Search PubMed⌕ Search

Biomedical subjects

M Morimoto

Publications and source records attributed to M Morimoto.

At least 289 records · Page 16Linked to original sources

Cloning of granulocyte colony-stimulating factor cDNA from human macrophages and its expression in Escherichia coli.

Human granulocyte colony-stimulating factor (hG-CSF) cDNA was cloned, by using a synthetic oligonucleotide probe, from an Okayama-Berg cDNA library of lipopolysaccharide-stimulated human peripheral blood macrophages. The cDNA encodes a polypeptide with an amino acid sequence which completely matches that of the known polypeptide with hG-CSF activity derived from human tumor cell lines. Expression in E. coli of high levels of the protein (about 10% of total cellular proteins) was accomplished under control of the trp promoter, and the purified protein was proved to have hG-CSF activity. Our data provide evidence that human peripheral blood macrophages do produce hG-CSF mRNA when stimulated exogenously, suggesting they are the producer of naturally occurring hG-CSF.

Base Sequence↗

[Recent advanced studies on mitomycins, antitumor activity and mode of action].

Mitomycin C (MMC) showed a wide antitumor spectrum with regression of various tumors and the optimal schedule of a single or intermittent administration against human tumor cells xenografted to nude mice, confirming the early reports obtained in rodent tumor system. The sensitivity of various human tumors xenografted to nude mice has been tested to antitumor agents to establish the system which could select the clinically active drugs. The effectiveness of MMC against human stomach cancers xenografted to nude mice clearly correlated to the clinical effect of MMC against gastric cancer. The covalent cross-link adducts between MMC and DNA were isolated in the bioreductive system of NADPH-cytochrome C reductase and NADPH, and the major monoadduct was determined as N2-(2'' beta 7'-diaminomitosen-1''-alpha yl)-2'-deoxyguanine. Importantly, bisadduct was isolated, and the structure was determined by spectroscopic method. DNA-DNA cross-link formation was shown by alkaline elution in cells treated with MMC. The activation of MMC has been characterized by the two electron transfer process, however, the one electron transfer process was proposed by electrochemical analysis. MMC was effective against hypoxic cells. Several cell lines resistant to MMC were isolated, and some MMC derivatives showed in vivo and in vitro anti-tumor activity against these resistant cells.

Animals↗

[Nationwide study of the antimicrobial susceptibility of clinical isolates of Proteus group in Japan].

We discussed the antimicrobial susceptibilities of Proteus group isolated in 1983 and 1984 and also the annual changes of the susceptibilities from 1980 to 1984. The tested strains were isolated in 103 hospitals in Japan. Antibiotics tested for this study were ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ), and gentamicin (GM). The MIC's were determined by the standard method of the Japan Society of Chemotherapy. Susceptibilities of the bacterial strains to the 4 antibiotics were described below: 1. Proteus mirabilis had good susceptibilities to all the antibiotics tested. 2. Susceptibilities of Proteus vulgaris were low to ABPC and CEZ, but high to CMZ and GM. 3. Proteus morganii showed low susceptibilities to ABPC and CEZ, and moderate to CMZ and GM. 4. Susceptibilities of Proteus rettgeri were low to ABPC and CEZ, and 25-40% of the strains were resistant to CMZ and GM. 5. Proteus inconstance had low susceptibilities to ABPC and CEZ, but fairly good to CMZ. About 55% of the strains showed resistance to GM. 6. There were no significant annual changes in susceptibilities of P. mirabilis, P. vulgaris and P. morganii to ABPC, CEZ and CMZ during the period from 1980 to 1984, but decreased susceptibilities to GM were noted in 1982. 7. There was no evidence of changes in susceptibilities of strains of P. rettgeri to ABPC and CMZ, but a tendency of decreasing susceptibilities to CEZ was shown from 1981. 8. P. inconstance showed no major changes in susceptibilities to ABPC, CMZ and GM. 9. Frequencies of resistant strains with MIC of 25 micrograms per ml or more in P. mirabilis, P. morganii and P. rettgeri were higher in 1982 and/or 1983 than the other years.

Ampicillin↗

Purification and characterisation of the extracellular D-glucosyltransferase from serotype c Streptococcus mutans.

A simple method of purification for the extracellular D-glucosyltransferase (GTase) from a serotype c strain Streptococcus mutans was developed using chromatography on DEAE-Sephacel and CM-cellulose. The GTase had a molecular weight of 155,000 and an isoelectric point of 7.4. The enzyme converted sucrose, in the absence of dextran T-10, into a branched (1----6)-linked alpha-D-glucan having some alpha-(1----3)-linked D-glucosyl residues. The GTase was similar to GTases which have been isolated from other strains of serotype c S. mutans and which synthesise water-soluble glucans. In addition, the amino acid composition of the GTase protein was relatively similar to those of the GTases from serotype g S. mutans which synthesise water-soluble and water-insoluble glucans.

Amino Acids↗

Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase.

