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Biomedical subjects

A Noda

Publications and source records attributed to A Noda.

At least 109 records · Page 6Linked to original sources
PubMed1995

Carboxy-terminal cytoplasmic domain of mouse butyrophilin specifically associates with a 150-kDa protein of mammary epithelial cells and milk fat globule membrane.

A cDNA encoding mouse butyrophilin was obtained by reverse transcriptase-coupled polymerase chain reaction (RT-PCR) using poly (A)+ RNA from lactating mouse mammary gland as a template and screening a cDNA library with the RT-PCR-amplified fragment as a probe. DNA sequencing and computer analysis revealed that it has a rather long 3'-untranslated sequence and that the carboxy-terminal cytoplasmic domain was well conserved between mouse and bovine butyrophilins. To elucidate the biological function of butyrophilin, the cytoplasmic region expressed as fusion protein with glutathione S-transferase (GST) was purified and incubated with the cell lysate of mouse mammary epithelial cell lines, COMMA-ID and HC11. A 150-kDa protein was shown to specifically associate with the cytoplasmic domain and the protein increased in amount when the cells were treated with basal medium supplemented with lactogenic hormones such as prolactin, insulin and glucocorticoid. N-terminal amino acid sequencing indicated that the protein is xanthine dehydrogenase/oxidase which has been cloned from mouse liver. Further, the cytoplasmic domain also bound xanthine dehydrogenase/oxidase from bovine milk fat globule membrane. These results suggest that butyrophilin might be physiologically associated with xanthine dehydrogenase/oxidase and might function in a complex form in milk fat secretion.

Amino Acid Sequence↗
PubMed1995

A bovine IgG heavy chain contains N-acetylgalactosaminylated N-linked sugar chains.

A 56K protein co-purified with bovine milk fat globule membrane (MFGM) proteins bound to Wisteria floribunda agglutinin (WFA) like most MFGM glycoproteins. Treatment with N-glycanase or beta-N-acetylhexosaminidase abolished the lectin binding to the protein. Amino acid sequence and immunoblot analyses revealed that the 56K protein is an IgG heavy chain. Lectin column chromatography of the oligosaccharides released by hydrazinolysis from the purified IgG heavy chains revealed that 0.08% of the total N-linked sugar chains bind to a WFA-agarose column, suggesting that they contain the beta-N-acetylgalactosaminylated structure.

Acetylgalactosamine↗
PubMed1995

Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA.

p21Sdi1 (also known as Cip1 and Waf1), an inhibitor of DNA synthesis cloned from senescent human fibroblasts, is an inhibitor of G1 cyclin-dependent kinases (Cdks) in vitro and is transcriptionally regulated by wild-type p53. In addition, p21Sdi1 has been found to inhibit DNA replication by direct interaction with proliferating cell nuclear antigen. In this study we analyzed normal human fibroblast cells arrested in G0 and determined that an excess of p21Sdi1 was present after immunodepletion of various cyclins and Cdks, in contrast to mitogen-stimulated cells in early S phase. Expression of antisense p21Sdi1 RNA in G0-arrested cells resulted in induction of DNA synthesis as well as entry into mitosis. These results suggest that p21Sdi1 functions in G0 and early G1 and that decreased expression of the gene is necessary for cell cycle progression.

Adenovirus E1A Proteins↗
PubMed1995

Increase in expression level of p21sdi1/cip1/waf1 with increasing division age in both normal and SV40-transformed human fibroblasts.

p21sdi1/cip1/waf1 gene, whose product inhibits Cyclin/Cdk kinase and blocks cell proliferation, is known to be up-regulated by p53 and to be expressed at high levels in senescent human fibroblasts. The present paper reports that p21 expression level was much lower in SV40tsT-antigen transformed cells than in normal cells and that after inactivation of tsT-antigen it recovered to that of normal cells. However, cell division age-dependent increase in expression level of p21 occurred not only in normal human fibroblasts but also in SV40tsT-antigen transformed fibroblasts with active T-antigen. These results suggest that cell age-dependent increase in p21 occurs independently upon the function of T-antigen binding proteins including p53, while the basal expression level of p21 is up-regulated by p53 as previously reported.

Antigens, Polyomavirus Transforming↗
PubMed1995

Increased expression of p21Sdi1 in adrenocortical cells when they are placed in culture.

