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Biomedical subjects

T Morinaga

Publications and source records attributed to T Morinaga.

At least 91 records · Page 5Linked to original sources
PubMed1985

Conjugation of poly(styrene-co-maleic acid) derivatives to the antitumor protein neocarzinostatin: pronounced improvements in pharmacological properties.

An anticancer agent of intermediate molecular weight and having both a hydrophilic and hydrophobic nature was developed by utilizing the antitumor protein neocarzinostatin (NCS; Mr = 12000) as a prototype drug. The modification was achieved by reacting the two amino groups on NCS with an anhydride group of partially half-esterified (p-E-) or partially hydrolyzed (p-H-) poly(styrene-co-maleic anhydride) (SMA) in 0.8 M NaHCO3. The SMA samples with narrow molecular weights distributions (Mw = ca. 2000) were prepared by copolymerizing styrene and maleic anhydride in cumene followed by fractionation by means of a column-elution method. The derivatives p-E- or p-H-SMA were then formed by using the appropriate monoalcohols or H2O, respectively. These SMA derivatives contain about 2 mol of anhydride residues/mol of SMA. The reaction product, SMA-conjugated NCS (designated as SMANCS), was purified by dialysis followed by gel filtration with Sephadex G-75. The complete reaction yielded essentially a single product, biantennary SMANCS. The molecular weight of the pure SMAMCS was estimated by various methods, including polyacrylamide gel electrophoresis with NaDodSO4, HPLC in the gel permeation mode, fluorescence polarization, and a decrease in both nitrogen and protein contents. These results agree with the apparent molecular weight of about 16000. Characters of SMANCS was considerably altered from that of parental NCS: solubility characteristics in both organic and aqueous solvents were changed, the biological half-life in blood was prolonged 10 times, and antitumor activity became more pronounced, but the toxicity was reduced to one-fourth of the parental NCS. Thus, the present study has provided a method of improving biologically active substances by polymer conjugation.

Animals↗
PubMed1985

Isolation of cDNA clones encoding a T-cell receptor beta-chain from a beef insulin-specific hybridoma.

cDNA clones coding for a T-cell receptor beta-chain were isolated from a beef insulin/IAd-reactive T-cell hybridoma, A20.2.15, and its complete amino acid sequence was deduced. This beta-chain gene utilizes the same V beta segment as a thymocyte beta-chain gene (86T1) and rearranges to the 5' proximal J-C locus (J beta 1-C beta 1), thus providing definitive evidence of a beta-chain gene from a functional hybridoma that utilizes C beta 1. The amino acid sequence of the V beta gene in A20.2.15 is identical to 86T1, thus suggesting the absence of somatic mutation in the beta-chain of A20.2.15. Southern blot analysis revealed a somatic DNA rearrangement unique to the A20.2.15 hybridoma. The expression of this gene in the hybridoma was confirmed by RNA dot hybridization. All 24 beta-chain clones so far isolated from the A20.2.15 hybridoma contained C beta 1, suggesting that the beta-chain gene of the fusion partner BW5147 is not expressed in the hybridoma.

Amino Acid Sequence↗
PubMed1985

[Clinical studies with cefoperazone in the biliary disease].

The concentration of cefoperazone (CPZ) in serum and bile was estimated after intravenous drip infusion of 1 g of the drug in 11 patients, who have performed cholecystectomy, choledocholithotomy and T-tube drainage for gallstone diseases. Administration of cefazolin (CEZ) 1 g was compared by the cross over method. After 1 g intravenous drip infusion of CPZ, the mean serum concentration was 88.3 +/- 24 micrograms/ml at 1 hour, 52 +/- 11.7 micrograms/ml at 2 hours and 36.5 +/- 10 micrograms/ml at 4 hours. The maintenance period of serum concentration was inclined to be longer in CPZ than in CEZ. After 1 g intravenous drip infusion of CPZ, the mean bile concentration reached to 810 +/- 459 micrograms/ml in 2 hours and it was maintained as high as 562 +/- 319 micrograms/ml even after 4 hours. On the other hand, after 1 g intravenous drip infusion of CEZ, the mean bile concentration was only 28.7 +/- 26 micrograms/ml in 1 hour and was low level in the progress. As compared with the highest concentration of CPZ and CEZ in same patient, the mean bile concentration of CPZ (942 +/- 525 micrograms/ml) was about 30 times higher than that of CEZ (28.6 +/- 26.3 micrograms/ml). There was no difference in the group of Gram-positive cocci between minimum inhibitory concentration (MIC) of CPZ and that of CEZ. While MIC of CEZ in the group of Gram-negative bacilli was from 0.78 to over 400 micrograms/ml, MIC of CPZ in that group was from 0.10 to 50 micrograms/ml. The value in CPZ was lower than that in CEZ at all strains. No side effects was seen in all patients.