Staurosporine, microbial alkaloid which has been known to have antifungal activity was found to inhibit markedly phospholipid/Ca++dependent protein kinase (protein kinase C) from rat brain, with an IC50 value of 2.7 nM. However, it had little effect on the binding of 3H-phorbol-12, 13-dibutyrate (PDBu) to protein kinase C. The inhibition of protein kinase C was not competitive with phospholipid. This compound also showed the strong cytotoxic effect on the growth of HeLa S3 cells, with an IC50 value of 4 X 10(-12)M under the condition of 72 hr-exposure.

Alkaloids↗

Rare variants of Hodgkin's disease of the thymus: report of two cases and proposal for effective clinical management.

We treated two patients with rare variants of Hodgkin's disease of the thymus. One was a 17-year-old girl with a thymoma-like shadow on the chest X-rays, an increased erythrocyte sedimentation rate and an elevated eosinophil count. Pathologically, a mixed cellularity variant of thymus Hodgkin's disease was evident. The other patient was 22-year-old girl with evidence of mediastinal tumor on the chest X-rays. Pathological examination revealed Hodgkin's disease of the lymphocyte predominance variety. She also had Von der Haeve syndrome. In both cases, Hodgkin's disease was suspected by scintiscanning, using three kinds of radioisotope, 201Thallium-chloride, 67Garium-citrate and 75Selenomethionine. Radical excision of the lesion plus preoperative and postoperative irradiations were carried out. Both are well 6 and 5 years after the treatment, respectively. We propose a new diagnostic procedure and a method of treatment for such patients.

Adolescent↗

Scintiscanning demonstration of thymoma: comparative study on scintiscans using 201Tl, 67Ga and 75Se.

Thymus scintigraphy was performed using 201Tl-chloride, 67Ga-citrate and 75Se-selenomethionine on 30 thymoma patients with or without myasthenia gravis. Mass negativity was observed in 6 out of 17 (35.3 per cent) and 3 out of 13 cases (23.1 per cent), respectively. A rate of 70 per cent (21 cases out of 30) of mass positivity was observed by thymus scan using 201Tl. With regard to the relation between thymus scan and cell type, 201Tl-scan exhibited a high rate of mass positivity, regardless of the cell type while the 75Se-scan showed a trend toward mass positivity in epithelial cell predominant cases. With 201Tl, mass positivity was observed when the CPM/g ratio for tumors and blood exceeded 3.0. This trend can serve as an index for the suitability of supplementary chemo- and radiotherapies, as well as for prognosis in cases of relapse, and in those for whom excision was not complete.

Gallium Radioisotopes↗

Synergistic anticellular and antiviral activities of human recombinant interferon-gamma and -beta.

The synergism of anticellular and antiviral activities of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) was examined in vitro using human melanoma SK-MEL-28 cells. Some differences were detected in the kinetics of anticellular activity between both IFNs, namely the inhibitory effect of ReIFN-beta occurred earlier than that of ReIFN-gamma. Significant synergism was detected in the anticellular activity of both IFNs when growth curves and isobolograms were examined. A difference between ReIFN-gamma and ReIFN-beta was also detected in antiviral activity. The antiviral activity of ReIFN-gamma against vesicular stomatitis virus (VSV) was significantly weaker than that of ReIFN-beta, even though both IFNs exhibited almost equivalent antiviral activities against Sindbis virus. However, ReIFN-gamma and ReIFN-beta exhibited synergistic antiviral activities against both VSV and Sindbis virus. The analysis of cell cycle distribution by flow cytometry revealed that there were some differences in the distribution pattern between cells treated with ReIFN-gamma alone, ReIFN-beta alone, or ReIFN-gamma and ReIFN-beta in combination. ReIFN-beta induced a prolongation or accumulation of S phase, whereas the effect of ReIFN-gamma was cycle-nonspecific. The combination of ReIFN-gamma and ReIFN-beta induced a decrease of G1 phase and an increase of G2M phase. These results suggest that ReIFN-gamma and ReIFN-beta used in combination were more effective in inhibiting the growth of human tumor cells and the proliferation of viruses than IFN used individually.

Antineoplastic Agents↗

Antitumor effect of human recombinant interferon-gamma and -beta against human osteosarcoma transplanted into nude mice.

The antitumor activity of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) against human osteosarcoma G-292 cells was compared in vitro and in vivo. Both IFNs inhibited the growth of G-292 cells cultured in vitro and transplanted into nude mice in vivo. In in vivo experiment, both IFNs injected i.t. were more effective at inhibiting the growth of G-292 cells than systemic administration such as i.v., i.p. or s.c. In comparing the various routes of systemic administration of both IFNs, i.v. injection was slightly more effective. Both IFNs exhibited more significant growth inhibition when they were administered every day for 10 d, as compared with a single or intermittent administrations, suggesting that the antitumor activity of both IFNs was time-dependent. Significant difference was not detected in the in vivo antitumor activity between both IFNs when they were compared on the basis of their antiviral units. However, the time dependency for antitumor effect of ReIFN-beta was more significant than that of ReIFN-gamma. ReIFN-gamma and ReIFN-beta used in combination exhibited synergistic antitumor activity both in vitro and in vivo, though the in vivo synergism of both IFNs was not so effective as that of in vitro: These results indicate that both ReIFN-gamma and ReIFN-beta are effective at inhibiting the growth of human osteosarcoma in vivo.

