Specific antigen of tumor cell transformed by DNA extracted from SV-40 virus

In the immunofluorescent study it has been revealed that rabbit sera immunized with transformed cells induced by SV-40 DNA, produce circulating antibody capable of re:lcting with intranuclear antigens synthesized by SV-40 complyte virus transforming process, In addition, the result confirmed that SV-40 DNA replicates DNA-containing viruses in the host cell and that also the genome coding for the synthesis of SV-40 tumor antigen is resposible for viral DNA.</p

Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6.

We investigated the diagnostic significance of IL-6 for lymph node metastasis and/or hepatic metastasis from colorectal cancer in 65 patients and evaluated the contributions of 8 factors (IL-6, HGF, IL-1beta, TNF-alpha, TGF-beta1, ELAM-1, ICAM-1, VCAM-1) toward Dukes.s classification of 53 patients. We also examined IL-6 expression in tumor tissue. From the receiver operating characteristic (ROC) curve analysis, an optimal cutoff value of 5.8 pg/ml was determined to classify lymph node and/or hepatic metastasis, and that of 6.3 pg/ml was determined to classify hepatic metastasis. These values indicated sensitivities of 55.0% and 71.4%, and specifi cities of 100% and 88.6%, respectively. IL-6, HGF, and ELAM-1 were very useful for distinguishing among Dukes.s A/B group, C group, and D group. In all cases with high IL-6 values (more than 25.0 pg/ml), immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. IL-6 is strongly suspected to be involved in lymph node and/or hepatic metastasis by promoting it through HGF, and serum IL-6 value (pg/ml) would be useful diagnostically to estimate whether or not there is a high risk of lymph node and/or hepatic metastasis

Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein–deficient Mice

The nerve axon is a good model system for studying the molecular mechanism of organelle transport in cells. Recently, the new kinesin superfamily proteins (KIFs) have been identified as candidate motor proteins involved in organelle transport. Among them KIF1A, a murine homologue of unc-104 gene of Caenorhabditis elegans, is a unique monomeric neuron– specific microtubule plus end–directed motor and has been proposed as a transporter of synaptic vesicle precursors (Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, and N. Hirokawa. 1995. Cell. 81:769–780). To elucidate the function of KIF1A in vivo, we disrupted the KIF1A gene in mice. KIF1A mutants died mostly within a day after birth showing motor and sensory disturbances. In the nervous systems of these mutants, the transport of synaptic vesicle precursors showed a specific and significant decrease. Consequently, synaptic vesicle density decreased dramatically, and clusters of clear small vesicles accumulated in the cell bodies. Furthermore, marked neuronal degeneration and death occurred both in KIF1A mutant mice and in cultures of mutant neurons. The neuronal death in cultures was blocked by coculture with wild-type neurons or exposure to a low concentration of glutamate. These results in cultures suggested that the mutant neurons might not sufficiently receive afferent stimulation, such as neuronal contacts or neurotransmission, resulting in cell death. Thus, our results demonstrate that KIF1A transports a synaptic vesicle precursor and that KIF1A-mediated axonal transport plays a critical role in viability, maintenance, and function of neurons, particularly mature neurons

Sorption-desorption column tests to evaluate the attenuation layer using soil amended with a stabilising agent

Sorption-desorption column tests using acrylic columns (ϕ 5 cm × h 10 cm) were employed to evaluate the sorption performance of an attenuation layer against geogenic contamination. The attenuation layer material was silica sand amended with 1, 5, or 10% of a stabilising agent. The main component of the agent was magnesium oxide. The sorption behaviour of the materials was determined by a fluoride solution (C₀ = 80 mg/L F-), while the desorption behaviour was determined by distilled water. Breakthroughs (C/C₀ > 0.05) occurred after approximately 1, 20, and 50 PVF for stabilising agent contents of 1, 5, and 10%, respectively. The one-dimensional advection-dispersion equation modelled the breakthrough curves obtained from the tests. The predictions gave unrealistic estimates, especially for the breakthrough point where C/C₀ = 0.05. For the 1% agent content, approximately 20% of the sorbed mass, Ss, was desorbed, but the percentage of desorbed mass, Sd, was much smaller for the higher agent contents. The difference between the sorbed and desorbed masses was defined as the immobilised fraction, Ss - Sd. For the 5% agent content, Ss - Sd = 4.0 mg/g. The results suggest that when silica sand is amended with magnesium oxide as an agent, the mixture can immobilise the fluoride in the attenuation layer

