前立腺癌に対するPepleomycin(Bleomycin Derivative, NK-631)の効果

未治療の前立腺腺癌2症例に本剤を投与し，その効果を検討した。症例1： 71歳， 排尿困難，左大腿部痛を主訴として1978年6月15日当科受診。前立腺は超鶏卵大，石様硬，表面不整，骨盤へ浸潤。左ソケイ部にくるみ大の硬いリンパ腺を触知。骨シンチで多数の転移を認めた。 前立腺の針生検組織像は分化型腺癌であった。pepleomycin 200 mg (1回10mg，静注， 週3回)の投与により前立腺癌，左ソケイ部リンパ腺の著明な縮小がみられ，血清酸ホスファターゼ値が治療前6.5K.A.U.から9.5K.A.U まで低下した。治療終了後の生検組織像は癌細胞の変性，壊死組織の線維化が目立った。　　症例2: 74歳，排尿困難で1978年8月19日当科受診。前立腺は鶏卵大，硬，周囲に浸潤。骨シンチで転移巣が多数あり，前立腺生検組織像は未分化型腺癌であった。 pepleomycin投与で自覚症状は症例1ほどの改善はみられず，前立腺癌そのものもあまり縮小しなかったが，残尿は80mlから10mlへ減少した。治療後の前立腺生検所見でも癌細胞の空胞化が著明に認められた。なお副作用としては症例1では著明な皮膚変化がみられたが，症例2でぎ軽度の口内炎を認めるにとどまった。NK 631 投与前後で血中FSH，LH，testosteroneを測定したところ，両症例ともに投与終了後FSH，LH，t estosterone値は投与前値の約1/2となっていた (Table 2)。 つまり， NK 631 の抗腫瘍作用はDNA合成抑制によるということになっているが，前立腺癌に対する抗腫聖書効果はNK631 の下重体抑制による睾丸のLeydig cellよりのandrogen分泌抑制も関与している可能性があることが示唆された。本剤の下垂体抑制効果については今後検討されるべき課題であると考える。Since the new bleomycin derivative-pepleomycin was reported to be effective for experimentally induced adenocarcinoma of stomach in rats, it was administered in two cases of prostatic cancer. Satisfactory response was obtained in well differentiated carcinoma, meanwhile only histological effect was observed in undifferentiated one. It seems that the effect of pepleomycin on prostatic cancer was brought about by the suppression of DNA synthesis of tumor and also of pituitary function resulting in decreased androgen secretion from Leydig cells

Comparative Description of the Expression Profile of Interferon-Stimulated Genes in Multiple Cell Lineages Targeted by HIV-1 Infection

Immediately after viral infections, innate immune sensors recognize viruses and lead to the production of type I interferon (IFN-I). IFN-I upregulates various genes, referred to as IFN-stimulated genes (ISGs), and some ISGs inhibit viral replication. HIV-1, the causative agent of AIDS, mainly infects CD4+ T cells and macrophages and triggers the IFN-I-mediated signaling cascade. Certain ISGs are subsequently upregulated by IFN-I stimulus and potently suppress HIV-1 replication. HIV-1 cell biology has shed light on the molecular understanding of the IFN-I production triggered by HIV-1 infection and the antiviral roles of ISGs. However, the differences in the gene expression patterns following IFN-I stimulus among HIV-1 target cell types are poorly understood. In this study, we hypothesize that the expression profiles of ISGs are different among HIV-1 target cells and address this question by utilizing public transcriptome datasets and bioinformatic techniques. We focus on three cell types intrinsically targeted by HIV-1, including CD4+ T cells, monocytes, and macrophages, and comprehensively compare the expression patterns of ISGs among these cell types. Furthermore, we use the datasets of the differentially expressed genes by HIV-1 infection and the evolutionarily conserved ISGs in mammals and perform comparative transcriptome analyses. We defined 104 ‘common ISGs’ that were upregulated by IFN-I stimulus in CD4+ T cells, monocytes, and macrophages. The ISG expression patterns were different among these three cell types, and intriguingly, both the numbers and the magnitudes of upregulated ISGs by IFN-I stimulus were greatest in macrophages. We also found that the upregulated genes by HIV-1 infection included most ‘common ISGs.’ Moreover, we determined that the ‘common ISGs,’ particularly those with antiviral activity, were evolutionarily conserved in mammals. To our knowledge, this study is the first investigation to comprehensively describe (i) the different expression patterns of ISGs among HIV-1 target cells, (ii) the overlap in the genes modulated by IFN-I stimulus and HIV-1 infection and (iii) the evolutionary conservation in mammals of the antiviral ISGs that are expressed in HIV-1 target cells. Our results will be useful for deeply understanding the relationship of the effect of IFN-I and the modulated gene expression by HIV-1 infection

