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Biomedical subjects

K Fukunaga

Publications and source records attributed to K Fukunaga.

At least 271 records · Page 15Linked to original sources
PubMed1985

[Pharmacokinetics and clinical studies on cefminox in the field of obstetrics and gynecology].

Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and the penetration of CMNX into pelvic dead space exudate were good. The mean peak serum level after single intravenous injection was 190.8 micrograms/ml. The level in pelvic dead space exudate reached a peak of 36.6 micrograms/ml 4 hours after an intravenous injection of 1 g and 6.5 micrograms/ml after 12 hours, thus the level over MIC against main pathogenic organisms was maintained for a long time. CMNX was administered against gyneco-obstetrical infections such as intrauterine, intrapelvic, adnexal infections and postoperative wound infections with daily dose of 2 g and was effective in 11 cases out of 12 cases (91.7%), and 81.8% of bacteriological effect was obtained. No side effect was observed. From the above results the usefulness of CMNX in the field of obstetrics and gynecology was suggested.

Adolescent↗
PubMed1985

[Pharmacokinetics and clinical studies on cefpimizole in the field of obstetrics and gynecology].

Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of AC-1370 into intrapelvic genital organs were good. The peak serum level in the uterine artery after an intravenous drip infusion for 30 minutes was 49.0 micrograms/ml. High concentrations were obtained also in genital organ tissues; the maximum concentrations were 24.4 approximately 39.0 micrograms/g after an intravenous drip infusion. The changing patterns of the tissue concentrations were similar to those in the serum. The penetration of AC-1370 into intrapelvic dead space exudate was good. The level reached a peak of 35 micrograms/ml at 2 approximately 4 hours after an intravenous drip infusion with 1 g and 3.7 micrograms/ml after 12 hours. AC-1370 was effective in 20 out of 21 cases (95.2%) with gynecoobstetrical infections such as intrauterine, intrapelvic infection and mammitis, administered with 1 approximately 2 g twice a day. Few side effects were observed.

Absorption↗
PubMed1985

[Fundamental and clinical studies on fosfomycin sodium in the field of obstetrics and gynecology].

Fosfomycin sodium (FOM-Na) was studied both fundamentally and clinically in the field of obstetrics and gynecology with following results. It showed good transference into the uterine tissues when given intravenously. The peak concentrations achieved in the uterine tissues following intravenous administration of 2 g of FOM-Na were 26.56 to 53.48 micrograms/g when given as one shot injection and 20.16 to 39.47 micrograms/g as drip infusion. In the serum of vein and uterine artery, peak concentrations of 163.6 to 143.40 micrograms/ml and 120 to 113.12 micrograms/ml were reached following one shot injection and drip infusion, respectively. In general, FOM-Na concentrations in the uterine tissues showed similar changes as those observed for serum concentrations. Clinically, FOM-Na was used in the treatment of 17 cases of obstetrical and gynecological infections at 2 g per dose twice daily as intravenous drip infusions. In all of these cases, good clinical efficacy was obtained. No side effects were observed.

Adnexa Uteri↗
PubMed1984

Ca2+, calmodulin-dependent phosphorylation, and inactivation of glycogen synthase by a brain protein kinase.

Glycogen synthase from skeletal muscle was phosphorylated by a Ca2+, calmodulin-dependent protein kinase from brain, with concomitant inactivation. About 0.7 mol phosphate/mol subunit was sufficient for a maximal inactivation of glycogen synthase. Further phosphorylation of the enzyme had no effect on the activity. The concentrations required to give half-maximal phosphorylation and inactivation of glycogen synthase were 1.1 and 0.5 microM for Ca2+, and 22 and 11 nM for calmodulin, respectively. The molar ratio of the subunit of the protein kinase to calmodulin was 2-3:1 for half-maximal phosphorylation and inactivation of glycogen synthase. The Km values for glycogen synthase and ATP were 3.6 and 114 microM, respectively, for phosphorylation. Phosphate was incorporated into sites Ia, Ib, and 2 on glycogen synthase, and site 2 was the most rapidly phosphorylated. These results indicate that the brain Ca2+, calmodulin-dependent protein kinase is probably involved in glycogen metabolism in the brain as a glycogen synthase kinase.

