[Eosinophilia and hepatocellular carcinoma associated with von Recklinghausen's disease].
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Carcinoma, Hepatocellular↗
Biomedical subjects
Y Sakata
Publications and source records attributed to Y Sakata.
Differential binding of plasminogen to crosslinked and noncrosslinked fibrins: its significance in hemostatic defect in factor XIII deficiency.
In spontaneous fibrinolysis of an alpha 2-plasmin inhibitor-deficient plasma clot or tissue-type plasminogen activator-induced fibrinolysis in a purified system without alpha 2-plasmin inhibitor, the lysis was faster when factor XIII-mediated crosslinking of fibrin to fibrin did not occur. During the initial period, the binding of plasminogen to fibrin steadily increased with incubation time. The initial level and subsequent increase of the binding, which may be critical for the subsequent development of fibrinolysis, were more remarkable when fibrin was not crosslinked. The amount of glu- or lys-plasminogen bound to noncrosslinked fibrin was around 4 or 1.5 times larger than the amount of the respective plasminogen bound to crosslinked fibrin. Plasmin was also found to be bound to noncrosslinked fibrin twice as much as the amount bound to crosslinked fibrin. Structural changes induced by crosslinking of fibrin alpha-chain may reduce either the affinity or the number of available complementary sites to lysine binding sites of plasmin(ogen), thereby decreasing the binding of plasmin(ogen) to fibrin. These results suggest that an increased affinity of noncrosslinked fibrin for plasmin(ogen) is contributory to the accelerated fibrinolysis observed in factor XIII deficiency, in addition to an absence of crosslinking of alpha 2-plasmin inhibitor to fibrin.
Enzyme Activation↗
[Fundamental and clinical studies of ceftazidime in the pediatric field].
Ceftazidime ( CAZ ), a newly-developed parenteral cephem antibiotic, was administered to 8 children; by one shot intravenous (i.v.) injection in the doses of 20 and 40 mg/kg each to 2 children, and by 30 minutes' i.v. drip infusion in the doses of 10 and 20 mg/kg each to 2 children, and the serum levels, urinary levels and recovery rates were determined. CAZ was also administered to 2 patients with purulent meningitis, one complicated with subdural abscess and the other with bacteremia, in the doses of 19.2 and 50.7 mg/kg, respectively, by one shot i.v. injection, and the CSF level of CAZ was determined. In addition, CAZ was administered to 2 children with acute bronchitis, 1 with chronic bronchitis, 37 with pneumonia, 3 with pleuropneumonia, 1 each for purulent meningitis, purulent meningitis accompanied with subdural abscess and purulent meningitis with bacteremia, 5 with urinary tract infections and 3 with purulent lymphadenitis (total 54 children), in the mean dose of 85.8 mg/kg/day mostly in 4 divided doses by one shot i.v. injection for 9 days on the average, and clinical effectiveness and bacteriological response were evaluated in these cases, and adverse events and abnormal laboratory findings were examined in the 66 cases which included 12 drop-out cases. 1. After the administration of CAZ to 4 children; 20 and 40 mg/kg each to 2 children, by one shot i.v. injection, the mean serum levels got to the peak of 115.8 and 199.5 mcg/ml, respectively, at 5 minutes. The results were good, showing dose response. The mean half-lives were 1.48 and 1.37 hours, respectively. After the administration of 10 and 20 mg/kg of CAZ each to 2 children by 30 minutes' i.v. drip infusion, the mean serum levels got to the peak of 58.5 and 80.0 mcg/ml, respectively, on completion of the administration, showing dose response. The mean half-lives were 1.06 hours in the former 2 cases, and 1.38 and 3.26 hours, respectively, in the latter 2 cases. The reason for the prolongation observed in 1 case was not clear. 2. In the above mentioned each 2 cases receiving one i.v. injection, the mean urinary levels got to the peak of 4,240 and 4,445 mcg/ml, respectively, at 0-2 hours after the administration , and the urinary recovery rates during the first 6 hours were high, 95.7% and 99.5%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Protective effect of FR35447 on experimental cerebral infarction.
The protective effect of 2-(5-chloro-2-phenoxyanilino)-2-imidazoline [FR35447] on cerebral infarction was examined in animal models. FR35447 in p.o. doses of 1 mg/kg or more caused a marked reduction of arachidonate-induced cerebral infarction in rats. Since FR35447 (10(-6) M) inhibited platelet aggregation induced by adrenaline plus the divalent cation ionophore A23187, as did yohimbine (10(-6) M), the protective effect of FR35447 is presumed to be due to its blocking activity on the alpha 2 adrenoceptors of platelets. However, additional mechanisms appear to participate in the protective effect of FR35447 on cerebral infarction. A ten-day treatment with FR35447 in p.o. doses of 1 to 10 mg/kg/day decreased serum lipid peroxide levels in vitamin E deficient rats, suggesting that FR35447 may have free radical scavenging activity. Moreover, FR35447 (greater than or equal to 10(-5) M) increased red cell deformability. These effects of FR35447 suggest that it may be useful in preventing or treating cerebral infarction.