Meteor Radar Study of Ionospheric Wind at Kyoto

This paper describes the results of meteor radar observations which have been carried out at Kyoto University since December, 1977. The radar, a coherent pulse doppler radar with a transmitting frequency of 31.57 MHz and a nominal peak power of 10 kW, is able to detect wind fields at meteor regions of 80-110 km. The solar semidiurnal tide generally dominates the wind oscillations at these heights, while a diurnal tide of comparable magnitude reveals itself in a less regular manner. Some anomalies in the amplitude and phase characteristics of the tides are shown, which might be related to a possible interaction with winds and waves, or to some disturbed conditions in the earth's atmosphere. Also planetary scale waves such as quasi-2-day oscillations and resonantly magnified gravity-mode waves have also been found there. Hence, the meteor radar, together with its cooperation with other observations, will helps us understand the dynamical process of atmospheric waves on a global scale

Plasmon-enhanced molecular fluorescence from an organic film in a tunnel junction

Scanning tunneling microscope (STM)-excited molecular fluorescence from H2TBP porphyrin (H2TBPP) thin films on Au (111), Ag, highly oriented pyrolytic graphite (HOPG), and indium tin oxide (ITO) surfaces has been investigated in air. Molecular fluorescence was observed from the H2TBPP films on Au and Ag, but it was extremely weak or undetectable from films on HOPG and ITO. The maximum intensity of molecular fluorescence from H2TBPP/Ag is at least 100 times stronger than that from H2TBPP/HOPG. Strong enhancement of molecular excitation by substrate surface plasmons is suggested for the STM-excited molecular fluorescence from H2TBPP only on the noble metal substrates

Plasmon-enhanced molecular fluorescence from an organic film in a tunnel junction

Scanning tunneling microscope (STM)-excited molecular fluorescence from H2TBP porphyrin (H2TBPP) thin films on Au (111), Ag, highly oriented pyrolytic graphite (HOPG), and indium tin oxide (ITO) surfaces has been investigated in air. Molecular fluorescence was observed from the H2TBPP films on Au and Ag, but it was extremely weak or undetectable from films on HOPG and ITO. The maximum intensity of molecular fluorescence from H2TBPP/Ag is at least 100 times stronger than that from H2TBPP/HOPG. Strong enhancement of molecular excitation by substrate surface plasmons is suggested for the STM-excited molecular fluorescence from H2TBPP only on the noble metal substrates

Oligoene and cyanine features of tetracyano quinoidal oligothiophenes

This paper interprets a palette of spectroscopic data on tetracyano thienoquinoidal molecules of different sizes oriented towards the elucidation of their electronic behavior and other aspects of interest in materials chemistry. It also provides a contextualization of these properties between those of even oligoenes (carotene-like) and those of odd cyanines as a function of the reduction state. A complete UV-Vis-NIR electronic absorption, fluorescence emission and infrared spectroscopic study in part helped by quantum chemical calculations in the framework of the DFT theory has been carried out. The study encompasses the neutral and charged states. The optical properties of these compounds in the neutral state are controlled by the competition of bright (electric dipole–dipole allowed) and dark (electric dipole–dipole forbidden) singlet excited states. In the anionic state, the trimeric compounds disclose behaviors compatible with being either charge localized or delocalized mixed valence systems. Interestingly, we show the π-dimerization of a radical anion of a thienoquinoidal compound forming a π-dimer dianion as a manifestation of the delocalization of the charge in the charged monomer. The hexamer compound in the neutral state discloses incipient diradical character which permits the detection of a NIR emission band from the dark state at energies well below 1 eV. As thiophene benzo-annulation minimizes the diradical character, it forces the confinement of the charge in the vicinity of the terminal dicyanomethylene groups in the dianion. The oxidized species of the compounds have been also analyzed as models of charge localization states. The competition between doublet and quartet high spin states in the radical cations has been explored with the objective of visualizing potential molecules able to produce SOMO–HOMO energy inversion. (...)The authors thank the Spanish Ministry of Science, Innovation and Universities MCIU (PGC2018-098533-B-100 and RED2018-102815-T), and the Junta de Andalucı´a, Spain (UMA18FEDERJA057). We also thank the Research Central Services (SCAI) of the University of Málaga

Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo

For eradication of HIV-1 infection, it is important to elucidate the detailed features and heterogeneity of HIV-1-infected cells in vivo. To reveal multiple characteristics of HIV-1-producing cells in vivo, we use a hematopoietic-stem-cell-transplanted humanized mouse model infected with GFP-encoding replication-competent HIV-1. We perform multiomics experiments using recently developed technology to identify the features of HIV-1-infected cells. Genome-wide HIV-1 integration-site analysis reveals that productive HIV-1 infection tends to occur in cells with viral integration into transcriptionally active genomic regions. Bulk transcriptome analysis reveals that a high level of viral mRNA is transcribed in HIV-1-infected cells. Moreover, single-cell transcriptome analysis shows the heterogeneity of HIV-1-infected cells, including CXCL13high cells and a subpopulation with low expression of interferon-stimulated genes, which can contribute to efficient viral spread in vivo. Our findings describe multiple characteristics of HIV-1-producing cells in vivo, which could provide clues for the development of an HIV-1 cure

Extracellular cyclophilin A possesses chemotaxic activity in cattle

International audienceCyclophilin A (CyPA) was originally discovered in bovine thymocytes as a cytosolic binding protein of the immunosuppressive drug cyclosporine A. Recent studies have revealed that in mice and humans, CyPA is secreted from cells in injured or infected tissues and plays a role in recruiting inflammatory cells in those tissues. Here we found that in cattle abundant level of extracellular CyPA was observed in tissues with inflammation. To aid in investigating the role of extracellular CyPA in cattle, we generated recombinant bovine CyPA (rbCyPA) and tested its biological activity as an inflammatory mediator. When bovine peripheral blood cells were treated with rbCyPA in vitro, we observed that rbCyPA reacts with the membranous surface of granulocytes, monocytes and lymphocytes. Chemotaxis analysis showed that the granulocytes migrate toward rbCyPA and the migration is inhibited by pre-treatment with an anti-bovine CyPA antibody. These results indicate that, as for mice and humans, extracellular CyPA possesses chemotactic activity to recruit inflammatory cells (e.g., granulocytes) in cattle, and could thus be a potential therapeutic target for the treatment of inflammation

Comprehensive Investigation on the Interplay between Feline APOBEC3Z3 Proteins and Feline Immunodeficiency Virus Vif Proteins

As the hosts of lentiviruses, almost 40 species of felids (family Felidae) are distributed around the world, and more than 20 feline species test positive for feline immunodeficiency virus (FIV), a lineage of lentiviruses. These observations suggest that FIVs globally infected a variety of feline species through multiple cross-species transmission events during a million-year history. Cellular restriction factors potentially inhibit lentiviral replication and limit cross-species lentiviral transmission, and cellular APOBEC3 deaminases are known as a potent restriction factor. In contrast, lentiviruses have evolutionary-acquired viral infectivity factor (Vif) to neutralize the APOBEC3-mediated antiviral effect. Because the APOBEC3-Vif interaction is strictly specific for viruses and their hosts, a comprehensive investigation focusing on Vif-APOBEC3 interplay can provide clues that will elucidate the roles of this virus-host interplay on cross-species transmission of lentiviruses. Here, we performed a comprehensive investigation with 144 patterns of a round robin test using 18 feline APOBEC3Z3 genes, an antiviral APOBEC3 gene in felid, and 8 FIV Vifs and derived a matrix showing the interplay between feline APOBEC3Z3 and FIV Vif. We particularly focused on the interplay between the APOBEC3Z3 of three felids (domestic cat, ocelot, and Asian golden cat) and an FIV Vif (strain Petaluma), and revealed that residues 65 and 66 of the APOBEC3Z3 protein of multiple felids are responsible for the counteraction triggered by FIV Petaluma Vif. Altogether, our findings can be a clue to elucidate not only the scenarios of the cross-species transmissions of FIVs in felids but also the evolutionary interaction between mammals and lentiviruses