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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 685 records · Page 38Linked to original sources

Measurement of immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K in human liver tissues: overproduction of immunoreactive prothrombin in hepatocellular carcinoma.

Des-gamma-carboxy prothrombin is an abnormal prothrombin which increases in the plasma of patients with hepatocellular carcinoma. To clarify the process of des-gamma-carboxy prothrombin synthesis, immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K (phylloquinone and menaquinone) concentrations were determined in human liver tissue, including hepatocellular carcinoma. In the patients with elevated plasma des-gamma-carboxy prothrombin levels, both immunoreactive prothrombin and des-gamma-carboxy prothrombin significantly increased in hepatoma tissues compared with non-cancerous liver tissue. On the other hand, no significant difference was observed in the endogenous vitamin K (K1, MK-4, MK7) concentrations between hepatoma and noncancerous portions, in either the cases with or without increase of plasma des-gamma-carboxy prothrombin. These data strongly suggested that in the patients with an increase of plasma des-gamma-carboxy prothrombin, overproduction of prothrombin in hepatoma plays in important role in the synthesis of des-gamma-carboxy prothrombin.

Analysis of Variance↗

Molecular biology of type A endogenous retrovirus.

Intracisternal A particles (IAPs) are retrovirus-like structures consistently observable in a variety of mouse tumor cells such as myeloma and hybridoma and in early embryonic cells derived from rodents but nothing is known of their infectivity. Mouse IAPs contain a gag-like protein, a reverse transcriptase and a polyadenylated RNA molecule (IAP RNA). DNA sequences complementary to IAP RNA (IAP genome) are interspersedly present in rodent such as mice, rats, Chinese hamsters and Syrian hamsters at several hundred to a thousand copies per haploid genome. Molecularly cloned IAP genomes from two species Mus and Syrian hamster were 6 to 8 kb in length with LTRs of about 0.4 kb long. The nucleotide sequence of the Syrian hamster IAP genome, H18, predicted a typical LTR-gag-prt-pol-env-LTR structure, although many stop codons were present in the region corresponding to env. The comparison of the deduced amino acid sequences of the pol region showed IAP (type A), mouse mammary tumor virus (MMTV) (type B), and squirrel monkey retrovirus (SMRV) (type D) genomes to be closely related. By using a DNA fragment encoding the pol region of the Syrian hamster IAP genome, human endogenous retroviruses termed HERV-K, were cloned from a fetal human liver gene library. Typical HERV-K genome was 9.5 kb in length having LTRs of about 1.0 kb. The HERV-K provirus could encode gag (666 codons), prt (334 codons), pol (937 codons), and env (618 codons) genes. HERV-K was shown to be closely related to types A, B and D retroviruses. The HERV-K genomes are present at about 50 copies per haploid human genome. In several human tumor cell lines, the HERV-K genome was expressed as 8.8 kb poly(A)+ RNA which appeared to be a full-size transcript of this genome. In the human breast cancer cell line T47D, stimulation of HERV-K genome expression was observed following female steroids treatment. In a detailed investigation on the organization of HERV-K proviruses in human genome, we found repetitive sequences homologous to the LTR region of the HERV-K genome. They were about 630 bp in length with an A rich tail at 3' end and found to be a SINE type nonviral retroposon. These elements were present at 4,000 to 5,000 copies per haploid human genome.

Animals↗

[Epidemiological studies of air pollution and health effects in areas near roadways with heavy traffic in Tokyo].

Recent concern regarding health effects of air pollution in Japan has concentrated mainly on traffic-induced air pollution and its health effects in large cities. In Japan, where many people in large cities have been living near major roadways, the increase of automobile exhaust due to heavy traffic congestion will predictably cause a greater impact on people living near major roadways. We surveyed the characterization of residential suspended particulate matter (SPM) and nitrogen dioxide (NO2) concentrations along the major roadways in Tokyo, along with a health survey on the respiratory conditions of residents living in the same area, to examine the relationships between indoor pollutant levels, prevalence of respiratory symptoms and distance from roadways. The environmental monitoring was conducted in five phases. Using a newly developed SPM sampler and NO2 filter badge, continuous 4 day (96 hours) measurements were conducted in two hundred residential homes for four weeks. NO2 was measured in the living room, kitchen and outside of each home, while SPM was monitored in the living room. Health information was collected in October 1987 using ATS-DLD self-administered questionnaires. Of the 1,093 homes investigated, responses from 805 homes were received. The following results were obtained. SPM and NO2 concentrations showed large variations. Indoor pollution levels mostly depended on indoor sources, i.e. cigarette smoking and unventilated space heaters, and the effects of those indoor sources were influenced by the building structure with respect to air tightness. An association between increase in pollutant levels and the distance from the roadway was observed. However its effect is small compared to indoor source effects. The prevalence rate of respiratory symptoms was higher in those areas nearest roadways with heavy traffic both in children and adults. These results suggest the presence of a relationship between automobile exhaust and health effects.

