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Biomedical subjects

K Fukunaga

Publications and source records attributed to K Fukunaga.

At least 253 records · Page 14Linked to original sources
PubMed1988

[Studies on imipenem/cilastatin sodium in the perinatal period].

Pharmacokinetic, bacteriological and clinical studies of imipenem/cilastatin sodium (IPM/CS) were carried out in the perinatal period, and the results obtained are summarized as follows: Effects of IPM on bacterial growth curves of Staphylococcus aureus (sensitive and resistant strains) and Escherichia coli (sensitive strains) in amniotic fluid were determined. The bactericidal effects of IPM increased in amniotic fluid and remarkable increases against resistant strains were demonstrated. IPM and CS were detected promptly after intravenous drip infusion to pregnant women, and reached peak levels shortly after administration in maternal plasma. Placental penetration of IPM and CS to the fetus was favorable. After intravenous drip infusion of 500 mg/500 mg of IPM/CS, drug concentrations in the umbilical cord plasma and the amniotic fluid exceeded MICs against main pathogenic organisms. Clinically, IPM/CS was effective in the treatment of perinatal infections without any side effect. The above results demonstrated that IPM/CS is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Adult↗
PubMed1988

[Bacteriological, pharmacokinetic and clinical studies on the use of ceftriaxone in the perinatal period].

Laboratory studies and clinical evaluation of ceftriaxone (CTRX) were carried out with mothers and infants in perinatal period. The presence of synergistic effect between CTRX and amniotic fluid were studied using a broth dilution method. Stronger effects were recognized when both agents were present together compared to each agent alone by the fact that values of MIC and MBC became closer together for Escherichia coli as well as for Streptococcus agalactiae. Against the growth of E. coli, a synergism was observed, but for S. agalactiae, only an additive effect was found. The placental transmission of CTRX upon the administration was rapid, and the blood CTRX level reached its peak shortly after the intravenous administration of the drug. The transport of the drug into the fetus through placenta was excellent and one dose of 1 g of CTRX gave drug concentrations in the umbilical cord serum and amniotic fluid higher than MIC's against main pathogenic organisms. According to these results, it should be possible to treat or prevent perinatal infections by a dose of one gram per day of CTRX, once or twice daily. Cases of perinatal infections were treated with CTRX. An effective treatment without side effects was obtained. No physical abnormalities nor unusual laboratory test results were recognized in neonates delivered from mothers who received CTRX administration. The penetration of CTRX into mothers' milk was low, thus the drug transfer into neonates through the breast-feeding should not be a problem. It appears, from the above study, that CTRX is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Adult↗
PubMed1987

Phosphorylation sites of bovine brain myelin basic protein phosphorylated with Ca2+-calmodulin-dependent protein kinase from rat brain.

The phosphorylation sites of myelin basic protein from bovine brain were determined after phosphorylation with Ca2+-calmodulin-dependent protein kinase. Four phosphorylated peptides were selectively and rapidly separated by reversed-phase high-performance liquid chromatography. Partial sequencing of the phosphorylated peptides by automated Edman degradation revealed that Ca2+-calmodulin-dependent protein kinase phosphorylated serine-16, serine-70, and threonine-95 specifically, as well as serine-115, which is located on the experimental allergic encephalitogenic determinant of the protein. Of the four amino acid sequences determined, two sequences surrounding phosphorylated amino acids, -Lys-Tyr-Leu-Ala-Ser(P)16-Ala- and -Arg-Phe-Ser(P)115-Trp-Gly-, have both sides of each phosphoserine residue occupied by hydrophobic amino acids, and a basic amino acid, arginine or lysine, is located at the position 2 or 4 residues amino-terminal to the phosphoserine residue. In contrast, the two other sequences surrounding phosphorylated amino acids, -Tyr-Gly-Ser(P)70-Leu-Pro-Glu-Lys- and -Ile-Val-Thr(P)95-Pro-Arg-, have a basic amino acid at the position 2 or 4 residues carboxyl-terminal to the phosphoamino acid residue.