Animals↗

Analysis of receptors, cell surface antigens, and proteins in human melanoma cell lines resistant to human recombinant beta- or gamma-interferon.

We studied the mechanisms of resistance to interferon (IFN) in two human melanoma cell lines, SK-MEL-28/beta cells resistant to human recombinant beta-interferon (ReIFN-beta) and SK-MEL-28/gamma cells resistant to human recombinant gamma-interferon (ReIFN-gamma). SK-MEL-28/beta cells were resistant to both ReIFN-beta and IFN-alpha, but not ReIFN-gamma or natural gamma-interferon (IFN-gamma), and SK-MEL-28/gamma cells were resistant to both ReIFN-gamma and IFN-gamma, but not ReIFN-beta or IFN-alpha. SK-MEL-28/s cells, sensitive to both ReIFN-beta and ReIFN-gamma, had receptors for ReIFN-beta and ReIFN-gamma. Furthermore ReIFN-beta and IFN-alpha shared the common receptors as judged by competition assays, while the receptors for ReIFN-gamma were independent in SK-MEL-28/s cells. The Kd values of binding of both IFNs to SK-MEL-28/beta or SK-MEL-28/gamma cells were essentially equivalent to those to SK-MEL-28/s cells. Both labeled IFNs were internalized rapidly into all cell lines at 37 degrees C. No significant difference in internalization was found between IFN-sensitive and -resistant cells. Each cell line expressed HLA-AB and Mr 97,000 protein antigens, the expressions of which were enhanced by ReIFN-beta and ReIFN-gamma. Partial resistance to the enhancement of both antigens by both IFNs was seen in the resistant cells. Finally ReIFN-gamma, but not ReIFN-beta, induced a Mr 56,000 protein in SK-MEL-28/s cells. This effect of ReIFN-gamma was also detected in SK-MEL-28/beta cells, but not SK-MEL-28/gamma cells. These results provide some information concerning the nature of IFN-resistant cells. The receptors had no significant correlation with the resistance, while the expression of HLA-AB or Mr 97,000 protein antigens or the induction of proteins had some correlation with the resistance.

Antigens, Neoplasm↗

Different kinetics of antiviral and anticellular activities between human recombinant and natural interferon-gamma arising from different receptor-binding properties.

Human recombinant interferon-gamma (ReIFN-gamma) and human natural interferon-gamma (IFN-gamma) showed significant differences in antiviral and anticellular activities. Namely, ReIFN-gamma exhibited antiviral activity against Sindbis virus and anticellular activity against HeLa S3 cells at significantly lower concentrations as compared with IFN-gamma at short exposure times of between 1 and 4 hr. This difference of activities was explicable in terms of different binding activities of the two IFNs to the receptors. The binding of 125I-ReIFN-gamma to the receptors was competitively decreased in a dose dependent manner by unlabeled ReIFN-gamma, whereas the competition by unlabeled IFN-gamma was significantly weaker. The results of pretreatment of the cells with unlabeled ReIFN-gamma or IFN-gamma suggested that the binding of IFN-gamma to the receptors was slower than that of ReIFN-gamma. ReIFN-gamma and IFN-gamma exhibited greater colony formation-inhibitory activity against HeLa S3 cells, as compared with IFN-alpha or ReIFN-beta. ReIFN-gamma also inhibited DNA, RNA and protein syntheses of HeLa S3 cells more potently than ReIFN-beta. However, the 2'-5' oligoadenylate (2'-5' A) synthetase activity in ReIFN-gamma-treated cells was significantly lower than that in ReIFN-beta-treated cells, suggesting that 2'-5' A synthetase does not play a major role in the anticellular activity of ReIFN-gamma, at least against HeLa S3 cells.

2',5'-Oligoadenylate Synthetase↗

Sero-epidemiological study on hepatitis A and B virus infection among dentists in the Philippines.

Dentists in the Philippines were surveyed for evidence of past hepatitis A and B virus infections. Of the 234 dentists examined, 201 (85.9 per cent) were found to have been infected by HA virus and 137 (58.5 per cent) had been infected by HB virus. The proportion with evidence of past HB virus infection increased as the years in dental practice increased. This increment with age was not found in the general population of the Philippines. It is considered that the incremental pattern could be attributed to the summation of risk during many years of providing dental treatment. Comparing the proportion of dentists with HBV antibodies (anti-HBs/c) in the Philippines, Japan, USA and Denmark, the Philippine dentists were found to be more frequently infected than dentists in the other countries. However, the increment in the proportion positive for HBV as the years in practice advanced was consistent with that found in Japan. The prevalence of post HA virus infection in Philippine dentists was higher than the proportion for dentists in Japan but in both countries it is probable that dentists are infected at the same rate as the general population.

Adult↗