In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen,N,N-[11C]dimethyltryptamine

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [¹¹C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [¹¹C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [¹¹C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors.     

Flow karyotypes and chromosomal DNA contents of genus Triticum species and rye (Secale cereale)

The flow cytometry and chromosome imaging method were jointly used for analyzing genome content and chromosomal DNA content of hexaploid wheat (AABBDD), hexaploid triticale (AABBRR), tetraploid wheat (AABB), and AA, BB, DD genome donors and RR genome rye. Their genome sizes were 34.4 pg, 40.9 pg, 26.2 pg, 12.1 pg, 13.7 pg, 10.5 pg, and 16.9 pg, respectively. The 2C nuclear DNA content of BB genome donor with 13.7 pg was the highest value among the other genome donors, AA or DD. The genome content of tetraploid wheat, unlike hexaploid wheat or hexaploid triticale, was larger than the sum of the genomes of AA and BB genome donors. The DNA content of each chromosome ranged from 1.22 pg in DD genome donor to 2.61 pg in rye. Each chromosome peak was divided into three to four groups. Only one chromosome was included in the highest chromosomal DNA peak in hexaploid wheat, tetraploid wheat, DD genome donor and rye but two chromosomes in AA, BB genome donors, and hexaploid triticale. Correlation between 2C nuclear DNA content and chromosome density volume was the highest value compared with the other chromosomal parameters of chromosome area, or chromosome length.     

Characterization of certain hepatocyte-proliferating and/or protective factors induced by the sensitization of freezing-thawing hepatic tissue

Although tumor cryosurgery would be expected to produce beneficial immunological effects from the enhancement of anti-tumor activity, under certain conditions the tumor may become enlarged and metastases promoted due to increased immunosuppressive activity and a high zone tolerance. In the present study, we examined whether hepatocyteproliferating factors were produced by the inoculation of freezing-thawing hepatic tissue (FTHT). Serum obtained from rats inoculated with FTHT increased DNA synthesis, according to measurement by [³H]thymidine incorporation in primary cultured rat hepatocytes. This increase was dependent on the serum concentration, with serum obtained on day 14 after the inoculation being the most potent for hepatocyte proliferation. The sensitized serum promoted DNA synthesis nearly as much as serum obtained from a 70% hepatectomized rat, but slightly less than 10ng/ml hepatocyte growth factor. The sensitized serum also protected hepatocytes from carbon tetrachloride (CCI₄)-induced hepatotoxicity. Optical density measured by the 3-(4,5-dimethyl-thiazole-2-yl)-2,5-diphenyl tetrozolium bromide (MTT) cytotoxicity assay was increased, and the release of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in medium was decreased by treating hepatocytes damaged by CCI₄ with the sensitized serum. These results suggest that certain hepatocyte-proliferating and protective factors are induced in serum by the inoculation of freezing-thawing hepatic tissue, and that the sensitized serum may be useful in the treatment of liver failure.     

Model analysis of the contribution of atrial contraction to ventricular filling

We studied the contribution of atrial contraction to ventricular filling by modelling the right heart and the associated vasculature. Right atrial and ventricular contractions were represented by periodically varying volume elastances which are independent of loading conditions. The values of these elastances were experimentally determined. The systemic veins, the tricuspid valve and the pulmonary arteries were all represented by impedance networks. For these impedances we used as much experimentally obtained information as possible. The dynamic pressure and flow waveforms observed in the model under control conditions generally agreed with those reported in the literature. We therefore proceeded to analyze the effects of changing the time interval between atrial systole and ventricular systole, atrial contractility, heart rate, and blood inertance. There was an optimal atrial systole-ventricular systole interval of about 0.1 sec for ventricular filling. Stroke volume of the ventricle was enhanced by an increase in atrial contractility, a decrease in heart rate, and an increase in blood inertance. The effect of changing atrial compliance was found to be dependent on heart rate. Contribution of atrial contraction to ventricular filling was also found to be more significant during exercise than at rest.     

Vinyl polymerization by metal complexes, 14. Synthesis of 2-substituted and 2,4-disubstituted imidazole-copper(II) complexes as initiator systems for vinyl polymerization

A series of the copper(II) complexes of the type CuL₄X₂ (L: ligand, X: anion) was prepared with the following substituted imidazoles as ligands 2-ethyl- ( 1a ), 2-ethyl-4-methyl- ( 1b ), 2-phenyl- ( 1c ), 2-undecyl- ( 1d ), and 2-heptadecylimidazole ( 1e ). The structures of these complexes were confirmed by elemental analysis, reflection spectra of the crystals as well as IR-spectroscopy. Polymerization of acrylonitrile was tested in the presence of each imidazole-copper(II) complex in dimethyl sulfoxide solution.     

Functional monomers and polymers, 105. Synthesis of poly(β-alanine) from a new type of active amino acid ester

Active β-alanine esters having dipeptide groups, which are capable of forming hydrogen bonds between the side chains, were prepared in the form of hydrogen chloride salts. The polycondensation of these salts was studied in non-polar solvents, in the presence of triethylamine. In the case of the ester with β-alanyl-β-alanine as dipeptide moiety, the polycondensation proceeded smoothly in chloroform solution. To explain the characteristic feature of the polycondensation, an ordered aggregation of the ester molecules is assumed to play an important role. The ester with glycylglycine as dipeptide moiety, however, did not undergo a polycondensation.     

Directed differentiation of telencephalic precursors from embryonic stem cells

We demonstrate directed differentiation of telencephalic precursors from mouse embryonic stem (ES) cells using optimized serum-free suspension culture (SFEB culture). Treatment with Wnt and Nodal antagonists (Dkk1 and LeftyA) during the first 5 d of SFEB culture causes nearly selective neural differentiation in ES cells ( approximately 90%). In the presence of Dkk1, with or without LeftyA, SFEB induces efficient generation ( approximately 35%) of cells expressing telencephalic marker Bf1. Wnt3a treatment during the late culture period increases the pallial telencephalic population (Pax6(+) cells yield up to 75% of Bf1(+) cells), whereas Shh promotes basal telencephalic differentiation (into Nkx2.1(+) and/or Islet1/2(+) cells) at the cost of pallial telencephalic differentiation. Thus, in the absence of caudalizing signals, floating aggregates of ES cells generate naive telencephalic precursors that acquire subregional identities by responding to extracellular patterning signals.     

Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity

Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency.     

Vinyl polymerization by metal complexes, 30. On the initiation mechanism of vinyl polymerization by the system copper(II) chelate of poly(vinyl alcohol)/carbon tetrachloride: Spin trapping and gelation studies

The initiation mechanism of vinyl polymerization by a copper(II) chelate of poly(vinyl alcohol) was studied in aqueous solution in the presence of carbon tetrachloride, in order to determine the free radical species formed during the initiation step. Trichloromethyl radicals were ascertained to be the main initiation species, by spin trapping and gelation experiments. Differences in polymerization activity between methyl methacrylate and acrylonitrile are discussed.