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Y Nagaoka

Publications and source records attributed to Y Nagaoka.

At least 19 recordsLinked to original sources
PubMed2006

Synthesis and cancer antiproliferative activity of new histone deacetylase inhibitors: hydrophilic hydroxamates and 2-aminobenzamide-containing derivatives.

New series histone deacetylase inhibitors comprising a hydroxamic acid or 2-aminobenzamide group as a zinc-chelating function were synthesized and evaluated for antiproliferative activities against a panel of human cancer cells. The 2-aminobenzamide series inhibitors generally had the potency in cell growth inhibitions comparable to that of MS-275. Among them, the compound having a (3,4-difluorobenzyl)(2-hydroxyethyl)amino group at one end and a 2-aminobenzamide group at the other of molecule showed the most promising profile as an anticancer drug candidate, since it had a comparatively low toxicity as did MS-275 against a normal fibroblast cell CCD-1059SK. Additionally, the derivative exhibited a high recovery in human plasma stability test.

Antineoplastic Agents↗
PubMed2003

Sequences and diversity of 17 new Ovar-DRB1 alleles from three breeds of sheep.

To investigate the genetic diversity of the sheep MHC (Ovar) class II DRB1 locus, we amplified exon 2 of Ovar-DRB1 alleles by polymerase chain reaction (PCR) and determined the nucleotide sequences of both resultant strands after cloning. In our study of a total of 97 sheep of three breeds, namely, Suffolk, Cheviot and Corriedale, we identified 18 previously published alleles and 17 new alleles. These alleles were 83.4 to 94.1% identical at the nucleotide level and 71.4 to 90.9% identical at the amino acid level to Ovar-DRB1*0101. We identified six new alleles in Cheviot sheep and 11 new alleles in Suffolk sheep. Furthermore, we identified 15, 6 and 1 allele in Suffolk, Cheviot and Corriedale sheep, respectively, that have only been found in these breeds to date. Analysis of the frequencies of the various Ovar-DRB1 alleles in each breed indicated that Ovar-DRB1*0702 was the most frequent allele in Suffolk sheep (23.9%), Ovar-DRB1*0203 was the most frequent allele in Cheviot sheep (27.5%) and Ovar-DRB1*0201 was the most frequent allele in Corriedale sheep (25.0%). A comparative analysis of the positions of polymorphic residues in the first extracellular domain of the DRB genes of sheep, humans and mice revealed an extraordinary similarity amongst the positions of polymorphic residues that are associated with the antigen recognition site (ARS). Moreover, the extent of polymorphism seems to be similar in sheep, humans and mice.

Amino Acid Sequence↗
PubMed2003

Technical note: DNA typing for ovine MHC DRB1 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

The ovine major histocompatibilty complex (Ovar) class II DRB1 second exon was amplified by polymerase chain reaction (PCR) from DNA samples of 52 Suffolk sheep. Polymerase chain reaction products were characterized by the restriction fragment length polymorphism (RFLP) technique using nine restriction enzymes, RsaI, HaeIII, SacI, SacII, DdeI, NciI, Hin1I, EcoRI, and BstNI, yielding 13 types. Sequencing of cloned PCR products identified 16 Ovar-DRB1 alleles. Collectively, all PCR-RFLP patterns exactly matched those predicted from DNA sequences. These findings strongly indicate that the PCR-RFLP method using a combination of nine restriction endonucleases is a very powerful tool in Ovar typing.

Alleles↗
PubMed2002

A case of true malignant histiocytosis: identification of histiocytic origin with use of immunohistochemical and immunocytogenetic methods.

