[Effect of alcohol drinking on blood coagulation and fibrinolytic systems].
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Alcohol Drinking↗
Biomedical subjects
H Sumi
Publications and source records attributed to H Sumi.
Platelet aggregation is inhibited by phycolectins.
Lectins from four marine algal species were examined for interaction with human platelets. The lectin designated hypnin A, from the red alga Hypnea japonica, inhibited adenosine diphosphate (ADP)- or collagen-induced human platelet aggregation in a dose-dependent manner. Complete inhibition was observed at concentrations of 100 and 5 micrograms/ml of the lectin with ADP (2 microM) and collagen (0.2 microgram/ml)-induced platelet aggregation, respectively. At the inhibitory concentration of 0.5 to 100 micrograms/ml, the lectin did not induce aggregation of resting platelets. Lectins from the other three algal species also inhibited ADP-induced human platelet aggregation. These results indicate that the algal lectins are a new group of inhibitors and may be useful to study glycoconjugates on platelet membranes and to design novel platelet aggregation inhibitors.
Adenosine Diphosphate↗
Modulation of the receptor for urokinase-type plasminogen activator in macrophage-like U937 cells by inflammatory mediators.
Macrophages in the tissues have been shown to express receptor for urokinase-type plasminogen activator (uPAR) on their cell surface which plays an important role in cell invasion and attachment. We examined the effects of inflammatory mediators on the expression of uPAR employing U937 cells which have monocyte/macrophage-like characteristics. U937 cells were incubated with various mediators such as interleukins (IL), tumor necrosis factors (TNF), dexamethasone, thrombin, fibrin fragment D, bradykinin, complement C5a, and components of the extracellular matrix. The uPAR expression on the cell surface was then analyzed by radio-ligand binding assay using 125I-scuPA. The strongest enhancement of uPAR was observed in the cells stimulated by TNF alpha and TNF beta. IL-1 beta, IL-6, and C5a also increased the uPA binding sites with various patterns of affinity change. Dexamethasone decreased the uPA binding sites without changing the affinity. Fibrin fragment D and IL-3 reduced the affinity without changing the number of receptors. These findings suggest that the expression of uPAR in inflammatory cells could be modulated by various inflammatory mediators.
Bradykinin↗
Chemical modification of earthworm fibrinolytic enzyme with human serum albumin fragment and characterization of the protease as a therapeutic enzyme.
The strongest fibrinolytic protease (F-III-2) in the six enzyme proteins purified from earthworm, Lumbricus rubellus [N. Nakajima et al., Biosci. Biotech. Biochem., 57, 1726-1730 (1993)] has been modified chemically with fragmented human serum albumin (mol. wt., 10,000-30,000). The modified enzyme lost the antigenicity of the native enzyme and reacted with the antisera against human serum albumin, the human serum albumin fragments, and the conjugate with the native enzyme to form precipitation lines, which fused with each other. The conjugate was significantly more resistant to inactivation by protease inhibitors in rat plasma. The enzyme was a non-hemorrhagic protein and did not induce platelet aggregation. The enzyme kept potent proteolytic activity for fibrin and fibrinogen than that of human plasmin. The enzyme easily solubilized actual fibrin clots (thrombi) of whole blood induced by thrombin in a rat's vena cava. The continuous fibrinolysis for fibrin suspension in an enzyme reactor system using the modified enzyme immobilized to oxirane-activated acrylic beads has been achieved without any inactivation of the activity at least for more than 1 month. The N-terminal amino acid sequence of the protein was also investigated and the sequence showed local similarity to those of the serine proteases such as plasmin and chymotrypsin.
Amino Acid Sequence↗
A unique strong fibrinolytic enzyme (katsuwokinase) in skipjack "Shiokara," a Japanese traditional fermented food.
