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Biomedical subjects

K Morikawa

Publications and source records attributed to K Morikawa.

At least 289 records · Page 16Linked to original sources
PubMed1987

Pharmacological studies of the new centrally acting muscle relaxant 4'-ethyl-2-methyl-3-pyrrolidinopropiophenone hydrochloride.

The pharmacological properties of 4'-ethyl-2-methyl-3-pyrrolidinopropiophenone hydrochloride (HSR-770), a new centrally acting muscle relaxant, were investigated in experimental animals. HSR-770, within a dose range of 1-10 mg/kg i.v., relaxed alpha- and gamma-rigidities in rats, the dose required to relax gamma-rigidity being lower than the dose required to relax alpha-rigidity. When HSR-770 was intraduodenally (i.d.) administered within a dose range of 25-50 mg/kg, the relaxant activity on alpha-rigidity was potent and long-lasting in comparison with eperisone or tolperisone. HSR-770 inhibited flexor reflex more strongly than patellar reflex in a dose-dependent manner within a dose range of 2.5-10 mg/kg i.v. or 25 and 50 mg/kg i.d. in anesthetized cats. In spinal cts, HSR-770 (5 and 10 mg/kg i.v.) inhibited flexor reflex but this potency was weaker than that in anesthetized cats. HSR-770 (12.5-50 mg/kg i.d.) inhibited he crossed extensor reflex in anesthetized rats. In spinal cats, HSR-770 inhibited mono- and polysynaptic reflex potentials to the same extent and also depressed dorsal root reflex potential at 5 and 10 mg/kg i.v. HSR-770 at a dose (50 mg/kg p.o.) which exerted muscle relaxant activity on both rigidity and flexor reflex, had little effect on spontaneous motor activity (mice), hexobarbital-induced sleeping time (mice) and conditioned avoidance response (rats). These results indicate that HSR-770 is a potent centrally acting muscle relaxant and that its central nervous system depressant activity is relatively weak.

Anemia↗
PubMed1986

Calcium-independent induction of cytocidal activity of polymorphonuclear leukocytes by phorbol myristate acetate-like tumor promoters.

Tumor promoters were tested for the ability to induce cytocidal activity of polymorphonuclear leukocytes (PMNs), and the extracellular calcium-dependency of their PMN cytotoxicities were examined in comparison with that by some immunomodulators. Immunomodulators such as linear beta-1, 3-D-glucan (TAK) induced potent cytocidal activity of PMNs. The induction was dependent on extracellular Ca2+. Tumor promoters such as phorbol 12-myristate 13-acetate (PMA) and its derivatives, teleocidin which is structurally unrelated to PMA, and croton oil as an example of mixture also induced potent PMN cytotoxicities. In the latter cases, however, the induction was not dependent on extracellular Ca2+. The ability of these tumor promoters to induce PMN cytotoxicity correlated well with their skin-tumor promoting activities. These results indicate that inductions by PMA-like tumor promoters are distinguishable from those by TAK-like immunomodulators in not being Ca2+-dependent. The application of Ca2+-independent PMN cytotoxicity to detect PMA-like tumor promoters is discussed.

Animals↗
PubMed1986

The nucleotide sequence of the fission yeast DNA topoisomerase II gene: structural and functional relationships to other DNA topoisomerases.

We have determined the complete nucleotide sequence of a 5.3-kb long genomic DNA fragment of the fission yeast Schizosaccharomyces pombe that encodes DNA topoisomerase II. It contains a 4293 bp long single open reading frame. The predicted polypeptide has 1431 residues (mol. wt 162,000) and shows three characteristic domains; the large C-terminal region, which consists of alternating acidic-basic stretches and might be a chromatin-binding domain, the NH2 half domain homologous to the ATP-binding gyrB subunit of bacterial gyrase and the central-to-latter part which is homologous to the NH2 domain of the catalytic gyrA subunit, suggesting a possible evolutionary consequence of the gene fusion of the bacterial gyrase subunits into the eucaryotic DNA topoisomerase II gene. We have found that the cloned fission yeast TOP2 gene can complement the budding yeast top2 mutation, although the fission yeast TOP2 protein sequence is only 50% homologous to the recently determined sequence of budding yeast (J.C. Wang, personal communication). Conversely, the budding yeast TOP2 gene can complement the fission yeast top2 mutations, indicating that their DNA topoisomerase II genes are functionally exchangeable.

Amino Acid Sequence↗
PubMed1986

The therapeutic effects of an immunopotentiator, PS-K, on 3-methylcholanthrene-induced autochthonous tumors in C57BL/6 mice in combination with the surgical removal of primary sites.

