[alpha 2-Plasmin inhibitor-plasmin complex (PIC)].
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Antifibrinolytic Agents↗
Biomedical subjects
Y Sakata
Publications and source records attributed to Y Sakata.
Effect of glycosidase inhibitors on the biosynthesis of alpha 2-plasmin inhibitor and antithrombin III in Hep G2 cells.
We studied the effect of the glucosidase I inhibitor, N-methyl-1-deoxynojirimycin (MdN) and the mannosidase inhibitor, 1-deoxymannojirimycin (dMM) on the biosynthesis and secretion of alpha 2-plasmin inhibitor (alpha 2-PI) and antithrombin III (ATIII) in cultures of human hepatoma (Hep-G2) cells. Incubation with 1 mM MdN decreased secreted alpha 2-PI activity and antigen levels by about 40%, whereas those of ATIII were not affected. Neither inhibitor affected the messenger RNA levels as determined by Northern blotting. Pulse-chase studies using [35S]-methionine showed that MdN decreased alpha 2-PI and ATIII secretion rates. By the 18 h chase, MdN had decreased secreted alpha 2-PI to 50-60%, with little effect on ATIII. Intracellular forms of alpha 2-PI or ATIII synthesized by cells treated with 1 mM MdN were sensitive to endoglycosidase H (Endo H), whereas almost all the secreted forms were resistant, suggesting the presence of complex-type oligosaccharides. In the presence of 1 mM dMM, cells synthesized Endo H-sensitive alpha 2-PI and ATIII with similar secretion rates. These results suggest that retention of glucose on N-linked oligosaccharides not only retards the exit of alpha 2-PI and ATIII, but also changes the catabolic rate of alpha 2-PI in the endoplasmic reticulum.
1-Deoxynojirimycin↗
Clinical study of biological response modifiers as maintenance therapy for hepatocellular carcinoma.
We conducted a randomized, controlled trial comparing 5-fluorouracil (5-FU) with or without biological response modifiers (BRMs) as a maintenance therapy for hepatocellular carcinoma (HCC) after treatment with percutaneous ethanol injection (PEI), transcatheter arterial embolization (TAE) or arterial infusion of antitumor agents (AI). A total of 58 cases of HCC were classified into 4 groups as follows: group I, PSK with 5-FU (n = 15); group II, lentinan with 5-FU (n = 15); group III, OK-432 with 5-FU (n = 12); and group IV, 5-FU alone as the control (n = 16). The mean survival time, mortality rate, time to progression, and T4/T8 ratio of lymphocytes in the peripheral blood were compared among the four groups. There was no significant difference in the background factors among the groups. In group I, the T4/T8 ratio of lymphocytes was reduced after the therapy. No significant difference was found among the groups in terms of the mean survival time, mortality rate, or time to progression. PEI for initial therapy was superior to the other therapies in terms of the mean survival time and mortality rate. These results suggest that the addition of BRM to maintenance therapy with 5-FU exerts no prognostic benefit on HCC patients treated with PEI, TAE, or AI.
Aged↗
Estimation of faecal pollution based on the amounts of urobilins in urban rivers.
An attempt was made to establish a new indicator for faecal pollution in aquatic environments using a sensitive determination method for urobilins, which are only present in mammalian faeces and urine. Assessment of urobilin stability was followed by determination of the amount of urobilins in river water. When river water containing urobilins was shaken at room temperature, the number of total and faecal coliforms increased, while urobilins decreased only in small amounts, indicating that urobilin is relatively stable in river water and hence can serve as a useful indicator for the estimation of faecal pollution of river water. The amount of urobilins in the river waters increased steeply from the mid-point of a stream near a sewage treatment plant, while amounts in the upper stream were very low. The amount of urobilins in river water increased after rainfall. Findings suggested that urobilin, i.e. sewage, originated from the output of the sewage treatment plant and raw sewage.
Journal Article↗
Potentiation of infectivity and pathogenesis of influenza A virus by a house dust mite protease.
