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Biomedical subjects

K Adachi

Publications and source records attributed to K Adachi.

At least 541 records · Page 30Linked to original sources
PubMed1985

Studies of an immunomodulator, swainsonine. I. Enhancement of immune response by swainsonine in vitro.

Swainsonine isolated from Metarhizium sp., was found to enhance the activities of the mouse immune system in vitro. Concanavalin A stimulated lymphocyte proliferation and proliferative response in mixed lymphocytes culture, which were suppressed by immunosuppressive factor obtained from serum of sarcoma 180 tumor bearing mouse, were restored to normal levels by the addition of swainsonine. Furthermore, the concanavalin A induced incorporation of [3H]thymidine into mouse spleen cells was remarkably increased by treatment with swainsonine over a wide dose range, From studies using fluorescence activated cell sorting, swainsonine was shown to enhance the expression of concanavalin A receptors of spleen cells.

Adjuvants, Immunologic↗
PubMed1985

[Serum levels and clinical evaluation of CA 19-9 in various diseases].

We evaluated the clinical significance of serum CA 19-9 in various cancers, benign diseases and healthy controls. The percentage of positive cases for CA 19-9 (higher than 37 U/ml) was 83% in pancreas cancer, 78% in biliary tract cancer and 75% in urinary tract cancer. Benign diseases showed a low frequency of positive cases for CA 19-9, and their serum levels of CA 19-9 were low. Benign diseases with high serum levels of CA 19-9 were rarely seen, but they were easy to differentiate from malignant tumors by simultaneous examination of other tumor markers. In cancer patients with high serum levels of CA 19-9, CA 19-9 showed a weak positive correlation to CEA and ferritin.

Antigens, Neoplasm↗
PubMed1985

[Phase I-II study of recombinant interferon gamma].

A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses.

Adult↗
PubMed1985

[A combination chemotherapy using mitomycin C, vincristine and cisplatin (MVP) for advanced cervical cancer].

Nine patients with advanced cervical cancer were treated with a combination chemotherapy (MVP) consisting of mitomycin C 8 mg/m2 i.v. days 1 and 8, vincristine 1 mg/m2 i.v. days 1 and 8, and cisplatin 15 mg/m2 i.v. days 1 to 5. The regimen was repeated at 4-week intervals. Of nine patients with measurable metastatic disease, there was 1 complete response (CR), 4 partial responses (PR), and 4 with no change, with an overall response rate (CR + PR) of 56% (5/9). The median duration of responses was 6 months, ranging from 1.8 to 9.1 months. The median survival time from initiation of the chemotherapy was 11 months for responders, and 15+ months for non-responders, respectively. Patients with no prior chemotherapy had a 60% (3/5) response rate and 2 patients out of 4 who had received prior chemotherapy responded; furthermore, metastatic lesions in extrapelvic regions (lung) responded well. Leukopenia less than 3,000/mm3 occurred in 68% of cases and the median nadir was 1,900/mm3 (700-2900). Thrombocytopenia less than 10 X 10/mm3 occurred in 37% of cases and the median nadir was 5.15 X 10/mm3 (3.2-9.0). Non-hematological toxicities were nausea and vomiting, renal dysfunction and peripheral neuropathy, but these were reversible and tolerable.

Adenocarcinoma↗
PubMed1985

[Therapeutic effect of cefotaxime in the field of pediatrics].

Cefotaxime (CTX) was administered to 130 children with various bacterial infections of 41 to 400 mg/kg/day for 2 to 21 days. The clinical effect of CTX was very satisfactory in respiratory tract infection, urinary tract infection and meningitis. The overall clinical effect was excellent in 59, good in 39, fair in 17 and failure in 8 with effective rate of 79.7%. During this therapy, side effects were seen in 3 cases, diarrhea in 1 and rash in 2. Abnormal laboratory findings were seen in 5 cases, elevation of GOT in 1, GOT, GPT and A1-P in 1, GOT, GPT and T. Bil. in 1, elevation of BUN, increase of number of basophils and albuminuria in 1 and observation of albuminuria in 1. The above results demonstrate that CTX is a clinically useful antibiotic for the therapy of pediatric infections.

Adolescent↗
PubMed1984

Characterization of cyclic AMP-requiring yeast mutants altered in the catalytic subunit of protein kinase.

The cyr2 mutant of yeast, Saccharomyces cerevisiae, required cAMP for growth at 35 degrees C. The cyr2 mutation was suppressed by the bcy1 mutation which resulted in deficiency of the regulatory subunit of cAMP-dependent protein kinase. The DEAE-Sephacel elution profile of cyr2 cAMP-dependent protein kinase was markedly different from that observed for the wild-type enzyme. With histone as substrate, the cAMP-dependent protein kinase activity of cyr2 cells showed 100-fold greater Ka value for activation by cAMP at 35 degrees C than that of the wild-type cells, while the Kd value for cAMP of the mutant enzyme was not altered. The electrophoretic character, molecular weight, and pI value of the regulatory subunit of the mutant enzyme were the same as those of the wild-type enzyme. When histone, trehalase, and glutamate dehydrogenase were used as substrate, the free catalytic subunit of the mutant enzyme showed a markedly decreased affinity for ATP and was more thermolabile compared to that of the wild-type enzyme. The results indicated that the cyr2 phenotype was produced by a structural mutation in the cyr2 gene coding for the catalytic subunit of cAMP-dependent protein kinase in yeast.

