Novel imidazole compounds as a new series of potent,orally active inhibitors of 5-lipoxygenase

Replacement of the dihydroquinolinone pharmacophore of Zeneca's ZD2138 by ionizable imidazolylphenyl moiety has lead to the discovery of a novel series of potent and orally active 5-lipoxygenase (5-LO) inhibitors. The synthesis and structure-activity relationship (SAR) of this series of compounds are described herein.     

Mortalin imaging in normal and cancer cells with quantum dot immuno-conjugates

Quantum dots are the nanoparticles that are recently emerging as an alternative to organic fluorescence probes in cell biology and biomedicine, and have several predictive advantages. These include their ⑴broad absorption spectra allowing visualization with single light source, ⑵exceptional photo-stability allowing long term studies and ⑶narrow and symmetrical emission spectrum that is controlled by their size and material composition. These unique properties allow simultaneous excitation of different size of quantum dots with a single excitation light source, their simultaneous resolution and visualization as different colors. At present there are only a few studies that have tested quantum dots in cellular imaging. We describe here the use of quantum dots in mortalin imaging of normal and cancer cells. Mortalin staining pattern with quantum dots in both normal and cancer cells mimicked those obtained with organic florescence probes and were considerably stable.     

CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53

The INK4a locus on chromosome 9p21 encodes two structurally distinct tumor suppressor proteins, p16(INK4a) and the alternative reading frame protein, ARF (p19(ARF) in mouse and p14(ARF) in human). Each of these proteins has a role in senescence of primary cells and activates pathways for cell cycle control and tumor suppression. The current prevailing model proposes that p19(ARF) activates p53 function by antagonizing its degradation by MDM2. It was, however, recently shown that stabilization of p53 by p14(ARF) occurs independent of the relocalization of MDM2 to the nucleolus. We have identified a novel collaborator of ARF, CARF. It co-localizes and interacts with ARF in the nucleolus. We demonstrate that CARF is co-regulated with ARF, cooperates with it in activating p53, and thus acts as a novel component of the ARF-p53-p21 pathway.     

Male-killing Wolbachia in the butterfly Hypolimnas bolina

Some lines of the butterfly Hypolimnas bolina L. (Lepidoptera: Nymphalidae) are characterized by their female‐biased sex ratio. In these lines, most males die before reaching the middle larval stage. However, the cause of the bias remains unclear. We detected the proteobacterium Wolbachia in all individuals in the female‐biased butterfly lines and in some of the lines with a normal sex ratio. Tetracycline treatment of adult females of a female‐biased line led to a significant increase in both the hatch rate of their eggs (F1) and the male‐to‐female ratio of F1 pupae. In addition, certain assays of tetracycline treatment on mother butterflies significantly increased the male to female ratio of F1 adults. Known bacterial sex ratio distorters other than Wolbachia were not detected by diagnostic PCR assay, nor by the sequencing of 16S rDNA amplified using general prokaryotic 16S rDNA primers. These results strongly suggest that the distortion of the sex ratio is due to the killing of males by the inherited Wolbachia. Sequences of the 16S rDNA amplified using Wolbachia‐specific primers, the cell division protein gene (ftsZ), the molecular chaperone groE genes (groE operon), and the Wolbachia surface protein gene (wsp) from Wolbachia in lines belonging to three subspecies of the butterfly (bolina, jacintha, and philippensis) revealed no variation among lines nor between female‐biased lines and a normal one.     

Fractionation of Nitrogen Isotopes by Glutamine Synthetase Isolated from Spinach Leaves

The isotopic fractionation of nitrogen in the reaction in vitroof glutamine synthetase isolated from spinach (Spinacia oleraceaL.) leaves was calculated from the changes in natural ¹⁵N abundance(     

