Changes in plasma levels of t-PA, PAI-1 and t-PA-PAI-1 complex in patients with cerebrovascular thrombosis infused with t-PA.
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Biomedical subjects
Publications and source records attributed to K Sakakibara.
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The relationships between tissue plasminogen activator (tPA), its fast acting inhibitor (PAI-1) and euglobulin clot lysis time (ELT) were investigated with healthy volunteers' plasma. Turbidimetric clot lysis assay by the microtiter plate reader was utilized for ELT with a slight modification. Both tPA and PAI-1 showed the significant correlation with ELT. tPA had a significantly positive, not negative, correlation with ELT (R = 0.387, p less than 0.001). Higher correlation coefficients (R = 0.580, p less than 0.001 and R = 0.599, p less than 0.001) were obtained between ELT and total PAI-1 or free PAI-1 than tPA or tPA-PAI-1 complex (R = 0.427, p less than 0.001). The positive correlation was also obtained between tPA and PAI-1. These data suggest that PAI-1 is a highly important factor for ELT, especially, the amounts of free PAI-1 being the key factor to determine the ELT, which can represent the potential activity of the fibrinolytic system.
The concentrations of two components of the complement system (C1q and C3) were measured in the urine and blood in 10 normal subjects and 134 patients with primary and secondary glomerulonephritis by using a highly sensitive enzyme immunoassay. The values of urinary excretion of C1q and C3 were well correlated to the ratios of fractional clearance of these complement proteins to that of neutral dextran of 55 A, which was used to minimize the influences of glomerular sieving because of their comparable molecular size to these complement components. The rate of renal tubular reabsorption of C1q and C3 were at least 89.2 and 93.4% of filtrated C1q and C3, respectively. Urinary C1q and C3 were excreted significantly in cases of membranoproliferative glomerulonephritis (MPGN), membranous glomerulonephritis, IgA nephropathy with both mesangial and capillary immune complex (IC) deposit and also in case of active lupus nephritis. On the other hand, the concentrations of these complement components were low in case of minimal lesion nephrotic syndrome, mild proliferative glomerulonephritis, inactive lupus nephritis and diabetic nephropathy without any immune staining. There was a significant correlation between the urinary excretion of C1q or C3 and intraglomerular IC deposition, especially IC deposition along the glomerular capillary wall. However, the degree of the excretion of these proteins was not correlated to the degree or permselectivity of proteinuria. The correlations between urinary C1q and C3 were observed in cases of IgA nephropathy with both mesangial and capillary deposit and MPGN, although we couldn't see the correlation in the other glomerular diseases. It is suggested that urinary excretion of such complement components represents the fixation of complement by deposited intraglomerular IC. The measurement of urinary concentration of these complement components provides a new clue to investigation or diagnosis of glomerular diseases.
Blood was taken from healthy 15 males and 10 females at 9:30 h, 10:00 h and 12:30 h. The euglobulin fraction was prepared and clotted by the addition of human thrombin. The clot lysis time shortened significantly from 9:30 h to 10:00 h (p less than 0.01) and further to 12:30 h (p less than 0.01). Plasma levels of tissue plasminogen activator (t-PA) antigens did not change from 9:30 h to 10:00 h, but slightly and significantly to 12:30 h (p less than 0.01). Plasma levels of free plasminogen activator inhibitor-1 (PAI-1) and complex of t-PA-PAI-1 decreased from 9:30 h to 10:00 h (p less than 0.02) and to 12:30 h (p less than 0.01). Plasma levels of total PAI-1 (free plus complex) decreased from 9:30 h to 10:00 h (p less than 0.01) and to 12:30 h (p less than 0.01). These results suggest that a major factor contributing to the enhanced fibrinolytic activity of the euglobulin fraction may be a level of PAI-1 (free and total).
In this report, the efficacy of cyclosporine A and two monoclonal antibodies, anti-L3T4 and anti-Lyt-2.2, was assessed on first-set rejection of cardiac xenografts. Neither cyclosporine nor anti-Lyt-2.2 monoclonal antibody prolonged the survival of heart xenografts. Anti-L3T4 enhanced acceptance of rat hearts transplanted to C57BL/6 mice 5-fold relative to that observed in control recipients; it did not, however, prolong acceptance of hamster hearts transplanted to mice. Histologic analysis indicated that the cellular infiltrate within rejected hearts was composed of greater than 95% lymphocytes; of these, greater than 99% were Thy-1- and sIg-. These results suggest that rejection of xenogeneic hearts is mediated by unconventional lymphoid cells. This is discussed in the context of whether rejection of allografts and xenografts occur by similar or dissimilar mechanisms.