Katsuwokinase (KK) is a unique fibrinolytic enzyme recently found in skipjack "Shiokara," a Japanese traditional salt-fermented food. A crude enzyme extracted from skipjack Shiokara (Katsuwonus pelamis) showed a very strong fibrinolytic activity above 45 CU/g (fibrin plate method) based on plasmin. KK not only hydrolyzed fibrin but also several synthetic amido substrates, particularly pyro-Glu-Gly-Arg-pNA. The fibrinolytic activity of KK was not affected in the presence of 10% NaCl, was stable in the pH range from 1 to 10 at 37 degrees C for 30 min, and was inhibited by DFP, SBTI, BPTI, and aprotinin but not by epsilon-amino-n-caproic acid and t-4-amino-methylcyclohexane carboxylic acid. The crude enzyme contained at least four kinds of KK, and the major form purified had a pI value of approximately 5.0 and a molecular weight of 35,000. The N-terminal amino acid sequence of 21 residues, I-V-G-G-Y-E-Q-Z-A-H-S-Q-P-H-Q-V-S-L-N-S-G-, had 80% homology with that of trypsin. The fibrinolytic activity of the purified enzyme was approximately 2.6 times greater than that of plasmin by molar ratio, demonstrating its identity as a new and very potent fibrinolytic enzyme.
Amino Acid Sequence↗
[Effect of Bacillus natto-fermented product (BIOZYME) on blood alcohol, aldehyde concentrations after whisky drinking in human volunteers, and acute toxicity of acetaldehyde in mice].
Effects of Bacillus natto-fermented product (BIOZYME) on blood alcohol and aldehyde concentrations after drinking whisky (corresponding to 30-65 ml ethanol) were studied in 21 healthy volunteers. When 100 ml of BIOZYME was orally administrated to the volunteers before drinking whisky, the time delay of both blood factors to attain maximum concentrations were observed. The maximum decrease in blood alcohol and aldehyde concentrations were about 23% and 45% (p < 0.005), respectively, at 1 hr after drinking whisky. The aldehyde lowering effect of BIOZYME was continued for at least 4 hr after whisky drinking. Concentration of the breath alcohol was also sharply decreased by BIOZYME administration. The breath alcohol concentration in the administered group (0.18 +/- 0.11 mg/l) was found to be lowered about 44% than that of the control group (0.32 +/- 0.11 mg/l) (p < 0.0005, n = 21), at 1 hr after drinking whisky. In acute toxicity experiments of aldehyde in mice (12 mmol AcH/mg), BIOZYME showed the survival effect as with alpha-D-Ala (134% increase of the living, at 40 min after i.p. administration) (p < 0.005, n = 22). These findings reveal the Bacillus natto produced BIOZYME as a reasonable, safety and useful anti-hangover agent.
Adult↗
Study of estramustine binding protein: its relationship to androgen dependency and histological differentiation in human prostatic carcinoma tissue.
For the purpose of elucidating the clinical significance of estramustine binding protein (EMBP), EMBP concentration in human prostatic carcinoma (PC) tissue was measured by radioimmunoassay (RIA) using an antibody raised against rat EMBP and was compared with dihydrotestosterone (DHT) level and histological differentiation in the same tissue. The mean concentrations of EMBP in 20 untreated and 6 hormonally refractory PC were 112.6 +/- 120.7 and 218.0 +/- 102.3 ng/g tissue, respectively. In the 20 untreated PC, the EMBP concentration was not significantly different between the high and low tissue DHT groups. On the other hand, the EMBP concentration was significantly higher in moderately and poorly differentiated PCs as compared with well-differentiated PC, whereas the DHT level was highest in well-differentiated and lowest in poorly differentiated PC. Furthermore, in the 6 hormonally refractory PC, the EMBP concentration was higher in spite of a lower tissue DHT level in comparison with untreated PC. These results suggest that the EMBP concentration does not reflect androgen status in PC tissue but might reflect the malignant potential of the tumor.
Aged↗
Potent fibrinolytic enzyme from the lysate of Katsuwonus pelamis digestive tract (Shiokara): purification and characterization.
