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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 739 records · Page 41Linked to original sources

Structures of the sugar chains of recombinant human granulocyte-colony-stimulating factor produced by Chinese hamster ovary cells.

Recombinant human granulocyte-colony-stimulating factor (G-CSF) was purified from Chinese hamster ovary cells transfected with human G-CSF cDNA. The recombinant human G-CSF was treated with alkaline borohydride and the oligosaccharide-alditols liberated were fractioned by gel filtration on a Bio-Gel P-4 column, followed by high-performance liquid chromatography by use of a strong anion exchanger. Two oligosaccharide-alditols were obtained and their structures were identified by component analysis and 500-MHz 1H-NMR spectroscopy. The structures of the sugar chains were NeuAc alpha 2-3Gal beta 1-3GalNAcol and NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-6)GalNAcol.

Animals↗

Transformation by viral and cellular oncogenes of a mouse BALB/3T3 cell mutant resistant to transformation by chemical carcinogens.

The mouse cell line MO-5 is resistant to transformation by various chemical carcinogens and also by UV irradiation (C. Yasutake, Y. Kuratomi, M. Ono, S. Masumi, and M. Kuwano, Cancer Res. 47:4894-4899, 1987). Northern (RNA) blot analysis showed active expression of ras and myc genes in MO-5 and BALB/3T3 cells. The effect of transfection of various oncogenes on transformation was compared in MO-5 cells and parental BALB/3T3 cells. Activated c-H-ras, c-N-ras, and v-mos gene induced transformation foci of MO-5 and BALB/3T3. Introduction of the polyomavirus middle T-antigen (mTag) or the Rous sarcoma virus-related oncogene v-src, however, efficiently transformed BALB/3T3 but not MO-5 cells. Expression and phosphorylation of mTag and the associated c-src proteins were observed in mTag-transfected clones of MO-5 as in BALB/3T3 and phosphorylation of the src protein was observed in v-src-transfected BALB/3T3 and MO-5 clones. Hybrids between mTag- or v-src-induced transformants of BALB/3T3 and untransformed MO-5 maintained the transformation phenotype, suggesting that no dominant suppressor of transformation exists in MO-5. A hybrid clone between BALB/3T3 and MO-5 induced efficient transformation foci after transfection with the mTag gene, suggesting that the deficient transformation phenotype of MO-5 was recessive. Instead, some other alteration of MO-5, plausibly membrane function, might lead to abortive transformation by chemical carcinogens and also by mTag and the v-src gene product.

Animals↗

Relationship between forced expiratory flow and tracheal sounds. Possible effect of vortices on flow.

We measured both tracheal sounds and forced expiratory flows simultaneously in 20 normal subjects and 4 patients with stenosis of the main bronchus. Spectral analysis of the tracheal sounds revealed development of discrete line spectra, the frequencies of which ranged between 488 and 942 Hz. There was a positive correlation between these frequencies and the peak flows (r = 0.601). We speculate that the origin of these line spectra are vortices rather than the vibrations of the wall. It is postulated that the pressure drops caused by vortices make the airways more susceptible to collapse and may lead to flow limitation.

Adult↗

Effects of coronary thrombolysis on left ventricular ejection fraction in patients with acute myocardial infarction.

Left ventriculograms were performed on 65 patients with acute myocardial infarction, once upon admission and again 3 months later. In 29 cases urokinase was injected intravenously and/or intracoronarily. The other 17 were treated without urokinase. In 8 out of 29 patients whose infarct-related coronary arteries remained completely occluded following urokinase therapy, the global ejection fraction was reduced from 54 +/- 3% during the acute stage to 46 +/- 5% during the chronic stage (p less than 0.001). However, for the 21 patients whose coronary arteries were successfully recanalized, the 2 values were the same (52 +/- 2%). The highest global ejection fractions were seen in 19 spontaneously recanalized patients (acute: 54 +/- 2%, chronic: 55 +/- 2%). For the 8 unsuccessful patients, the regional ejection fraction for the infarcted portion was reduced from 20 +/- 5% during the acute stage to 18 +/- 6% during the chronic stage. But for the successful patients there was an improvement from 22 +/- 2% during the acute stage to 27 +/- 2% during the chronic stage. Again, the regional ejection fraction was the highest for the spontaneously recanalized group, being 31 +/- 2% and 36 +/- 3% during the acute and chronic stages, respectively. These results indicate that if the coronary artery remains occluded during the acute stage the reduced left ventricular function continues to deteriorate even more during the chronic stage. Successful coronary thrombolysis, however, might salvage the infarcted myocardium as well as preserve the function of the left ventricle.

