NF‐IL6 is a nuclear factor that specifically binds to an IL1‐responsive element in the IL‐6 gene. In this study the gene encoding NF‐IL6 has been cloned by direct screening of a lambda gt11 library using NF‐IL6 binding sequence as a ligand. The full‐length cDNA encoded a 345 amino acid protein with a potential leucine zipper structure and revealed a high degree of homology to a liver‐specific transcriptional factor, C/EBP, at the C‐terminal portion. The bacterial fusion protein bound to the CCAAT homology as well as the viral enhancer core sequences as in the case of C/EBP. Recombinant NF‐IL6 activated the human IL‐6 promoter in a sequence‐specific manner. Southern blot analysis demonstrated the high‐degree conservation of the NF‐IL6 gene through evolution and the existence of several other related genes sharing the DNA‐binding domain. NF‐IL6 mRNA was normally not expressed, but induced by the stimulation with either LPS, IL‐1 or IL‐6. Interestingly, NF‐IL6 was shown to bind to the regulatory regions for various acute‐phase protein genes and several other cytokine genes such as TNF, IL‐8 and G‐CSF, implying that NF‐IL6 has a role in regulation not only for the IL‐6 gene but also for several other genes involved in acute‐phase reaction, inflammation and hemopoiesis.

Human B cell stimulatory factor 2 (BSF-2) was originally characterized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (Mr) 26,000 similar or identical to interferon beta 2, hybridoma plasmacytoma growth factor and hepatocyte stimulating factor. IL-6 has been proposed as a name for this molecule. It is now known that BSF-2 has a wide variety of biological functions and that its target cells are not restricted to normal B cells. Responses are also seen in T cells, plasmacytomas, hepatocytes, haematopoietic stem cells, fibroblasts and rat phoeochromocytoma, PC12 (Satoh, T. et al., manuscript in preparation). Of particular interest to this report is that human BSF-2 is a potent growth factor for murine plasmacytomas and hybridomas. This observation suggested to us that constitutive expression of BSF-2 or its receptor could be responsible for the generation of human myelomas. In this study we report that myeloma cells freshly isolated from patients produce BSF-2 and express its receptors. Moreover, anti-BSF-2 antibody inhibits the in vitro growth of myeloma cells. This is direct evidence that an autocrine loop is operating in oncogenesis of human myelomas.

Small-angle X-ray scattering (SAXS) is used to demonstrate the presence of density fluctuations in ambient water on a physical length-scale of Ϸ1 nm; this is retained with decreasing temperature while the magnitude is enhanced. In contrast, the magnitude of fluctuations in a normal liquid, such as CCl4, exhibits no enhancement with decreasing temperature, as is also the case for water from molecular dynamics simulations under ambient conditions. Based on X-ray emission spectroscopy and X-ray Raman scattering data we propose that the density difference contrast in SAXS is due to fluctuations between tetrahedral-like and hydrogen-bond distorted structures related to, respectively, low and high density water. We combine our experimental observations to propose a model of water as a temperature-dependent, fluctuating equilibrium between the two types of local structures driven by incommensurate requirements for minimizing enthalpy (strong near-tetrahedral hydrogen-bonds) and maximizing entropy (nondirectional H-bonds and disorder). The present results provide experimental evidence that the extreme differences anticipated in the hydrogen-bonding environment in the deeply supercooled regime surprisingly remain in bulk water even at conditions ranging from ambient up to close to the boiling point.density fluctuations ͉ liquid-liquid hypothesis ͉ small angle X-ray scattering ͉ water structure ͉ X-ray spectroscopy L iquid water shows many anomalies in its thermodynamic properties such as compressibility, density variation and heat capacity (1-4). In the low-temperature regime, below the freezing point, these properties deviate strongly from normal and theories, related to a liquid-liquid phase transition between high and low density water, have been proposed to account for these anomalies (5). Although the anomalies are extreme in the supercooled region they are also present at ambient conditions where most of waters' physical, chemical and biological processes of importance occur. In contrast, water at ambient conditions has traditionally been considered as a homogeneous distribution of near-tetrahedral hydrogen-bonded (H-bonded) structures with thermal fluctuations increasing with temperature. This picture has been challenged by recent studies based on X-ray Raman (XRS) and conventional X-ray absorption spectroscopy (XAS) (6), and X-ray emission spectroscopy (XES) (7), suggesting two distinct local structures with tetrahedral as a minority and a highly hydrogen-bond (H-bond) distorted asymmetrical as the majority. In particular the proposed predominant asymmetrical structure has caused intense debate in the last years (see refs. 7 and 8 for detailed discussion).SAXS and small-angle neutron scattering (SANS) provide the most direct probes of density variations or fluctuations on large length scales in a liquid. Through an enhancement of the structure factor at low momentum transfer, Q, small deviations from the average electron density at different length scales can be reliably identified (9). Previous SAXS studies of w...

Japanese mortality due to colorectal cancer is on the rise, surpassing 49,000 in 2015. Many new treatment methods have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2016 for the treatment of colorectal cancer (JSCCR Guidelines 2016) were prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines were prepared by consensus reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches, and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2016.

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