Expression of the cell cycle inhibitor p21Sdi1/WAF1/Cip1 was investigated in a differentiated cell type, the adrenocortical cell, at different stages of culture, from the preparation of cells from the adrenal gland to senescence after long-term growth. In bovine adrenocortical cells, expression of SDI1 was much higher in culture than in vivo. Elevation of SDI1 mRNA, accompanied by elevation of the level of a protein reacting with anti-p21Sdi1 antibodies, was observed as early as 3 h after the start of the tissue dissociation procedure used to prepare cells for culture. This level of expression was then maintained during plating and subsequent long-term growth in culture. Growth and quiescence in bovine adrenocortical cells can be modulated by inclusion or removal of FGF from the culture medium. In these cells SDI1 mRNA was not increased by long-term mitotic quiescence resulting from FGF deprivation. In cultured fetal human adrenocortical cells, SDI1 mRNA was also detected at all stages of the culture life span, including 2 days after isolation of cells from the adrenal gland and plating in culture. Mid-life-span cells had higher SDI1 mRNA than senescent human fibroblasts. Clones of human adrenocortical cells nearing senescence in culture had somewhat higher SDI1 mRNA than early passage cells. Thus, SDI1 expression in adrenocortical cells is not associated with mitotic quiescence either in vivo or in vitro, yet isolation of the cells and culturing them exerts a powerful inductive influence on its expression.

Adrenal Cortex↗
PubMed1995

Determination and properties of acetyl conjugate of N-desisopropylpropranolol, AcNDP.

1-Acetamino-3-(1-naphthyloxy)-2-propanol (AcNDP) detected in human urine was formed as a metabolite of propranolol (PL) via 1-amino-3-(L-naphthyloxy)-2-propanol (N-desisopropylpropranolol, NDP). The excreted amount of AcNDP was determined by GC-MS using an isotope dilution method. More than 40% of total AcNDP in 24 h urine was detected 10 h after the oral administration of PL to two volunteers, and the total amounts during 24 h urine were at least 1.9-3.9% of the PL dose. As AcNDP is an intermediate metabolite of PL, its urinary amount cannot be determined exactly. Incidentally, AcNDP was chemically stable and was not formed from NDP when acetyl CoA was added to the inactivated hepatocyte system. Thus, the acetylation of NDP, an aliphatic primary amine, was confirmed to be catalyzed by N-acetyltransferase, and interestingly, the acetyl conjugation was inhibited not by sulfamethazine but by p-amino benzoic acid.

Acetamides↗
PubMed1995

9-Hydroxymethyl-10-carbamoylacridan in human serum is one of the major metabolites of carbamazepine.

In sera of 29 patients under the chronic administration of carbamazepine (CBZ, dose: 10.9 +/- 4.3 mg/kg/day), a ring-contracted metabolite of CBZ was detected at a relatively higher concentration of 0.57 +/- 0.30 mu g/ml (mean +/- S.D.) by high-performance liquid chromatogaphic assay. The structure of the metabolite was identified as 9-hydroxymethyl-10-carbamoylacridan (HMCA) by the liquid chromatography-mass spectral examination, and also by comparison with the authentic sample. Although HMCA was already reported in a few papers as a minor metabolite of CBZ in human urine, any reliable report for the determination of HMCA in human blood has never been published. Our results show that HMCA is one of the major metabolites of CBZ.

Acridines↗
PubMed1995

Cardiac hypertrophy in obstructive sleep apnea syndrome.

Fifty-one middle-aged male patients with obstructive sleep apnea syndrome (OSAS) were evaluated using two-dimensional echocardiography, 24-h blood pressure measurements, polysomnography, and plasma norepinephrine (NE) measurements. Among these patients, left ventricular hypertrophy (LVH) (left ventricular posterior wall thickness [LVPWT] or interventricular septal thickness [IVST] > or = 12 mm) and right ventricular hypertrophy (RVH) (right ventricular wall thickness [RVT] > or = 5 mm) were present in 41.2% (21/51) and 11.8% (6/51). LVH was present in 50.0% of group 2 patients (apnea index > or = 20) and in 30.5% of group 1 patients (apnea index < 20). All patients with LVH had hypertension. RVH was present in 21.4% of group 2 patients and none of the group 1 patients. IVST, LVPWT, LV mass, LV mass/body surface area (BSA), and obesity index were significantly greater in group 2 than in group 1. Apnea index and the duration in which nocturnal oxygen saturation was decreased under 90% (duration of SaO2 < 90%), were significantly correlated with LV mass/BSA and 24-h mean blood pressure. Apnea index, number of apneas, duration of nocturnal oxygen saturation less than 90%, weight, and obesity index were significantly greater in patients with both LVH and RVH than in patients without LVH and RVH, or those with only LVH. Plasma NE after waking significantly increased compared with that before sleep (p < 0.05). The ratio of plasma NE levels after waking to those before sleep was significantly correlated with the duration of SaO2 < 90% (r = 0.83, p < 0.05), but not with apnea index. These results suggest that frequent episodes of oxygen desaturation and/or arousal responses caused by apnea may contribute to the complication of LVH and RVH in the long term, and apnea-induced cyclical increases in blood pressure and the resulting sustained elevation in blood pressure associated with the increase in afterload and sympathetic activity may play a role in the development of LVH.