Chronic Disease↗

Reduced early diastolic extension in the infarcted portion in patients with old myocardial infarction.

To study relaxation characteristics of the infarcted myocardium, cyclic changes in the global left ventricular (LV) volume were measured in 20 patients with old myocardial infarction (OMI) and 17 normals (Normal) and those in the regional segment length were measured in 9 patients with anterior old myocardial infarction (anterior OMI) and 11 normals. The LV volume was calculated by using biplane LV cineangiograms. The regional segment length was calculated by measuring the spatial length between the 2 points of the ramifying branches on the left coronary arteries by using biplane coronary cineangiograms. The LV filling volume before atrial contraction (VR) was significantly less in the OMI compared with that in the normals (Normal 38 +/- 6 (mean +/- SD) ml/m2 vs 30 +/- 7 ml/m2: p less than 0.01), while filling volume by atrial contraction (Va) did not significantly differ (Normal 15 +/- 4 ml/m2 vs OMI 17 +/- 5 ml/m2). The lengthening of the segmental wall during diastole before atrial contraction (%LR) in the infarcted portion was 5.0 +/- 2.9% which was also significantly less than that in the non-infarcted portion (9.6 +/- 4.2%). The extent of lengthening by atrial contraction (%La) did not differ between the 2 portions (non-infarcted portion 3.8 +/- 1.1% vs infarcted portion 3.5 +/- 1.2%). Reduction of %LR was speculated to be caused by the incomplete relaxation in the myocardium adjacent to the infarcted portion and stiff myocardium in the infarcted portion. This study suggests that the infarcted myocardium may lead to a reduction of diastolic expansion before atrial contraction.

Angina Pectoris↗

Withdrawal of endogenous somatostatin induces secretion of growth hormone-releasing factor in rats.

Secretion of GH occurs in episodic bursts under the dual control of two hypothalamic peptides, GH-releasing factor (GRF) and GH-inhibiting factor (somatostatin, SRIF). Recent studies in rats suggest that episodic GH secretion is generated by the periodic release of GRF, which is associated with the simultaneous withdrawal of SRIF secretion. To test the possibility that GRF discharge is functionally coupled with the withdrawal of SRIF, we investigated whether acute withdrawal of SRIF can induce GRF release by the rat hypothalamus using highly specific antisera against SRIF and rat GRF. In conscious unrestrained rats, i.v. administration of SRIF antiserum at the period of the GH trough induced a rapid onset of the GH secretory surge with a peak value of 309 +/- 67 micrograms/l (mean +/- S.E.M.) 30 min after injection. Pretreatment with antiserum to rat GRF resulted in a approximately 83% suppression of the GH surge induced by SRIF antiserum without affecting the trough GH values. GRF antiserum also significantly inhibited the spontaneous GH surge. In urethane-anaesthetized rats, as in conscious rats, an acute phasic GH release was caused by SRIF antiserum despite the interference of anaesthesia with spontaneous GH secretion. A further surge-like GH secretion was not restored during the next several hours, however, with the GH secretory profile being characterized by a tonic increase in the baseline levels of GH. In the anaesthetized rat antiserum to rat GRF, having no effect on basal GH levels, similarly inhibited by approximately 66% the acute GH surge induced by SRIF antiserum and decreased by about 30% the later sustained rise in GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Protective effect of human granulocyte colony-stimulating factor on bacterial and fungal infections in neutropenic mice.