Non-decoupling effects in supersymmetric Higgs sectors

A wide class of Higgs sectors is investigated in supersymmetric standard models. When the lightest Higgs boson (h) looks the standard model one, the mass (m_h) and the triple Higgs boson coupling (the hhh coupling) are evaluated at the one-loop level in each model. While m_h is at most 120-130 GeV in the minimal supersymmetric standard model (MSSM), that in models with an additional neutral singlet or triplet fields can be much larger. The hhh coupling can also be sensitive to the models: while in the MSSM the deviation from the standard model prediction is not significant, that can be 30-60 % in some models such as the MSSM with the additional singlet or with extra doublets and charged singlets. These models are motivated by specific physics problems like the mu-problem, the neutrino mass, the scalar dark matter and so on. Therefore, when h is found at the CERN Large Hadron Collider, we can classify supersymmetric models by measuring m_h and the hhh coupling accurately at future collider experiments.Comment: 16pages, 6figures. To be published in Physics Letters

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (&amp;lt;65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency &amp;lt; 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

EGFR Down-regulation Predicts anti-EGFR Response

ABC, antibody-binding capacity; ADCC, antibody-dependent cellular cytotoxicity; ATCC, American Type Culture Collection; BSA, bovine serum albumin; CR, complete response; CRC, colorectal cancer; CT, computed tomography; ECACC, European Collection of Authenticated Cell Cultures; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ETS, early tumor shrinkage; FBS, fetal bovine serum; FISH, fluorescent in situ hybridization; HRP, horseradish peroxidase; HSRRB, Health Science Research Resources Bank; IHC, immunohistochemistry; MesNa, Mercaptoethanesulfonic acid sodium; mCRC, metastatic colorectal cancer; mAb, monoclonal antibody; mAbs, monoclonal antibodies; PARP, poly (ADP-ribose) polymerase; PBS, phosphate buffered saline; PD, progressive disease; p-ERK, phosphorylated ERK; PNA-LNA, peptide nucleic acid-locked nucleic acid; PR, partial response; PVDF, polyvinylidene difluoride; RECIST, Response Evaluation Criteria in Solid Tumors; RIKEN BRC, RIKEN BioResource Center; SD, stable disease; SDS, sodium dodecyl sulfate; SDS-PAGE, SDS-polyamide gel electrophoresis; TBS-T, Tris-buffered saline with 0.1% Tween; TGF-α, transforming growth factor-α

Assessment of Coronary atherosclerosis in patients with familial hypercholesterolemia by coronary computed tomography angiography

The aims of this study were (1) to determine whether the accumulation of coronary plaque burden assessed with coronary computed tomography angiography (CCTA) can predict future events and (2) to estimate the onset and progression of coronary atherosclerosis in patients with familial hypercholesterolemia (FH). Consecutive 101 Japanese patients with heterozygous FH (men= 52, mean age 56 ± 16years, mean low-density lipoprotein cholesterol 264 ± 58mg/dl) who underwent 64-detector row CCTA without known coronary artery disease were retrospectively evaluated by assigning a score (0 to 5) to each of 17 coronary artery segments according to the Society of Cardiovascular Computed Tomography guidelines. Those scores were summed and subsequently natural log transformed. The periods to major adverse cardiac events (MACE) were estimated using multivariable Cox proportional hazards models. During the follow-up period (median 941days), 21 MACE had occurred. Receiver operating characteristic curve analyses identified a plaque burden score of 3.35 (raw score 28.5) as the optimal cutoff for predicting a worse prognosis. Multivariate Coxregression analysis identified the presence of a plaque score ≥3.35 as a significant independent predictor of MACE (hazard ratio= 3.65; 95% confidence interval 1.32 to 25.84, p<0.05). The regression equations were Y= 0.68. X- 15.6 (r= 0.54, p <0.05) in male and Y= 0.74. X- 24.8 (r= 0.69, p <0.05) in female patients with heterozygous FH. In conclusion, coronary plaque burden identified in a noninvasive, quantitative manner was significantly associated with future coronary events in Japanese patients with heterozygous FH and that coronary atherosclerosis may start to develop, on average, at age 23 and 34years in male and female patients with heterozygous FH, respectively