Adenosine Triphosphate↗
PubMed1984

Phosphorylation and activation of calmodulin-sensitive cyclic nucleotide phosphodiesterase by a brain Ca2+, calmodulin-dependent protein kinase.

A Ca2+, calmodulin-dependent protein kinase from rat brain with a MW of 640,000 phosphorylated calmodulin-sensitive phosphodiesterase from the brain cytosol. The Km of the enzyme for the phosphodiesterase was 5.0 microM and the Vmax was 212 nmol/mg/min. The amount of phosphate incorporated into the phosphodiesterase was 0.7 mol/mol subunit. Phosphorylation of the phosphodiesterase enhanced the enzyme activity by about 20% for hydrolysis of a higher concentration of cyclic AMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

[Fundamental and clinical studies on sulbactam/cefoperazone in the field of obstetrics and gynecology].

A combination of sulbactam, a beta-lactamase inhibitor, plus cefoperazone (SBT/CPZ = 1/1) was studied in the field of obstetrics and gynecology, and the results were following: Absorption and transfer into genital organ tissues were good. With the 1g intravenous injection the maximum serum concentrations in the uterine artery were 88.6 micrograms/ml for CPZ and 50.0 micrograms/ml for SBT, and the maximum tissue concentrations were 12.2-17.4 micrograms/g for CPZ and 9.8-21.4 micrograms/g for SBT. When the 2 g was administered, the maximum tissue concentrations were 11.9-26.7 micrograms/g for CPZ and 6.0-8.0 micrograms/g for SBT. These elimination showed the similar trend as their serum levels, and their tissue levels were higher than MIC80 for the main organisms. Their penetration into the intrapelvic dead space exudate was also good and showed that the peak levels were 30.1 micrograms/ml for CPZ and 17.4 micrograms/ml for SBT at 2 hours after the 2 g intravenous injection. The peak levels of 34.4 micrograms/ml for CPZ and 8.8 micrograms/ml for SBT at 6 hours after 2 g intravenous drip infusion were obtained. Their elimination was slow, and the concentration higher than MIC80 for main organisms was maintained for a long period of time. For gyneco-obstetrical infections such as adnexitis, intrauterine, intrapelvic and external genital organ infections, a daily dose of 2-4 g of SBT/CPZ produced a 100% clinical efficacy in 10 patients and a 88.9% bacteriological effect. The eradication ratio was more than 80% against beta-lactamase producing organisms. Side effects were few. The above results indicated that SBT/CPZ was useful in the field of obstetrics and gynecology.

Adult↗
PubMed1984

[Pharmacokinetics and clinical studies on ceftriaxone in the field of obstetrics and gynecology].

Ceftriaxone (Ro 13-9904, CTRX), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of CTRX into intrapelvic genital organs were good. The peak serum level in the uterine artery after a single intravenous injection and that after an intravenous drip infusion for 30 approximately 60 minutes, both with 1 g, were 162.5 micrograms/ml and 84.4-93.8 micrograms/ml, respectively. High concentrations were obtained also in genital organ tissues; the maximum concentration was 93.8 micrograms/g by intravenous injection and 56.3-59.4 micrograms/g by intravenous drip infusion. Changes in the tissue concentration were similar to those in the serum, the level over MIC80 against main pathogenic organisms being maintained for a long time. The penetration of CTRX into intrapelvic dead space exudate was good. The level reached a peak of 18.8 micrograms/ml 2 hours after an intravenous injection with 1 g and 13.3 micrograms/ml after 12 hours, while the level over MIC80 against main pathogenic organisms was maintained for a long time. CTRX was effective in 15 out of 16 cases (93.8%) with gyneco-obstetric infections such as intrauterine, intrapelvic, adnexal infections, and postoperative would infections, administered with 1 g twice a day. No side effects were observed.

Adult↗
PubMed1984

Isolation and characterization of B cell differentiation factor (BCDF) secreted from a human B lymphoblastoid cell line.