Strong fibrinolytic enzyme was purified from the lysate of Katsuwonus pelamis digestive tract (Japanese traditional fermented food, "shiokara"). The enzyme was an alkaline trypsin-like serine protease, and a pH- and salt-resistant protein. The N-terminal amino acid sequence of the enzyme showed similarity with those of trypsin from other organisms. The molecular weight and isoelectric point of the enzyme were estimated to be 38,000 and 4.65, respectively. The enzyme is probably useful as a thrombolytic agent.
Amino Acid Sequence↗
Characterization of potent fibrinolytic enzymes in earthworm, Lumbricus rubellus.
Stable and potent fibrinolytic enzymes (six homogeneous proteins) were purified to homogeneity from extracts of the lyophilized powder of an earthworm, Lumbricus rubellus. The molecular weight of each enzyme estimated by SDS-polyacrylamide gel electrophoresis was different from those by gel filtration chromatography in the six purified proteins. The exact molecular weight of each enzyme (F-III-2, F-III-1, F-II, F-I-2, F-I-1, and F-I-0) measured by ion-spray MS analysis was 29,662, 29,667, 24,664, 24,220, 24,196, and 23,013, respectively. The isoelectric point (pI) of each enzyme was 3.40, 3.60, 4.20, 4.00, 4.30, and 4.85, respectively. The enzymes were single polypeptide chains. They had a very strong fibrinolytic activity and the maximum reactivity for chromogenic substrates from pH 9-11. The enzymes, acidic proteins that had abundant asparagine and aspartic acid, and low lysine in their amino acid composition, did not contain component sugars. The enzymes were stable at from pH 1-11 and up to 60 degrees C. Studies on substrate specificity and inhibition indicated that these enzymes were alkaline trypsin-like serine proteases. N-Terminal amino acid sequences of the enzymes had local similarities to those of trypsin-like enzymes such as elastase and coagulation factor IX. From the results of amino acid sequence, amino acid composition analyses and immunological analyses, it was suggested that these six enzyme proteins were derived as isozyme(s) from at least four different genes.
Amino Acid Sequence↗
Indirect strong inhibition by acid-stable trypsin-plasmin inhibitor (ASTPI) of the activations of elastase and plasma fibrinolysis in a dog model of acute pancreatitis.
Acid-stable trypsin-plasmin inhibitor (ASTPI) had almost no direct effect on the increased levels of the plasma enzymes elastase, plasmin and plasminogen activators in an acute pancreatitis model in the dog, whereas it strongly inhibited the activation of such enzymes by intravenous administration. In vivo experiments also showed strong inhibition by ASTPI of pancreas tissue elastase and plasma fibrinolysis. Anti-shock and anti-pancreatitis effects of ASTPI observed in clinical therapy may be related to this "indirect inhibition".
Acute Disease↗
Effect of medroxyprogesterone acetate on immunohistochemical expression of estradiol in endometrial carcinoma.
The effect of medroxyprogesterone acetate (MPA) on the immunohistochemical expression of estradiol (E2) was investigated in 25 cases of endometrial carcinoma. Twenty-three cases of the endometrial carcinomas showed positive immunoreactivity for E2. The immunohistochemical expression of E2 was more intensive in carcinoma cells than in stromal cells. Although the morphologic alterations induced by MPA treatment were observed only in 2 cases who were administered more than 30,000 mg of MPA, the staining intensity in most cases appeared to decrease after the treatment. The decrease in E2 immunoreactivities of cancer cells as well as of stromal cells in Grade 1 or Grade 2 was significant. These results suggest that MPA might decrease the E2 content in endometrial carcinoma cells as well as in stromal cells.
Endometrial Neoplasms↗
Purification and characterization of a cystatin-type cysteine proteinase inhibitor in the human hair shaft.
We found a cysteine proteinase inhibitor in human hair shaft extract treated with 0.01 M Tris HCl buffer, pH 8.0. A yield of 0.2 mg of purified cysteine proteinase inhibitor was obtained from 86 g of hair shaft. The cysteine proteinase inhibitor had a molecular mass of 13 kDa as determined by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was more stable to heat and pH than most proteins and had a pI of 4.7. Immunologically, its antigenicity was the same as that of cystatin A, but differed from that of cystatin B and C, and kininogen. The amino-acid sequence of the first 30 residues from the NH terminus of the inhibitor was identical to that of cystatin A from human epidermis. Hair shaft cysteine proteinase inhibitor is thus considered to be identical to epidermal cystatin A.