Adult↗

[Application of capillary isotachophoresis to analysis of serum protein].

Capillary isotachophoresis is a useful method for the analysis of many ion components of various sizes of molecules. Analysis of human serum protein was performed with the Shimadzu capillary isotachophoresis IP-3A. The leading electrolyte system consisted of 5.0 mM hydrochloric acid with 10 mM ammediol as the counter ion and the viscous agent (0.2% HPMC 4000) was added to the leading electrolyte. The terminating electrolyte was 10 mM 6-amino caproic acid with 10 mM ammediol as buffer, corrected to pH 10.8 by the addition of barium hydroxide. IP-3A can be fitted three types of capillary tube of 0.5 mm I.D., 0.3 mm I.D. and 0.2 mm I.D. The human serum was mixed with spacer solution (2% ampholine and amino acid mixture) at a volume ratio 1:3.1.0 microliter of preparation mixture was injected and detected by UV-signal at 280 nm with capillary tube of 0.5 mm I.D. 1.0 microliter of 10 fold preparation mixture was analyzed with capillary tube of 0.2 mm and 0.3 mm I.D. The analysis with the capillary tube of 0.2 mm I.D. or 0.3 mm I.D. is more sensitive than that of 0.5 mm I.D., but the system with smaller I.D. tubes had a tendency to get clogged. Human sera of 61 persons were respectively mixed with spacer solution at a volume ratio 1:3 and each 1.0 microliter of preparation mixture was injected and detected by UV-signal at 280 nm with capillary tube of 0.5 mm I.D. The peak height ratios (albumin minor peak height/albumin main peak height) were classified into 3 types.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[An unresectable colon cancer with a diffuse metastases that turned resectable following thermotherapy with chemoimmunotherapy].

Reported is the case of a 66-year-old woman who complained of a pain in the upper abdomen. A barium enema revealed a stenosis in the transverse and sigmoid colon and since her ileus worsened, an emergency operation was performed, which revealed an unresectable transverse colon cancer with a diffuse peritoneal metastases. After closing the wound, the patient was treated with local thermotherapy of the abdomen using an RF wave in combination with chemotherapy and immunotherapy. Later, since the tumor could not be palpated and the tumor markers dissipated, a reoperation was performed, and it was found that diffuse metastases had completely disappeared from the peritoneum. Further, a histopathological study did not disclose any tumor cells. Therefore, as the cancer was remarkably reduced, a partial transverse and descending colon colectomy was performed.

Aged↗

[Intra-arterial infusion of cisplatin and caffeine for a recurrent malignant fibrous histiocytoma].

We treated a 43-year-old man with recurrent malignant fibrous histiocytoma in right distal femur with intra-arterial infusion of cisplatin and caffeine 5 years after wide excision and chemotherapy. At the time of the first recurrence in the lateral aspect of thigh, intra-arterial infusion of CDDP (120 mg/m2) was ineffective. We treated him with radiation (7000 rad), and there was no evidence of tumor by radiological evaluation. The second local recurrence was treated with intra-arterial infusion of CDDP (120 mg/m2/1 hour) and caffeine (1.2 g/m2/24 hours x 3 days), and the tumor disappeared, radiologically and histologically. Caffeine did not increase the nephrotoxicity of CDDP, and no insomnia nor palpitation was seen. Intra-arterial infusion of CDDP and caffeine could be useful to increase the effect of CDDP for regional chemotherapy.

Adult↗

[Clinical efficacy of ifosfamide for liver metastasis of breast cancer].

Chemotherapy for liver metastasis of breast cancer has rarely been found effective. We devised a new regimen of chemotherapy for recurrent breast cancer mainly using ifosfamide. It was found clinically applicable and particularly effective for liver metastasis. The tumor decreased in size and the levels of various tumor-markers markedly decreased following drug administration. This treatment has made for longer survival for some patients. Side effects could be well controlled with steroid hormones and Na-bicarbonate.

Antineoplastic Combined Chemotherapy Protocols↗

Increased expression of glutathione S-transferase gene in cis-diamminedichloroplatinum(II)-resistant variants of a Chinese hamster ovary cell line.