Amino Acid Sequence↗
PubMed1987

Phosphorylation and inactivation of brain glycogen synthase by a multifunctional calmodulin-dependent protein kinase.

Glycogen synthase was partially purified from canine brain to about 70% purity. The purified enzyme showed differences from the properties of the skeletal muscle enzyme with respect to molecular weights of the holoenzyme and subunit and phosphopeptide mapping. The multifunctional calmodulin-dependent protein kinase from the brain phosphorylated brain glycogen synthase with concomitant inactivation of the enzyme. Although about 1.3 mol of phosphate/mol subunit was maximally incorporated into glycogen synthase, 0.4 mol of phosphate/mol subunit was sufficient for the maximal inactivation of the enzyme. The results indicate that brain glycogen synthase is regulated in a calmodulin-dependent manner similarly to the skeletal muscle enzyme, but that the brain enzyme is different from the skeletal muscle enzyme.

Animals↗
PubMed1987

Inactivation and reactivation of the multifunctional calmodulin-dependent protein kinase from brain by autophosphorylation and dephosphorylation: involvement of protein phosphatases from brain.

The multifunctional calmodulin-dependent protein kinase (calmodulin-kinase) from rat brain was autophosphorylated in a Ca2+- and calmodulin-dependent manner. The activity of the autophosphorylated enzyme was independent of Ca2+ and calmodulin. Calmodulin-kinase was dephosphorylated by protein phosphatase C from bovine brain, which is the catalytic subunits of protein phosphatases 1 and 2A. The holoenzyme of protein phosphatase 2A was also involved in the dephosphorylation of the enzyme. The autophosphorylated sites of calmodulin-kinase were universally dephosphorylated by protein phosphatase C. Calmodulin-kinase was inactivated and reactivated by autophosphorylation and dephosphorylation, respectively. Furthermore, the regulation of calmodulin-kinase by autophosphorylation and dephosphorylation was observed using calmodulin-kinase from canine heart. These results suggest that the activity of calmodulin-kinase is regulated by autophosphorylation and dephosphorylation, and that the regulation is the universal phenomenon for many other calmodulin-kinases in various tissues.

Animals↗
PubMed1987

[Clinical studies of BRL 28500 (clavulanic acid/ticarcillin) in the treatment of pelvioperitonitis and Douglas' abscess].

Clinical studies were conducted on BRL 28500 (a formulation containing 15 parts ticarcillin plus 1 part clavulanic acid). BRL 28500 was administered at doses of 1.6 g or 3.2 g b.i.d., generally for 10 days by drip infusion to patients with pelvioperitonitis or Douglas' abscess. The results obtained were summarized as follows. 1. Clinical efficacy was evaluated in 18 patients (pelvioperitonitis 14, Douglas' abscess 4), but 8 patients out of a total of 26 patients were excluded. 2. In the evaluation of clinical improvement by doctors in charge, clinical improvement rates were 44.4% on day 3, 88.2% on day 5. 3. On the basis of committee judgement, the clinical efficacy rate was 100%. 4. The bacteriological eradication rate of causative organisms was 100% in 11 patients (15 strains). Five strains out of a total of 15 strains produced beta-lactamase. 5. As a side effect, nausea was observed in 1 case. In laboratory examination, liver function abnormalities were observed in 1 case. 6. Regarding usefulness as judged by doctors in charge, the satisfactory rate was 83.3%. From the above results, it has been concluded that BRL 28500 is very useful in the treatment of pelvioperitonitis and Douglas' abscess.

Abscess↗
PubMed1987

[Pharmacokinetic and clinical studies on cefuzonam in obstetrics and gynecology].

