Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 23 leukaphereses were performed on five normal, healthy donors for the purpose of providing granulocyte transfusions to septic leukemia patients with granulocytopenia. Dexamethasone 7.25 to 7.50 mg was given orally 10 to 12 hours prior to each donation, and an average of 304 ml of hydroxyethyl starch (HES) was given intravenously during each procedure. During the period of observation for each donor, there was no significant change of total leukocyte and platelet counts, total bilirubin, alkaline phosphatse, LDH, SGOT, creatinine, BUN, and uric acid determinations. Changes in the concentrations of serum protein, albumin, cholesterol, and glucose were thought to be due to hemodilution. Partial thromboplastin and prothrombin times remained within normal limits following collection procedures. Hemoglobin levels decreased transiently following the first three leukaphereses in all donors, but fell progressively to 11.8 gm/dl in one donor undergoing seven procedures in a 35-day period. Dexamethasone and HES in these doses can be given safely to multiply leukapheresed donors.
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PMID:The safety of dexamethasone and hydroxyethyl starch in the multiply leukapheresed donor. 5 93

A 52-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T), a newly developed anti-allergic agent, was carried out in beagles by oral administration of 30, 90, 270 and 810 mg/kg/day for 52 weeks. The recovery study was carried out by the withdrawal for 5 weeks using control and the 810 mg/kg groups. The results are as follows: 1. Observation of general conditions revealed soft feces, mucous feces, and diarrhea in both sexes of the 270 and 810 mg/kg groups during the administration period, and these findings disappeared during the withdrawal period. One female of the 810 mg/kg group exhibited tremors in the legs and neck, staggering, a decrease of spontaneous motor activity, and clonic convulsions in Week 17 of administration and died on Day 118. One male of the same group exhibited whole body tremors and staggering from Week 32 to Week 52. 2. Body weight gain tended to be inhibited in males of the 810 mg/kg group during the administration period. The body weight of the female that died decreased rapidly after the appearance of neurological symptoms. The body weight of the male that exhibited neurological symptoms decreased after their appearance but later increased. 3. There were no abnormal changes in food consumption in all of the sacrificed dogs. The female that died did not eat at all after the appearance of neurological symptoms. The male that exhibited neurological symptoms did not eat at all for 1 week after their appearance, but the food consumption returned to normal thereafter. 4. Prothrombin times were prolonged in males of the 270 and 810 mg/kg groups at Week 26, and activated partial thromboplastin times were prolonged in males of the 810 mg/kg group at Week 52. 5. Plasma levels of alkaline phosphatase, GPT and LDH were elevated in some males and females of the 810 mg/kg groups. 6. No abnormalities due to IPD-1151T administration were found in urinalysis, opthalmological examination, electrocardiography, and fecal occult blood examination, or organ weights. 7. Autopsies including histopathological and electron microscopic examinations on the sacrificed dogs revealed no abnormalities. Subserosal hemorrhage in the base of the heart, congestion in the lungs, congestion and vacuolation in the liver and slight cell infiltration around vessels of the brain were found in the female that died.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A fifty two-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T) in dogs]. 132 Dec 56

We reported a rare case of triple cancers with acute lymphoblastic leukemia (ALL) associated with disseminated intravascular coagulopathy (DIC) after the operations of colon cancer and primary lung cancer. A 78-year-old Japanese male, who had been operated upon for colon cancer (adenocarcinoma) on March 1981, metastatic brain tumor (adenocarcinoma) on December 1986, and primary lung cancer (squamous cell carcinoma) on February 1987, was admitted to our hospital because of severe general malaise on December 6 1987. On admission, he had mild hepatosplenomegaly and hemorrhage diathesis such as purpura. Serum LDH increased to 2,515 mU/ml. The white blood cell count was 6,210/microliters with 53% leukemia cells, and the platelet count was 12,000/microliters. A bone marrow was infiltrated with 96.0% leukemia cells. The leukemia cells stained positively for PAS and negatively for peroxidase. Immunological examination of leukemia cells showed that HLA-DR, TdT, B1 and J5 were positive and cytoplasmic Igmu and surface Ig were negative, indicating common ALL. The coagulation studies revealed that the activated partial thromboplastin time was prolonged to 42.0 seconds, FDP increased to 79.9 micrograms/ml, and antithrombin-III decreased to 62%. Chromosome analysis showed a 48, XY, +2, +21q-, t(9;22) karyotype. He was diagnosed as having Ph1 positive ALL associated with DIC. He was treated with vindesine, prednisolone, L-asparaginase, and adriamycin and complete remission (CR) was achieved after two months. But on August 1988, 8 months after CR, ALL and brain tumor relapsed and he died of pneumonia on September 19, 1988.
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PMID:[Ph1 positive acute lymphoblastic leukemia with DIC after operation of colon and lung cancer]. 281 Jul 93

