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Biomedical subjects

N Nakamura

Publications and source records attributed to N Nakamura.

At least 127 records · Page 7Linked to original sources
PubMed2001

Direct targeting of cis-Golgi matrix proteins to the Golgi apparatus.

The targeting route of newly synthesized GM130 and GRASP65 to the Golgi apparatus was investigated by three different approaches. First, localization of pulse labeled GM130 and GRASP65 in normal rat kidney (NRK) cells was traced by subcellular fractionation followed by immunoprecipitation. Immediately after the pulse labeling, GM130 and GRASP65 were found in the Golgi but not in the endoplasmic reticulum (ER) membrane fractions, whereas a control Golgi membrane protein was still found in the ER membrane fractions. Second, epitope tagged GM130 and GRASP65 were expressed in NRK cells by plasmid microinjection into the nuclei and their localization was analyzed by immunofluorescence. When ER to Golgi transport was inhibited by prior microinjection of a GTP-restricted mutant of Sar1 protein into the cytosol, the expressed GM130 and GRASP65 showed clear Golgi localization. Last, binding of GM130 and GRASP65 to the membranes was analyzed in vitro. In vitro synthesized GM130 and GRASP65 specifically bound to purified Golgi membranes but not to microsomal membranes. The bound GM130 and GRASP65 were found to form a complex with pre-existing counterparts on the Golgi membrane. These results strongly suggested that GM130 and GRASP65 are directly targeted to the Golgi membrane without initial assembly on the ER and subsequent vesicular transport to the Golgi apparatus.

Animals↗
PubMed2001

Cytotoxic alkaloids and a flavan from the bulbs of Crinum asiaticum var. japonicum.

A new pyrrolophenanthridone alkaloid, criasiaticidine A (1), was isolated from the bulbs of Crinum asiaticum var. japonicum, together with pratorimine (2), lycorine (3) and 4'-hydroxy-7-methoxyflavan (4). The structure of the new alkaloid was determined to be 4,5-etheno-9,10-dihydroxy-6-phenanthridone by spectroscopic means. The cytotoxicity of the isolated compounds 1-4 was evaluated in vitro against Meth-A (mouse sarcoma) and Lewis lung carcinoma (mouse lung carcinoma) tumor cell lines. Furthermore, 3 was examined for in vivo antitumor activity with LLC tumor cells.

Alkaloids↗
PubMed2001

The heterocyclic ring fission and dehydroxylation of catechins and related compounds by Eubacterium sp. strain SDG-2, a human intestinal bacterium.

A human intestinal bacterium, Eubacterium (E.) sp. strain SDG-2, was tested for its ability to metabolize various (3R)- and (3S)-flavan-3-ols and their 3-O-gallates. This bacterium cleaved the C-ring of (3R)- and (3S)-flavan-3-ols to give 1,3-diphenylpropan-2-ol derivatives, but not their 3-O-gallates. Furthermore, E. sp. strain SDG-2 had the ability of p-dehydroxylation in the B-ring of (3R)-flavan-3-ols, such as (-)-catechin, (-)-epicatechin, (-)-gallocatechin and (-)-epigallocatechin, but not of (3S)-flavan-3-ols, such as (+)-catechin and (+)-epicatechin.

Biotransformation↗
PubMed2001

Triterpenes and lignans from Artemisia caruifolia and their cytotoxic effects on meth-A and LLC tumor cell lines.

One new triterpene, 3beta-hydroxy-29-norcycloart-24-one (1), and four new lignans, caruilignans (2-5), together with six known compounds were isolated from the aerial part of Artemisia caruifolia BUCH.-HAM. ex TOXB. Their structures were determined by various spectroscopic means. Most of the isolated lignans were moderately cytotoxic to Meth-A cells with ED50 values of 5-10 microg/ml, but not to Lowis lung carcinoma (LLC) cells. An oxime derivative of 1 showed more potent cytotoxic activity against Meth-A and LLC cells than the original triterpene 1.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Kaempferol acetylrhamnosides from the rhizome of Dryopteris crassirhizoma and their inhibitory effects on three different activities of human immunodeficiency virus-1 reverse transcriptase.

