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Biomedical subjects

M Hirano

Publications and source records attributed to M Hirano.

At least 559 records · Page 31Linked to original sources
PubMed1987

Development of potent aldose reductase inhibitors having a hydantoin structure.

Seventeen hydantoin derivatives were tested as inhibitors of aldose reductase, an enzyme believed to participate in the initiation of diabetic complications. Nine compounds with high inhibitory activities (IC50 values against purified rat lens aldose reductase less than or equal to 1.06 X 10(-6)M) were tested further for their abilities to prevent sorbitol accumulation induced by exposure of excised rat lens and sciatic nerve to a high glucose concentration (50 mM). Seven active compounds among them inhibited sorbitol accumulation by about 50% or more at a concentration of 10(-5)M. These seven compounds were given orally to streptozotocin-induced diabetic rats at a dose of 50 mg/kg/day and were assessed for their abilities to prevent both sorbitol accumulation in two tissues (lens and sciatic nerve) and myo-inositol depletion in the sciatic nerve. 1-[(2,4,5-Trichlorophenyl)sulfonyl]hydantoin, 1-[(2,5-dichlorophenyl)sulfonyl]hydantoin, and 1-[(beta-naphthyl)sulfonyl]hydantoin were found to be the most effective: they inhibited sorbitol accumulation in the sciatic nerve completely and that in the lens by more than 92%. It is conceivable from this study that the three compounds are promising for further investigation targeted to the treatment of diabetic complications.

Aldehyde Reductase↗
PubMed1987

A phase II study of (2"R)-4'-0-tetrahydropyranyladriamycin (THP) in hematological malignancies.

A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13-34 mg/m2 for 3-5 consecutive days or 35-50 mg/m2 at 3-4 week intervals. Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6. The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for acute leukemia and malignant lymphoma.

Acute Disease↗
PubMed1987

Treatment of acute leukemia and malignant lymphoma with (2"R)-4'-O-tetrahydropyranyladriamycin.

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3-4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m2 THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR + PR) was noted in 10 (40%) of 25 patients treated every 3-4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.

Adult↗
PubMed1987

Intramucosal distribution of the glossopharyngeal sensory fibers of cats.

In order to determine distribution of the sensory fibers of the glossopharyngeal nerve (IX) in the pharynx of cats, wheat germ agglutinin-horseradish peroxidase was injected into the superior and inferior ganglia of IX. Results were as follows: Labeled peripheral sensory nerve fibers in the pharynx were recognized ipsilaterally. The pharyngeal branch of IX innervated the nasopharyngeal mucosa at the level of the torus tubarius. The tonsillo-lingual branch was divided into four rami. The first ramus innervated the caudal one-third of the tongue and the vallate papillae. The second ramus innervated the palatine tonsil and the caudal half of the soft palate. The third ramus supplied a part of the radix linguae, the vallecula epiglottica and the lingual aspect of the epiglottis. The fourth ramus supplied the hypopharyngeal mucosa rostral to the middle level of the aryepiglottic fold.

Afferent Pathways↗
PubMed1987

Production of chimeric protein coded by the fused viral H-ras and human N-ras genes in Escherichia coli.

A new method for the production of a chimeric protein of two related genes has been developed. The nucleotide sequences of the region from the N terminus to the 86th amino acid (aa) residue of human N-ras and of the Harvey sarcoma virus (Ha-MuSV) H-ras are 80% homologous. We isolated the DNA fragment encoding the N-terminal portion up to the 70th aa residue from plasmid pH-1 which encodes the total genome of Ha-MuSV, and the DNA fragment encoding the C-terminal portion from the 40th aa to the C terminus from plasmid p6a1 which includes the human N-ras cDNA but lacks the N-terminal portion. After partial digestion of both fragments with phage lambda exonuclease, which creates 3'-protruding ends, a hybrid was formed between 73% homologous single-stranded DNA portions at the 3' ends of both fragments. The hybrid was recloned on pBR322 after repairing with Escherichia coli DNA polymerase I and DNA ligase. The chimeric v-H/N-ras gene composed of the N-terminal portion of v-H-ras gene and the remaining region of N-ras gene was inserted into an expression vector containing two tandem trp promoters and a terminator, and expressed in E. coli. The chimeric protein was found to accumulate to approx. 10% of total cellular proteins.

Amino Acid Sequence↗
PubMed1987

Construction and characterization of plasmid and lambda phage vector systems for study of transcriptional control in Escherichia coli.