Adult↗
PubMed1984

Further characterization of the effects of alpha-1-acid glycoprotein on the passage of human erythrocytes through micropores.

Effects of human alpha-1-acid glycoprotein (AG) on the passage of human red blood cell(s) (RBC) through membrane filters with micropores were examined in vitro. RBCs, with a mean major diameter of 7.2 micron, that had been suspended at 1% in physiological phosphate-buffered saline (PBS), were filtered through membrane filters of various pore diameters under positive pressure. The percentages of cells that passed through the micropores and of cells hemolyzed during filtration were determined. RBCs suspended in PBS did not pass through micropores that had an average pore diameter of 3 micron; instead hemolysis took place. Neither temperature nor applied pressure affected cell passage; but when AG at 0.1 mg/ml or above was added to an RBC-suspension, it promoted cell passage through the 3 micron micropores and reduced the degree of hemolysis. The effects of AG were dose dependent up to a concentration of 0.5 mg/ml. The addition of AG to an RBC-suspension that contained 90% human serum had the same additive effects. Washing AG-treated RBCs with normal saline produced a marked decrease in cell passage through the 3 micron pores. Fluorescence antibody staining revealed that the exogenous AG was localized on the membrane surface of the RBCs. Our results suggest that the AG bound to the surface of the RBCs acts as a lubricant between the RBCs and the wall of the micropore; this would facilitate RBC-passage through the micropores.

Erythrocyte Deformability↗
PubMed1984

[A double-blind comparison between cefaclor and cephalexin in the treatment of dental infections].

A comparative clinical study of cefaclor (CCL) with cephalexin (CEX) was carried out by randomized double-blind techniques in order to contemplate the clinical efficacy, side effects and usefulness in treatment of 243 patients with dental infections. In the CEX group, CEX was orally administered 4 times a day at a daily dosage of 1,000 mg for 3 to 5 days. In the CCL group, CCL was orally administered 3 times a day at a daily dosage of 750 mg for 3 to 5 days and 1 capsule of placebo was also given every evening in order to keep the blindness of the administration. Evaluable cases for efficacy of athe drugs were 213 consisting of 108 for CCL and 105 for CEX. There were no significant differences in background of the patients and severity of the disease between 2 treatment groups. Clinical effectiveness on the 3rd day was 89.7% in CCL group and 78.6% in CEX group, showing significant difference between 2 treatment groups. Clinical effectiveness on the final day of administration was 94.4% in CCL group and 92.4% in CEX group, showing no significant difference between 2 treatment groups. Side effects were found in 10.5% of 114 patients receiving CCL and in 4.5% of 112 patients with CEX, and there was no significant difference between 2 treatment groups. The side effects were mostly gastrointestinal origin. According to the judgement by physicians in charge, no significant difference was seen in clinical usefulness between the 2 drugs.

Adult↗
PubMed1983

The use of mannan-Sepharose 4B affinity chromatography for the purification of endo-beta-N-acetylglucosaminidase from Bacillus alvei.

In order to facilitate the isolation of endo-beta-N-acetylglucosaminidase for the structural analysis of glycoconjugates, we have isolated a strain of Bacillus alvei which produces a high level of endo-beta-N-acetylglucosaminidase. We have also devised a simple procedure for the purification of endo-beta-N-acetylglucosaminidase from B. alvei using mannan-Sepharose affinity chromatography. By using this method, endo-beta-N-acetylglucosaminidase was purified 3300-fold with 85% yield from the crude enzyme obtained by ammonium sulfate precipitation of the culture medium. The molecular weight of this enzyme was estimated to be about 66 000 by gel filtration. When using (Man)6(GlcNAc)2-Asn-Dns as substrate, the optimal activity occurs at pH 6.5 with Km of 1.9 mM. The action of endo-beta-N-acetylglucosaminidase toward several glycopeptides was also studied.

Acetylglucosaminidase↗
PubMed1983

Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report.

A clinical evaluation of arterial infusion of high-molecular-weight antitumor agent SMANCS dissolved in lipid lymphographic agent (thiodol) in 44 patients with mostly unresectable hepatoma is described. The treatment regimen demonstrated significant merits both therapeutically and diagnostically. Marked antitumor effects were shown in the decreased serum alpha-fetoprotein levels (86% of cases) and tumor size (95% of cases), and in survival period and histological findings. Furthermore, there was increased diagnostic sensitivity using CT scan, plain X-rays or ultrasound. The procedure of selective arterial administration of 3-4 mg of SMANCS in 3-4 ml of ethiodol per dose was simple to perform and was required only once every 3-4 weeks. Both ethiodol and the drug accumulated more selectively in tumor than in any other tissues and their activity remained for more than 3 weeks. Only minimal side-effects were associated with SMANCS and ethiodol during this study.

Adult↗
PubMed1983

Primary structures of human alpha-fetoprotein and its mRNA.