We investigated the therapeutic effects of an immunopotentiator PS-K on recurrent or metastatic tumors observed after the surgical removal of MCA-induced primary tumors in autochthonous C57BL/6 mice and on the survival time of treated mice. The MST of mice treated with PS-K at various times (59.8-63.4 days) was prolonged as compared with that of mice treated by surgery alone (48.6 days). Local recurrence of tumors was found in 36 of 66 mice (54.6%) treated by surgery alone, whereas it was inhibited significantly (P less than 0.05) when treatment with PS-K was started 1 day after the surgery and occurred in 22 of 64 mice (34.4%) when PS-K was given for 5 days in 1 week, or in 22 of 66 mice (33.3%) when PS-K was administered twice a week for 7 weeks. The MSTs of mice with local recurrence were also found to be prolonged as compared with those of mice treated by surgery alone (54.8-67.5 days vs 49.8 days). The MSTs of mice without tumor recurrence were also prolonged significantly (P less than 0.05-0.001) by combinations of PS-K at various times, although most of the mice died of metastatic tumors even in the groups of mice where a combined treatment with PS-K had been administered. The above findings suggest that the administration of PS-K inhibits the growth of recurrent or metastatic tumor cells in autochthonous mice after the surgical removal of the primary tumors.

Adjuvants, Immunologic↗
PubMed1986

Enhanced susceptibility of target KMT-17 cells to activated macrophages by treatment with the antitumor agent bleomycin.

We observed that after KMT-17 cells had been treated with bleomycin (BLM), even with a dose as high as 160 micrograms/ml, they were still able to form colonies in soft agar. We then studied the susceptibility of KMT-17 cells treated with BLM to activated macrophages. During a colony inhibition assay, BLM-treated KMT-17 cells were found to be much more susceptible to activated macrophages than nontreated KMT-17 cells, moreover, a tumor neutralizing assay showed that the growth of BLM-treated KMT-17 cells was also significantly inhibited by activated macrophages as compared with nontreated KMT-17 cells. Macrophages activated by both BLM and the Nocardia rubra cell wall skeleton were able to mediate such tumor inhibition activity in BLM-treated KMT-17 cells. Activated macrophages did not seem to have strong antitumor activity against nontreated KMT-17 cells in vivo, however, the life span of the rats which were inoculated i.p. with KMT-17 cells was significantly expanded after the tumor-bearing rats were given BLM i.p. The data presented here suggest that not only does BLM have a direct tumoricidal effect on KMT-17 cells, it also regulates immunosensitivity of targets to immune effectors. We also discuss the mechanism for enhancing the susceptibility of KMT-17 cells to activated macrophages brought about by treatment with BLM.

Animals↗
PubMed1986

Generation of cytotoxic T lymphocyte responses to allo-H-2 antigens in allogeneic bone marrow chimeras histocompatible at the H-2 subregions.

The present study was performed to determine whether H-2 matching is required for full cytotoxic T lymphocyte (CTL) responses to allo-H-2 antigens in allogeneic bone marrow chimeric mice. A number of irradiated, bone marrow-reconstituted chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant strains and AKR recipient mice were prepared. Spleen cells obtained from such chimeras and normal control mice were activated in vitro by culturing them with irradiated stimulator cells. It was shown that spleen cells from [4R----AKR], [(4R X 3R)F1----AKR] or [AQR----AKR] chimeras, which were histocompatible on the left hand-side of the H-21 subregion between donor and recipient mice, generated greater CTL activities than those that were seen with spleen cells of [3R----AKR] or [5R----AKR] chimeras, which were histoincompatible in this region. We were unable to demonstrate suppressor cell activity of the spleen cells of [3R----AKR] chimeras cultured with stimulator cells. Although spleen cells from [3R----AKR] chimeras showed substantial proliferative responses to stimulator cells (MLR) and to Con A and LPS, IL2 activities of supernatants from Con A-activated spleen cells (Con A SN) of the chimeras were significantly lower than those of [4R----AKR] or [(4R X 3R)F1----AKR] chimeras. Furthermore, vigorous CTL activities were obtained with either spleen cells or thymocytes from [3R----AKR] chimeras when rat Con A SN was added to the MLR cultures. These observations suggest that the numbers of precursor CTLs in the cells from [3R----AKR] chimeras are at the same level as those of [(4R X 3R)F1----AKR] or normal mice and that the low CTL activities generated by spleen cells of [3R----AKR] chimeras compared to H-2I-matched chimeras are due in large measure to deficiency in IL2 production by the splenic T cells of the [3R----AKR] chimeras.

Animals↗
PubMed1986

A study on location of synthetic site which mainly synthesizes and delivers fifth component of complement system in vivo.

Tissue sites for synthesis of the fifth component of complement (C5) in vivo have been investigated by using allogeneic bone marrow chimeras and bone marrow chimeras which were transplanted in addition with hepatocytes. Our prior studies have demonstrated that bone marrow chimeras which had been prepared by transplanting marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients lacked detectable levels of C5 in the sera. However, when such potentially C5-deficient [C5(+)---C5(-)] chimeras were introduced into their spleens by means of injections of fully dispersed single cell suspensions of hepatocytes isolated from the C5-sufficient donor strain, they accepted the transplantation of hepatocytes for prolonged periods and developed a measurable amount of C5 in the sera. These results indicate that C5 protein in sera is not synthesized in significant amount by cells that are descendants of bone marrow cells but rather that this complement component is synthesized and delivered to the blood in vivo by somatic cells including liver cells that are not derivatives of the bone marrow.