Cefuzonam (CZON), a new cephem antibiotic agent, was studied in terms of its pharmacokinetics and clinical efficacy in the field of obstetrics and gynecology, and the results were summarized as follows. 1. The absorption and the tissue penetration of CZON into intrapelvic genital organs were good. The peak serum level in uterine artery after an intravenous drip infusion of 1.0 g was 49.0 micrograms/ml, and the highest peak level of 23.0 micrograms/g in tissues was obtained. After drip infusion of 2.0 g, the peak serum level in uterine artery was 137 micrograms/ml and the highest peak tissue concentration was 54.6 micrograms/g. Tissue concentrations of the drug changed in a similar pattern to serum levels and a dose-dependent response was recognized. 2. The penetration of CZON into intrapelvic dead space exudate was good. The level reached a peak of 8.17 micrograms/ml 4 hours after and intravenous drip infusion of 1.0 g and diminished slowly. 3. The clinical efficacy of CZON at a daily dose of 2 g was evaluated in 21 cases of obstetrics and gynecologic infections. The efficacy rate was 85.7% (18/21 cases). Bacteriologically, the eradication rate obtained was 93.3%. No side effects or abnormal laboratory values were observed.

Adult↗
PubMed1986

Purification and characterization of a multifunctional calmodulin-dependent protein kinase from canine myocardial cytosol.

A calmodulin-dependent protein kinase from canine myocardial cytosol was purified 1150-fold to apparent homogeneity with a 1.5% yield. The purified enzyme had a Mr of 550,000 with a sedimentation coefficient of 16.6 S, and showed a single protein band with a Mr of 55,000 (55K protein), determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme had a specific activity of 1.6 mumol/mg protein/min, and Ka values of 67 nM and 1.1 microM for calmodulin and Ca2+, respectively, using chicken gizzard myosin light chain as substrate. Calmodulin bound to the 55K protein. The purified enzyme had a broad substrate specificity. Endogenous proteins including glycogen synthase, phospholamban, and troponin I from the canine heart were phosphorylated by the enzyme. These results suggest that the purified enzyme works as a multifunctional protein kinase in the Ca2+, calmodulin-dependent cellular functions of the canine myocardium, and that the enzyme resembles enzymes detected in the brain, liver, and skeletal muscle.

Animals↗
PubMed1986

Regulation of the actin-activated Mg-ATPase of brain myosin via phosphorylation by the brain Ca2+, calmodulin-dependent protein kinases.

We have previously isolated two Ca2+, calmodulin-dependent protein kinases with molecular weights of 120,000 (120K enzyme) and 640,000 (640K enzyme), respectively, by gel filtration analysis from rat brain. Chicken gizzard myosin light-chain kinase and the 120K enzyme phosphorylated two light chains of brain myosin, whereas the 640K enzyme phosphorylated both the two light chains and the heavy chain. The phosphopeptides of the light chains digested by Staphylococcus aureus V8 protease were similar among chicken gizzard myosin light-chain kinase, the 120K enzyme, and the 640K enzyme. Only the seryl residue in the light chains and the heavy chain was phosphorylated by the enzymes. The phosphorylation of brain myosin by any of these enzymes led to an increase in actin-activated Mg-ATPase activity. The results suggest that brain myosin is regulated by brain Ca2+, calmodulin-dependent protein kinases in a similar but distinct mechanism in comparison with that of smooth muscle myosin.

Actins↗
PubMed1986

Liver function in moderate obesity--study in 534 moderately obese subjects among 4613 male company employees.

The influence of moderate obesity on the liver was assessed in 4613 male company employees including 534 moderately obese subjects (30-50 percent overweight). Serum levels of transaminases and gammaglutamyl transferase activities were significantly higher in moderately obese male non-drinkers than in non-obese non-drinkers. Twenty-four percent of male non-drinkers with moderate obesity had abnormal levels of sGPT and 47 percent of moderately obese male non-drinkers had significant hepatic steatosis as assessed by computed tomography. Although most previous studies on this subject were concerned with morbid obesity accompanying only those of more than 50 percent overweight or those who required surgery, the results of this study clearly indicate that moderately obese subjects also have frequent liver dysfunction.

Alanine Transaminase↗
PubMed1986

[Fundamental and clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology].