Partition of polysaccharide-coated liposomes in aqueous two-phase systems

Hydrophobized polysaccharides such as cholesterol-bearing pullulan (CHP), dextran (CHD) and mannan (CHM) effectively coat the liposomal surface. Partition of the hydrophobized polysaccharide-coated liposomes in an aqueous two-phase system (PEO (top)/pullulan (bottom) or PEO (top)/dextran (bottom)) was investigated (PEO = poly(ethylene oxide)). Conventional liposomes without a polysaccharide coat mostly locate at the interface between the two polymer phases. The polysaccharide-coated liposomes, on the other hand, were partly partitioned to the bottom polysaccharide phase depending on the structure of the hydrophobized polysaccharide on the liposomal surface. The affinity between the polysaccharide on the liposomal surface and that in the bulk bottom phase controls the efficiency of partition. The sequence of interaction strength between the two carbohydrates as the following: for the PEO/dextran two-phase system, dextran_(liposome)-dextran_(bulk) > mannan_(liposome)-dextran_(bulk) > pullulan_(liposome)-dextran_(bulk); while for the PEO/pullulan system, the sequence of interaction strength was pullulan_(liposome)-pullulan_(bulk) > dextran_(liposome)-pullulan_(bulk) ≈ mannan_(liposome)-pullulan_(bulk).     

Seroepidemiology of hepatitis C virus infection in Japan and HCV infection in haemodialysis patients

Abstract: Since January 1990, Japanese Red Cross Blood Centres have introduced hepatitis C virus screening with a first-generation ELISA. From April to December 1992, approximately 0.98% among 10905 489 blood donations screened by a second-generation assay were anti-HCV-positive in all Japan. Seropositivity of anti-HCV increased with the age and serum transminase value in both sexes. In blood donors having a history of transfusion, the anti-HCV reactive rate was 7.4%. The results of the study made by the Japanese Red Cross Non-A, Non-B Hepatitis Research Group show the effectiveness of implementation of HCV screening to prevent posttransfusion hepatitis. Consecutive haemodialysis patients with chronic renal failure are at risk for inflection by a variety of blood-borne agents transmitted within dialysis units. Because of their immunocompromised state, they frequently also have an unusual susceptibility to a variety of nosocomial infections, such as HBV, and HTLV-I. We tested the prevalence of anti-HCV in 1423 (848 males and 575 females) haemodialiysis patients from 18 hospitals in Kumamoto Prefecture, Japan using the Orhto first generation anti- HCV screening assay. There were 316 patients (22.2%) positive for HCV antibodies. The second-generation test was positive in most haemodialysis patients who were eractive to the firs-generation assay. The prevalence of HCV infection increased with the duration of haemodialysis, yet there was a high frequency of HCV seropositivity even wihtout blood transfusion. Acquisition of HCV in dialysis patients could be explained by HCV seropositivity even without blood (all haemodialysis are done with disposable kits, and needles), by secondary HCV infection after the immunodeficiency of haemodialysis, or by HCV infection of the kidney or glomerular deposition of immune HCV/anti-HCV complexes leading to chronic renal failure (as with HBV infection of the liver and kidney).     

Induction of mitochondrial migration in the slime mold Physarum polycephalum

Mitochondrial migration in a microplasmodium of Physarum polycephalumwas studied by litgh and electron microscopy. The mitochondriawere dispersed evenly in the microplasmodium of Physarum polycephalumin shaken cultures but when the microplasmodia were left unshakenin a liquid culture for more than 3 hr, the mitochondria migratedtoward the peripheral area and came into contact with an semi-electrontransparent layer beneath the cell membrane. Once the peripherallocalization of mitochondria was established in unshaken culture,subsequent reversal to the shaken cultures induced a reversion.These results suggest that mitochondrial migration is reversiblyindicated by culture condition. (Received June 19, 1978; )     

Suppression of lipid peroxidation by {beta}-carotene in illuminated chloroplast fragments: Evidence for {beta}-carotene as a quencher of singlet molecular oxygen in chloroplasts

The effect of ß-carotene on light-induced lipid peroxidationwas examined in heptane-extracted chloroplasts. Lipid peroxidationwas suppressed by 50% when the extracted chloroplasts were reconstitutedwith ß-carotene. However, ß-carotene addedto unextracted chloroplasts did not affect the lipid peroxidation.As the molal ratio of ß-carotene to chlorophyll duringthe reconstitution increased, the rate of the lipid peroxidationdecreased but became independent of the molal ratio above thevalue of 0.3. The results led to the conclusion that ß-carotenein thylakoid membranes functions as an efficient quencher ofsinglet molecular oxygen which induces the lipid peroxidation. (Received April 20, 1978; )