Common house dust mites (e.g., Dermatophagoides farinae) excrete a serine-type (Df) protease. Df protease obtained from cultured mites enhanced viral replication in vitro via proteolytic cleavage of viral hemagglutinin (HA) into HA1 and HA2, which confers potent viral infectivity. Its potency is 2- to 5-fold higher than bovine trypsin or human plasmin. Df protease also markedly accelerated virus propagation in vivo: A minute quantity of protease (estimated delivered amount, 0.8-3.2 micrograms) produced approximately 4- to 100-fold increases in infectious virus in the mouse lung. Similar augmentation of viral replication by Df protease was observed in ferret models of nasopharyngeal infections of influenza virus. All extracts from ordinary house dust contained a serine-type protease that cleaved HA into HA1 and HA2. Thus, mite protease in house dust may enhance the pathogenesis of influenza virus.
Amino Acid Sequence↗
[A child with iritis due to Chlamydia pneumoniae infection].
A case of uncommon iritis due to Chlamydia pneumoniae (C. pneumoniae) is reported. The patient was a 9-year-old boy who had suffered from cough, pharyngeal pain, and low grade fever. The symptoms persisted for more than 1 month in spite of an oral cephem antibiotic. Ophthalmalgia, congestion around the iris and cough had lasted with alleviation and exacerbation. A diagnosis of C. pneumoniae infection was made by specific polymerase chain reaction (PCR) method and microimmunofluorescence test (MIF). The symptoms subsided with administration of clarithromycin (CAM: 300 mg/day) for 2 weeks. Because of the simultaneous alleviation of iritis, C. pneumoniae infection was considered to introduce the iritis. Much remains to be clarified about this pathogenesis of iritis and more detailed evaluations are required.
Child↗
Transcriptional activities of a winged bean Kunitz chymotrypsin inhibitor gene promoter in stable and transient expression systems.
Sequential deletions of the promoter region of the WCI-3b gene, which encodes the major chymotrypsin inhibitor of winged bean, were constructed and their expression was analyzed in transgenic tobacco plants and in bombarded winged bean seeds. In transgenic tobacco plants, a critical promoter region which is important for high levels of expression in seeds was identified, but deletion of this region had essentially no effect when bombarded into winged bean seeds.
Chymotrypsin↗
Changes in plasma catecholamines during fever induced by bacterial endotoxin and interleukin-1 beta.
We have examined whether or not the release of catecholamines into the blood circulation of rabbits during fever is mediated by prostaglandins. The plasma levels of catecholamines (epinephrine and norepinephrine) were measured in 2 ml of blood withdrawn from the marginal ear vein. At an ambient temperature of 21 +/- 1 degree C, intravenous injection of either lipopolysaccharide (LPS, 4 micrograms/kg) or human recombinant interleukin-1 beta (rIL-1 beta, 1 microgram/kg) produced a biphasic fever accompanied by an increase in the plasma level of catecholamines. Pretreatment with intravenous indomethacin (1 mg/kg) markedly suppressed the increase in catecholamines induced by LPS and rIL-1 beta. In contrast, although intracerebroventricular injection of rIL-1 beta (20 ng) produced fever, it did not produce a significant change in plasma catecholamine levels. Similarly, intrahypothalamic injection of prostaglandin E2 (200, 800 ng) induced fever, but did not cause a significant change in catecholamine concentrations. These results suggest that IL-1 acts via prostaglandins on the peripheral tissues to release catecholamines into the circulation.
Animals↗
Phagocytic ability of polymorphonuclear cells and macrophage is not decreased in aged bed ridden patients.
The phagocytic ability of polymorphonuclear cells and macrophages from aged, bed ridden patients was investigated. Phagocytosis of carbon in aged bed ridden patients did not differ from that of young controls, and extent of upregulation of granulocytes phagocytosis in response to elevation of incubation temperature was also similar between the two groups. Morphological changes of macrophages in response to ingestion of colloidal carbon was more prominent in young controls. These data suggest that a depressed phagocytosis is not an important factor in the increased susceptibility to infections of aged bed ridden patients, although the reactivity of macrophages may be more closely related to the infection defence.