A subclone of a human B lymphoblastoid cell line, CESS-2, spontaneously secreted a kind of BCDF (B-BCDF) in their culture supernatant without any stimulation. B-BCDF induced IgG and IgM secretions in human B lymphoblastoid cell lines, CESS cells and CL-4 cells, respectively. BCDF-responsive CESS cells expressed IgG on their surface, whereas CESS-2, which were able to secrete B-BCDF, did not express surface IgG. B-BCDF could induce Ig-secretion in SAC-stimulated low density peripheral B cells, but did not induce Ig secretion in nonstimulated B cells. B-BCDF did not show any IL 2, BCGF, or gamma-interferon activities. B-BCDF was highly purified by gel filtration on an AcA-34 column, by chromatofocusing and ion exchange chromatography on an HPLC system, and by gel filtration on an HPLC column. Highly purified preparations showed a single protein band in SDS-PAGE analysis. The m.w. and isoelectric points of the factor were 20,000 and pH 5.1 to 5.2, respectively. The minimum protein amount required for Ig induction in B cell lines was 16 ng/ml.

Antibody-Producing Cells↗
PubMed1984

[Study of cefoperazone in the field of obstetrics and gynecology. Susceptibility of clinical isolates to cefoperazone and cefoperazone concentrations in the exudate of the pelvic dead space].

As indexes for administration of cefoperazone (CPZ) in the treatment of gyneco-obstetrical infections, sensitivities to CPZ of important pathogenic organisms and CPZ concentrations in the exudate of the pelvic dead space were determined, and a pharmacokinetic analysis was made on the results. Sensitivities to CPZ were determined for freshly isolated organisms from gynecological material consisting of 227 strains of 7 aerobic bacteria and 70 strains of 1 anaerobic bacterium, in a total of 297 strains. MIC80 values of CPZ against E. coli, K. pneumoniae, P. aeruginosa, E. cloacae, C. freundii, S. aureus, S. epidermidis and B. fragilis were 0.39, 0.78, 6.25, 25, 50, 12.5, 12.5 micrograms/ml and 6.25 micrograms/ml, respectively. On the whole, these activities are relatively superior to those of other antibiotics. CPZ concentrations in the exudate of the pelvic dead space and their changes with time after 2 g single dose by drip infusion were Cmax 93.89 micrograms/ml, Tmax 1.53 hours, T 1/2 4.33 hours and AUC 759.4 hr X micrograms/ml. After 1 g single dose, they were Cmax 37.7 micrograms/ml, Tmax 3.2 hours, T 1/2 2.78 hours and AUC 339.2 hr X micrograms/ml. Similarly, after 2 g single dose intravenously, they were Cmax 111.02 micrograms/ml, Tmax 0.761 hours, T 1/2 6.22 hours and AUC 1,083.9 hr X micrograms/ml, and after 1 g single dose, they were Cmax 29.1 micrograms/ml, Tmax 2.65 hours, T 1/2 4.82 hours and AUC 296.9 hr X micrograms/ml. Similarly, after 2 g single dose intramuscularly, they were 39.4 micrograms/ml, Tmax 2.70 hours, T 1/2 8.19 hours and AUC 584.7 hr X micrograms/ml, and after 1 g single dose, they were Cmax 26.4 micrograms/ml, Tmax 5.79 hours, T 1/2 5.53 hours and AUC 435.7 hr X micrograms/ml. As indicated, there were noted dose-dependent responses and the kinetics of CPZ exudate concentrations varied with the administration routes. Whatever the dose level and the administration route were, CPZ exudate concentrations covered MIC80 values against important clinical isolates for 10 to 12 hours. This suggests that we can well expect of the antibacterial activity of this drug by any of these administration routes and dosages on the intrapelvic lesions.

Bacteria↗
PubMed1983

Purification and characterization of myosin light-chain kinase from porcine myometrium and its phosphorylation and modulation by cyclic AMP-dependent protein kinase.