Carrier Proteins↗
PubMed1984

Relationship between tetramer-dimer assembly and the stability of Hb Malmö (alpha 2 beta 2 97Gln).

The effects of the mutation of the alpha 1 beta 2 contact in Hb Malmö (alpha 2 beta 2 97(FG4)His----Gln) on oxygen-binding properties, ease of dissociation into dimeric hemoglobin and stability were studied. The P50 value of Hb Malmö in the absence of organic phosphates was 1.9 mmHg, in contrast to 8.8 mmHg of Hb A. The n-value of Hb Malmö was 1.6. The overall free energy of interaction of oxygen with Hb Malmö was about 25% that of Hb A. The Adair constant, K1, of Hb Malmö was about 10-times larger than that of Hb A, but the K4 of Hb Malmö was similar to that of Hb A. The liganded form of Hb Malmö was found to dissociate into dimers more readily than Hb A by gel filtration on Sephadex G-100. Dissociation into dimeric hemoglobin was enhanced in dilute solutions. Increased instability during mechanical agitation of diluted samples was greater for Hb Malmö than for Hb A. The denaturation rate constants of tetramers of the oxyform of Hb A and Hb Malmö were about 20-times greater than those of dimers of these hemoglobins. The instability of Hb Malmö depends on a greater alpha 1 beta 2 dissociation constant compared with that of Hb A. These findings allow an examination of the role of the intersubunit contact in determining the functional properties and the stability of the hemoglobin molecule.

Drug Stability↗
PubMed1984

Demonstration of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase isozymes by monoclonal antibodies.

Calmodulin-dependent cyclic nucleotide phosphodiesterase from bovine brain is found to be composed of two distinct subunits, 60,000- and 63,000-dalton polypeptides. Peptide mapping of the subunits by partial proteolysis demonstrated that the 60-kDa polypeptide is not derived from the 63-kDa species. The interaction of the enzyme with three monoclonal antibodies, A6, C1, and A2, and the analysis of immunocomplexes by sucrose density gradient centrifugation revealed that calmodulin-dependent cyclic nucleotide phosphodiesterase exists in three different forms, i.e. (a) homodiamer of 60-kDa, (b) heterodimer of 60- and 63-kDa, and (c) homodimer of 63-kDa. A6 antibody reacts with both 60- and 63-kDa polypeptides indicating that they are immunologically related. C1 and A2 antibodies react with only 60-kDa polypeptide species. By using C1 Sepharose 4B affinity column chromatography, the 63-kDa homodimer which did not bind to the column (Fraction I) was separated from the 60-kDa polypeptide containing isozymes (the heterodimer and the 60-kDa homodimer) which were retained on the column and later eluted as a mixture (Fraction II). Fraction I, the 63-kDa homodimer enzyme, has higher Vmax toward cGMP as substrate than cAMP whereas the opposite was found with Fraction II. The specific activity of Fraction II enzyme toward cAMP was approximately 500 mumol/min/mg, the highest value ever reported for brain calmodulin-dependent cyclic nucleotide phosphodiesterase preparations.

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

Cloning of DNA complementary to rat liver fatty acid synthetase mRNA.

Clones, containing DNA complementary (cDNA) to rat liver fatty acid synthetase mRNA, were constructed and identified. cDNA of these clones was then used as a probe to quantify mRNA. The cDNA was synthesized to partially purified rat liver fatty acid synthetase mRNA. Double-stranded cDNA was then prepared and inserted into the PstI site of pBR322 using oligo(dG) X oligo(dC) tailing. Initial selection of the clones was by differential colony hybridization employing [32P]cDNA synthesized from poly(A)-rich mRNA, enriched and non-enriched in fatty acid synthetase mRNA, as probes. Plasmids, containing specific sequences complementary to the fatty acid synthetase mRNA, were identified by hybrid-arrest translation. Cloned cDNA inserts ranged from 300 to 1400 base pairs. Cloned cDNA was employed to probe for mRNA in hybridizations via the dot-blot method. These studies demonstrated an increase in fatty acid synthetase mRNA during dietary induction, which suggests that regulation may involve changes in transcription or changes in post-transcriptional processing of the mRNA.

Animals↗
PubMed1984

Polymerization of AS hybrid hemoglobin. Potent inhibitory effect of hemoglobin A on the polymerization of AS hybrid hemoglobin.

