Steady-state tokamak discharge via dc helicity injection.
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Journal Article↗
Biomedical subjects
M Ono
Publications and source records attributed to M Ono.
Altered function and structure of low-density lipoprotein receptor in compactin (ML236B)-resistant mutants of Chinese hamster cells.
Mutants resistant to compactin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, have been previously isolated from the Chinese hamster V79 cell line. Two compactin-resistant mutants, MF-1 and MF-2, show altered responses to human low-density lipoprotein (LDL). Accumulation of fluorescent-labeled LDL was much reduced. Ligand blotting showed LDL receptor activity in MF-1 and MF-2 cells of about one half to one third that of V79. Internalization and degradation of LDL in MF-1 or MF-2 cells were about one tenth those in V79 cells, suggesting that the LDL binding as well as the LDL internalization of the compactin-resistant clones was altered. Down-regulation of LDL receptor activity as well as hydroxymethylglutaryl CoA reductase was observed in V79 cells treated with LDL, while there appeared to be much less down-regulation in MF-1 and MF-2 cells. Using anti-LDL receptor antibody, MF-1 and MF-2 cells were found to produce smaller-sized mature forms of LDL receptor: the molecular mass of the mutant LDL receptor was 3-5 kDa smaller than that of the parental LDL receptor. Altered O-linked oligosaccharides or amino acid sequence might account for the decreased molecular mass and aberrant properties of the LDL receptor in MF-1 and MF-2.
Animals↗
Low binding capacity and altered O-linked glycosylation of low density lipoprotein receptor in a monensin-resistant mutant of Chinese hamster ovary cells.
We have studied function and structure of the low density lipoprotein (LDL) receptors in a monensin-resistant (Monr-31) mutant isolated from Chinese hamster ovary (CHO) cells. To assay the ability of the receptor to bind LDL, we employed three methods, 125I-LDL binding to the cells at 4 degrees C, 125I-LDL binding to the receptor-phospholipid complex (Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1980) J. Biol. Chem. 255, 11442-11447), and ligand blotting (Daniel, T.O., Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1983) J. Biol. Chem. 258, 4606-4611). The LDL receptor number was similar in both CHO and Monr-31, but the binding affinity was reduced in the mutant. The semi-quantitative immunoblotting assay with an antibody directed against the COOH-terminal 14 amino acids and the ligand-blotting assay with LDL also showed that the relative steady-state level of the receptor in Monr-31 was comparable to that in CHO, whereas the binding capacity of the receptor in Monr-31 was lower than that in CHO. The precursor and degradation forms of the LDL receptors produced in the mutant cells were similar in size to those in the parental cells, but the apparent molecular mass of the mature receptor protein in sodium dodecyl sulfate-polyacrylamide gels was reduced about 5000 daltons in the mutant. These results suggest a structural change at the NH2-terminal LDL binding domain. Tests of the effects of tunicamycin, endo-alpha-N-acetylgalactosaminidase (O-glycanase), and sialidase (neuraminidase) on the molecular size of the mature receptors indicated that the reduced size of the receptor in the mutant cells resulted from altered oligosaccharide chain(s) linked to serine/threonine residues in the binding domain. We compared the molecular sizes and binding activity of human LDL receptors in several clones derived from CHO and Monr-31 cells which were transfected with human LDL receptor cDNA. The human LDL receptors produced in the transfected clones of Monr-31 were also smaller in molecular size and lower in binding capacity than those produced in the transfected clones of CHO. These results suggest that both structural and functional alteration of the LDL receptor of Monr-31 is not caused by a mutation in the structural gene of the LDL receptor but by altered processing or maturation of the receptor. The correlation of the decrease in molecular size and reduced binding capacity of the LDL receptor is discussed.
Animals↗
Effect of 5-azacytidine on malignant transformation of a mutant derived from the mouse BALB/c 3T3 cell line resistant to transformation by chemical carcinogens.