Three new kaempferol glycosides, called crassirhizomosides A (1), B (2) and C (3), were isolated from the rhizome of Dryopteris crassirhizoma (Aspidiaceae), together with the known kaempferol glycoside, sutchuenoside A (4). The structures of 1-3 were determined as kaempferol 3-alpha-L-(2,4-di-O-acetyl)rhamnopyranoside-7-alpha-L-rhamnopyranoside, kaempferol 3-alpha-L-(3,4-di-O-acetyl)rhamnopyranoside, and kaempferol 3-alpha-L-(2,3-di-O-acetyl)rhamnopyranosside-7-alpha-L-rhamnopyranoside, respectively, by chemical and spectroscopic means. Inhibitory effects of 1-4 and kaempferol on human immunodeficiency virus reverse transcriptase-associated DNA polymerase (RNA-dependent DNA polymerase and DNA-dependent DNA polymerase) and RNase H activities were investigated.

Carbohydrates↗
PubMed2001

Inhibitory effects on HIV-1 protease of tri-p-coumaroylspermidine from Artemisia caruifolia and related amides.

From a methanol extract of Artemisia caruifolia, which showed a moderate inhibitory activity on HIV-1 protease in a preliminary screening, N1,N5,N10-tri-p-coumaroylspermidine and three dicaffeoylquinic acids were isolated. The former compound was found to appreciably inhibit HIV-1 protease. Of related amides which were chemically synthesized, N1,N5,N10,N14-tetra-p-coumaroylspermine and N1,N4,N7,N10,N13-penta-p-coumaroylte-traethylenepentamine inhibited HIV-1 protease more potently than N1,N5,N10-tri-p-coumaroylspermidine.

Amides↗
PubMed2001

New paeonilactone-A adducts formed by anaerobic incubation of paeoniflorin with Lactobacillus brevis in the presence of arylthiols.

During the course of preparing anticonvulsant paeonimetabolin-I adducts, new paeonilactone-A adducts: 9-phenylthiopaeonilactone-A, 9-(o-tolylthio)paeonilactone-A, 9-(m-tolylthio)paeonilactone-A, 9-(p-tolylthio)-paeonilactone-A and 9-(2-naphthylthio)paeonilactone-A, were obtained along with expected paeonimetabolin-I adducts by anaerobic incubation of paeoniflorin from peony roots with Lactobacillus brevis in the presence of the aromatic thiols, phenylthiol, o-tolylthiol, m-tolylthiol, p-tolylthiol and 2-naphthylthiol. The structures of these compounds were determined by spectroscopic methods including two dimensional (2D) NMR.

Anaerobiosis↗
PubMed2001

Protective effect of Salvia miltiorrhiza on angiotensin II-induced hypertrophic responses in neonatal rat cardiac cells.

The effect of the root of Salvia miltiorrhiza (SM) on angiotensin II (Ang II)-induced hypertrophic responses was examined in cultured neonatal rat cardiac cells (cardiomyocytes and non-cardiomyocytes). The methanol eluate fraction (SM2) of the water extract and the ethyl acetate-insoluble fraction (SM3) and its soluble fraction (SM4) partitioned from the methanol extract were prepared. Treatment with SM4 (5-80 microg/ml), not SM2 and SM3, for 24 h produced dose-dependent cytotoxicity against cardiac cells relative to the reduction in viability and the morphological injury of cardiomyocytes. SM2 or SM3 in the absence of Ang II affected neither hyperplastic nor hypertrophic growth of both cell types. However, SM3 (40 microg/ml) attenuated the positive chronotropic responsiveness of cardiomyocytes to Ang II (1 nM) stimulation, whereas Ang II-induced increase in non-cardiomyocyte number was decreased only by SM2 (40 microg/ml) treatment. Furthermore, SM3 suppressed Ang II-induced enlargement of cell size by preceding Ang II-induced induction of immediate early response gene (c-jun) expression in cardiomyocytes, while SM2 decreased Ang II-induced DNA synthesis in non-cardiomyocytes. Moreover, three phenolic compounds and tanshinone IIA that differed quantitatively among three SM fractions were identified by reverse-phase high performance liquid chromatography. Thus, the present findings indicate that the root of SM is an effective inhibitor of Ang II action and has a plural effective constituent, which possess different pharmacological activities on Ang II-induced hypertrophy and hyperplasia in cultured neonatal rat cardiac cells.

Angiotensin II↗
PubMed2001

Molecular cloning of feline hepatocyte growth factor (HGF) cDNA.