Animals↗
[Tuberculosis epidemic in a nursery school].
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Adolescent↗
Synthesis, structure, and hypochromism of (2,9)(6,9)purinophane.
The title compound 1 was synthesized via 8 steps from phthalimide derivative 2. The molecular structure of 1 was determined by X-ray analysis and the relationship between the hypochromism and the stacking mode of two purine rings was discussed.
Indicators and Reagents↗
[Clinical trials of cefmetazole for pneumonia and pyothorax caused by Staphylococcus aureus resistant to cefazolin].
Cefmetazole (CMZ), an antibiotic agent of the cephamycin group, is resistant to beta-lactamase and has a broad antibacterial spectrum covering Gram-positive cocci and Gram-negative bacilli. However, it has not been indicated for Gram-positive cocci. We examined its clinical, bacteriological and side effects in 2 infants with pneumonia and 2 with pyothorax, which had been suggested to be caused by CEZ-resistant and CMZ-sensitive Staphylococcus aureus or other inflammatory organisms by a disc sensitivity test, for 2 years and 3 months from January, 1981 to March, 1983. The patients aged 1 to 22 months, and a mean daily dose of 108 to 115 mg/kg was divided into 2 to 4 equal doses and injected into the vein at one shot for a mean fo 19 days. The following results were obtained: The clinical effect of CMZ was evaluated to be good in 1 and fair in 1 of 2 infants with pneumonia, and excellent in 1 and good in 1 of 2 with pyothorax. Bacteriologically, S. aureus was removed in an infant with pneumonia and in 2 with pyothorax. Bacteriological test was not conducted in the remaining 1 with pneumonia. No side effects were found in any cases. Eosinophilia appeared as an abnormal clinical test value in a case, but the number of eosinophils became normal after termination of the medication. As mentioned above, CMZ manifested an excellent clinical effect in infants with pneumonia or pyothorax caused by S. aureus although the number of the patients was small. From the results the antibiotic agent can be expected to be effective in these disease.
Age Factors↗
Pharmacokinetics and bacteriological effect of ceftazidime in experimental Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli meningitis.
The pharmacokinetics and bacteriological effect of ceftazidime were evaluated in rabbits experimentally infected with Streptococcus pneumoniae, Haemophilus influenzae type b, and Escherichia coli K1. The mean penetration of ceftazidime into cerebrospinal fluid after single-dose or constant-infusion administration ranged from 7.8 to 14.9%. The median cerebrospinal fluid bactericidal titers were 1:64 against S. pneumoniae and H. influenzae and 1:128 against E. coli. The bacterial colony counts in cerebrospinal fluid were reduced by 58% to 100% (-2.3 to -3.9 log10 CFU/ml) in 3 h and by 100% (-3.2 to -5.1 log10 CFU/ml) in 9 h of constant infusion, whereas in untreated infected animals, bacterial counts increased from +1.4 to +2.1 log10 CFU/ml in 9 h. These data on ceftazidime compare favorably with those on penicillin, chloramphenicol, netilmicin, and moxalactam in this experimental meningitis model.
Animals↗
Treatment of DIC with antithrombin III concentrates.
We administered AT III concentrates to 21 patients with DIC who failed to respond initially to heparin therapy. About 60% of these 21 patients were effectively treated with AT III concentrates by enhancing the effect of heparin and alleviating the burden of excessive plasma transfusions on the cardiovascular system.
Adult↗
[Clinical evaluation of josamycin for the treatment of Mycoplasma pneumonia in children].
