Distribution and characterization of anandamide amidohydrolase in mouse brain and liver

Anandamide (N-Arachidonoylethanolamine) amidohydrolase catalyzing hydrolysis of anandamide was characterized in mice. The enzymatic activity was highest in the liver, followed by the brain and testis. Negligible activity was found in heart, lung and spleen. The activity in brain and liver was mainly localized in the microsomal fractions. Kinetic experiments demonstrated that Km (microM) and Vmax (nmol/min/mg protein) for the brain microsomes were 9.3 and 2.58, respectively, while those for the hepatic microsomes were 180 and 18.9, respectively. The activity in the microsomes from the liver and brain was markedly inhibited by Cu2+, Hg2+, Se4+, phenylmethylsulfonylfluoride and sodium dodecylsulfate. Brain but not hepatic microsomal enzyme activity was inhibited by delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Kinetic parameters demonstrated that the inhibition by the cannabinoids was competitive in nature. Relatively high distribution of the enzyme activity in brain suggests an importance of the enzyme in the central nervous system to regulate the neuromodulatory fatty-acid amides.     

CD7, HLA-DR, CD38 positive acute undifferentiated leukemia with subcutaneous tumor and thymoma

A case of acute undifferentiated leukemia (AUL), accompanied by subcutaneous tumor and thymoma is reported. The analysis of immunophenotype showed that the leukemic blasts were positive for CD7, HLA-DR, CD38 and CD34 in 17.5% but negative results were obtained for other lymphoid and myeloid antigens. The leukemic blasts had a rearranged immunoglobulin heavy chain (IgH) gene and T cell receptor delta (TCR-delta) chain gene chromosomal abnormality, 47, XY, +8, t(13; 17) (q12; q21), -17, +M was observed. In general, the CR rate is low and prognosis is poor in patients with AUL. In our case, CR was not achieved by the therapy with JALSG-ALL87 protocol, but was achieved by subsequent treatment with high dose ara-C therapy and combination chemotherapy including intermediate-dose ara-C, mitoxantrone, etoposide and prednisolone.     

Formation of acrylamide in a processed food model system, and examination of inhibitory conditions

Acrylamide (AAm) is formed from asparagine (Asn) and reducing sugar during cooking of foods at high temperature. We examined the formation of AAm in a model system using a glass fiber filter paper, and looked for suitable conditions for inhibiting AAm formation. In frying, the formation rate was about 10 times that in a moistureless oven. Increase of frying temperature and frying time increased AAm formation when the residual moisture was 5% or less. AAm increased with increasing amount of glucose (Glc) addition up to 1:1 with respect to Asn, but then decreased. On the other hand, in the case of fructose, as the amount added was increased, AAm increased accordingly. The AAm formation rate with respect to Asn increased when valine (Val) was co-present in a Glc and Asn reaction system. Cysteine and lysine inhibited the AAm formation rate. Pathways for the formation of AAm are proposed.     

Isolation and characterization of a parvovirus of rabbits

The isolation and characterization of a new virus from rabbit stool are described. The virus replicated in rabbit kidney cell cultures and agglutinated human group O erythrocytes at 4 degrees C. It was stable at acid pH and resistant to chloroform and heat treatment. The growth of the virus was inhibited by 5-iodo-2-deoxyuridine, and virions were stained red with acridine orange, suggesting that they contain single-stranded deoxyribonucleic acid. The density of virions was 1.41 to 1.44 g/ml in CsCl, and the sedimentation value was 137S in sucrose at 4 degrees C. The infectious particles had cubic symmetry and were 27 to 28 nm in diameter by electron microscopy. By these properties this virus can be classified as a member of the parvovirus group. Antibody response was demonstrated in the rabbit from which this virus was recovered. A number of rabbits from a commercial source were found to contain hemagglutination-inhibiting antibody to this virus.     