We report here an autopsy case of true malignant histiocytosis. The patient was a 67-year-old woman who exhibited fever, wasting, hepatosplenomegaly, and progressive pancytopenia. The bone marrow aspiration disclosed hemophagocytosing cells, which resembled histiocytes. The molecular analysis did not show the clonal gene rearrangement of T-cell receptor or immunoglobulin heavy chain. Although the patient had been started on methylprednisolone pulse therapy and chemotherapy with etoposide, she died from cerebral hemorrhage. The autopsy specimens of spleen and liver showed extensive infiltration of atypical cells, for which histiocytic origin was identified with an immunohistochemical method using monoclonal antibodies against CD11c, CD68, macrophage colony-stimulating factor (M-CSF), M-CSF receptor, lysozyme, antitrypsin and alpha1-antichymotrypsin. Recent investigations have disclosed that in most cases diagnosed as malignant histiocytosis, hemophagocytosis was reactive and not evoked by histiocytic malignancy. True malignant histiocytosis, for which histiocytic origin is confirmed, is extremely rare.

Aged↗
PubMed2001

Total synthesis of (-)-neplanocin a by using lithium thiolate-initiated Michael-aldol tandem cyclization reaction.

(-)-Neplanocin A (1), S-adenosylhomocystein hydrolase inhibitor, was synthesized. The characteristic of this synthesis is a stereoselective construction of five-membered ring of neplanocin A by intramolecular aldol reaction of the lithium enolate that was generated by conjugate addition of lithium thiolate. TBS-protected chiral omega-oxo-alpha,beta-unsaturated ester 16, which was prepared from D-mannitol, was treated with 1.2 equiv of lithium benzylthiolate in THF at -20 degrees C to give three separable cyclization products in good yields and stereoselectivity. After conversions of protective groups, the benzylsulfanyl part of 21 was removed by oxidation to sulfoxide and subsequent thermal elimination to give the requisite double bond. Through the functional group transformations of 30, total synthesis of (-)-neplanocin A (1) was accomplished.

Adenosine↗
PubMed2001

Electronic and steric control in regioselective addition reactions of organolithium reagents with enaldimines.

A reaction mode of imines derived from naphthalene-1-carbaldehyde and acyclic alpha,beta-unsaturated aldehydes with organolitium reagents was dependent on the characteristic nature of a substituent on the imine nitrogen atom. An imine having an electron-withdrawing aryl group on the nitrogen atom behaves as a 1,2-directing imine toward organolithium reagents. In contrast, an imine bearing an alkyl or a bulky aryl group favors 1,4-addition of organolithium reagents. Electronic and steric tuning of a substituent on the imine nitrogen atom for a reaction mode was rationalized on the basis of molecular orbital calculations.

Journal Article↗
PubMed2001

Recognition of tRNA by aminoacyl-tRNA synthetase from hyperthermophilic archaea, Aeropyrum pernix K1.

To study the recognition sites of tRNA for archaeal aminoacyl-tRNA synthetase, several aminoacyl-tRNA synthetase genes from hyperthermophilic archaeon, Aeropyrum pernix K1 were cloned and expressed. All the expressed enzymes showed extreme thermostability. Expressed threonyl-tRNA synthetase threonylated not only archaeal (A. pernix and Haloferax volcanii) threonine tRNAs but also Escherichia coli threonine tRNA. However, threonyl-tRNA synthetase from H. volcanii did not threonylate E. coli threonine tRNA.

Desulfurococcaceae↗
PubMed2001

[Carbon-carbon bond formation based on alkenylphosphonates].

We have been engaged in the development of asymmetric conjugate addition reactions of lithium thiolates, organolithiums and organocopper reagents under the control of external chiral ligands and we have also developed an efficient asymmetric Horner-Wadsworth-Emmons (HWE) reaction using an external chiral Ligand. We attempted to synthesize axial chiral allenes by combination of these conjugate addition reaction and HWE reaction. In the course of this study, we found that Michael-aldol reaction of alkenylphosphonates 1 using LDA and aldehydes results in the direct formation of alpha,beta-unsaturated hydroxyphosphonate 4, which was efficiently converted to allene by treatment with KH or KH-18-crown-6. Furthermore, allenes were synthesized by sequential double HWE reaction in one-flask manner starting from methylenebisphosphonate 8. The key to success is a metal exchange of intermediate lithium alkoxide 4-Li to potassium alkoxide 4-K by the addition of t-BuOK. As our continuous study of carbon-carbon bond formation based on alkenylphosphonates, a cyclization reaction of bisalkenylphosphonate 6 was developed. Although the treatment of 6 with organolithium reagents afforded a mixture of addition-cyclization product 9 and deprotonation-cyclization product 10, the treatment of 6 with LDA gave 10 selectively. These cyclization methods were applied to the synthesis of efficient chiral phosphine ligands.