Thirty-one strains of Mycoplasma pneumoniae were tested for drug sensitivity to both josamycin (JM) and erythromycin (EM), to evaluate the efficacy of JM for mycoplasmal pneumonia in children. In addition to the sensitivity tests of 31 M. pneumoniae strains against JM and EM, 50 patients, between the ages of 3 years 1 month and 13 years 3 months, suspected of suffering from mycoplasmal pneumonia were treated with 50 or 200 mg JM tablets at an average daily dose of 43.1 mg/kg t.i.d. or b.i.d. for an average period of 14 days; an additional 31 patients between the ages of 2 years 9 months and 11 years, suspected of suffering from this disease were treated with tablet or dry syrup of EM, with the exception of EM estolate, t.i.d. or b.i.d. at an average daily dose of 72.5 mg/kg for an average period of 15 days. Patients were selected in 37 and 22 mycoplasmal pneumonic patients respectively for JM and EM. Clinical and bacteriological effects, efficacy and side effects of the drugs on this disease were studied and the following results were obtained. Drug sensitivity test Of all 31 strains tested for JM sensitivity the populations which exhibited 0.125 mcg/ml were most abundant (18/31, 58.1%) and MIC pattern of all strains were distributed from 0.0313 to 0.125 mcg/ml. In the EM group, 61.3% (19/31) of the populations were sensitive at 0.015 mcg/ml, exhibiting the dominant distribution pattern and MIC range of all organism varied from 0.0078 to 0.0313 mcg/ml. Resistant strains were found to neither JM nor EM. EM was approximately 2 to 10 times more active than JM in MIC evaluation. Clinical effects of JM by daily doses Clinical effects relative to the daily dose were evaluated in 3, 7, 10 days after administration of drugs. The response was favorable, according to assessments of the attending doctors, in 96.7, 100% and 95.8% of the patient group given JM in a daily dose of 40-49 mg/kg, the group to which the largest number of patients belonged. Similar favorable results were obtained by the assessments of Evaluation Committee, showing 86.7, 96.7% and 100% of favorable response. Upon comparison, in the same interval, of these results with those of the groups given EM in a daily dose of 50 mg/kg, the group in which the largest number of patients were seen, there was no significant difference in the assessments either of the attending doctors or of the Evaluation Committee.(ABSTRACT TRUNCATED AT 400 WORDS)
Age Factors↗
[Clinical effects of an ampicillin suppository (KS-R1) in urinary tract infection of children].
Clinical effects of ampicillin suppository (KS-R1) were examined in 24 children (11 male and 13 female) aged from 5 months to 7 years 5 months with urinary tract infection. KS-R1 was rectally given to the patients at doses of average 45.6 mg/kg/day divided into 3 to 4 times for average 8 days. Clinical effectiveness was 95.8%. Bacteriologically, the eradication of isolated organisms was observed in 10 (71.4%) out of 14 cases, the decrease in 3 (21.4%) and the persistence in 1 (7.1%). The discharge of suppository within 5 minutes after insertion was observed in 8.7% of patients without diarrhea and in 6.9% of patients with diarrhea. The evacuation rate of the bowels within 10 minutes after insertion was observed in 5.9% of patients without diarrhea and in 41.9% of patients with diarrhea. It was suggested that the administration of KS-R1 to childish patients with diarrhea should be careful. As to the side effects, diarrhea was observed in 2 cases (7.1%) and the elevation of GPT and GOT in 1 case (3.6%).
Age Factors↗
Fibrin-associated plasminogen activation in alpha 2-plasmin inhibitor deficiency.
The clot formed from the plasma of a patient with congenital deficiency of alpha 2-plasmin inhibitor underwent a spontaneous extensive fibrinolysis. Radiolabeled fibrinogen was added to the plasma before clotting, and the whole process of the fibrinolysis was followed by measuring the release of radiolabels. Plasminogen activation was also followed by measuring the amidolytic activity that developed. There was an initial latent period, followed by an exponential increase of fibrinolytic activity. During the latent period, there was little or no release of radiolabels and no development of amidolytic activity. During the latent period, the clot was washed thoroughly to remove unbound proteins from fibrin and was incubated in buffered saline. The washed clot still underwent fibrinolysis, similar to the original plasma clot, suggesting that the plasminogen/plasminogen activators bound to fibrin during the initial latent period are responsible for fibrinolysis. The amount of plasminogen bound to fibrin during the latent period was close to the amount of plasminogen activated during the whole process of fibrinolysis. When the amount of plasminogen bound to fibrin was decreased by epsilon aminocaproic acid, the extent of fibrinolysis was decreased in parallel with the decrease of the amount of the bound plasminogen. This suggests that the amount of plasminogen bound to fibrin is one of the determinants of the rate of the fibrinolytic process.
Enzyme Activation↗
[Experimental study of an ampicillin suppository (KS-R1) in adults and children].
