dexamethasone as an internal standard. The procedure consisted of disintegration of tablets, extraction with acetone-ethanol (9:1) and injection for micro-HPLC on an ODS micro column, using acetonitrile-water (28:72) for beta-methyldigoxin tablets and methanol-water (1:1) for digoxin tablets; the effluent was monitored by UV detection at 220 nm. The average values of the contents in beta-methyldigoxin and digoxin tablets were 99.6 and 100.2% of the labelled amounts, respectively. The proposed method is sufficiently precise and sensitive to examine the content uniformity of tablets.
Usually, human thyrocytes in primary culture rapidly lose their thyroid function and fail to synthesize or release thyroid hormone after 3-5 days of culture. By culturing thyroid follicles obtained from patients with Graves' disease in medium supplemented with TSH and a low concentration of fetal calf serum (1%), thyrocytes can maintain thyroid function for several days. We have found that the addition of dimethylsulfoxide to culture medium (1.7%) furthermore enhanced and maintained thyroid function (de novo synthesis and release of [125I] thyroxine) for more than 13 days, probably by inhibiting dedifferentiation of thyrocytes. The present bioassay will be also useful for detecting thyroid stimulating immunoglobulin in patients with Graves' disease.