Adult↗
PubMed1995

Induction of senescent cell-derived inhibitor of DNA synthesis gene, SDI1, in hepatoblastoma (HepG2) cells arrested in the G2-phase of the cell cycle by 9-nitrocamptothecin.

BACKGROUND: Recent studies have demonstrated that the plant-derived alkaloid camptothecin (CPT) and its derivative, 9-nitro-CPT (9NC), are cytotoxic in tumorigenic cells but cytostatic in nontumorigenic cells in vitro and in vivo. Also, CPT induces differentiation of human leukemia cells in vitro along specific lineages. In this study, we have investigated the effects of 9NC on nontumorigenic HepG2 cells derived from human hepatoblastoma. A newly discovered senescent cell-derived inhibitor (SDI1) plays a critical role in the cell cycle, so we evaluated the effect of 9NC on the expression of the SDI1 gene. EXPERIMENTAL DESIGN: The effects of 9NC on HepG2 cells were evaluated by monitoring DNA synthesis, morphologic and ultrastructural changes of cells, and perturbation in the cell cycle and by assessing the levels of p53 protein and SDI1 mRNA. RESULTS: Treatment of HepG2 cells with 9NC results in a dose-dependent inhibition of cell proliferation and DNA synthesis. Flow cytometric analysis of DNA content showed that 9NC-treated HepG2 cells are arrested in the G2-phase of the cell cycle. Light and electron microscopic examination revealed that 9NC at low concentrations induces morphologic and growth features that resemble properties highly differentiated or senescent cells, i.e., increased cell size and decreased nuclear/cytoplasmic ratio, as well as enlarged numbers of lysosomes, mitochondria, and lipid in the cytoplasm. No significant alteration in the p53 protein level was noted in 9NC-treated cells. In contrast to untreated, logarithmically grown HepG2 cells, 9NC-treated cells arrested at the G2-phase of the cell cycle and contained increased levels of SDI1 mRNA. Kinetic studies revealed gradual increases in SDI1 mRNA synthesis. CONCLUSIONS: Induction of SDI1 mRNA by 9NC represents the first documentation that the SDI1 gene can be overexpressed in the G2-phase of the cell cycle and provides a valuable cell culture system to dissect the events controlling the G2 checkpoint. In addition, this finding corroborates the hypothesis that genes up-regulated in senescent cells can also be induced in tumor-derived immortalized cells.

Antineoplastic Agents↗
PubMed1995

[Expression of sdi1, a potent inhibitor of cdk2 kinase, cdk2 and G1 cyclins and mutation of sdi1 in human gastric carcinomas].

Sdi1, also known as Cip1/Waf1, is a potent inhibitor of G1 cyclin-dependent kinases, which is induced by wild type p53 but not by mutant p53. Expression of mRNAs for sdil, cdk2 and G1 cyclins was examined in gastric carcinomas. All the cell lines expressing very low or undetectable level of sdil mRNA contains p53 gene abnormalities, while the cell lines expressing high level of sdil shares wild type p53 gene. An exception was a cell line MKN-28 with mutated p53 gene which expressed mRNAs for sdi1, cdk2 and G1 cyclins at high levels, p21 point mutation was detected in one (MKN-28) of the eight cell lines. These result suggest that low level of sdil and subsequent overexpression of cdk2 and G1 cyclins might be involved in deregulated growth of gastric carcinomas. It is likely that gene alteration of sdil and subsequent loss of function may have implication for cdk2 and G1 cyclins expression.