KS-R1, a new rectal suppository of ampicillin (ABPC) sodium, was compared with oral and parenteral ABPC in terms of absorption and excretion in childish patients and healthy adult male volunteers. In addition, the irritation of KS-R1 to the rectum was studied. 1. Eight healthy adult male volunteers received 250 mg (potency) of KS-R1 rectally and 125 mg of ABPC intravenously in a cross-over study. Then, 4 of them were given intramuscularly 250 mg of ABPC, and 3 of the remaining 4 volunteers were given 250 mg of ABPC orally. The rectal administration of 250 mg of KS-R1 resulted in a mean peak ABPC plasma level (Cmax) of 2.6 mcg/ml at 30 minutes, and then ABPC levels declined with biological half-life (T2/1) of 0.55 hour. The peak time (Tmax) of occurrence after rectal dose of KS-R1 was earlier than that after oral dose of ABPC, and was equal to that after intramuscular dose of ABPC. Cmax after rectal dose of KS-R1 was equal to that after the oral dose, and was about 40% of the value attained with the intramuscular dose. Urinary recovery of ABPC during 6 hours after rectal dose of KS-R1 was 24.0%, compared with 34.0% for the oral dose, 59.6% for the intramuscular dose and 61.4% for the intravenous dose. The relative bioavailability of KS-R1, calculated on the basis of urinary recovery after intravenous administration of ABPC, was about 40%. 2. When KS-R1 (250 mg) was given to 2 adult volunteers 3 times daily for 5 days, no remarkable difference was found in plasma concentration and urinary recovery of ABPC. The pharmacokinetic parameters following the last administration were similar to those following a single administration of KS-R1. 3. KS-R1, oral ABPC and intravenous ABPC were administered at the dose of 125 mg (potency) to 5, 4 and 3 children and at the dose of 250 mg (potency) to 5, 3 and 3 children, respectively. Peak plasma level (Cmax) of ABPC after rectal administration of 125 mg and 250 mg of KS-R1 was reached in 15 minutes, indicating 4.8 and 7.1 mcg/ml, respectively. Peak time (Tmax) of ABPC after the rectal doses of KS-R1 was about 2 hours earlier than that after oral doses of ABPC. Cmax after KS-R1 was 3-4 times as high as that after the oral doses. Area under the curve (AUC) with KS-R1 was 1.38-1.55 times greater than that of oral ABPC, and about 24% of the values obtained with intravenous doses of ABPC. Urinary recoveries of ABPC rectal doses of KS-R1 were 30.4 to 45.6%, compared with 29.2 to 30.8% for the oral doses and 61.1 to 76.1% for the intravenous doses.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Oral↗
[Experimental and clinical evaluation of an ampicillin suppository (KS-R1) in children].
Plasma levels of ampicillin (ABPC) after the single rectal insertion of KS-R1 at doses of 125 and 250 mg in 154 children reached a peak at 11 approximately 15 minutes in children of age less than 1 year old, at 16 approximately 20 minutes in children of 1 approximately 3 years, 4 approximately 6 years and more than 7 years old with the highest levels of 11.50, 8.69, 10.33 and 8.30 micrograms/ml, respectively. Highest plasma levels of ABPC were 6.48, 8.00, 12.32 and 17.83 micrograms/ml by the administration of KS-R1 at doses of less than 10.9 mg/kg, 11.0 approximately 15.9, 16.0 approximately 20.9 mg/kg and more than 21.0 mg/kg, respectively, with dose-dependent response which were observed at 11 approximately 15 minutes or 16 approximately 20 minutes. There was no difference of plasma levels between the administration of 125 and 250 mg of KS-R1. The pain of insertion was observed in 0.6% of total 167 cases, the feeling of defecation in 2.4% and the discharge of suppository or its dissolved material or defecation within 30 minutes after insertion in 12.6%, without the influence of patients ages and dosage level. These figures were almost the same as those after the insertion of other suppositories such as erythromycin suppository or antipyretic suppository. Clinical effectiveness of KS-R1 was examined in 51 childish patients with various infections. KS-R1 was rectally given to them at doses of average 41.6 mg/kg/day divided into 3 to 4 times for 7 days. All cases showed excellent and good effects. Bacteriologically, all pathogens which were isolated from 12 patients were eradicated.
Age Factors↗
[Experimental and clinical evaluation of latamoxef in newborn and premature infants].