Pregnancy-related acute renal failure (ARF) can include reversible tubular necrosis as well as irreversible cortical necrosis. Though pathogenetic mechanism are not fully understood, disseminated intravascular coagulation (DIC) probably plays a primary role. We report 25 cases of pregnancy-related ARF: 13 were associated with preeclampsia or eclampsia and 12 with obstetric complications. The following parameters were studied: partial thromboplastin, prothrombin and thrombin time, fibrinogen, anti-thrombin III and FDP levels, platelet count, whole blood clot lysis time and area, fragmented red cells (schistocytes) in the blood smear, hemoglobin, aptoglobin and LDH concentrations. DIC was scored in arbitrary units ranging from 12 to 36 and related to the clinical picture, renal outcome and the treatment employed. Five patients had irreversible renal damage, while 19 recovered fully; one patient died and no renal histology was available. The DIC score did not seem to have a significant relation to the severity of renal damage.
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PMID:The role of intravascular coagulation in pregnancy related acute renal failure. 322 77

There have been many reports of cases in which chronic increases in the numbers of natural killer (NK) cells have been reported. Whether this is reactive or neoplastic in nature has been debated. We report the first case of an aggressive NK cell leukemia in an adult with establishment of an NK cell line. A 70-year-old man had two spontaneous episodes of jejunal perforation and one month later developed a severe febrile illness with moderate splenomegaly. Hemoglobin was 13.1 g/L, and WBC count was 1.8 X 10(9)/L with 2% large granular lymphocytes (LGLs). Platelet count was 143 X 10(9)/L; prothrombin time (PT) and partial thromboplastin time (PTT) were normal. Bone marrow was infiltrated with 25% to 30% LGLs; serum lysozyme was normal. Serum LDH was initially 1,191 U/L and rose to 6,408 (normal 240 to 525 U/L). Ten days later, the WBC count increased to 99.9 X 10(9)/L with 70% LGL cells; the PT and PTT increased, and the platelet count dropped. No bacterial or viral cause of fever was identified. The cells from peripheral blood were LGLs that stained positively for acid phosphatase. All of the LGLs reacted with a monoclonal antibody reactive with NK cells (LEU-11b). Functionally, the patient's peripheral blood mononuclear cells (PBMs) demonstrated 100 times more lytic activity against K562 tumor cell lines than did normal PBMs. The patient's PBMs were propagated in vitro. The cultured cells showed the morphological, cytochemical, immunological, and functional characteristics of NK cells. In addition, partial trisomy involving chromosome 1 q with duplication in regions of q21 through q31 was observed in all metaphases analyzed. The extra chromosome 1q with duplication in regions q21 through q31 was translocated to the p-terminal of chromosome 5. One percent to 5% of normal PBMs comprise NK cells; in most cases, leukemias arise from normal phenotypic counterparts. This case demonstrated that aggressive NK cell leukemia may occur in adults. In addition, the chromosomal abnormalities suggest that this is not a reactive process but a malignancy.
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PMID:Aggressive natural killer cell leukemia in an adult with establishment of an NK cell line. 395 37