The concentrations of two different plasminogen activators(PAs), urokinase (UK), tissue-type plasminogen activator (t-PA) and urinary trypsin inhibitor (UTI) were determined in the urine and blood from 48 normal subjects and 92 patients with glomerulonephritis using highly sensitive enzyme immunoassay (EIA). The values of UK clearance were approximately 1.5-fold larger than those of creatinine clearance and at least 60.8% of UK was reabsorbed in the renal tubules, which suggest that one of major secretion site of UK is located in the outer region of the glomerular basement membrane (GBM), that is glomerular epithelium. Decreased urinary excretion of UK was observed in the glomerular disease depending on their severity and correlated with the increasing degree of FDP D-dimer excretion. On the other hand, the values of t-PA clearance were quite smaller than those of creatinine clearance, which suggest that urinary t-PA originated from the blood circulation or the inner side of the GBM (possibly glomerular endothelium) and filtrated from the GBM. Like UK, urinary t-PA also decreased in glomerular diseases. UTI which is highly anionic and has a comparable size with albumin was excreted increasingly in glomerulo-nephritis due to loss of the anionic charge barrier of the GBM. No significant correlations were noted between UTI excretion and UK or t-PA excretion.
In order to forecast the survival of patients, we collected 417 cases of common epithelial carcinoma of the ovary as a population for this study, then selected 141 cases who had survived more than 3 years and 131 cases who had died within 3 years as a sample of statistical inference. The sample was computerized inputting 25 factors which were obtained mainly on the first surgery. We selected 8 factors with 46 items considering their weight to forecast the prognosis on convenience. The selection of factors was carried out by following three basic principles. First, we selected factors that retained high partial correlation coefficients. Second, we selected factors which did not overlap each other in their contents. Third, we selected factors which were not decided intentionally. Accordingly, the score for forecasting the 3-year survival of patients with ovarian carcinoma was framed. The correct discrimination rate of the score when it was judged at the 0 point was 86.8% in the sample group. However, in the sample group outside the population, it was 83.1%.
Extracorporeal shock-wave lithotripsy (ESWL) was first applied for calculi of the bile duct system in 1985. Recent improvement of the crushing apparatus has enabled us to crush the biliary calculus more accurately than before, and moreover, to conduct the procedure without anesthesia, and to treat easily. We performed ESWL in 30 cases of calculus in the cholecyst using MPL-9000 (Dornier Co., Ltd.) which is said to be a crushing device of a new generation. Here, the study is presented. The results of crushing effect demonstrate the efficacy in 26 of 30 cases (87%), and disappearance rate in 18 cases (60%) at present after an average follow-up period of 4.4 months. The disappearance cases were mainly those with a single calculus (75% disappearance rate) or pure cholesterol calculus (100%). Concerning the complications, right upper abdominal pain which was expected to accompany excretion of the crunched fragments was recognized in 10 cases (33%), it was not seen in cases in which laparotomy or endoscopic papillotomy was performed.
Three mouse IgG1 monoclonal antibodies (MoAbs) reactive predominantly with cytoplasmic antigens of mucinous type ovarian tumors were produced. OM-A MoAb was reactive with 11 of 14 mucinous type and two of three endometrioid type ovarian tumors, although only a minor population of the tumor cells was positive in the latter type. This MoAb was not reactive with serous type, clear cell type, or other types of ovarian tumors, nor with various types of uterine carcinoma. Normal adult and fetal tissues of female genital organs were not positive with this MoAb. Among nongynecological carcinomas, three of six metastatic tumors to the ovary from the gastrointestinal tract, one of five gastric carcinomas, and one of eight lung adenocarcinomas were positive. As for normal adult and fetal tissues of nongynecological origin, epithelium of the normal stomach, small bowel, and bronchus as well as epithelium of fetal small and large bowel and secretory products were weakly positive. Thus, this MoAb showed a selected specificity against mucinous and endometrioid types of ovarian tumors. OM-B MoAb showed a broader specificity than OM-A, reacting with all mucinous type, two of three endometrioid type, and three of 16 serous type ovarian tumors, but not with clear cell type tumors. Adenoma type, but not squamous type, cervical carcinomas and one-half of endometrial carcinomas were positive. This antigen is present in cervical mucosa, but not in ovary or endometrium. OM-C MoAb showed a specificity similar to, but broader than that of, OM-B; i.e., 11 of 14 mucinous type, two of three endometrioid type, nine of 16 serous type, and one of nine clear cell type ovarian tumors were positive. It is reactive with adenoma type uterine carcinoma and normal mucosa of the uterine cervix and with normal surface epithelium of the oviduct. Among nongynecological tumors, OM-B antigen was present in metastatic tumors to the ovary as well as in gastric and pancreatic carcinomas, while OM-C was in metastatic tumors to the ovary and gastric and colonic carcinomas. Thus, the serological analysis showed that these three MoAbs showed selective specificities to mucinous and endometrioid types of ovarian tumors. Preliminary characterization of these three OM antigens suggested that these are distinct from carcinoembryonic antigen or ABH blood group-related antigens.