BALB/c 3T3 and its derivative MO-5, isolated as a monensin-resistant clone, showed a very low rate of spontaneous malignant transformation. Treatment of BALB/c 3T3 cells with benzo(alpha)pyrene, 4-nitroquinoline-N-oxide, N-methyl-N'-nitro-N-nitrosoguanidine, N-methyl-N-nitrosourea, or UV light irradiation significantly enhanced the rate of transformation, whereas the treatment of MO-5 cells with these carcinogens had only a slight if any effect. Exposure of MO-5 as well as BALB/c 3T3 to 5 or 10 microM 5-azacytidine for 3 to 7 days significantly increased the number of transformation foci. The Luria-Delbrück fluctuation test showed that spontaneous mutation frequency (mutants/cell/generation) was 1.2 X 10(-6) for BALB/c 3T3 and 7.1 X 10(-7) for MO-5, respectively, when appearance of cadmium-resistant clones was tested. N-Methyl-N'-nitro-N-nitrosoguanidine enhanced induced mutation frequency of ouabain-resistant and cadmium-resistant mutants of BALB/3T3 but it only slightly enhanced that of MO-5. Methylation status of DNA of MO-5 was compared with that of BALB/c 3T3 by comparing the cleavage patterns generated by the isoschizomeric restriction enzymes HpaII and MspI. DNA of MO-5 was found to be more methylated than that of BALB/c 3T3 in the vicinity of c-myc as well as the metallothionein-I gene. Aberrant DNA methylation in MO-5 and the cellular sensitivity to transformation by chemical carcinogens or 5-azacytidine are discussed.
4-Nitroquinoline-1-oxide↗
Induction of neutrophilic granulocytosis in mice by administration of purified human native granulocyte colony-stimulating factor (G-CSF).
Mice were subcutaneously (sc) injected once a day for up to 15 days with a purified human native G-CSF sample at a dose of 2.5 micrograms/injection or with control samples with or without added endotoxin. In the G-CSF-treated mice, blood neutrophil counts began to rise as early as 2 hours after the first injection, reached a level 8 times above the preinjection level after 15 days of injections with marked elevation of all progenitor cell levels in spleen, and returned to normal within 48 hours after cessation of the injections. Such neutrophilia was observed even when endotoxin-resistant C3H/HeJ mice were used, but not in control mice. It is possible that repeated G-CSF injections after administration of cyclophosphamide (CY) in mice could accelerate recovery of granulopoiesis with a rather transient rise in blood neutrophil counts.
Animals↗
Chinese hamster ovary cell mutant with defective down-regulation of low density lipoprotein receptors.
A monensin-resistant clone (Monr-31) shows a related series of differences from its parental Chinese hamster ovary (CHO) cell line in the cellular response to several ligands. The uptake and metabolism of low density lipoprotein (LDL) in the mutant cells are defective. Accumulation of fluorescent-labeled LDL as well as internalization and degradation of 125I-LDL are greatly reduced in Monr-31 cells. The receptor number for LDL on the cell surface of Monr-31 is about one-third that for CHO cells, but affinity constants for both cell lines are similar. Electrophoretic analysis shows a slightly reduced molecular weight of LDL receptor in Monr-31 cells in comparison to that in CHO cells. The internalization index (internalization plus degradation per binding) of LDL of the mutant is about one-half that of CHO cells, suggesting a failure of internalization of LDL as well as LDL binding. Hybrids (hyb-1, -2, and -3) between CHO and Monr-31 cells show LDL binding and LDL internalization activities comparable to that of CHO cells, suggesting that the altered LDL response in Monr-31 cells is recessive. Addition of exogenous LDL to culture medium down-regulates the LDL receptor activity of CHO, hyb-2, and hyb-3 cells, whereas no such down-regulation is seen in Monr-31 cells. Probably as a result of the failure of down-regulation, the prominent inhibition of sterol synthesis from acetate and 3-hydroxy-3-methylglutaryl-coenzyme A reductase observed in CHO cells is scarcely detectable in Monr-31 cells. As a correlated result, sterol synthesis from acetate is 6-fold higher in the mutant. The failure of down-regulation of LDL receptors in Monr-31 cells is discussed in relation to the altered binding and internalization of LDL.
Animals↗
Ehlers-Danlos syndrome. A variant characterized by the deficiency of pro alpha 2 chain of type I procollagen.