Cultured bovine aortic endothelial cells acquired the ability to initiate coagulation after treatment with endotoxin or phorbol ester. The acquired procoagulant activity was identified as tissue factor since cells treated with endotoxin or phorbol ester activated factor X only in the presence of factor VIIa, and factor X activation could be completely blocked by a specific antibody to bovine tissue factor apoprotein. The generation of tissue factor activity was evident after 6 hours of incubation and was dependent on RNA and protein synthesis, as indicated by the inhibitory effects of actinomycin D and cycloheximide. Endotoxin and phorbol ester are toxic to cultured endothelial cells as evidenced by release of LDH and detachment from the culture dish. Surviving endothelial cells lose their stress fibers and assume a cytoskeletal organization characteristic of mobility or radial extension. Because these changes in cell shape occurred parallel with the acquisition of procoagulant activity, the effects of drugs interfering with organization of the cytoskeleton were tested. Cytochalasins B and D, vinblastine, and colchicine, each decreased the generation of tissue factor activity when cells were exposed to endotoxin or phorbol ester. Trifluoperazine, a calmodulin antagonist, also prevented the generation of tissue factor activity in a dose-dependent fashion. Thus, perturbation of endothelial cells by treatment with phorbol ester or endotoxin induces potent tissue factor procoagulant activity. This cellular response appears to require protein and RNA synthesis, normal cytoskeletal functions, and the Ca++-calmodulin system.
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PMID:Cellular requirements for tissue factor generation by bovine aortic endothelial cells in culture. 408 33

We analyzed historical control data of clinical pathology testings provided by sixty-seven member companies of the Japan Pharmaceutical Manufacturers Association covering study populations of approximately 7,000 rats/sex, 5,000 dogs/sex, and 700 monkeys/sex. This paper assesses the relationship between conditions of sample collection, methods of measurement, etc. and potential factors contributing to variations in reference data, based on weighted means and standard deviations thereof derived from data for rats, dogs and monkeys for those parameters measured using methods most common to the participating facilities. Parameters included erythrocyte count (RBC), hematocrit (Ht), hemoglobin concentration(Hb), reticulocyte count (Rt), platelet count, total leukocyte count (WBC), differential leukocyte count (%WBC), coagulation time (activated partial thromboplastin time: APTT, prothrombin time: PT), and serum/plasma levels of GOT, GPT, ALP, LDH, glucose, cholesterol, triglycerides (TG), total protein, albumin, urea nitrogen (UN), creatinine, sodium (Na), potassium (K), calcium (Ca), chloride (Cl), inorganic phosphorus (Ip), and CPK. Analyses of the data revealed species differences in RBC, Ht, Rt, platelet count, WBC, %WBC, ALP, LDH, glucose, cholesterol, TG, total protein, UN, creatinine, Ca, Ip, and CPK. There were strain differences in rats in platelet count, WBC, GOT, ALP, UN, creatinine, and CPK. Sex differences were noted for Hb, Ht, WBC, ALP, glucose, cholesterol, TG, total protein, A/G ratio, UN, and Ip. Age differences were observed with RBC, Hb, Ht, Rt, %WBC, GOT, GPT, ALP, LDH, cholesterol, TG total protein, Ip, and CPK. APTT, PT, ALP, glucose, TG and UN were found to be subject to the influence of fasting/feeding. In rats, Ht, WBC, CPK and K showed differences by the site of bleeding. Observed values for LDH and CPK varied with specimen type, plasma or serum; serum assay values showed greater variation than plasma values.
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PMID:Clinical pathology reference ranges of laboratory animals. Working Group II, Nonclinical Safety Evaluation Subcommittee of the Japan Pharmaceutical Manufacturers Association. 835 5