A combination of imipenem (MK-0787), a new carbapenem antibiotic, plus cilastatin sodium (MK-0791), a dehydropeptidase inhibitor (MK-0787/MK-0791 = 1:1) was studied in the field of obstetrics and gynecology and the following results were obtained. Absorption and penetration into genital organ tissues were good. Following a 0.5 g/0.5 g intravenous drip infusion, the maximum plasma concentration in uterine arterial blood was 20.8 micrograms/ml, and the maximum concentrations of the drug in tissues were 9.9 approximately 16.8 micrograms/g, and these levels of MK-0787 exceeded the MIC values against main causative organisms. Rates of elimination of the drug from the tissue and from the plasma were similar. Against gynecological and obstetrical infections, a dose of 0.5 g/0.5 g twice daily for an average duration of 6.3 days produced a clinical efficacy ratio of 94.4% (17/18) and a bacteriological effects rating of 76.9% (10/13). As side effects, one patient showed an eruption and another had an elevated GOT and GPT. Based on the above results, MK-0787/MK-0791 appears to be effective against gynecological and obstetrical infections.

Adult↗
PubMed1986

[Pharmacokinetic and clinical studies of cefotiam in the perinatal period].

Pharmacokinetic studies and clinical evaluations of cefotiam (CTM) were carried out in perinatal mothers and infants and following results were obtained. The drug was promptly absorbed after intravenous injection or intravenous drip infusion in pregnant women, producing dose-related peak serum levels. Placental transfer to the fetus was effective. After intravenous injection or intravenous drip infusion of 1-2 g of CTM, drug concentration of the umbilical cord blood, amniotic fluid and fetal blood exceeded MICs of the drug against main pathogenic organisms. By administration of the dose of 1-2 g twice a day, therefore, perinatal infections should be successfully prevented or treated. Clinically, CTM was effective in the treatment of perinatal infections. Moreover, newborn infants delivered from mothers receiving CTM treatment had drug concentrations higher than MICs of CTM against main pathogenic organisms. Blood CTM concentrations in infants, however, did not remain high very long after birth, and these infants did not exhibit any abnormalities in laboratory tests. Penetration of CTM into mother's milk was ineffective, thus the transfer of CTM from milk to newborn infants was negligible. These results demonstrated that CTM is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Adult↗
PubMed1986

[Pharmacokinetic and clinical studies of ceftazidime in perinatal period].

Pharmacokinetic studies and clinical evaluations of ceftazidime (CAZ) were carried out in perinatal mothers and infants, and following results were obtained. The CAZ was promptly absorbed after intravenous injection or intravenous drip infusion in pregnant women, producing dose-related peak serum levels. Placental transference to the fetus was good. After intravenous injection or intravenous drip infusion of 1.0-2.0 g of CAZ, drug concentration in umbilical serum and amniotic fluid exceeded MICs of CAZ against main pathogenic organisms. Levels of CAZ in umbilical serum ranged 0.2-15.6 micrograms/ml after 1.0 g intravenous injection or intravenous drip infusion, and 0.7-27.2 micrograms/ml after 2.0 g intravenous injection, and those in amniotic fluid were 1.4-21.3 micrograms/ml after 1.0 g administration and 2.0-27.0 micrograms/ml after 2.0 g administration. According to the above results, it is possible to successfully prevent or treat perinatal infections by twice a day administration of CAZ at 1.0-2.0 g/dose. Clinically, CAZ was effective in the treatment of perinatal infections and the prophylaxis of intrauterine amniotic infection without any side effect. Moreover, newborn infants delivered from mothers receiving CAZ treatment did not have any abnormalities in laboratory test. The penetration of CAZ into mother's milk was low, thus the transfer of CAZ from milk to newborn infants should be low. The above results demonstrated that CAZ is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.

Bacterial Infections↗
PubMed1985

Simple and rapid identification of phosphorylated peptides from bovine brain myelin basic protein by reversed-phase high-performance liquid chromatography.