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In a study designed to determine the merit of preserving ovarian function and childbearing capability in women with unilateral malignant ovarian tumors, the results of radical surgery (n = 86) and conservative surgery (n = 106) were compared. The mean length of survival was slightly but not significantly shorter following conservative surgery. There were 15 recurrences (14%) and 11 deaths among the conservative surgery group. The incidence of metastasis to the preserved ovary was high. In the most cases restoration of normal menses was fairly rapid after initial treatment, but this appeared to depend on whether or not chemotherapy was given postoperatively, the specific agents used, and the duration of their administration. Hypergonadotropic hypogonadism was the most common finding among the anovulatory patients. Sixteen women experienced a total of 27 pregnancies and 18 normal infants were born. Abortion was induced when conception occurred during a course of chemotherapy. These findings are encouraging in terms of the feasibility of preserving childbearing capability in ovarian cancer patients. However, they also underscore the necessity for close, long-term follow-up, which will be improved as new technologies become available.
Endodermal sinus tumor (EST) arising in the endometrium is an extremely rare malignant neoplasm. To the authors' knowledge, this is only the second report of an EST arising in this location. The tumor was exophytic, 2.4 cm in diameter, and was located in the fundus uteri. It had infiltrated the circumambient endometrium slightly. Preoperative serum alpha-fetoprotein (AFP) levels were markedly elevated, 1580 ng/ml. The patient received a simple abdominal hysterectomy and bilateral salpingo-oophorectomy followed by combination chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide. To date, there has been no evidence of tumor recurrence, and serum AFP titers, which had returned to normal 7 weeks after surgery, continue to remain within normal limits. We believe this is the first successful treatment of a documented case of primary EST of the endometrium.
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The concentration of urinary fibrin(ogen) degradation products (FDP) was determined by using enzyme immunoassay and radio immunoassay, and their urinary levels were compared with histologically classified types of glomerulonephritis. Urinary FDP levels were higher in the severe type of proliferative glomerulonephritis and at the active phase of systemic lupus erythematosus (SLE). They were also high in the membranous glomerulonephritis. Molecular weight of urinary FDP of a patient with severe proliferative glomerulonephritis was determined to be 150,000 and 68,000, respectively after gel filtration. Urinary FDP levels were higher in patients with glomerular fibrin deposit than in patients without fibrin deposit or normal volunteers. The amounts of excreted protein in urine was not related to the amounts of FDP. Decrease in the reciprocal of serum creatinine levels resulted in high urinary FDP levels, indicating that high urinary FDP levels may represent deterioration of renal function.
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The synthesis and antibacterial activity of sodium (3S,4R)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-(O-substituted oxyimino)acetamido]-2-azetidinone-1-sulfonates having various substituted ethyl groups at the C-4 position are described. Among various substituents explored, the (substituted isothiuronio)ethyl groups were found to have strong antibacterial activity against a variety of Gram-negative bacteria, and moreover, the ethylene isothiuronium derivative exhibited moderate antibacterial activity against Staphylococcus aureus.
Seven tumor markers (CA125, CA19-9, TPA, IAP, CEA, ferritin, LDH) were measured in 24 patients with ovarian cancer. The positive rates in untreated cases of ovarian cancer were 87.5% for CA125, 35.5% for CA19-9, 10% for CEA, 77.8% for IAP, 63.6% for TPA, 28.6% for LDH and 35.3% for ferritin. Among these, CA125 was the most available marker for detecting tumor growth or regression during each respective clinical course by serial measurement. Serial changes in serum alpha-fetoprotein (AFP) levels during treatment were studied among 27 patients with ovarian embryonal carcinoma. AFP decreased with a half-life of about 7 days, and was restored to the normal range within 10 weeks after the initial surgery and chemotherapy (VAC) in all cases. In subsequently fatal cases, AFP rose again during 10 to 30 weeks after the initial treatment.
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