UR-12670 is a novel and potent PAF antagonist, eg., it displaces [3H]WEB-2086 from PAF receptors in rabbit platelet membranes (Ki = 0.6 nM) and inhibits PAF-induced increase in vascular permeability in rat trachea (100%), thymus (44%), seminal vesicles (100%) and stomach (54%) at a dose of 0.01 mg/kg i.v. Since PAF is thought to be an important mediator in endotoxic shock, the effect of pretreatment with UR-12670 on changes in vascular permeability, disseminated intravascular coagulation (DIC) and plasma biochemical parameters were determined in a rat model of acute endotoxemia. UR-12670 and the reference PAF antagonist, lexipafant (10 mg/kg i.v.), strongly inhibited lipopolysaccharide (LPS, 25 mg/kg i.v.)-induced plasma leakage in the trachea (49 and 100%, respectively) and seminal vesicles (81 and 100%), as assessed by the Evans blue extravasation method. Only lexipafant inhibited the increase in vascular permeability in the thymus (36%). Neither PAF antagonist was effective in the stomach. Both UR-12670 and lexipafant at 10 mg/kg i.v. attenuated the LPS-induced variation of some DIC markers, such as activated partial thromboplastin time increase (56 and 58%, respectively) and the fibrinogen concentration decrease (53 and 31%), whereas the increase in prothrombin time was not affected. Increased plasma acid phosphatase (ACP, a lysosomal activation marker) and lactate dehydrogenase (LDH, a tissue damage marker) activity elicited by LPS was attenuated by pretreatment with 10 mg/kg i.v. of either UR-12670 or lexipafant (ACP: 55 and 48%; LDH: 50 and 33%). LPS-induced hyperglycemia (46 and 37%) and hyperlactacidemia (100% both) were also inhibited. UR-12670 protected against several shock symptoms, confirming the role of PAF in the pathogenesis of rodent endotoxemia.
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PMID:Effects of a new platelet-activating factor antagonist, UR-12670, on several endotoxic shock markers in rats. 951 29

Hirudin, the anticoagulatory polypeptide of the leech Hirudo medicinalis, strongly inhibits thrombus formation by specifically interacting with thrombin. For diagnostic purposes, hirudin should be superior to other anticlotting compounds because it only minimally alters the mineral, protein, and cellular blood constituents. To test this hypothesis, hirudinized and routinely processed venous blood from 80 healthy volunteers and patients was subjected to a variety of automated blood tests. A strong correlation was found between the results of automated complete blood counts obtained from K(2)-ethylenediaminetetraacetic acid (EDTA) anticoagulated and hirudinized blood (1000 antithrombin units [ATU] hirudin/ml). In addition, clinical chemistry and serological infection parameters (asparlat amintransferase [ASAT], lactate dehydrogenase [LDH], sodium, and so on, and antibodies against hepatitis B and C and human immunodeficiency virus [HIV]1/2, respectively) correlated well when measured in serum as compared with hirudinized plasma. Contrary to single clotting factors, global coagulation parameters (activated partial thromboplastin time [aPTT], prothrombin time [PT]) could not be measured in hirudinized blood. Recombinant hirudin neither interfered with immunophenotyping of mononuclear cells using FACScan analysis, nor did it alter the detection of Wilms' tumor gene expression by RT-PCR technology even at high doses (5000 ATU hirudin). Thus, a hirudin-containing blood sampling tube can be designed as a universal blood sampling tube (UBT) for testing the majority of diagnostic blood parameters.
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PMID:Measurement of hematological, clinical chemistry, and infection parameters from hirudinized blood collected in universal blood sampling tubes. 1154 57

The effect of epigallocatechin-3-O-gallate (EGCG), a major component of green tea, on platelet preservation was evaluated. Single donor platelets (N = 10) were collected and preserved by the standard method. EGCG was added to the platelet concentrates before preservation and then the functional and biochemical parameters were monitored throughout the storage period. After 6 days of preservation, the aggregability of the platelets was significantly maintained by addition of 50 and 100 microg/ml of EGCG. Platelet prothrombinase activity was also significantly retained by the addition of EGCG. The accumulation of P-selectin and RANTES in the plasma preserved with EGCG was less than those preserved without EGCG, which indicated that EGCG might inhibit platelet activation. Furthermore, EGCG reduced the increase of LDH in plasma during preservation and inhibited the activation of caspase-3 and cleavage of gelsolin, thereby showing that EGCG could inhibit the apoptosis of platelets. These results suggest that EGCG may play an effective role in preserving platelets by inhibiting the activation and apoptosis of platelets.
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PMID:Preservation of platelets by adding epigallocatechin-3-o-gallate to platelet concentrates. 1977 12


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