Aging↗
[A case of chronic hemorrhagic pyothorax treated by extraperiosteal air plombage method].
A 64-year-old female patient was admitted with severe exertional dypnea. She had undergone left pneumonectomy because of lung tuberculosis at the age of 31. Her chest X-ray showed total opacity of the left hemithorax and mediastinal deviation to the right. The examination of the pleural effusion revealed neither malignant cells nor micro-organisms. She underwent surgery, by extraperiosteal air plombage method, successfully. Five months after the operation, her lung function and chest X-ray improved dramatically and exertional dyspnea was diminished. We conclude that the extraperiosteal air plombage method is a useful technique for patients with chronic hemorrhagic pyothorax.
Chronic Disease↗
Enterococcus faecium meningitis in a child.
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Child, Preschool↗
[Pharmacokinetic, bacteriological and clinical studies on cefozopran in the pediatric field].
Cefozopran (CZOP, SCE-2787), a newly developed parenteral cephem antibiotic, was administered to children with bacterial infections. We determined its antibacterial activity, pharmacokinetics, efficacy and safety in these patients. 1. Antibacterial activity MICs of cefmetazole, ceftazidime, cefuzonam, flomoxef and CZOP were determined against a total of 19 strains. For Gram-positive cocci, MICs of CZOP ranged from 0.39 to 0.78 microgram/ml against Staphylococcus aureus (3 strains), from 0.05 to 6.25 micrograms/ml against Streptococcus pneumoniae (5 strains), and 12.5 micrograms/ml against Enterococcus faecalis (1 strain). These MICs were generally similar to those of other cephems, but the MIC of CZOP against E. faecalis was lower than those of the other cephems examined. For Gram-negative bacilli, MICs of CZOP were 25 micrograms/ml against Citrobacter freundii (1 strain), and 6.25 micrograms/ml against Pseudomonas aeruginosa (1 strain). These values were similar to or lower than those of other cephems, MICs of CZOP against Haemophilus influenzae (7 strains) ranged from 0.1 to 0.39 microgram/ml. However, the MIC of CZOP against Serratia marcescens (1 strain) was higher than 100 micrograms/ml, and CZOP was as ineffective as the other cephems against this organism. 2. Pharmacokinetics CZOP was administered to children at 20 or 40 mg/kg via intravenous injection, and determinations were made for its serum concentrations, urinary concentrations and concentrations in cerebrospinal fluid (CSF) using the bioassay. Serum concentrations at 30 minutes after administration were 60.4 micrograms/ml with a dose of 20 mg/kg to one patient and 93.9 and 99.0 micrograms/ml with 40 mg/kg to two patients. The corresponding half-lives were 1.55 hours for 20 mg/kg administration, and 1.10 and 3.41 hours for 40 mg/kg, while the AUCs were 136.5 micrograms.hr/ml for 20 mg/kg, and 194.4 and 264.5 micrograms.hr/ml for 40 mg/kg. The rates of urinary recovery in the first 8 hours after administration were 45.0% in the patient receiving 20 mg/kg, and 84.6 and 97.6% in the two patients receiving 40 mg/kg. The concentrations in the CSF determined in 3 patients with purulent meningitis ranged from 2.6 to 16.0 micrograms/ml 1 hour after administration, and the CSF/serum concentration ratio ranged from 6.5 to 39.0%. These values for pharmacokinetic parameters obtained in the bioassay were similar to those obtained using HPLC. 3. Clinical evaluation Forty-eight patients were clinically evaluated. Of these patients, 75% were less than 3 years of age and there were slightly more male children than female children.(ABSTRACT TRUNCATED AT 400 WORDS)
Bacteria↗
[Bacteriological, pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field].