Latamoxef (LMOX) was administered as a one-shot intravenous injection of 10 mg/kg or 20 mg/kg to 28 newborn and immature infants of 1 to 28 days of age. For 6 hours following the administration, the concentrations of the drug in the plasma and in the urine were monitored and the urinary recovery rate was determined. In addition, 17 patients, consisting of newborns, immature infants and suckling infants, aged 0 days to 2 months and diagnosed as having various bacterial infections, were also treated with LMOX; the mean daily dosage was 103 mg/kg, administered in 2 to 6 divided doses as one-shot intravenous injections for an average duration of 11 days. These patients were subjected to the analysis for the clinical efficacy and bacteriological efficacy of the therapy. Furthermore, with the inclusion of 35 drop-out cases, a total of 52 patients was investigated for the occurrence of side effects by the LMOX therapy. The findings of these studies are summarized below. The patients were divided into 5 groups on the basis of age: 3 days old or less, 4--7 days, 8--14 days, 15--21 days and 22--28 days. Only in the 8--14 day-old group administered LMOX at 20 mg/kg, the maximum mean plasma concentration of the drug occurred at the time of 15 minutes postadministration, although some individuals showed peaks at 5 minutes. In all of the other age groups, for both the 10 and 20 mg/kg dosages, the maximum plasma concentration of LMOX occurred 5 minutes postinjection. In each of the age groups, a dose response was seen between the 2 dosage levels. However, a comparison of each group and control infants in terms of the LMOX plasma concentration at 30 minutes after injection revealed that the concentrations in the patients in this study were low. In terms of the half-life of the drug at the 2 dosage levels, both the mean and individual values in each of the age groups were longer than the half-lives in control infants. This tendency was especially marked in the case of infants 7 days of age or less. The values for the AUC also tended to be larger in the younger patient groups. A good level of LMOX was detected in the urine during each of the 0--2, 2--4 and 4--6 hour periods following administration.(ABSTRACT TRUNCATED AT 400 WORDS)
Bacterial Infections↗
Synthesis of model compounds for the interaction between modified nucleic acid bases.
In order to study the stacking interaction of modified nucleic acid bases, which is assumed to be responsible for the anomalous thermostability of thermophile tRNA, several model compounds 1-6 are synthesized. On the basis of their hypochromicities, the interaction between bases are discussed.
Chemical Phenomena↗
[Late complications of radiotherapy in testicular tumor].
During the past 21 years, 105 patients with germinal testicular tumor were treated in our hospital; 86 out of 105 patients were irradiated postoperatively. Late radiation injury was observed in 14 patients: Cutaneosigmoidal fistula in 1 patient, ileus (jejunum necrosis) in 1 patient, gastric ulcer in 1 patient, duodenal ulcer and stenosis in 1 patient, lung fibrosis in 1 patient, radiation cystitis in 1 patient, severe lymph edema of lower extremity in 1 patient, muscle atrophy of lower extremity in 1 patient, lower extremity growth disturbances in 3 children and severe abdominal cutaneosubcutaneal fibrosis in 3 patient. Two cases of late radiation injury are presented and discussed.
Adolescent↗
[Clinical studies on cefadroxil in the field of pediatrics].
The newly developed cefadroxil (CDX) dry syrup in a mean daily dose of 32.9 mg/kg t.i.d. or q.i.d. was administered to children for a period of 8 days on the average; viz. a total of 64 cases consisting of 39 cases of tonsillitis, 2 of tonsillitis complicated with otitis media, 1 of bronchitis, 1 of pneumonia, 14 of scarlet fever, and 7 of urinary tract infections; and its clinical and bacteriological effects, and adverse reactions were examined, leading to the following results. 1. The clinical effects were "good" or "excellent" in any of 39 cases of tonsillitis, 2 of tonsillitis complicated with otitis media, 1 of pneumonia, 14 of scarlet fever, and 7 of urinary tract infections, and "fair" only in a case of bronchitis, showing the high efficacy of 98.4%. 2. The clinical effects by daily dose were compared only in the great cases of tonsillitis between the 2 daily dose groups of 30 mg/kg or below and 31 to 40 mg/kg, and both groups showed "good" or "excellent" results, but the latter group revealed that the excellent rate was greater by 20.8% than that of the former group. 3. The frequency of daily administration was 3 times or 4 times and the cases of 4 times administration were few in any disease. In comparison of clinical effects between the 3 times group and the 4 times group in the whole cases, no significant difference was observed between both groups but it is desirable to make the 4 times administration in view of the pharmacokinetics. 4. The bacteriological effects could be judged in 15 cases, namely bacteria were eradicated in 14 cases and unchanged in 1 case, showing a good result of the eradication rate as 93.3%. 5. No adverse reaction was observed and the laboratory test values showed eosinophilia in 7 cases (15.9%) and abnormal elevations of GPT in 1 case (4.5%), of GOT and GPT in 2 case (9.1%), of LDH in 1 case (4.8%) and of BUN in 1 case (4.8%), but 4 of the 7 cases with eosinophilia seemed attributable to underlying diseases or objective diseases. From the above it can be said that this preparation is a useful drug in mild bacterial diseases.
Adolescent↗