The in vivo effects of purified natural human granulocyte colony-stimulating factor (h G-CSF) on bacterial and fungal infections were examined in mice treated with cyclophosphamide (CPA). Induction of severe neutropenia was prevented by repeated daily injections of h G-CSF at a dose of 2.5 micrograms/day for 4 days after the CPA treatment. Although control mice died shortly after the bacteria inoculation at day 4, most of the mice in whom the numbers of blood neutrophils were restored by h G-CSF injections were saved from death. At the site of the bacteria inoculation in the h G-CSF-treated mice many mature neutrophils were observed to migrate in a dose-dependent way. Furthermore, the dose of antibiotics required for elimination of infections was proved to be much less in the h G-CSF treated mice than that in the non-treated mice. These findings indicate that h G-CSF can be used efficiently for prevention and treatment of bacterial and fungal infections, particularly in patients with neutropenia.

Agranulocytosis↗

[Cancer-associated alterations of human hepatocellular carcinoma beta-glucuronidase--study on phosphorylation by 3', 5'-cyclic AMP dependent-protein kinase].

beta-Glucuronidase purified from human hepatocellular carcinoma consisted of a major subunit with molecular weight of 64,000 (64K-Da) and a minor 76K-Da subunit, whereas the hydrolase from normal liver had almost exclusively 64K-Da subunit. beta-Glucuronidase from the hepatoma and normal liver could serve as a substrate for a cAMP-dependent protein kinase. The rate of phosphorylation reaction of the hepatoma beta-glucuronidase was rapid, whereas that of the normal liver beta-glucuronidase was slow and much lower. Stoichiometry of beta-glucuronidase was 4.3 mol and 0.46 mol of phosphate per mol of the beta-glucuronidase from the hepatoma and normal liver, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of 32P-labeled beta-glucuronidase indicated that the 64K-dalton subunit was phosphorylated both in hepatoma and normal liver beta-glucuronidase. Tryptic peptide mapping of 32P-labeled beta-glucuronidase from hepatoma identified two distinct phosphopeptides (X and Y). The peptide from hepatoma hydrolase was phosphorylated predominantly at the X, while the peptide Y was the major phosphopeptide in the hydrolase of normal liver. Two-dimensional analysis of phosphoamino acids revealed two sites, phosphoserine and phosphothreonine.

Carcinoma, Hepatocellular↗

[Experimental study of the treatment of uterine leiomyosarcoma in the mouse with progestogen].

Because of its rare occurrence in the human, the endocrinologic and receptor-related aspects of an uterine leiomyosarcoma (LMS) are poorly understood when compared to what is known of, say, human endometrial cancer. Thus, to increase our understanding, we have succeeded, by the string method, in inducing an uterine LMS in the mouse and have studied the possibility of hormonal therapy as a method of treatment. The findings of our study are enumerated as follows: 1. The induced uterine LMS had an estrogen receptor, which was confirmed by a biochemical assay and, morphologically, by a PAP (the peroxidase anti-peroxidase technique); 2. The growth of this tumor was significantly inhibited by MPA (medroxyprogesterone acetate) therapy (100 mg/kg); 3. After MPA therapy, the estrogen receptor levels were increased, especially in the nucleus; and, 4. The growth of a secondary tumor, transplanted after the initial hormone therapy, was not inhibited by the readministration of MPA. Our results suggest that this experimentally-induced uterine LMS in the mouse provides a useful means to study therapeutic treatment, and may assist in furthering our understanding of human uterine LMS and lead to finding an effective therapy.

Animals↗

[A case of cystadenocarcinoma of the liver complicated by gastric cancer--a review of 83 cases of primary cystic liver cancer in the literature].