Asymmetrically cross-linked AS hybrid hemoglobin (Hb AS-fumarate) was prepared by reacting a mixture of oxy-Hb A and oxy-Hb S with a cross-linking agent, bis(3,5-dibromosalicyl)fumarate. Kinetics of the polymerization of Hb AS-fumarate in 1.8 M phosphate buffer showed that Hb AS-fumarate polymerized similarly to Hb S-fumarate despite the presence of a beta A chain. The kinetics of the polymerization of a mixture of Hb AS-fumarate and Hb S-fumarate was similar to that of Hb S-fumarate or Hb AS-fumarate alone. However, when Hb AS-fumarate was mixed with Hb A, the delay time prior to polymerization of the mixture was markedly prolonged. Although the solubility of Hb AS-fumarate was similar to that of Hb S-fumarate, it nearly doubled upon the addition of Hb A. Analysis of Hb A in the polymer phase showed that a significant amount (35-40%) of Hb A copolymerized with Hb AS-fumarate. No such effect was observed when Hb A was mixed with Hb S-fumarate, where the delay time prior to polymerization and the solubility of the mixture were regulated by the concentration of Hb S-fumarate in the mixture. The strong inhibitory effect of Hb A on the polymerization of Hb AS hybrid hemoglobin may help explain the benign clinical course in sickle cell trait.

Chromatography, High Pressure Liquid↗
PubMed1984

Regulation of NAD-dependent glutamate dehydrogenase by protein kinases in Saccharomyces cerevisiae.

The active NAD-dependent glutamate dehydrogenase of wild type yeast cells fractionated by DEAE-Sephacel chromatography was inactivated in vitro by the addition of either the cAMP-dependent or cAMP-independent protein kinases obtained from wild type cells. cAMP-dependent inhibition of glutamate dehydrogenase activity was not observed in the crude extract of bcy1 mutant cells which were deficient in the regulatory subunit of cAMP-dependent protein kinase. The cAMP-dependent protein kinase of CYR3 mutant cells, which has a high K alpha value for cAMP in the phosphorylation reaction, required a high cAMP concentration for the inactivation of NAD-dependent glutamate dehydrogenase. An increased inactivation of partially purified active NAD-dependent glutamate dehydrogenase (Mr = 450,000) was observed to correlate with increased phosphorylation of a protein subunit (Mr = 100,000) of glutamate dehydrogenase. The phosphorylated protein was labeled by an NADH analog, 5'-p-fluorosulfonyl[14C]benzoyladenosine. Activation and dephosphorylation of inactive NAD-dependent glutamate dehydrogenase fractions were observed in vitro by treatment with bovine alkaline phosphatase or crude yeast cell extracts. These results suggested that the conversion of the active form of NAD-dependent glutamate dehydrogenase to an inactive form is regulated by phosphorylation through cAMP-dependent and cAMP-independent protein kinases.

Adenosine Triphosphate↗
PubMed1984

Polymerization of binary mixtures of hemoglobin S and carbamylated hemoglobin S.

To study the mode of interaction between hemoglobin (Hb) S and carbamylated Hb S, the kinetics of polymerization of various mixtures of deoxy-Hb S and NH2 termini carbamylated Hb S in concentrated phosphate buffer was determined. These mixtures were found to polymerize with a clear demonstration of a delay time as does each hemoglobin in its pure form. Both the delay and the polymerization times were prolonged as the fraction of carbamylated Hb S was increased. Electrophoretic analysis of the polymer fraction showed that the amount of carbamylated Hb S increased linearly in the polymer phase with increases in the fraction of carbamylated Hb S in the starting mixture. The ratio of Hb S to carbamylated Hb S in the polymer phase was slightly higher than that in the initial solution mixture, suggesting that Hb S polymerizes more easily than carbamylated Hb S. To examine the role of hybrid hemoglobin in the binary mixtures of carbamylated Hb S and Hb S, we compared the rate of polymerization under which hybrid formation may be prevented or allowed to take place. It was found that the rate of polymerization for the mixtures of carbamylated Hb S and Hb S mixed in the oxy state did not differ from that mixed in the deoxy state. In addition, polymerization occurred even when the critical concentration of each component in the mixture was lower than that of either pure Hb S or pure carbamylated Hb S. These results suggest that all hemoglobin species can participate in the nucleation and polymerization steps of mixtures of carbamylated Hb S and Hb S.

Amino Acid Sequence↗
PubMed1984

Calcium-activated, phospholipid-dependent protein kinase in pig epidermis.

We investigated calcium-activated, phospholipid-dependent protein kinase in pig epidermis. Pig epidermal homogenates were centrifuged at 30,000 g for 30 min, and the supernatant was applied on a DEAE-cellulose column for purification. The partially purified enzyme was stimulated by simultaneous addition of Ca2+ and phospholipid. Successive addition of small amounts of diolein further activated the enzyme activity. The calcium-activated phospholipid-dependent protein kinase preferentially phosphorylated serine residues and its endogenous substrate protein in the pig epidermis has a molecular weight of about 97,000.

Animals↗