Antibacterial activities were determined and pharmacokinetics and a clinical studies were performed on biapenem (L-627), a novel parenteral carbapenem antibiotic, in infections in children. The following results were obtained: 1. MICs of L-627 against clinical isolates were as follows: Among Gram-positive bacteria, MICs were 0.78 microgram/ml to > 100 micrograms/ml against 3 strains of methicillin-resistant Staphylococcus aureus (MRSA), and 0.10 microgram/ml to 0.39 microgram/ml against 8 strains of methicillin-sensitive S. aureus (MSSA), MICs against 5 of them were similar to those of imipenem (IPM), and MICs against 3 of them were slightly higher than those of IPM. MICs were < or = 0.025 microgram/ml to 0.39 microgram/ml against 7 strains of Streptococcus pneumoniae, and were similar to those of IPM, and lower than those of ceftazidime (CAZ) and piperacillin (PIPC). Among Gram-negative bacteria, MICs were 0.78 microgram/ml and 3.13 micrograms/ml against 2 strains of Haemophilus influenzae, and were similar to those of IPM. 2. Maximum plasma concentrations determined by the bioassay method after intravenous infusion of L-627 over 30 minutes at doses of 6.0 and 12.0 mg/kg, respectively, in 2 different pairs of 2 children each (total 4 cases) were observed upon completion of the treatment. Maximum concentrations at a dose of 6.0 mg/kg were 28.8 micrograms/ml and 24.6 micrograms/ml, and at a dose of 12.0 mg/kg were 65.4 micrograms/ml and 39.6 micrograms/ml, exhibiting a dose response. Plasma half lives in the beta phase were 0.97 and 1.20 hours at 6.0 mg/kg, and 0.72 and 0.94 hour at 12.0 mg/kg. Plasma concentrations determined by the HPLC method were lower than those determined by the bioassay. 3. Urinary excretion rates in the first 5.5 hours after the 6.0 mg/kg dose were 81.4 and 75.3%, and after the 12.0 mg/kg dose were 91.0 and 73.8%, and these values were higher than those obtained using HPLC. 4. Concentrations of L-627 in cerebrospinal fluid were determined in 2 cases of purulent meningitis. In one case, 30.3 mg/kg of L-627 was infused intravenously over 30 minutes and concentrations on days 1, 3, 7 and 14 observed at 60, 60, 45 and 45 minutes after respective dosages were 7.60, 1.30, 1.42 and 0.38 microgram/ml. Cerebrospinal fluid-plasma concentration ratio was determined on days 7 and 14 to be 5.5 and 1.2% respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Bacterial Infections↗
[A case of curatively operated gastric cancer with peritonitis carcinomatosa treated by intraperitoneal administration of CDDP.Etoposide and EAP therapy].
Intraperitoneal administration of cisplatin (CDDP) etoposide (VP-16) and EAP therapy (combination chemotherapy with CDDP, adriamycin (ADM) and etoposide provided the curative resection for advanced gastric cancer with peritonitis carcinomatosa in a 48-year-old woman. She suffered from epigastralgia. CT shows the ascites, and ultrasonography shows Schnitzler metastasis. First, CDDP 100 mg and etoposide 200 mg were given intraperitoneally. Then, the ascites completely disappeared. Next, the patient underwent EAP therapy, after which Schnitzler metastasis disappeared, and total gastrectomy was performed. Macroscopically, it was of H0P0N0S2. Histopathologically, it was poorly differentiated adenocarcinoma and n0s2. She has been doing well with no evidence of recurrence for 18 months after operation.
Adenocarcinoma↗
[Randomized controlled study of sequential methotrexate and 5-fluorouracil therapy with or without 5'-deoxy-5-fluorouridine against advanced gastrointestinal cancer. Hirosaki Cooperative Study Group for Cancer Chemotherapy].
Seventy-five patients with gastrointestinal cancer were entered in this study. The number of eligible cases were 38 in the group treated with sequential methotrexate (MTX)/5-fluorouracil (5-FU) with 5'-deoxy-5-fluorouridine (5'-DFUR) (group A) and 34 in the group without 5'-DFUR (group B). The treatment schedules were as follows: MTX/100 mg/m2 was given intravenously (i.v.) followed by 5-FU 600 mg/m2 i.v. 2 hours later and leucovorin 15 mg/body i.v. 8 and 20 hours later. This cycle was repeated once a week. In group A, 5'-DFUR 1,200 mg/body/day was given orally 5 consecutive days per week. Three of 35 cases in group A showed PR, while no case showed PR in group B. Median survival time was 5.0 months in group A and 5.3 months in group B, respectively. Gastrointestinal toxicity was commonly observed, and diarrhea was more frequent in group A (p < 0.05).