The clinical findings and biochemical studies are described for a 30-year-old man with Ehlers-Danlos syndrome. Type analysis of collagen produced by cultured fibroblasts revealed the lack of a detectable pro alpha 2 chain of type I procollagen. The intracellular degradation rate of newly synthesized collagen was higher than that of normal cells, resulting in the reduction of net collagen production. Clinical manifestations characterized by cardiovascular abnormalities due to decreased collagen deposition in the aortic valve and the wall of aorta, hypermobility of the joints, and hyperextensibility of the skin in this patient may be closely related to the observations described above.
Adult↗
Monoclonal antibodies to restricted and cross-reactive idiotopes on monoclonal rheumatoid factors and their recognition of idiotope-positive cells.
Four human monoclonal rheumatoid factors (MRF) were used to raise a panel of mouse monoclonal antibodies (mAb) which were selected in a solid-phase radioimmunoassay for binding to MRF but not normal IgM. Three mAb, each raised against a different MRF, bound to the majority of MRF and also to most polyclonal RF. Four other mAb bound selectively to the MRF against which they were raised and to no other MRF, and rarely to any polyclonal RF. Competition studies using cold and radiolabeled mAb further indicated that these mAb recognize distinct and different epitopes on MRF. RF activity of MRF was inhibited by 3 of the 4 mAb binding to a single MRF and 2 of the 3 mAb binding to multiple RF. It was thus concluded that of this panel of mAb 3 recognized cross-reactive idiotopes and the remainder demonstrated highly restricted idiotopes on MRF. These mAb identified MRF idiotope-bearing cells in the peripheral blood of 3 of the MRF donors (and a further subject with type II essential cryoglobulinemia), with a frequency ranging from 0.3-10% of all mononuclear cells with the mAb to restricted idiotopes or 1.5-17% with mAb to cross-reactive idiotopes. These anti-idiotopic mAb should thus provide a highly specific means of identifying and monitoring MRF-producing cells in vivo.
Antibodies, Monoclonal↗
Bonding behavior between two bioactive ceramics in vivo.
The purpose of this study is to examine the chemical bonding mechanism between bioactive ceramics in vivo. Two experiments were performed. In the first experiment, rectangular specimens (5 mm X 5 mm X 25 mm) of apatite-wollastonite containing glass-ceramics (designated A.W-GC) were used. In the second experiment, plates (15 mm X 10 mm X 2 mm) of A.W-GC and three types of hydroxyapatite (designated HA) were used. The sintering temperature and porosity (%) of the three types of HA were 1200 degrees C (0.4%), 1000 degrees C (4.8%), and 800 degrees C (45%), respectively. In each experiment, two pairs of specimens of identical material, one bound with silk thread, the other not bound, were implanted subcutaneously into rats. In the first experiment, bonding of only bound specimens was observed at 3 and 6 months after implantation. The observation of interface by SEM-EPMA showed that a Ca-P-rich layer formed between the two specimens. In the second experiment, bonding of both bound and nonbound A.W-GC produced identical results 1 month after implantation. For HA sintered at 800 degrees C and 1000 degrees C, bonding was observed in every specimen. This phenomenon might be caused by the chemical change of hydroxyapatite occurring at different sintering temperatures. The Ca-P-rich layer was observed between two plates. These results suggest that self-repair of bioactive ceramic is possible under certain conditions.
Animals↗
Mouse Balb/c3T3 cell mutant with low epidermal growth factor receptor activity: induction of stable anchorage-independent growth by transforming growth factor beta.
A mutant clone (MO-5) was originally isolated as a clone resistant to Na+/K+ ionophoric antibiotic monensin from mouse Balb/c3T3 cells. MO-5 was found to show low receptor-endocytosis activity for epidermal growth factor (EGF): binding activity for EGF in MO-5 was less than one tenth of that in Balb/c3T3. Anchorage-independent growth of MO-5 was compared to that of Balb/c3T3 when assayed by colony formation capacity in soft agar. Coadministration of EGF and TGF-beta efficiently enhanced anchorage-independent growth of normal rat kidney (NRK) cells, but neither factor alone was competent to promote the anchorage-independent growth. The frequency of colonies appearing in soft agar of MO-5 or Balb/c3T3 was significantly enhanced by TGF-beta while EGF did not further enhance that of MO-5 or Balb/c3T3. Colonies of Balb/c3T3 formed in soft agar in the presence of TGF-beta showed low colony formation capacity in soft agar in the absence of TGF-beta. Colonies of MO-5 formed by TGF-beta in soft agar, however, showed high colony formation capacity in soft agar in the absence of TGF-beta. Pretreatment of MO-5 with TGF-beta induced secretion of TGF-beta-like activity from the cells, while the treatment of Balb/c3T3 did not induce the secretion of a significant amount of TGF-beta-like activity. The loss of EGF-receptor activity in the stable expression and maintenance of the "transformed" phenotype in MO-5 is discussed.