Animals↗
PubMed1986

Electron microscopic study of 5S rRNA crystals from Thermus thermophilus HB8.

Several types of crystals were grown from 5S rRNA, which was purified from the highly thermophilic bacterium, Thermus thermophilus HB8. Crystal lattice parameters were determined by X-ray and electron diffraction. One type of crystal was suitable for electron microscopy after staining with uranyl acetate. Two projections derived from micrographs taken at different tilt angles were processed for image analysis. This result enabled us to deduce the arrangement of molecules within the crystal lattice.

Crystallization↗
PubMed1986

[Effects of 3-methyl-4-oxo-2-phenyl-N-[2-piperidinyl) ethyl]-4H-1-benzopyran-8-carboxyamide hydrochloride monohydrate (FL-155), a new anti-pollakiuria agent, on rhythmic bladder contractions in anesthetized rats].

The effects of FL-155, which was synthesized to develop a new orally-active anti-pollakiuria agent, on the rhythmic bladder contractions were studied in anesthetized rats. At a pressure exceeding 10 cm H2O in the bladder, a rhythmic bladder contraction was observed up to at least 120 min. This response was abolished by a spinal (C1 level) cut, cuts of both pelvic nerves, thiopental (3.0 mg/kg, i.v.) or lidocaine (1.0 mg/kg, i.v.); and atropine (0.01 mg/kg, i.v.) strongly inhibited the amplitude of the response. FL-155 and flavoxate, in intravenous (0.3-3.0 mg/kg and 1.0-3.0 mg/kg, respectively) and intraduodenal (12.5-100 mg/kg and 200-400 mg/kg, respectively) administrations, dose-dependently abolished the rhythmic bladder contractions, and FL-155 was 8-16 times more potent than flavoxate in intraduodenal administrations. These results suggest that the rhythmic bladder contraction in anesthetized rat may be a polysynaptic reflex through pelvic nerves and the central nervous system (supraspinal level), and FL-155 appears to be a candidate for an orally active anti-pollakiuria agent.

Animals↗
PubMed1986

Pharmacological studies of 2-(3-(3-(1-piperidinylmethyl)-phenoxy)propylamino)-4 (3H)-quinazolinone (NO-794), a new histamine H2-receptor antagonist.

The pharmacological profile of a new histamine H2-receptor antagonist, 2-(3-(3-(1-piperidinylmethyl)phenoxy)propylamino)-4 (3H)-quinazolinone (NO-794), was studied. NO-794 was a potent and selective histamine H2-receptor antagonist in the guinea-pig atria and gastric mucosal cells. NO-794 (1 X 10(-5) M) did not interact with H1-, muscarinic and beta 1-receptors. In guinea-pig atria, antagonism of NO-794 was unsurmountable. The onset of action of NO-794 was slow, and this antagonism was apparently irreversible not only on the guinea-pig atria but also on the gastric mucosal cells. In addition, NO-794 inhibited gastric acid secretion in pylorus ligated rats when administered intraduodenally. These results indicate that NO-794 is a powerful and unique histamine H2-receptor antagonist and may be useful in the treatment of peptic ulcer.

Animals↗
PubMed1986

Natural killer cell activity against a variety of target cell lines in normal persons: NK-target sensitivity and effect of age and sex on NK levels.

Natural killer (NK) cells have been implicated as first line of defence mechanism for carcinogenesis in humans. A lot of studies of depressed NK activity in patients with malignancies have supported this. Two major problems, however, in these studies are the choice of normal controls and target cells. To study this problem, peripheral mononuclear cells (PBMC) of sixty-six normal subjects from young and elderly, males and females were tested for NK function against twenty target cell lines with a microcytotoxicity assay. The result was shown that no sex or age difference existed with respect to NK function, except for a slight but significant decreased in NK activity of young female to K562 target cells. Target cells were divided into four groups by their NK sensitivity, namely, high, moderate, low and refractory sensitive. In general, NK activity of healthy persons is considered to remain stable and polyspecific in our results.

Adolescent↗
PubMed1986

[Leakage neutrons and X-rays in a therapeutic microtron facility].

Measurements of dose equivalent rate distribution in a medical microtron facility were done for neutrons and X-rays originated from 14 MV or 8 MV X-ray irradiation by the microtron. Measured data are described with empirical formulas for convenience of quantitative reconstruction of the data. A formula consisting of a simple power function agrees well with measured data except for thermal neutrons, and is understood to describe the dose rate separating into the scattered and unscattered components in the case of the point source. The thermal neutron distribution in the maze is described with another formula of an exponential function. A discrepancy was observed between the X-ray distribution in the maze from 14 MV X-ray irradiation and that from 8 MV irradiation. This is estimated to be caused by a contribution of capture gamma-rays increasingly emitted in the case of 14 MV X-ray irradiation.

Neutrons↗