Alkadienes↗
PubMed2001

Liver segment S2 is consistently located at the dorsal side of S3 but sometimes at the right and/or caudal side of S3.

After preparing the frontal section including the origin of the left portal trunk at the hilar region, the left anatomical lobes of 111 human livers were dissected to reveal the segmental configuration based on the supplying portal vein branches. S2 was consistently located dorsal to S3. However, in contrast to the description in common textbooks for medical students, 19.8% of the specimens carried a paradoxical segmental configuration showing a "caudal and/or rightward" S2 in combination with a "cranial and/or leftward" S3 in the frontal section through the ventral part of the hilar region. The caudal and rightward cases were associated with a specific arrangement of S2 and S3 segmental stems in which the S3 stem ran relatively upward to spread over S2 or both stems ran almost horizontal, respectively. In routine diagnostic radiology, identification of S2 and S3 might sometimes be biased by the generally accepted notion that S2 should be located at the dorsal, cranial and left side of S3.

Humans↗
PubMed2001

Initial remission-inducing effect of very low-dose cyclosporin monotherapy for minimal-change nephrotic syndrome in Japanese adults.

AIM: Cyclosporin A (CsA) in combination with corticosteroids can be used effectively in steroid-sensitive nephrotic syndrome. However, reports documenting the effectiveness ofCsA monotherapy against such a condition have been scarce. In 11 adults with minimal-change nephrotic syndrome, we have tried very low-dose CsA in the hope of inducing remission without using either corticosteroid or any other immunosuppressive drugs. PATIENTS AND METHODS: Indications for treatment included steroid-sensitive relapsing nephrotic syndrome (7 patients) and first-episode nephrotic syndrome (4 patients). In all patients, corticosteroid and cytotoxic agents had not been given before entry. CsA was administered orally at an initial dose of 2.4 (range 1.5 - 3.1) mg/kg per day. RESULTS: Analysis of the clinical course revealed that 8 of 11 patients entered complete remission after a mean duration of 44 +/- 31 days, whereas 3 patients failed to enter remission to CsA alone, resulting in complete remission combined with methylprednisolone pulse therapy without conventional oral prednisolone. CsA dosages and trough levels between responders and non-responders were similar. Non-responders had much higher levels of serum total cholesterol and higher daily urinary excretion of protein than those of responders, respectively. No patients had significant decrease in creatinine clearance, development of hypertension or suffered from other CsA associated serious side-effects. CONCLUSION: The present data suggest that CsA monotherapy at a very low dose could induce complete remission in adult patients with minimal-change nephrotic syndrome. Conversely, severe hypercholesterolemia would be likely to inhibit the action of CsA against nephrotic conditions.

Adult↗
PubMed2001

[Configuration of the liver segment observed in the frontal section including the origin of the left portal trunk at the hepatic hilum].

After preparing threparing the frontal section including the origin of the left portal trunk at the hepatic hilum, 60 human livers (35, entirely; 25, partly) were dissected to reveal segmental configuration and the supplying portal vein branches. We usually observed two combinations of segments, i.e., S2, 4, 5 and 8 or S2, 3, 4, 5 and 8, in the frontal section including the origin of the left portal trunk. However, S8 was sometimes absent in the section when S4 extended to the right and/or upper side. S2 was consistently located dorsal to S3 despite the fact that 11.7% of the specimens carried an unexpected configuration showing a "lower" S2 in combined with an "upper" S3 in the frontal section. The latter case was associated with specific S2 and S3 segmental branches maintaining horizontal courses along a common plane. S4, S5 and S8 were usually arranged from the ventral to the dorsal aspect in this order. Four types of ventral short branches originated at or near the primary portal divisions and supplied the hilar parenchyme adjacent to S4 and/or the anterior segment (S5 or S8). These ventral short branches tended to be associated with the variations of the primary division. Dissection of the liver after frontal section provided a better understanding of the segmental configuration rather than an approach from the hepatic hilum.