The phosphorylation sites of the myelin basic protein from bovine brain were determined after phosphorylation with a cyclic 3':5'-phosphate-dependent protein kinase from the same source. Three phosphorylated peptides were selectively and rapidly separated, before and after dephosphorylation, by reversed-phase high-performance liquid chromatography on a styrene 250 column under alkaline conditions. Partial sequencing of the peptides by automated Edman degradation revealed that the serine-115 residue located in the main encephalitogenic determinant of the protein was a phosphorylation site, in addition to the two phosphorylation sites established (threonine-34 and serine-55).

Amino Acid Sequence↗
PubMed1985

Dephosphorylation of microtubule-associated protein 2, tau factor, and tubulin by calcineurin.

Calcineurin dephosphorylated microtubule-associated protein 2 (MAP2) and tau factor phosphorylated by cyclic AMP-dependent and Ca2+, calmodulin-dependent protein kinases from the brain. Tubulin, only phosphorylated by the Ca2+, calmodulin-dependent protein kinase, served as substrate for calcineurin. The concentrations of calmodulin required to give half-maximal activation of calcineurin were 21 and 16 nM with MAP2 and tau factor as substrates, respectively. The Km and Vmax values were in ranges of 1-3 microM and 0.4-1.7 mumol/mg/min, respectively, for MAP2 and tau factor. The Km value for tubulin was in a similar range, but the Vmax value was lower. The peptide map analysis revealed that calcineurin dephosphorylated MAP2 and tau factor universally, but not in a site-specific manner. The autophosphorylated Ca2+, calmodulin-dependent protein kinase was not dephosphorylated by calcineurin. These results suggest that calcineurin plays an important role in the functions of microtubules via dephosphorylation.

Animals↗
PubMed1985

Ca2+, calmodulin-dependent regulation of microtubule formation via phosphorylation of microtubule-associated protein 2, tau factor, and tubulin, and comparison with the cyclic AMP-dependent phosphorylation.

Isolated microtubule-associated protein 2 (MAP2), tau factor, and tubulin were phosphorylated by a purified Ca2+, calmodulin-dependent protein kinase (640K enzyme) from rat brain. The phosphorylation of MAP2 and tau factor separately induced the inhibition of microtubule assembly, in accordance with the degree. Tubulin phosphorylation by the 640K enzyme induced the inhibition of microtubule assembly, whereas the effect of tubulin phosphorylation by the catalytic subunit was undetectable. The effects of tubulin and MAPs phosphorylation on microtubule assembly were greater than that of either tubulin or MAPs phosphorylation. Because MAP2, tau factor, and tubulin were also phosphorylated by the catalytic subunit of type-II cyclic AMP-dependent protein kinase from rat brain, the kinetic properties and phosphorylation sites were compared. The amount of phosphate incorporated into each microtubule protein was three to five times higher by the 640K enzyme than by the catalytic subunit. The Km values of the 640K enzyme for microtubule proteins were four to 24 times lower than those of the catalytic subunit. The peptide mapping analysis showed that the 640K enzyme and the catalytic subunit incorporated phosphate into different sites on MAP2, tau factor, and tubulin. Investigation of phosphoamino acids revealed that only the seryl residue was phosphorylated by the catalytic subunit, whereas both seryl and threonyl residues were phosphorylated by the 640K enzyme. These data suggest that the Ca2+, calmodulin system via phosphorylation of MAP2, tau factor, and tubulin by the 640K enzyme is more effective than the cyclic AMP system on the regulation of microtubule assembly.

Animals↗
PubMed1985

[Clinical evaluation of aztreonam in the field of obstetrics and gynecology].

Aztreonam (AZT), a new monobactam antibiotic was evaluated on clinical efficacy and bacteriological response in gynecological and obstetrical infections, and the following results were obtained. AZT was given to 22 cases with obstetrical and gynecological infections at a dose of 1 g X 2 times daily and 86.4% of clinical efficacy, 45.5% of eradicated rate on diagnosis, 52.5% of bacteriological response on isolated organisms and 83.3% of bacteriological effect on cases isolated Gram-negative bacteria were assessed. Side effect incidence was very low.

Adolescent↗