So far as is known, this is the first reported case in the literature of a primary cystic liver cancer complicated with a gastric cancer. A 77-year-old female was admitted to hospital because of a swelling in the upper abdomen and appetite loss. CT scanning, an echogram, and an angiogram of the abdomen revealed a large cystic lesion which originated from the left lobe of the liver. A DIC indicated a gall stone, Further, upper GI fluoroscopy and endoscopy revealed a gastric cancer of the Borrmann II type, and thus a dome resection of the cyst, cholecystectomy, aad 3/4 partial gastrectomy was performed. The liver was found to contain much mucin. The histology indicated a cystadenocarcinoma of the liver, and an adenocarcinoma of the stomach of a poorly differentiated type.

Aged↗

Pharmacological studies of lappaconitine. Analgesic activities.

The analgesic activity of lappaconitine, which is contained in the root of Aconitum sinomantanum Nakai, was examined after oral and subcutaneous administration to mice or rats by using methods for screening of analgesics, i.e., hot plate, tail immersion, tail pinch, tail pressure, acetic acid-induced writhing, bradykinin-induced flexor reflex of hind limb and Randall-Selitto methods. The results were compared with those for morphine, indometacin and acetylsalicylic acid (ASA). Analgesic activities of lappaconitine were greater than those of indometacin and ASA, but generally about 2 to 5 times less than those of morphine. However, in the rat tail immersion test, orally administered lappaconitine exhibited more potent analgesic activity than morphine; in this test, lappaconitine was almost equipotent when given orally and subcutaneously, whereas the potency of orally administered morphine was only one-twentieth of that of subcutaneously administered morphine. Like morphine, lappaconitine increased the pain threshold of the normal paw as well as that of the inflamed paw when tested by the Randall-Selitto method. The results show that lappaconitine has strong analgesic activity, and further suggest that the central nervous system may be involved in the action on the pain threshold.

Aconitine↗

[Augmentation of murine organ-associated natural immune responses by cepharanthin].

Oral administration of cepharanthin (bisbenzylisoquinoline alkaloid) to mice was effective in the organ-associated immune responses. Cepharanthin, as a biological response modifier (BRM), augmented natural killer (NK) activity of leukocytes isolated from the spleen, lymph node, lung, and liver. The degree of NK augmentation was almost the same in these organs without lymph node, and reached to the maximum levels 3 days after cepharanthin administration. In addition, adherent leukocytes (greater than 95% macrophages) isolated from the lung or liver following cepharanthin administration also exhibited an augmented macrophage-mediated cytotoxicity. These results suggest that such organ-associated immune responses may play an important role in the antitumor and/or antimetastatic effects mediated by cepharanthin.

Administration, Oral↗

[Antitumor effect of cepharanthin--mechanism of the antimetastatic effect on Lewis lung carcinoma (3LL)].

The antitumor activity of cepharanthin against Lewis lung carcinoma (3LL) primary tumor and its pulmonary metastases was evaluated. Oral administration of cepharanthin to tumor-bearing mice at a daily dose of 5 mg/kg resulted in inhibition of 3LL primary tumor growth, preferential suppression of pulmonary metastases, and prolongation of survival time. The antimetastatic effect was not observed when tumor-bearing mice were treated with some blockers of immunocompetent cells, e.g. carrageenan or monoclonal anti-Thy 1.2 antibody. In ex vivo experiments, cepharanthin was also shown to augment the activities of murine alveolar macrophages and splenic natural killer (NK) cells. These results suggest that the antitumor or antimetastatic effect of cepharanthin might be expressed through host defense mechanisms, including macrophages, T lymphocytes and/or NK cells.

Alkaloids↗

[BALB/c3T3].

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Animals↗

Bonding behavior of three types of hydroxyapatite with different sintering temperatures implanted in bone.