Optical Nanoscale Pool‐on‐Surface Design for Control Sensing Recognition of Multiple Cations

General design of optical chemical nanosensors is needed to develop efficient sensing systems with high flexibility, and low capital cost for control recognition of toxic analytes. Here, we designed optical chemical nanosensors for simple, high‐speed detection of multiple toxic metal ions. The systematic design of the nanosensors was based on densely patterned chromophores with intrinsic mobility, namely, “building‐blocks” onto three‐dimensional (3D) nanoscale structures. The ability to precisely modify the nanoscale pore surfaces by using a broad range of chromophores that have different molecular sizes and characteristics enables detection of multiple toxic ions. A key feature of this building‐blocks design strategy is that the surface functionality and good adsorption characteristics of the fabricated nanosensor arrays enabled the development of “pool‐on‐surface” sensing systems in which high flux of the metal analytes across the probe molecules was achieved without significant kinetic hindrance. Such a sensing design enabled sensitive recognition of metal ions up to sub‐picomolar detection limits (～10^?11 mol dm^?3), for first time, with rapid response time within few seconds. Moreover, because these sensing pools exhibited long‐term stability, reversibility and selectivity in detecting most pollutant cations, for example, Cr(VI), Pb(II), Co(II), and Pd(II) ions, they are practical and inexpensive. The key result in our study is that the pool‐on‐surface design for optical nanosensors exhibited significant ion‐selective ability of these target ions from environmental samples and waste disposals.     

Structure-Based Design,Synthesis, and Biological Evaluation of Imidazo[4,5-b]Pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 2

We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one ( 1 ). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide ( 25 ) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors.     

A Metal-Free,Disulfide Oxidized Form of Superoxide Dismutase 1 as a Primary Misfolded Species with Prion-Like Properties in the Extracellular Environments Surrounding Motor Neuron-Like Cells

Superoxide dismutase 1 (SOD1) is a metalloenzyme with high structural stability, but a lack of Cu and Zn ions decreases its stability and enhances the likelihood of misfolding, which is a pathological hallmark of amyotrophic lateral sclerosis (ALS). A growing body of evidence has demonstrated that misfolded SOD1 has prion-like properties such as transmissibility between cells and intracellular propagation of misfolding of natively folded SOD1. Recently, we found that SOD1 is misfolded in the cerebrospinal fluid of sporadic ALS patients, providing a route by which misfolded SOD1 spreads via the extracellular environment of the central nervous system. Unlike intracellular misfolded SOD1, it is unknown which extracellular misfolded species is most relevant to prion-like properties. Here, we determined a conformational feature of extracellular misfolded SOD1 that is linked to prion-like properties. Using culture media from motor neuron-like cells, NSC-34, extracellular misfolded wild-type, and four ALS-causing SOD1 mutants were characterized as a metal-free, disulfide oxidized form of SOD1 (apo-SOD1^S-S). Extracellular misfolded apo-SOD1^S-S exhibited cell-to-cell transmission from the culture medium to recipient cells as well as intracellular propagation of SOD1 misfolding in recipient cells. Furthermore, culture medium containing misfolded apo-SOD1^S-S exerted cytotoxicity to motor neuron-like cells, which was blocked by removal of misfolded apo-SOD1^S-S from the medium. We conclude that misfolded apo-SOD1^S-S is a primary extracellular species that is linked to prion-like properties.     

Successful high-dose chemotherapy combined with autologous bone marrow transplantation in a case of refractory follicular lymphoma

This study investigated the association between two demographic and two psychological variables and treatment retention for 65 perinatal substance abusers. Subjects who lived in the community while attending day treatment were 6.125 times more likely to drp out than subjects who lived in a program-operated shelter (p < .0001). An interaction was found for pregnancy status and antisocial personality disorder (p < .0478). Subjects who were both pregnant and antisocial were 4.876 times more likely to remain in treatment than those who were neither pregnant nor antisocial. Degree of "treatment resistance," measured by the MMPI Negative Treatment Indicators (TRT) Scale, did not predict dropout. These findings indicate that supportive housing can play an important role in preventing dropout for perinatal substance abusers. Additionally, pregnancy may present a "window" of opportunity for treating a hard to reach population, drug abusing women with comorbid ASP.