We constructed a family of lambda phage and plasmid vectors which facilitate cloning and quantitative analysis of transcriptional regulator in both single and multiple copies. Their expression system was modified from the ara-trp-lac fusion operon of plasmid pMC81 [Casadaban and Cohen, J. Mol. Biol. 138 (1980) 179-207], which is designed to assay both promoters and terminators with a single vehicle. To eliminate transcriptional and translational polar effects liable to occur in the original fusion operon upon insertion of a foreign nucleotide sequence, intracistronic Rho-dependent terminators, that are present within the trpB gene and distal to the cloning site were deleted, and DNA spacers containing stop codons were introduced immediately before and after the cloning site. In analysis of the cloned trp regulatory region, the lambda phage system faithfully reproduced the tight regulation by tryptophan characteristic to the natural trp operon on the E. coli chromosome, whereas the plasmid counterpart exhibited a substantially relaxed response. Comparative studies on the relative strengths of various promoters and terminators have further demonstrated that the lambda phage vector system permits accurate assays of exceptionally strong promoters like Ptrp and lambda pL without disturbing the bacterial growth, while being sensitive enough for detecting low-level transcription under the control of weak promoters or potent terminators. Cloning with the lambda phage vector can be greatly facilitated by transferring the target regulatory site precloned with the plasmid onto the phage genome through in vivo recombination.

Bacteriophage lambda↗
PubMed1987

DNA segment containing C beta 1, a gene for the constant region of the beta chain of the T-cell antigen receptor, was inserted into chromosome 6 in cells from one patient with human T-cell leukemia.

DNA rearrangements that occurred in the vicinity of T-cell antigen receptor beta-chain gene clusters residing on chromosome 7 were examined in human T-cell acute lymphoblastic leukemia cells. In one patient, it was observed that, for the T-cell receptor beta-chain genes, a D beta 1-J beta 2.3 (where D is diversity and J is joining) junction was found on one chromosome, while the other chromosome kept the germ-line configuration. If this D beta-J beta junction was formed by the customary deletion mechanism, the C beta 1 gene (where C is constant) located between the D beta 1 and J beta 2.3 loci should have disappeared from this chromosome. The C beta 1 gene indeed was absent from the rearranged chromosome 7, but it was found on chromosome 6 as an inserted segment. The implications of the observations are discussed.

Animals↗
PubMed1987

Mass fragmentographic determination of gamma-aminobutyric acid and glutamic acid in discrete amygdaloid nuclei of rat brain.

A mass fragmentographic method for the simultaneous quantification of gamma-aminobutyric acid (GABA) and glutamic acid is described. In a convenient one-step reaction, the two amino acids were derivatized with pentafluoropropionic anhydride and pentafluoropropanol. The derivatization products were stable for several days. The technique has been applied to the assay of GABA and Glu in five amygdaloid nuclei of the rat brain. The GABA level was high in the central and medial nuclei, whereas the Glu level was high in the lateral and basal nuclei. The regional distribution of GABA was different from that of Glu within the amygdaloid nuclei.

Amygdala↗
PubMed1987

Three-dimensional vectorcardiography (3-D VCG) by computer graphics in old myocardial infarction.

By using computer graphics we rotated the vector loop and three coordinate axes to find the viewpoint where the infarctional changes are maximally exposed and demonstrated the advantage of the "3-D VCG" over the conventional VCG by defining the quantitative "MI index." The orthogonal electrocardiogram recorded by the Frank lead system was digitally measured and processed by a microcomputer. The loops and axes were rotated about the X axis (X-rot) and the Y axis (Y-rot). The spatial vector loop and orthogonal coordinates can be presented as viewed from any spheric direction. Eight quadrants were illustrated with four colors and red circles. The subjects consisted of 30 patients with old anterior myocardial infarction (MI) and 15 patients with old inferior MI. We measured the area of "Bite" in anterior MI and superior displacement in inferior MI. The MI index was defined and averaged in 361 directions. In anterior MI, the maximum mean index was obtained when X-rot is +90 degrees and Y-rot -40 degrees, viewed from upward and leftward, whereas in inferior MI it was obtained when X-rot is -50 degrees and Y-rot -80 degrees, viewed from downward and leftward. These values were significantly higher than those in conventional VCG projections, substantiating superior diagnostic sensitivity of 3-D VCG.

Adult↗
PubMed1987

Spontaneous tumors in F344/DuCrj rats from 12 control groups of chronic and oncogenicity studies.