Myosin light-chain kinase was purified from porcine myometrium to apparent homogeneity at about 262-fold with an Mr of 130 000 as determined by SDS-polyacrylamide gel electrophoresis and a sedimentation coefficient of 4.5 S. The approximate content of the soluble myosin light-chain kinase was estimated to be about 0.85 microM. The purified enzyme exhibited strict substrate specificity only for 20-kDa myosin light chain and Ka values of 0.6 nM and 0.3 microM for calmodulin and Ca2+, respectively. The enzyme was phosphorylated by the catalytic subunit of cyclic AMP-dependent protein kinase, which resulted in a decrease in the affinity for calmodulin of 4-7-fold without effect on the Vmax. The maximal amount of phosphate incorporated into the enzyme was 0.5-0.8 and 1.0-1.4 mol per mol of the enzyme in the presence and absence of Ca2+ and calmodulin, respectively. In the presence of a subsaturating concentration of calmodulin, the enzyme showed a lower sensitivity for Ca2+ by phosphorylation.

Animals↗
PubMed1983

Ca2+, calmodulin-dependent phosphorylation of glycogen synthase by a brain protein kinase.

A Ca2+, calmodulin-dependent protein kinase from brain with a Mr of 640 000 is capable of phosphorylating glycogen synthase from skeletal muscle. The reaction was inhibited by the addition of 1 mM EGTA and 50 microM trifluoperazine, but not by protein kinase inhibitor and heparin. The amount of phosphate incorporated into glycogen synthase was 1.4 mol/mol subunit. The phosphorylation sites of glycogen synthase were cyanogen bromide-treated peptides CB-1 and CB-2 and only the seryl residue was phosphorylated.

Animals↗
PubMed1983

Calmodulin and Ca2+- and calmodulin-dependent protein kinase in rat anterior pituitary gland.

Calmodulin and Ca2+- and calmodulin-dependent protein kinase were identified in the rat anterior pituitary gland. The concentration of calmodulin was 1.18 +/- 0.11 microgram/mg protein (n = 7) in the cytosol fraction. The calmodulin of the anterior pituitary gland co-migrated with brain calmodulin on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The Ka value of the partially purified enzyme for Ca2+ was 3.3 microM in the presence of 0.30 microM calmodulin. Trifluoperazine and chlorpromazine, calmodulin-interacting agents, inhibited enzyme activity, with Ki values of 1.3 and 2.6 X 10(-5) M, respectively. The enzyme was resolved into two peaks of activity, with sedimentation coefficients of 5.5 S and 16.5 S, by sucrose density gradient centrifugation. At least nine proteins were phosphorylated by the enzyme in a Ca2+- and calmodulin-dependent manner. In light of these results, the possibility that calmodulin and the calmodulin-activatable protein kinase system are involved in the mediation of the Ca2+ effect on hormone release from the anterior pituitary gland must be given consideration.

Animals↗
PubMed1983

Ca2+- and calmodulin-dependent phosphorylation of microtubule-associated protein 2 and tau factor, and inhibition of microtubule assembly.

Microtubule-associated proteins (MAPs) were phosphorylated by a Ca2+- and calmodulin-dependent protein kinase from rat brain cytosol. The maximal amount of phosphate incorporated into MAPs was 25 nmol of phosphate/mg protein. A Ka value of the enzyme for calmodulin was 57.0 nM, with MAPs as substrates. Among MAPs, MAP2 and tau factor were phosphorylated in a Ca2+- and calmodulin-dependent manner. The phosphorylation of MAPs led to an inhibition of microtubule assembly in accordance with its degree. This reaction was dependent on addition of the enzyme, Ca2+, and calmodulin, and had a greater effect on the initial rate of microtubule assembly rather than on the final extent. The critical tubulin concentration for microtubule assembly was unchanged by the MAPs phosphorylation. Therefore assembly and disassembly of brain microtubule are regulated by the Ca2+- and calmodulin-dependent protein kinase that requires only a nanomolar concentration of calmodulin for activation.

Adenosine Triphosphate↗
PubMed1983

Regulation by estrogen and progesterone of protein kinases in rabbit myometrium.