CDC2-CDC28 Kinases↗
PubMed1994

Simultaneous determination of antiepileptic drugs and their metabolites, including chiral compounds, via beta-cyclodextrin inclusion complexes by a column-switching chromatographic technique.

Using beta-cyclodextrin as a mobile-phase additive, a column-switching chromatographic system equipped with two 25-mm short ODS cartridge columns and two UV detectors was successfully employed for the simultaneous determination of some antiepileptic drugs and their metabolites, including chiral compounds, in human serum. The compounds examined were phenobarbital, zonisamide, phenytoin and its metabolites, S- and R-5-(p-hydroxyphenyl)-5-phenylhydantoin, R- and S-mephobarbital, carbamazepine and its main metabolites, 10,11-dihydro-10-11-epoxycarbamazepine and trans-10,11-dihydroxy-10,11-dihydrocarbamazepine (as a racemate), and allobarbital (as an internal standard).

Anticonvulsants↗
PubMed1994

Immunologically cross-reactive 57 kDa and 53 kDa glycoprotein antigens of bovine milk fat globule membrane: isoforms with different N-linked sugar chains and differential glycosylation at early stages of lactation.

Two glycoprotein antigens with molecular masses of 57 kDa (MGP57) and 53 kDa (MGP53) were co-purified from bovine milk fat globule membrane (MFGM) by immunoaffinity chromatography using a monoclonal antibody raised against the MFGM. Their N-terminal sequences of 22 amino acids determined were identical, and the sequence was homologous (about 60% identical) to the deduced amino acid sequence of mouse milk fat globule epidermal growth factor (EGF) factor 8 (MFG-E8) (Ref. [12], Stubbs, J.D. et al., Proc. Natl. Acad. Sci. USA, 87, 8417-8421, 1990). This suggests that MGP57/53 are bovine MFGM components 15/16 (PAS-6 and PAS-7), which have recently been reported to be bovine homologs of MFG-E8. N-Glycanase treatment of these glycoproteins reduced their molecular masses, and consequently the enzymatically deglycosylated MGP57 and MGP53 converged on a single band of 50 kDa as measured by SDS-PAGE, indicating that the polypeptide portions of these two distinct glycoprotein antigens are very similar or identical and that their N-linked sugar chains contributed to minor difference in their molecular masses. Western blot analyses using lectins also revealed that they were differentially glycosylated; MGP57 was stained with concanavalin A (Con A) more strongly than MGP53, whereas MGP 53 was stained well with soybean agglutinin (SBA). Reactivity with SBA remarkably increased during early stages of lactation. Two-dimensional gel electrophoresis showed that MGP57 and MGP53 were electrically heterogeneous; from day 9 after parturition, both glycoproteins fell in almost the same range of isoelectric points between 6.4 and 7.6, also, such glycoproteins from day 1 after parturition were more acidic, probably due to terminal sialylation of their sugar chains.

Amino Acid Sequence↗
PubMed1994

Evidence for a p53-independent pathway for upregulation of SDI1/CIP1/WAF1/p21 RNA in human cells.

SDI1 is an inhibitor of DNA synthesis that we isolated by expression screening cDNAs prepared from senescent, terminally nondividing human cells. Other groups then cloned this gene as a cyclin-dependent kinase (cdk)-interacting protein (CIP1, p21) that inhibits cdks; the gene was also isolated by screening for genes transactivated by p53 (WAF1). p53 levels are low in senescent and quiescent contact-inhibited or serum-deprived normal human cells, which we have found express high levels of SDI1 mRNA. This indicates that alternate pathways for upregulation of message level of this gene may exist. We therefore proceeded with the study presented here, treating human cells with a variety of growth-arrest-inducing agents, including some that damaged DNA, and found that RNA levels of SDI1 were increased in all cases that resulted in growth inhibition. More important, with the exception of gamma-radiation, most of these agents were able to elevate SDI1 message levels in cells lacking wild-type p53. At least two distinct kinetic profiles for RNA induction were observed, one that implicated p53 transactivation and occurred early enough to cause arrest, and another that clearly was p53 independent and suggested a role for the SDI1 gene product in the maintenance rather than in the cause of inhibition of DNA synthesis.

Antimetabolites↗
PubMed1994

Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen.