The types and incidences of spontaneous tumors in F344/DuCrj rats were examined in 960 males and 959 females served as the control groups of separate twelve 2-year chronic and oncogenicity studies carried out during a 1978-1983 period. The major tumors occurred at more than 5% incidence were leukemia (mononuclear cell), testicular interstitial cell tumor, preputial gland adenoma, pituitary anterior adenoma, thyroid C-cell adenoma, adrenal pheochromocytoma and subcutis fibroma for males, and leukemia, uterine endometrial polyp, pituitary anterior adenoma, thyroid C-cell adenoma and mammary gland adenoma/fibroadenoma in females. Analyses on age-related occurrence of tumors revealed that the incidences of most of the major tumors in males attained already to the plateau between 85 and 97 weeks of age while those in females showed a steep rise during the last interval of observation, 98 to 110 weeks of age. An intralaboratory heterogeneity in incidence was observed in the thyroid C-cell adenoma and the adrenal pheochromocytoma for males, and the anterior pituitary adenoma for females.

Adrenal Gland Neoplasms↗
PubMed1987

In vitro and in vivo evaluations of BMY-28100, a new oral cephalosporin.

A new semisynthetic oral cephalosporin, BMY-28100, was evaluated for in vitro and in vivo antibacterial activities in comparison with cefaclor and cephalexin. BMY-28100 showed in vitro activity 3- and 10-fold more potent than that of cefaclor against Staphylococcus aureus and Streptococcus pneumoniae, respectively. BMY-28100 was slightly better than cefaclor and about 4 times more active than cephalexin against Haemophilus influenzae and Neisseria gonorrhoeae. Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were comparably susceptible to BMY-28100 and cefaclor. The bactericidal activity of BMY-28100 against S. aureus, E. coli and P. mirabilis was equal to or twice as high as MIC value, which was similar to that of cefaclor. The stability of BMY-28100 against penicillinases was nearly comparable to that of cefaclor, whereas cefaclor was somewhat unstable to cephalosporinases. BMY-28100 was about twice as active as cefaclor against three Gram-positive bacterial infections. BMY-28100 was also more potent against infections of H. influenzae and P. mirabilis, but slightly less active against E. coli Juhl than cefaclor. Blood level parameters of BMY-28100 were significantly superior to those of cefaclor and slightly better than cephalexin in mice and rats. The urinary recovery of BMY-28100 was somewhat higher and comparable to that of cefaclor and cephalexin, respectively. BMY-28100 was more stable than cefaclor in human and calf sera at 37 degrees C.

Animals↗
PubMed1987

[Lymphocyte cytotoxicity against autologous tumor cells and the effect of interferon-beta on their activities. (2) Evaluation of large granular lymphocytes (LGL)].

Large granular lymphocytes (LGL) were obtained by Percoll density gradient centrifugation of peripheral mononuclear cells from 15 patients with hematological malignancies (10 acute leukemias and 5 non-Hodgkin's lymphomas). Five-hour 51Cr-release cytotoxic assay by LGL was performed against frozen autologous tumor cells in these patients. Mean percentage cytotoxicity by LGL was 5.6%, and this was enhanced to 15.0% by the addition of IFN-beta to the culture medium. A decrease of cytotoxicity was observed when LGL was treated with anti-Leu 11b antibody plus complement, or when LGL was pretreated with the unlabelled K562 as a competitive inhibition assay. The addition of monocytes also induced a decrease of cytotoxicity, suggesting that monocytes may act as a suppressive agent in autologous tumor cell killing by LGL.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

[Lymphocyte cytotoxicity against autologous tumor cells and the effect of interferon-beta on their activities. (1) Evaluation by modification of target tumor cells].

IFN is known to enhance NK activity against cultured cell lines such as K562, but not against frozen autologous tumor cells. In order to obtain increased NK cytotoxicity using IFN-beta, various modifications were performed on autologous tumor cells. IFN-beta induced more enhanced NK cytotoxicity of normal lymphocytes when frozen tumor target cells were cultured for 4-5 days in the medium, or when these cells were treated with Vibrio cholerae neuraminidase (VCN). However, in an autologous setting, IFN-beta did not enhance NK cytotoxicity against either cultured autologous tumor cells or VCN-treated tumor cells. Also, IFN-beta did not enhance cytotoxic T cell activity against autologous tumor cells induced by mixed lymphocyte-tumor cell culture, although IFN-beta was able to induce enhancement of allospecific cytotoxic T cells mediated by mixed lymphocyte culture.

Cells, Cultured↗