Hepatocyte growth factor (HGF) is a pleiotropic cytokine responsible for regeneration, development and maintenance of various organs, and growth, invasion and metastasis of tumor cells. A full-length feline HGF cDNA was cloned and sequenced by RT-PCR from cat liver. Feline HGF consists of 728 amino acid and contains alpha- and beta-chains encoded in a single open reading frame. The predicted amino acid sequence of feline HGF showed 93.2, 93.3 and 93.3% homology with those of human, mouse and rat HGF, respectively. The putative proteolytic processing site, all cysteine residues, and four potential glycosylation sites are conserved in all species. Therefore, feline HGF is expected to have a similar three-dimensional structure to human, mouse and rat HGF.

Amino Acid Sequence↗
PubMed2001

Endoscopic reconstruction of the anterior cruciate ligament with quadrupled hamstring tendons. A correlation between MRI changes and restored stability of the knee.

A total of 30 patients who underwent endoscopic reconstruction of the anterior cruciate ligament using quadrupled hamstring tendons, through a single drill hole in the femur, had MRI 24 to 28 months after operation. In 18 patients the scans revealed that both the anterior and posterior portions of the graft ran in parallel from the inside of the femoral to the tibial tunnel. In 12, the posterior bundle had moved anteriorly and the anterior bundle could not be identified at the anterodistal border of the femoral tunnel. The mean difference in the anterior laxity, when compared with the contralateral knee, was 2.0+/-1.7 mm and 4.3+/-2.8 mm for the two types, respectively. Damage to the anterior bundle may occur when using the endoscopic technique because of biomechanical disadvantages, including concentration of loading and repetitive bending stress in the anterior bundle at the opening of the femoral tunnel.

Adolescent↗
PubMed2001

Absence of somatic hypermutation of immunoglobulin heavy chain variable region genes in precursor B-lymphoblastic lymphoma: a study of four cases in childhood and adolescence.

Somatic mutation (SM) analysis provides a useful tool for understanding the suitable stage of differentiation of normal and neoplastic B cells. B-cell precursor neoplasms are considered to be somatically premutational. However, no reports have been made on the sequence analysis of SM in rearranged immunoglobulin heavy chain variable region (VH) genes in precursor B-lymphoblastic lymphoma (PB-LBL); as for B-cell acute lymphoblastic leukemia (B-ALL), the variable frequency of SM of the VH genes has been described. To better distinguish PB-LBL from B-ALL based on the stage at which differentiation occurs, we analyzed the SM of the VH genes in 4 children and adolescents with PB-LBL. In all 4 cases, there was no SM in complementarity-determining regions 1, 2, and 3 and in framework regions 2 and 3 of the VH genes, except for 1 mutation in 1 of 2 polymerase chain reaction products from 1 patient. Our data showed the absence of SM of lymphoma cells in PB-LBL, in addition to the developmentally regulated rearrangement of VH genes at the stage of B-cell precursor cells. The lack of mutation in VH gene sequences suggests that SM may differ between PB-LBL and B-ALL.

Adolescent↗
PubMed2001

Stable chromosome aberrations in atomic bomb survivors: results from 25 years of investigation.

Frequencies of stable chromosome aberrations from more than 3,000 atomic bomb survivors were used to examine the nature of the radiation dose response. The end point was the proportion of cells with at least one translocation or inversion detected in Giemsa-stained cultures of approximately 100 lymphocytes per person. The statistical methods allow for both imprecision of individual dose estimates and extra-binomial variation. A highly significant and nonlinear dose response was seen. The shape of the dose response was concave upward for doses below 1.5 Sv but exhibited some leveling off at higher doses. This curvature was similar for the two cities, with a crossover dose (i.e. the ratio of the linear coefficient to the quadratic coefficient) of 1.7 Sv (95% CI 0.9, 4). The low-dose slopes for the two cities differed significantly: 6.6% per Sv (95% CI 5.5, 8.4) in Hiroshima and 3.7% (95% CI 2.6, 4.9) in Nagasaki. This difference was reduced considerably, but not eliminated, when the comparison was limited to people who were exposed in houses or tenements. Nagasaki survivors exposed in factories, as well as people in either city who were outside with little or no shielding, had a lower dose response than those exposed in houses. This suggests that doses for Nagasaki factory worker survivors may be overestimated by the DS86, apparently by about 60%. Even though factory workers constitute about 20% of Nagasaki survivors with dose estimates in the range of 0.5 to 2 Sv, calculations indicate that the dosimetry problems for these people have little impact on cancer risk estimates for Nagasaki.