We report on hormonal regulation of protein kinases in the rabbit myometrium. The injection of estrogen or progesterone produced 5.2 +/- 0.7- or 4.7 +/- 0.4-fold increases, respectively, of the total activity when histone was used as the substrate in the cytosol fraction of the tissue. The analysis of the activity by DEAE-cellulose column chromatography revealed that estrogen had no effect on increases in the levels in both types I and II cAMP-dependent protein kinases, on the basis of mg protein, while progesterone produced a 50% decrease in type I cAMP-dependent protein kinase and a 50% increase in type II cAMP-dependent protein kinase. Thus, the activity ratio of types II to type I did not change by treatment with estrogen and increased from 2.8 to 7.9 with progesterone administration. As the activity patterns by treatment with human chorionic gonadotropin closely resembled those seen with progesterone, our findings in case of the latter hormone are probably valid. The results indicate that the levels of protein kinases in the myometrium are altered in response to estrogen and progesterone and may possibly be involved in the physiological functions of the tissue.

Animals↗
PubMed1983

Hormone treatments and pregnancy alter myosin light chain kinase and calmodulin levels in rabbit myometrium.

Myosin light chain kinase activity and the amount of calmodulin were measured in rabbit myometrium after the rabbits had been treated with oestrogen, progesterone and human chorionic gonadotrophin, and also during pregnancy. Injections of oestrogen and progesterone produced significant increases of of 2.8- and 2.1-fold in the enzyme activity/mg protein and of 1.4- and 1.2-fold in the calmodulin content/mg protein respectively. The increases seen with oestrogen treatment were inhibited by cycloheximide administration, suggesting that protein synthesis is involved in the process. Calmodulin increased about twofold in the particulate fraction under conditions of oestrogen and progesterone treatments and the raised level of calmodulin detected in the cytosol fraction was not due to translocation from the particulate fraction. During pregnancy the specific enzyme activity significantly increased in comparison with the values seen in samples from the non-treated rabbits. These findings suggest that myosin light chain kinase and calmodulin in the myometrium are under hormonal regulation and may play a role in expulsion of the fetus at the latter phase of pregnancy.

Animals↗
PubMed1983

[Laboratory and clinical studies on latamoxef in the field of obstetrics and gynecology].

Latamoxef (LMOX) is a new antibiotic synthesized by Shionogi Research Laboratory. Chemically LMOX is especially unique with a sulfur atom replacing the oxygen atom in the 1 position of the conventional cephalosporin nucleus, and in addition, this antibiotic has a cephamycin-like structure. The antibacterial activity of LMOX shows high potency against Gram-negative bacteria, but tends to be weak against Gram-positive bacteria. The tissue levels of LMOX in humans after intravenous injection of 1 g were examined. The levels in uterine and adnexa uteri tissue at 1 hour after administration were 25.4 and 27.4 micrograms/g respectively. LMOX was administered to 147 cases in infections of obstetric and gynecological field. The clinical effect according to disease was 94.6% for intrauterine infections, 95.0% for adnexitis, 87.0% intrapelvic infections, and 100% for external genital organ infections, making a total of 92.5%. The rate of occurrence of side effects or abnormal laboratory findings was similar to or slightly less than that seen with other beta-lactam antibiotics.

Adult↗
PubMed1983

[Fundamental and clinical studies of T-1982 (cefbuperazone) in the field of obstetrics and gynecology].

T-1982 (cefbuperazone), a new cephamycin antibiotic, was studied for its MICs against clinical isolates, transfer into uterine tissues and clinical efficacy in the field of obstetrics and gynecology. The following results were obtained. The MICs of T-1982 were measured against 397 strains of 13 species. In antibacterial activity, T-1982 was equal to CTT but inferior to CMZ against Gram-positive bacteria. Against Gram-negative bacteria, T-1982 was superior to CEZ and other cephamycin antibiotics, i.e. CMZ and CTT. The activity of T-1982 was almost equal to that of CMZ and superior to that of CTT against B. fragilis. T-1982 concentrations in various uterine tissues attained the peaks of 16.8-35.9 micrograms/g at 34 minutes after intravenous administration of 1 g, the tissue/serum ratios being 34-72%. The tissue concentrations were about 3-4 micrograms/g even at 5-5.5 hours after administration. T-1982 was intravenously administered at a dose of 1 g twice daily to 5 cases with obstetrical and gynecological infections. All the cases responded to the therapy. Elevated GOT and GPT were observed in 1 case, but they returned to normal on 8 days after the therapy.

Adnexa Uteri↗