We have isolated cis-diamminedichloroplatinum(II) (CDDP)-resistant variants, C/CDP-1 and C/CDP-2, from a Chinese hamster ovary (CHO) cell line after a stepwise exposure to increasing concentrations of CDDP, and a CDDP-sensitive revertant, R-1, from C/CDP-2 after continuous incubation for 5 months in the absence of CDDP, C/CDP-1 and C/CDP-2 showed 7- and 10-fold higher resistance to CDDP, respectively, compared to CHO cells. C/CDP-2 was cross-resistant to carboplatin, L-phenylalanine mustard (melphalan), and CdSO4, but not to other anticancer agents. Alkaline elution of DNA showed an increased amount of DNA interstrand cross-linking formation in CHO cells, but not in C/CDP-2 cells, when CHO and C/CDP-2 cells were cultured with CDDP. By contrast, alkaline elution of DNA showed increased formation of DNA cross-links when nuclei of C/CDP-2 cells were treated with CDDP. The activity of glutathione S-transferase (GST) of C/CDP-1 and C/CDP-2 was 4- and 6-fold higher than that of CHO cells, respectively. The cellular level of GST activity of R-1 was almost similar to that of CHO cells. Northern blotting analysis revealed that GST-pi mRNA in both C/CDP-1 and C/CDP-2 cell lines was increased more than 5-fold over that of CHO and R-1 cells. There is no apparent gene amplification of GST-pi gene in CDDP-resistant cell lines. Immunoblot assays showed a specific increase of GST-pi in C/CDP-1 and C/CDP-2, but no increase in GST-mu and GST-alpha. We also compared CDDP-resistant properties of a resistant variant, P/CDP-5, derived from human prostate cancer PC-3 cell line, with those of C/CDP-1 and C/CDP-2 cells and found no increased GST activity in P/CDP-5 cells. Multiple mechanisms might be considered for acquisition of CDDP resistance in various cell lines in culture.

Animals↗

Structures of two genes coding for melanin-concentrating hormone of chum salmon.

Two MCH genes coding for melanin-concentrating hormone (MCH) were isolated from a chum salmon liver DNA library and characterized. They were shown to be intronless genes with 0.63-kb exons, each of which commonly consisted of an about 80-bp 5'-untranslated region, a region coding for 132 amino acids (aa) MCH precursor protein and an approx. 160-bp 3'-untranslated region. About 20 bp upstream from the putative cap site, sequences were found corresponding to the TATA box. The two genes were 86% identical at the nucleotide sequence level. Sequences homologous to the chum salmon MCH genes were present in the genomes of other fish such as catfish, carp and Chinese grass carp, whereas no highly homologous sequence could be detected in other vertebrate genomes.

Amino Acid Sequence↗

Induction of manganese superoxide dismutase by tumor necrosis factor in human breast cancer MCF-7 cell line and its TNF-resistant variant.

Tumor necrosis factor (TNF)-resistant variant of human mammary cancer MCF-7 cell line was isolated by stepwise selection. The final TNF-resistant variant Tnf-1000 showed more than 100-fold higher resistance than the parental MCF-7 cell. Saturation kinetics for 125I-TNF binding showed that TNF-1000 cells had similar TNF receptor numbers as MCF-7 cells, but of a lower affinity. Induction of superoxide dismutase (SOD) was compared between MCF-7 and Tnf-1000 cells treated with TNF: SOD scavenges potentially toxic superoxide radicals. TNF induced more mitochondrial manganese SOD (SODm) in MCF-7 than in Tnf-1000 whereas there appeared to be no significant induction of cytosolic copper/zinc SOD (SODc) by TNF in both MCF-7 and Tnf-1000 cell lines. Acquirement of TNF-resistance in MCF-7 cells might be correlated with expression of SODm.

Breast Neoplasms↗

[Effect of cepharanthine on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207)--5-fluorouracil delivery into tumor tissue].

A study on the antitumor effect and distribution to tumor tissue of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) when administered with cepharanthine was performed using RPMI 4788 human colon cancer cell line or murine Sarcoma-180 tumor cells in vitro and in vivo. Combined treatment with FT-207 or 5-fluorouracil (5-FU) and cepharanthine showed a marked anti-proliferative effect on DNA synthesis of RPMI 4788 cells when measured by 3H-thymidine incorporation in vitro. Combination of FT-207 (1 microgram/ml) and cepharanthine (1 microgram/ml or 5 micrograms/ml) exhibited a similar antitumor effect to FT-207 (25 micrograms/ml). Also the DNA synthesis of RPMI 4788 cells was inhibited by low dose of 5-FU with cepharanthine similarly by high dose of 5-FU alone. On the other hand, Sarcoma-180 tumor was transplanted to the back of mice, and FT-207 (50 mumole/kg; 10 mg/kg) and cepharanthine were orally coadministered once at day 7 after tumor transplantation. This combined therapy significantly inhibited the growth of Sarcoma-180 tumor. Furthermore, antitumor activity of FT-207 was enhanced significantly by coadministration of cepharanthine daily for 10 days. The concentration of FT-207 or 5-FU in the tumor tissue, normal tissues and serum were measured in mice with Sarcoma-180 tumor. The mice were given FT-207 and cepharanthine orally once at day 7 (I) or daily for 10 days (II) after transplantation of Sarcoma-180 tumor cells. No remarkable difference was found in the concentration of FT-207 between tumor tissue and serum. The concentration of 5-FU in the tumor tissue was significantly higher than that in the serum. The ratio of 5-FU concentration in the tumor tissue to that in the serum (T/S) was 15.9 (I) or 13.0 (II) in the two administration systems. Maximum concentration of 5-FU was found when cepharanthine and FT-207 were given simultaneously at the molar ratio of 0.5:1, and this combination ratio seemed to be optimal. These results suggest that 5-FU is delivered and selectively accumulated into the tumor tissue by the presence of cepharanthine, but not in serum, and this mechanism should be correlated with antitumor activity shown by combination of FT-207 and cepharanthine. This mechanism is one of the reasons why the 5-FU concentration in the tumor tissue increases much more than that in normal tissues after administration of FT-207 by cepharanthine. Accordingly clinical application of cepharanthine is considered to be a useful adjuvant chemotherapy for cancer.