Cystatins↗
Fibrinolytic enzymes in ascites during experimental acute pancreatitis in rats.
The ascites accumulating during acute pancreatitis contain proteases that play a role in the progression of this disease. The proteases of the fibrinolytic system in the ascites were therefore studied in experimental acute pancreatitis induced in rats. Synthetic substrate assay and the fibrin plate method revealed high activities of proteases, including plasminogen activator, in the ascites. The plasminogen activator had a mol wt of about 50,000 by zymography. The plasminogen activator adsorbed on Lys-sepharose from the ascites was observed at the 100,000 mol wt position and in the 50,000-100,000 mol wt range on zymography and appeared at the 50,000 mol wt position after treatment by concentration. Its activity was enhanced by trypsin treatment. In other experiments, when incubated homogenate of normal pancreas lacking in zymographic activity was injected intraperitoneally into healthy rats, the recovered fluid displayed lytic zones between the 100,00 and 50,000 mol wt positions. These findings suggest that the ascites contained plasminogen activator, part of which was released by intrapancreatic substances and was present in the precursor form.
Acute Disease↗
Effect of various polyamino acids and D- and L-amino acids on the blood fibrinolytic system.
1. Comparative additional effects of 24 commercially obtained amino acids and their derivatives were studied by the whole blood clot lysis time (WBCLT) method. D-Arg and L-Lys (greater than 50 micrograms/ml) activated the fibrinolytic system, and poly-L-Glu (mol. wt 6000-90,000) (less than 50 micrograms/ml) were less effective. 2. Poly-L-Arg, poly-L-Lys and poly-(Lys-Ala-Glu-Tyr) accelerated the TPA inhibition in the presence of human plasma. 3. For in vivo experiments, 5 mg of poly-L-Glu were given intravenously to 10 rats. 4. The shortening of WBCLT and elevation of EFA (P less than 0.01) were found after 1 hr administration. 5. The main enzymes which increased in plasma were proved to be the endogenous plasminogen activators with mol. wt higher than 70,000, by zymography.
Amino Acid Sequence↗
Fibrinolysis relating substances in marine creatures.
1. Extracts with physiological saline solution were obtained from about 20 species of invertebrates and seaweed. Tosyl-L-Arg-MeOH hydrolysing and fibrin plate lytic activity were detected in the invertebrates Stichopus japonicus, Crassost gigas, Tapes japonica, and Kintai-gai as well as the seaweed Codiales codium. 2. These activities were all labile against heat (at 65 degrees C for 1 hr). Except for the extract from Stichopus japonicus, lytic activities against fibrin plates with and without plasminogen were similar. 3. The extract from S. japonicus showed plasminogen activating potency as well as the existence of urokinase (UK) activity enhancing factor. 4. On the other hand, the extract of the seaweed Hizikia fusiformis showed a strong UK inhibiting activity. 5. A fraction of fibrinolytic enzyme was obtained from the extract of S. japonicus by absorption to the celite affinity chromatography. It was orally administered to rabbits at a dosage of 40 mg/kg/day. 6. Fibrinolytic activity was determined periodically on the eugloblin fraction of plasma samples collected from these animals. 7. As compared with the pretreatment value, the activity increased about 2 times (P less than 0.01) and 3 times (P less than 0.005) after 4 and 8 weeks, respectively, of the treatment. 8. After 8 weeks of treatment, the kidney of treated rabbits was extracted with 2 M KCl. The activity of tissue plasminogen activator (free-type TPA) was revealed to be enhanced significantly (P less than 0.001) in the extracts. 9. The fibrinolytic enzyme increased in the blood was recognized by zymography to be mainly the UK type plasminogen activator with mol. wt of 53,000.