The present study suggests that bonding does not vary in hydroxyapatite (HA) with different sintering temperatures implanted in bone tissue. The apparent unimportance of strict temperature regulation greatly simplifies HA processing. Three samples of HA (15 mm x 10 mm x 2 mm, abraded with 2000 alumina powder), of which sintering temperatures and microporosity were 800 degrees (45%), 1000 degrees (4.8%), and 1200 degrees (0.4%), respectively, were prepared. They were implanted into the metaphysis of tibia of mature male rabbits. Segments of the tibia containing the HA were excised and prepared for the detaching test. The failure load, when an implant detached from the bone or the bone broke, was then measured. Failure loads in HA (800 degrees), HA (1000 degrees), and HA (1200 degrees) ten weeks after implantation did not differ. Those in HA (800 degrees), HA (1000 degrees), and HA (1200 degrees) 25 weeks after implantation were 2.58 +/- 1.88 kg, 6.46 +/- 1.43 kg, and 6.50 +/- 2.71 kg, respectively. The failure load in HA (800 degrees) versus HA (1200 degrees) and that in HA (800 degrees) versus HA (1000 degrees) differed significantly (p less than 0.05). The lower failure load of HA (800 degrees) 25 weeks after implantation can be explained by its weakened mechanical strength due to high porosity. Bonding between bone tissue and three types of HA did not vary as observed by contact microradiography, Giemsa surface staining, and scanning electron microanalyzer-energy dispersive X-ray microanalyzer.

Animals↗

Production of interleukin 1 alpha-like factor and colony-stimulating factor by a squamous cell carcinoma of the thyroid (T3M-5) derived from a patient with hypercalcemia and leukocytosis.

In order to elucidate the pathogenesis of humoral hypercalcemia and leukocytosis in a 71-year-old patient with squamous cell carcinoma of the thyroid, bone-resorbing activity (BRA) and colony-stimulating activity in the conditioned medium of T3M-5 cells, a clonal cell line established from the tumor, were studied. Gel chromatography of the concentrated conditioned medium revealed respective single peaks of colony-stimulating activity (Mr approximately 27,000) and BRA (Mr 15,000-20,000). BRA did not elicit parathyroid-hormone-like activity but greatly enhanced phytohemagglutinin-induced thymocyte proliferation. This interleukin 1 (IL-1)-like activity exactly coeluted with BRA upon gel chromatography, DEAE-Sepharose ion-exchange chromatography, and isoelectric focusing (pI, 4.7-5.2). BRA was partially inhibited by indomethacin and hydrocortisone, and completely inhibited by anti-IL-1 alpha antiserum, whereas anti-IL-1 beta antiserum had no effect. Furthermore, transplantation of T3M-5 cells into nude mice caused marked hypercalcemia as well as leukocytosis. These findings suggested that excessive production of colony-stimulating factor and IL-1 alpha-like factor by the squamous cell carcinoma was responsible for leukocytosis and hypercalcemia, respectively, in the tumor-bearing nude mice and in the patient. Since several similar cases have been reported in Japan, the syndrome of leukocytosis and hypercalcemia associated with certain solid tumors may constitute a new paraneoplastic syndrome.

Aged↗

A novel human nonviral retroposon derived from an endogenous retrovirus.

In a human genome, we found dispersed repetitive sequences homologous to part of a human endogenous retrovirus termed HERV-K which resembled mouse mammary tumor virus. For elucidation of their structure and organization, we cloned some of these sequences from a human gene library. The sequence common to the cloned DNA was ca. 630 base-pairs (bp) in length with an A-rich tail at the 3' end and was found to be a SINE (short interspersed repeated sequence) type nonviral retroposon. In this retroposon, the 5' end had multiple copies of a 40 bp direct repeat very rich in GC content and about the next 510 nucleotides were homologous to the 3' long terminal repeat and its upstream flanking region of the HERV-K genome. This retroposon was thus given the name, SINE-R element since most of it derived from a retrovirus. SINE-R elements were present at 4,000 to 5,000 copies per haploid human genome. The nucleotide sequence was ca. 90% homologous among the cloned elements.

Base Sequence↗