Isolation of hepatic drug metabolism inhibitors from the seeds ofMyristica fragrans

The hexane extract from Nutmeg, the seed ofMyristica fragrans significantly inhibited hepatic drug-metabolizing enzyme activity. Through systematic fractionation by SiO₂ column and vacuum liquid chromatography monitoring by bioassay, three components, myristicin, (I), licarin-B(II) and dehydrodiisoeugenol(III) were isolated as active principles. Compounds II and III, with a single treatment (200 mg/kg, i.p.) showed not only a significant prolongation of hexobarbital-induced sleeping time but also a significant inhibition of aminopyrine N-demethylase and hexobarbital hydroxylase activities in mice. Compounds I and II provoked a sleep episode at a subhypnotic dose of HB, suggesting that they posses CNS-depressant properties.     

Comparative analysis of NK/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1

Natural killer/T-cell lymphoma (NKTL) and peripheral T-cell lymphomas (PTCL) are prevalent in the Asian population and exhibit a high association with the Epstein-Barr virus (EBV). Moreover, differentiation of these two groups is often difficult and problematic. We investigated 35 cases of NKTL (22 nasal cases and 13 extranasal cases) and 30 cases of PTCL in terms of their clinical features, immunohistology, EBV positivity, EBV strain-type polymorphism and latent membrane protein 1 (LMP1) deletion variant distribution. Eighteen cases (82%) of nasal NKTL and seven (54%) of extranasal NKTL showed EBV positivity by EBV in situ hybridization. Fifteen cases (50%) of PTCL revealed EBV positivity. EBV strain type A was predominant in NKTL (18:5), and EBV strain types A and B were distributed evenly in PTCL (6:6). EBV-positive patients had significantly shorter survival than EBV-negative patients (P < 0.05), and EBV positivity correlated with advanced clinical stage (P < 0.05). Patients harboring type A EBV showed slightly poorer prognoses than those having type B, though it was not obviously statistically different (P = 0.07). The LMP1 deletion variant was prevalent in both NKTL (three wild-type LMP1, 15 deletion variants) and PTCL (three wild-type LMP1, eight deletion variants, two coexistent forms) patients, but did not have prognostic impact. Our results indicate that EBV acts as a negative prognostic factor in NKTL and PTCL, and that the intrinsic properties of a specific viral strain might influence the clinical behavior of these diseases.     

Anionic polymerization of fluorine-containing vinyl monomers, 12. Anionic polymerization mechanism of hexafluoro-1,3-butadiene

Initiation and propagation reaction mechanisms of the anionic polymerization of hexafluoro-1,3-butadiene (HEBD) were investigated. The initiation reaction with caesium tert-butoxide was found to be completed within 5 min although the reactions were carried out at a much lower temperature than that of the polymerization reaction. The initiation reaction was, therefore, inferred to take place in an anionic fashion by adding the tert-butoxide anion to HFBD. In order to clarify the propagation reaction mechanism of HFBD which yielded a polymer with a polyvinylene structure, the polymerization reactivity of HFBD and hexafluoro-2-butyne (HFBY), the isomerization of HFBD to HFBY, and the structural difference between poly(HFBD) and poly(HFBY) were discussed. In spite of the low yield of HFBY by the isomerization reaction under polymerization conditions, higher yields of poly(HFBD) were obtained. Judging from the X-ray analysis which showed that poly(HFBD) was highly crystalline and poly(HFBY) was amorphous, poly(HFBD) might not be produced by polymerization of HFBY. An addition reaction of the propagating anion to the carbon-2 of the HFBD monomer followed by isomerization at the propagating living end to yield poly[1,2-bis(trifluoromethyl)vinylene] is proposed.     

Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation

Accumulation of unfolded and malfolded proteins causes endoplasmic reticulum (ER) stress, stimulating unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) activation and activating caspase-12 located on the ER. Little is known about the relationship between the ER stress and polyglutamine [poly(Q)] aggregates. Poly(Q)72 repeats [poly(Q)(72)] induced the stimulation of ER stress signals such as JNK activation, upregulation of Grp78/Bip and caspase-12 activation in C2C5 cells. We prepared antiserum against the cleavage site of mouse caspase-12 at D(318) (anti-m12D318), and showed that poly(Q)(72) with perinuclear aggregates, cytoplasmic inclusions and nuclear inclusions stimulated JNK activation and anti-m12D318 immunoreactivity, but poly(Q)(72) with dispersed aggregates and small nuclear aggregates showed a significantly less effect. Poly(Q)(72) and poly(Q)(11) dispersed in cytoplasm did not. Anti-m12D318-positive cells showed apoptotic features. Unlike anti-m8D387 immunoreactivity, the anti-m12D318 immunoreactivity was not coaggregated with poly(Q). Ac-IETD-fmk (caspase-8 inhibitor) and Ac-DEVD-CHO (caspase-3 inhibitor) did not prevent the anti-m12D318 immunoreactivity induced by poly(Q)(72) aggregates. Anti-m12D318 immunoreactivity was detected in caspase-8(-/-) and caspase-3(-/-) mouse embryonic fibroblasts expressing poly(Q)(72) aggregates. Thus, caspase-12 was activated by poly(Q)(72) aggregates via a pathway independent of caspase-8 and caspase-3 activation, and caspase-12 activation was closely associated with poly(Q) aggregate-mediated cell death. Stimulation of ER stress signals may be involved in the pathogenesis of neurodegenerative disorders with poly(Q) expansion.     

Identification, characterization, and expression pattern of the chicken EKLF gene.

EKLF/KLF1 was the first of the Krüppel-like factors (KLFs) to be identified in mammals and plays an important role in primitive and definitive erythropoiesis. Here, we identify and characterize EKLF in the chicken (cEKLF). The predicted amino acid sequence of the zinc finger region of cEKLF is at least 87.7% similar to mammalian EKLF proteins and is 98.8% and 95% similar to the EKLF orthologues in Xenopus and zebrafish, respectively. During early embryonic development, cEKLF expression is seen in the posterior primitive streak, which gives rise to hematopoietic cells, and then in the blood islands and in circulating blood cells. cEKLF mRNA is expressed in blood cells but not in brain later in chicken embryonic development. cEKLF mRNA is increased in definitive compared with primitive erythropoiesis. The conserved sequence and expression pattern of cEKLF suggests that its function is similar to its orthologues in mammals, Xenopus, and zebrafish.     

Feline CD 4 molecules expressed on feline non-lymphoid cell lines are not enough for productive infection of highly lymphotropic feline immunodeficiency virus isolates

Summary To investigate whether the feline CD 4 (fCD 4) molecules are involved in infections of highly lymphotropic feline immunodeficiency virus (FIV) isolates, we expressed fCD 4 stably on Crandell feline kidney cells andFelis catus whole foetus 4 cells by transfection of a cDNA encoding the fCD 4 glycoprotein, and then infected them with TM 1 and TM 2 strains of FIV, which are unable to infect these cells productively. In spite of fCD 4 being expressed on these cells, no virus production was observed. This result indicates that fCD 4 expression alone cannot induce a productive infection of the FIV TM 1 and TM 2 strains.     

Favourable associations between the myosin heavy-chain and light-chain isoforms in human skeletal muscle

Histochemical and biochemical analyses were performed in order to examine the relationship between myosin light-chain (LC) isoforms and fibre-type distributions in whole human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis muscle in six healthy men, and analysed for the relative area occupied by each fibre type (percentage of fibre type area) and the molar ratio of each LC isoform. The percentage of type I fibre area was positively correlated with the molar ratio of slow LC (LC1s and LC2s) to total LC. The regression line was located below the line of unity. Also, the ratio of percentage of type II fibre area to that of type II fibre area was positively correlated with the molar ratio of the fast alkali LC LC1f to fast alkali LCs LC1f and LC3f. These results support previous study, having shown that in human skeletal muscle some type I fibres express various amounts of fast LC in addition to slow LC and suggest that fast myosin heavy-chain HCII a is favourably associated with LC1f, whereas HCIIb is favourably associated with LC3f.