Animals↗
2,7-Diamino-3,8-dimethylphenazine as the major mutagenic product from the reaction of 2,4-diaminotoluene with hydrogen peroxide.
The mutagenicity of 2,4-diaminotoluene (DAT) in Ames's Salmonella/microsome test was remarkably enhanced by treatment with hydrogen peroxide. Therefore, identification of the major mutagenic reaction product of 2,4-DAT with hydrogen peroxide at room temperature has been performed. Red precipitates were produced in a 2-day reaction mixture and were column chromatographed on silica gel. 5 fractions having mutagenic potency were obtained. The red crystalline needles, obtained as the major reaction product, were separated from fraction 2 and were subjected to high resolution mass spectrometry, 1H- and 13C-NMR spectrometry. The structure of the compound was determined to be 2,7-diamino-3,8-dimethylphenazine from physicochemical and chemical evidence. The compound induced 212 revertants/nmole in Salmonella typhimurium TA98 with 25 microliters S9 per plate.
Animals↗
Mutagenic reactivities of 3,4-dinitrobiphenyl derivatives.
3,4-Dinitrobiphenyl derivatives were mutagenic in Salmonella typhimurium TA98, TA98/1,8-DNP6 and in TA98NR. We describe here the specific reactivity of 3,4-dinitrobiphenyl derivatives with diluted sodium hydroxide solution and the determination of the amounts of released nitrous ion. 3,4-Dinitrobiphenyl derivatives begin to release nitrous ions when treated with NaOH solution at a concentration of 10(-3) N. The behavior of 4NQO and o-dinitrobenzene was the same as that of 3,4-dinitrobiphenyl derivatives. The residues of 3,4-dinitrobiphenyl derivatives, after releasing nitrous ions, were estimated to be hydroxy-nitrobiphenyls, as by GC/MS, we found the formation of o-nitrophenol in the reaction mixture of o-dinitrobenzene with aqueous NaOH solution. 3,4,4'-Trinitrobiphenyl, 3,4,3',4'-tetranitrobiphenyl and 4NQO had reduced mutagenic potency in Salmonella typhimurium TA98 following treatment with diluted NaOH. In order to elucidate the ultimate forms of 3,4-dinitrobiphenyl derivatives, we investigated the reaction of o-dinitrobenzene as a basic model substance of 3,4-dinitrobiphenyl, with nucleic bases in the presence of NaOH in nonaqueous solvent. o-Nitrophenyl guanine and adenine adducts were obtained.
Dinitrobenzenes↗
The clinical significance of the P15 wave of the somatosensory evoked potential in tentorial herniation.
Somatosensory evoked potentials (SEPs) to median nerve stimulation and auditory brainstem evoked potentials (BAEPs) were recorded in 16 comatose patients who had suffered transtentorial herniation (TH) due to intracranial haematoma, hydrocephalus or tumour. An attempt was made to correlate the changes in the N14-P15 component of the central conduction time (CCT) and the I-V interpeak latencies (IPLs) of the BAEP with the clinical severity of TH. The N14-P15 component was not affected in seven patients at the diencephalic or early third-nerve stage, and six of these seven showed normal I-V IPLs. All six patients at the late third-nerve/midbrain stage or worse, however, showed abnormalities in the N14-P15 components. Interestingly, five patients showed dissociation of SEP and BAEP abnormalities suggesting a differential sensitivity of the medial and lateral lemnisci in the brainstem to ischaemia and/or compression. All five patients in whom the P15 potential was absent on either side had a poor outcome and there was a correlation between the electrical failure in the N14-P15 component and the degree of brainstem damage caused by TH as assessed clinically. Reversible loss of the P15 potential by brainstem retraction has been shown in intraoperative SEP monitoring during aneurysm surgery. Prolonged compression of the upper brainstem seems to cause irreversible loss of the P15 which should be regarded as being due to irrecoverable brainstem dysfunction.