Adult↗
[Preventive effect of TJ-14, a kampo (Chinese herb) medicine, on diarrhea induced by irinotecan hydrochloride (CPT-11)].
Diarrhea is one of dose-limiting factors of irinotecan (CPT-11) and its incidence is over 60% in patients receiving this drug. Therefore, it is important to prevent diarrhea for more effective use of CPT-11. We used Hange-shashinto (TJ-14), an ethical Kampo (Chinese herb) Medicine, to prevent diarrhea induced by CPT-11. Twenty-three patients (9 lung cancer, 4 pancreatic cancer, 2 colorectal cancer, 4 malignant lymphoma, and 4 other types of cancer) entered in this study. All patients were treated with CPT-11 in combination with oral TJ-14 (7.5 g t.i.d.) every day starting prior to CPT-11 infusion. The dose of CPT-11 was 60-100 mg/m2/w, 120-150 mg/m2/2 w or 40 mg/m2/d x 3 days/w. Three of 23 patients could not evaluate the efficacy and safety of TJ-14 since they could not take TJ-14 due to its odor and taste. The efficacy and safety of TJ-14 was not evaluated in one patient also since the patient could not continue taking TJ-14 due to vomiting induced by CPT-11. Nine patients showed an excellent response (no diarrhea or only 1 day of ECOG Grade 1 diarrhea). 9 showed a good response (Grade 1 diarrhea that disappears within 3 days) and one did not reveal response. It is suggested that TJ-14 possesses a preventive effect against diarrhea induced by CPT-11.
Administration, Oral↗
[Pulmonary arteriovenous fistula with Rendu-Osler-Weber disease and its HLA typing--a review and report of 87 cases of fistula].
Seven cases with pulmonary arteriovenous fistula (PAVF) in our hospital were reviewed on clinical data and HLA antigens. Furthermore, 80 reported cases of PAVF in Japan were summarized about the association with Rendu-Osler-Weber disease (Osler disease). Thirty-six (41%) of the total 87 cases had Osler disease. Fistulas were single in 46 cases and multiple in 41; unilateral in 56 and bilateral in 31. Operations were performed in 61 cases, embolizations in 8 and no therapy in 18. The frequency of the bilateral fistulas and multiple ones was significantly higher in cases with Osler disease (n = 36) than in those without Osler disease (n = 51) (p < 0.025). In our 7 cases, 6 had Osler disease. Aggregation of platelets was decreased in one case. Contralateral fistulas were recurred in another case 8 years after surgery. Three cases with Osler disease had the HLA halotype A26Bw6Bw61 which did not coincide with that in previous reports. We concluded that various HLA halotypes might exist in Osler disease.
Adolescent↗
[Neoadjuvant chemotherapy for elderly advanced gastric cancer: a case report of MTX/5-FU sequential therapy followed by radical gastrectomy].
A 70-year-old-male was diagnosed as having gastric cancer (Borr. 2, 78 mm in size on the body region; mod. dif. adenocarcinoma). CT scan revealed direct invasion of the liver. A course of MTX/5-FU sequential therapy was started (MTX 100 mg/m2, 5-FU 500 mg/m2, i.v., weekly; interval, 2 hours) on March 23, 1992. The gastric tumor showed 67% reduction on week 8 and 86% on week 10. The liver invasion had almost disappeared by CT scan (total doses, MTX 1,040 mg, 5-FU 6,750 mg). On June 25, the tumor was completely resected by radical.gastrectomy. The pathological specimen showed a "submucosal carcinoma" (10 mm in size, Stage I). Twenty-two months after the operation, the patient is alive and in good health. No cancer recurrence has been found without post-operative chemotherapy.
Adenocarcinoma↗