Animals↗
A rapid and strong increase of plasminogen activator induced by experimental anaphylaxis in rabbits.
Anaphylactic shock was induced in rabbits by injecting bovine serum albumin (BSA) as an antigen. Measurements of the enzyme activities in the fibrinolytic system confirmed that a rapid and strong increase of plasminogen activator (PA) was induced during anaphylaxis. The euglobulin fibrinolytic activity (EFA) as estimated by the plasminogen-rich fibrin plate method rose significantly, peaking at 15 min after the BSA injection (when the arterial pressure was minimum). However, EFA was not detected by the plasminogen-poor fibrin plate method. The tissue-type PA (t-PA) activity using the natural substrate plasminogen increased significantly with a peak at 15 min. The amidolytic activity also simultaneously increased significantly using the t-PA substrate, H-D-Ile-Pro-Arg-pNA. The plasminogen activator inhibitor (PAI) activity remained at baseline levels until 30 min, but rose fourfold at 90 min. The main plasma fibrinolytic enzyme which increased in anaphylaxis was proved by zymography to be t-PA with a molecular weight (MW) of 69,000.
Amino Acid Sequence↗
[Short-term incubation study on inhibitory effect of chemohyperthermia against hormone-independent human prostatic carcinoma cell line (PC-3)].
The sensitivity of a hormone-independent human prostatic carcinoma cell line (PC-3) to chemohyperthermia was evaluated in vitro. The anticancer drugs used here were vincristine sulfate (VCR), peplomycin sulfate (PLM) and cis-diamminedichloroplatinum (CDDP). To evaluate cytotoxicity in short-term treatment, an inhibitory test on cell survival was more useful than a test on cell proliferation. With the inhibitory test on cell survival, the relationship of the administration method was examined to obtain better cell cytotoxicity, i.e., the cells were exposed to 1) the drug and heat at 43 degrees C simultaneously, 2) the drug followed by heat, or 3) heat followed by the drug. The combined treatment with drug and heat simultaneously produced more pronounced cytotoxicity than the treatment with heat followed by drug administration. The combined effect did not result from exposure to the drug followed by heat. Of the three drugs, the action of VCR and CDDP was potentiated with heat, but PLM was not.
Bleomycin↗
Novel thrombolytic therapy discovered from traditional oriental medicine using the earthworm.
Since a few thousand years ago, the earthworm has been used as a drug for various diseases in China and the Far East. However, modern scientific pharmacological studies have not so far been performed. We extracted a very strong fibrinolytic enzyme from the earthworm, Lumbricus rubellus. This enzyme was heat-stable and displayed a very broad optimal pH range. Purification of the enzyme was performed and three partially purified fractions were obtained. These three fractions were further subdivided, and six purified fractions (F-I-0, 1, 2, F-II, and F-III-1,2) were finally obtained. Based on results of their enzymatic activities against various substrates, the fraction I enzymes are thought to represent chymotrypsin-like enzymes and the fraction III enzymes to represent trypsin-like enzymes. The fraction II enzyme appears to be neither a trypsin-nor chymotrypsin-like enzyme nor an elastase. We therefore designed trials for in vivo experiments on human volunteers. 120 mg of lyophilized earthworm powder was administered orally to 7 healthy volunteers (aged 28-52 years old) three times after meals every day for 17 days. Blood was withdrawn once a day before and at 1, 2, 3, 8, 11 and 17 days after commencing the administration. The fibrin degradation products (FDP) value, tissue plasminogen activator (t-PA) antigen level and t-PA activities were measured in the blood. Before the administration, the t-PA antigen level was 5.6 +/- 0.38 ng/ml, and it gradually increased until the 17th day. The FDP level was increased on the 1st and 2nd day after the administration, but had decreased and normalized by the 17th day. The fibrinolytic activities also tended to show an increase during the experiment. These results suggest that earthworm powder represents a possible oral thrombolytic agent. The earthworm enzyme may thus be applicable for treating patients with thalassemia.
Administration, Oral↗