We here describe a rapid and simple expression screen method that has allowed us to isolate cDNAs coding for inhibitors of DNA synthesis from senescent human diploid fibroblasts. The assay involved transient transcriptional overexpression of a gene product encoded by a cDNA in a proliferating cell, on the assumption that this would be sufficient to block DNA synthesis in a short-term assay using tritiated thymidine autoradiography. Three cDNAs, referred to as senescent cell-derived inhibitors (sdi), that exhibit DNA synthesis-inhibitory activity when introduced into young cycling cells, were successfully identified. Expression of one of the cDNAs, sdi1, increased 10- to 20-fold in senescent compared with young cells and the increase in RNA closely paralleled the onset of the senescent phenotype and loss of cell proliferation. sdi1 expression was also increased in young cells made nondividing (quiescent) by deprivation of growth factors or contact inhibition. Following serum stimulation, RNA levels of sdi1 in quiescent cells were initially increased, but then declined to low levels just prior to the entry of the cells into S phase. In contrast, RNA levels of sdi1 in senescent cells failed to decline, suggesting a role for this gene in maintaining the senescent phenotype. The sdi1 gene has been mapped to the p arm of chromosome 6.

Amino Acid Sequence↗
PubMed1994

Detection of 1-acetamino-3-(1-naphthyloxy)-2-propanol as a new metabolite of propranolol.

1-Acetamino-3-(1-naphthyloxy)-2-propanol which is an acetyl conjugate of N-desisopropylpropranolol (AcNDP) was detected as a new metabolite of propranolol (PL) from the incubation medium of isolated rat hepatocyte system and from the urinary extracts of a patient under PL therapy as well as a healthy volunteer given PL. In the case of the hepatocyte systems, the optical selectivity of PL elimination and the metabolite formation were discussed by HPLC determination, and the effect of pretreatment by phenobarbital (PB) or 3-metylcholanthrene (3-MC) on the metabolism was also clarified.

Acetamides↗
PubMed1994

Electrocardiographic diagnosis of left ventricular hypertrophy improved by considering both QRS voltage and ST-T criteria.

We evaluated the usefulness of a combination of QRS voltage and the pattern of ST-T abnormality in the electrocardiographic diagnosis of left ventricular hypertrophy (LVH) in 100 middle-aged men: 32 normals, 59 with hypertension (HT), and 9 with hypertrophic cardiomyopathy (HCM) with evidence of LVH (RV5 or RV6 > or = 2.6 mV, SV1 + RV5 or SV1 + RV6 > or = 3.5 mV). They The subjects were classified into three groups based on ST-T pattern: normal (group N), early strain (group ES), and strain (group S). Echocardiographic evidence of LVH was present in 52.0% (52/100) of the subjects: 72.8% (43/59) of the patients with HT, all 9 patients with HCM, and none of the 32 normals. Echocardiographic evidence of LVH was present in 31.3% (20/64) of group N, 73.3% (11/15) of group ES, and all 21 subjects of group S. In patients with HT, the incidence of echocardiographic LVH was higher in group S (100%) than in both group ES (78.6%) and group N (60.6%). QRS voltage (RV5, RV6, RV5 + SV1, and RV6 + SV1) was significantly correlated with interventricular spetal thickness (IVST), IVST+LVPWT/2, and LV mass, as determined by echocardiography, in patients with LVH (IVST or left ventricular posterior wall thickness (LVPWT) of > or = 12 mm) (r = 0.55 to r = 0.75, p < 0.05), but not in patients without LVH (IVST and LVPWT < 12 mm). There were significant correlations between QRS voltage indices (RV5, RV6, RV5 + SV1, and RV6 + SV1) and IVST, IVST+LVPWT/2, and LV mass in group S (r = 0.68 to r = 0.86, p < 0.05), but not in group N. Values for IVST and LV mass were significantly greater in group S than in groups ES or N. The combination of QRS criteria and ST-T findings reflected the echocardiographic assessment of LVH, especially in patients with HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Alternative splicing of bovine terminal deoxynucleotidyl transferase cDNA.

Two cDNA fragments of terminal deoxynucleotidyl transferase, which contained new insertion sequences, were found from bovine thymus cDNA. One of the clones encoded 18 new amino acids and the other encoded 9 new amino acids. In the results of genomic structure analysis around the new insertion sequences, alternative splicing of the bovine terminal deoxynucleotidyl transferase gene was suggested.

Alternative Splicing↗