Aged↗
PubMed2001

[Serial changes in body composition in patients with chronic renal failure on peritoneal dialysis].

Nutritional status is one of the most important factors affecting mortality and morbidity in chronic dialysis patients. There are, however, few data on serial body composition changes in these patients. To investigate serial changes in body composition in patients on peritoneal dialysis, we measured intracellular fluid volume(ICF), extracellular fluid volume(ECF), body protein volume(BPV), body fat volume(BFV) and bone mineral content(BMC) using multifrequency bioelectrical impedance analysis (MF-BIA). MF-BIA was performed in 35 patients, consisting of 21 men and 14 women with a mean age of 51.3 +/- 10.9 years, before and after one year of observation. At the baseline in male patients, ICF was 37.0 +/- 3.4%, ECF 19.7 +/- 1.6%, BPV 20.7 +/- 1.7%, BFV 18.1 +/- 6.6% and BMC 4.5 +/- 0.4% of body weight, and in female patients ICF was 34.4 +/- 2.6%, ECF 17.8 +/- 1.9% BPV 19.0 +/- 1.6%, BFV 24.4 +/- 6.2% and BMC 4.5 +/- 0.4% of body weight. In the group of patients whose body weight increased more than 3 kilograms(n = 9), the increase rate of BFV was 32.3 +/- 20.2%, significantly higher than that of the other segments(p < 0.001). On the other hand, in the group of patients whose body weight decreased more than 3 kilograms(n = 5), each segment showed the same extent of decrease and there was no significant difference in the decrease rates among each segment. In the group of patients whose body weight was stable(n = 21), changes in each body composition segment were extremely small. It could be concluded that the body weight increase is due mainly to increase in BFV and body weight decrease results from a concurrent decrease in each body composition segment in peritoneal dialysis patients.

Adult↗
PubMed2000

Threonyl-tRNA synthetase of archaea: importance of the discriminator base in the aminoacylation of threonine tRNA.

To investigate the contribution of the discriminator base of archaeal tRNA(Thr) in aminoacylation by threonyl-tRNA synthetase (ThrRS), cross-species aminoacylation between Escherichia coli and Haloferax volcanii, halophilic archaea, was studied. It was found that E. coli ThrRS threonylated the H. volcanii tRNA(Thr) but that E. coli threonine tRNA was not aminoacylated by H. volcanii ThrRS. Results of a threonylation experiment using in vitro mutants of E. coli threonine tRNA showed that only the mutant tRNA(Thr) having U73 was threonylated by H. volcanii ThrRS. These findings indicate that the discriminator base U73 of H. volcanii tRNA(Thr) is a strong determinant for the recognition by ThrRS.

Escherichia coli↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 14). Comparison of the effects of 2- and 4-weeks intravenous administration of etoposide.

In order to examine whether effects on male reproductive organs following 2-weeks administration of Etoposide (ET) are detectable, ET was administered intravenously once a week to rats for 2 and 4 weeks at 5 and 10 mg/kg/week. No deaths and no drug-related changes in body weight or in gross pathology were observed. However, decreased testis and/or thymus weights were noted. And histopathological examination revealed decrease and/or loss of spermatogonia and spermatocytes in the testes. It was evident that the target cells of the test article in the male reproductive organs are spermatogonia. Atrophy of the medulla and increase of immature lymphocytes in the cortex of the thymus and increase of fatty cells and increase of immature hematopoietic cells in the bone marrow were also apparent. The histological changes in the testis, thymus and bone marrow suggest that ET inhibits cellular mitosis which reflects its mechanism of action as an anticancer agent. It is concluded that effects of ET on male reproductive organs can be detected by histopathological examination of the testes after 2-weeks repeated administration.

Animals↗