Alkaloids↗

[The effect of cepharanthine on the hemopoietic suppression by X-ray irradiation--hematological and histological studies].

The effects of cepharanthine on the suppression of hemopoiesis by X-ray irradiation were studied. A whole body X-irradiation (3 Gy) induced decrease of leucocyte count, nucleated cell count of bone marrow, myeloid stem cell count (CFU-C), and spleen weight. Oral administration of cepharanthine (25 mg/kg BW or 50 mg/kg BW) tended to decrease these damage on hemopoiesis, and increased spleen weight on 5th day after irradiation. Histological examinations revealed that the administration of cepharanthine accelerated the hemopoietic recovery in the red pulp of spleen.

Alkaloids↗

Insulin receptor and altered glucose transport in a monensin-resistant mutant of Chinese hamster ovary cell.

A monensin-resistant mutant Monr-31, derived from Chinese hamster ovary (CHO) cell line, has been shown to have a reduced number of insulin receptors and a reduction in glucose uptake in response to insulin. We have further investigated the possibility that altered glucose uptake in Monr-31 cells is related to an alteration in the activity of the insulin receptor. Uptake of glucosamine, 2-deoxy-D-glucose, and 3-O-methyl-D-glucose in Monr-31 cells was one-half to one-third that of CHO cells. The cellular content of the glucose transporter in Monr-31 was reduced to about one-third that of CHO as assayed by use of an antiglucose transporter antibody. After transfection with the human insulin receptor cDNA, we obtained clones CIR-0 from CHO, and MIR-2 and MIR-15 from Monr-31; CIR-0 expressed a tenfold higher level of the insulin-binding activity than did CHO, and MIR-2 and MIR-15 expressed a 20-fold higher level than did Monr-31. Glucose uptake in both CHO and CIR-0 was significantly enhanced by exogenous insulin, but not in Monr-31, MIR-2, and MIR-15. The beta-subunits of insulin receptor in CHO, CIR-0, Monr-31, and MIR-2 were similarly phosphorylated. The decreased glucose transport activity in Monr-31 cells is discussed in relation to the absence or presence of insulin receptor expression.

3-O-Methylglucose↗

Critical evaluation of polychlorinated biphenyl toxicity in terrestrial and marine mammals: increasing impact of non-ortho and mono-ortho coplanar polychlorinated biphenyls from land to ocean.

Residues of potentially toxic non-ortho chlorine substituted coplanar 3,3',4,4'-tetra-,3,3',4,4',5-penta-, 3,3',4,4',5,5'-hexachlorobiphenyl and their mono- and di-ortho analogs 2,3',4,4',5-penta, 2,3,3',4,4'-penta-, 2,3,3',4,4',5-hexa- and 2,2',3,3',4,4'-hexa-, 2,2',3,4,4',5-hexachlorobiphenyl) were determined in humans, dogs, cats (terrestrial), a finless porpoise (Neophocoena phocoenoides--coastal), Dall's porpoises (Phocoenoides dalli, dalli), Baird's beaked whales (Berardius bairdii) and killer whales (Orcinus orca--open ocean). Among the coplanar polychlorinated biphenyl (PCB) congeners, the concentration of the di-ortho congeners was the highest and the non-ortho congeners was the lowest. However, all three coplanar PCBs occurred at significantly higher levels than toxic polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The relative bioconcentration and metabolic capacity of terrestrial and marine mammals to these chemicals, suggest that the toxic threat of coplanar PCBs increases from land to ocean, but the reverse is true for PCDDs and PCDFs. The toxic threat of coplanar PCBs to higher aquatic predators such as cetaceans was principally assessed by 2,3,7,8-T4CDD Toxic Equivalent Analysis which is based on the induction of arylhydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD). Analysis indicates, in particular, that the bioaccumulation of toxic 3,3',4,4',5-penta- and 2,3,3',4,4'-pentachlorobiphenyls in carnivorous marine mammals is a cause for considerable concern.

Animals↗