Adolescent↗
PubMed2001

Lack of correlation between clinical characteristics and serum soluble Fas ligand levels in patients with multiple myeloma.

Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow and rarely cured by chemotherapy. Villunger et al. showed that the neoplastic plasma cells express Fas ligand (FasL), which transmits a signal of apoptosis upon ligation to Fas, and suggested that the FasL suppresses the T-cells activated against malignant cells, resulting in escape from tumour immunity. We examined serum soluble FasL (sFasL) levels in 35 multiple myeloma patients to evaluate the correlation between sFasL levels and clinical characteristics. The serum sFasL levels were not affected by the disease status, serum monoclonal protein levels, or other prognostic factors. We could not determine whether the expression of FasL is involved in the poor clinical course of the disease.

Adult↗
PubMed2001

[Mixed-type autoimmune hemolytic anemia after splenectomy for idiopathic thrombocytopenic purpura].

A 30-year-old woman was admitted because of anemia and jaundice in 1999. She had been diagnosed as having idiopathic thrombocytopenic purpura (ITP) in 1996, but had shown no response to prednisolone (PSL). Subsequent splenectomy in 1998, followed by further treatment with PSL, had also been ineffective. On admission in 1999, the direct and indirect Coombs tests gave positive results, the cold agglutinin titer was high with anti-I specificity (IgM), and warm-type autoantibody (IgG) was positive. Autoagglutination of the patient's red blood cells was 3+ at 37 degrees C. A diagnosis of mixed-type autoimmune hemolytic anemia (AIHA) associated with ITP was made. Mixed-type AIHA occurring after splenectomy for ITP is very rare, only one case having been reported to date.

Adult↗
PubMed2001

[Efficacy of radiofrequency catheter ablation in a patient with sinus node reentrant tachycardia].

We performed electrophysiological study and catheter ablation on a 62-year-old patient with supraventricular tachycardia(SVT). This SVT was reproducibly initiated and terminated by atrial stimulation during the electrophysiological testing. The P-wave morphology and atrial activation sequence of intracardiac electrograms were identical to those in normal sinus rhythm. SVT was terminated with carotid sinus massage that increased vagal tone, and for this reason, the reentry circuit of SVT could be localized in sinus node. On the basis of these findings, the SVT was diagnosed as sinus node re-entrant tachycardia and was successfully eliminated by radiofrequency catheter ablation. Radiofrequency catheter ablation would be effective in patients with sinus node reentrant tachycardia refractory to anti-arrhythmic drugs. It should, however, be performed with careful consideration to the influence of the sinus node.

Catheter Ablation↗
PubMed2001

Immunoglobulin heavy chain gene analysis of ocular adnexal extranodal marginal zone B-cell lymphoma.

PURPOSE: To clarify the cellular origin of extranodal marginal-zone B-cell lymphoma (EZML) of the mucosa-associated lymphoid tissue (MALT) type in ocular adnexa, the somatic mutation was analyzed in the immunoglobulin heavy-chain variable region (VH) gene. METHODS: Eight cases of EZML in the orbit and four in the conjunctiva were studied. The VH genes were amplified by a seminested PCR and sequenced directly. These were compared with the closest published VH germline segments to determine the somatic mutation frequency. Intraclonal microheterogeneity, which was termed the ongoing mutation frequency in the current study, was estimated by counting the number of single nucleotide substitutions in individual clones and dividing by the total number of nucleotides analyzed. Nine cases of gastrointestinal EMZL were also examined for comparison. RESULTS: The somatic mutation frequency varied between 2.0% and 12.7%, with a mean value of 7.9%. Ten cases with intraclonal microheterogeneity showed between one and six further substitutions. The average of ongoing mutation frequency was 0.11%, with a range of 0% to 0.25%. In the gastrointestinal EMZLs, the average of somatic mutation frequency was 8.5% (1.5%-14.2%) and of ongoing mutation frequency was 0.51% (0.25%-0.75%). CONCLUSIONS: The average of ongoing mutation frequency in ocular adnexal EMZL was lower than that in gastrointestinal EMZL. Both ocular adnexal and gastrointestinal EMZLs are derived from postgerminal center memory B cells, but the low ongoing mutation frequencies of ocular adnexal EMZL may result from less antigen stimulation and follicular colonization in the orbit relative to gastrointestinal EMZL.

Adult↗