DNA complementary to human alpha-fetoprotein (AFP)mRNA was cloned in the plasmid pBR322. Analysis of three overlapping cDNA clones revealed most of the nucleotide sequence of AFP mRNA, and the remaining nucleotides at the 5' end of the mRNA were elucidated from a cloned genomic DNA fragment. The amino acid sequence was deduced from the nucleotide sequence, which revealed 19 amino acids in the signal sequence and 590 amino acids in mature AFP. There are 15 regularly spaced disulfide bridges, which generate a folding structure having three repeating domains. There is one potential N-glycosylation site, Asn-Phe-Thr, in the amino acid sequence. In comparison with mouse AFP, 66% of the amino acid sequence was conserved, with the highest identity (72%) in domain 3, followed by domain 2 (67%) and domain 1 (59%). In comparison with human albumin, a 39% conservation of primary structure was found. Again, the similarity was the highest in domain 3 and the lowest in domain 1. Human AFP and human albumin are similar in overall structure, but certain parts of the molecules differ significantly in their predicted secondary structure.

Amino Acid Sequence↗
PubMed1982

Synthesis and secretion of alpha-fetoprotein and acute-phase alpha 2-macroglobulin by Zajdela rat ascites hepatoma.

Zajdela rat ascites hepatoma cells have been reported to be 'nonsecretors' of alpha-fetoprotein (AFP). Because of the potential of such cells in the study of defective secretory mechanisms of AFP and other serum proteins, we concluded a detailed investigation of the production of AFP in Zajdela cells growing in vivo. Three approaches were used: radioimmunoassay of intracellular and extracellular AFP and assays of AFP mRNA by molecular hybridization and cell-free translation. Radioimmunoassay showed that the AFP concentration in the hepatoma cells was extremely low (1.2 micrograms/g) as compared to known AFP-producing tissues such as fetal liver (600 micrograms/g). The assays of AFP mRNA by hybridization and translation supported the low level of AFP production in Zajdela cells, and we consider such cells to be poor producers of AFP and therefore not suitable for the study of defective mechanisms for AFP secretion. The Zajdela tumor cell intracellular concentration of acute-phase alpha 2-macroglobulin (AP alpha 2M) measured by radioimmunoassay was also found to be low (3.0 micrograms/g) compared to liver of Zajdela-bearing rats (80 micrograms/g). In view of these low levels of synthesis of AFP and AP alpha 2M in Zajdela hepatoma cells, little biological significance may be attached to the apparent nonsecretion of these onco-fetal proteins.

Animals↗
PubMed1982

Alphafetoprotein messenger RNA in human embryonal carcinoma grown in nude mice, and cloning of its complementary DNA.

Messenger RNA for human apha-fetoprotein (AFP) was partially purified from human testicular embryonal carcinoma grown in nude mice. DNA complementary to the mRNA was synthesized, tailed with oligo(dC) and inserted at the PstI site of the plasmid pBR322 tailed with oligo(dG). Escherichia coli strain LE392 was transformed with the chimeric plasmid and colonies were screened for human AFP mRNA sequences by hybridization with DNA complementary to mouse AFP mRNA (greater than 95% pure). Five colonies showed positive hybridization. The plasmid pHAF2, containing the largest insert, 900 nucleotides, was further characterized by hybrid-arrest of translation of AFP mRNA, restriction endonuclease mapping and partial nucleotide sequence analysis. It was found that the AFP complementary DNA (cDNA) sequence in pHAF2 corresponded to the 3'-end of AFP messenger RNA (mRNA), and showed a restriction map entirely different from that of mouse AFP cDNA clones previously reported.

Animals↗
PubMed1982

[Use of a lipid lymphographic agent, lipiodol, as a carrier of high molecular weight antitumor agent, smancs, for hepatocellular carcinoma].

Two advantages of the present therapeutic approach were described. Firstly, a selective deposition of lipiodol in tumor tissue was verified, thus more precise and accurate diagnosis by X-rays was possible either by CT or plain X-ray film. Secondly, pronounced accumulation of smancs in tumor tissue was observed, which established highly effective chemotherapy of unresectable hepatoma of 22 cases and 12 other cases based on (a) decrease in alpha-fetoprotein (86%), (b) tumor size (95%) and histology. Drug was given via the hepatic artery mostly 3-4 mg in 3-4 ml of lipiodol once every 3 to 4 weeks. Most patients have experienced a total dose of 6-8 mg in two cycles, but drug activity lasted more than 3 weeks. Neither hematosuppression nor anaphylaxis was observed. Major side effect was transient fever (38-39 degrees C) in about 50% of the cases which lasted no more than one week. Other minor side effect was abdominal pain during or after arterial infusion which lasted for about 20 min. Liver function was affected very slightly if any. Mild leukocytosis was observed in 65% of the patients.

Adult↗