Adolescent↗
Purification and characterization of a thiol-protease from Bacteroides gingivalis strain 381.
A protease from the culture supernatant of Bacteroides gingivalis 381, which hydrolyzes the chromogenic substrate Na-benzoyl-DL-arginine-p-nitroanilide (BAPNA), was partially purified by ammonium sulfate precipitation, gel filtration, and anion exchange chromatography. The molecular weight of this protease was determined by SDS-PAGE to be ca. 49,000. The optimum pH was around 7.6. The protease was stable at neutral pH and up to 40 degrees C. The isoelectric point was 4.9. The enzyme activity was enhanced by dithiothreitol, L-cysteine, and 2-mercaptoethanol and inhibited by p-chloromercuribenzoic acid, N-ethylmaleimide, and iodoacetic acid.
Bacterial Proteins↗
Protective effect of human granulocyte colony-stimulating factor on microbial infection in neutropenic mice.
A purified human granulocyte colony-stimulating factor (hG-CSF) was studied for its protective effect on the induction of neutropenia and enhanced susceptibility to microbial infections in mice receiving cyclophosphamide (CPA). A severe reduction in peripheral blood neutrophils was induced 4 days after injection with 200 mg of CPA per kg although the level normalized rapidly thereafter. When mice were injected subcutaneously once a day with 2.5 micrograms of hG-CSF beginning on the day after CPA injection, the reduction was prevented markedly, even 4 days later. On the other hand, in mice receiving CPA 4 days prior to infection, a weakened resistance to intraperitoneal challenge with a strain of Pseudomonas aeruginosa was induced. This weakened resistance was dose-dependently restored to normal by four daily injections with hG-CSF. A daily dose of 1.0 microgram was required for complete restoration, although hG-CSF did not directly inhibit bacterial growth in vitro. In hG-CSF-treated mice, morphologically mature neutrophils migrated rapidly into the peritoneal cavities where bacteria were inoculated, followed by a rapid elimination of bacteria from the locality as compared with controls. In addition, the same treatment with hG-CSF was able to protect significantly against systemic infections caused by Serratia marcescens, Escherichia coli, Staphylococcus aureus, and Candida albicans. These data show the possibility that prophylactic therapy with hG-CSF may augment the resistance of immunocompromised patients to infections.
Agranulocytosis↗
Stimulation of expression of the human endogenous retrovirus genome by female steroid hormones in human breast cancer cell line T47D.
Expression of the human endogenous retrovirus genome HERV-K, homologous to mouse mammary tumor virus, was investigated in cultured human tumor cells. In several cell lines, the HERV-K genome was expressed as an 8.8-kilobase 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 by progesterone was observed after estradiol treatment.
Breast Neoplasms↗
E-rosetting of guinea pig lymphocytes with lyophilized rabbit red cells after treatment with papain and glutaraldehyde.
Guinea pig lymphoid cells were reacted to form spontaneous rosettes (E-rosettes) with rabbit red blood cells before and after treatment with papain or a very low concentration (0.01%) of glutaraldehyde alone or both. The papain-glutaraldehyde-treated cells showed as high ability as papain-treated cells to rosette with lymphoid cells prepared from thymus, spleen, lymph node and peripheral blood of guinea pigs. Moreover, papain-glutaraldehyde-treated red cells were lyophilized and stored for 1 year without any change in their ability to form E-rosettes with these lymphoid cells. Binding between lymphocytes and treated or nontreated red cells was completely inhibited by specific anti-guinea pig thymocyte serum. Furthermore, a lymphocyte population enriched for B cells from lymph nodes or leukemic cells of strain 2 guinea pigs (B cells) did not show any substantial E-rosettes with nontreated or treated red cells. Scanning electron microscopy revealed no surface alteration in the treated cells when compared to those in nontreated red cells.
Aldehydes↗
[Indoor-outdoor relationships for nitrogen oxides].
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Air Pollutants↗