Detection of oncogene rearrangements in human non-Hodgkin's lymphomas.

Southern blot hybridization was used to detect the rearrangement and amplification of five proto-oncogenes (bcl-2, bcl-1, c-myc, c-myb and c-Ha-ras) and one tumor suppressor gene (RB-1) in 55 Japanese patients with non-Hodgkin's lymphoma; 16 with T-cell lymphomas and 39 with B-cell lymphomas (7 follicular and 32 diffuse lymphomas). Genetic abnormalities of the proto-oncogenes were detected in 7 of the 55 (13%). Genetic abnormalities of bcl-2 plus other genes were detected in 5 of 7 cases of follicular lymphoma (71%), rearrangements of bcl-2 and c-myc, rearrangement of bcl-2 and amplification of c-myb. Genetic abnormalities were observed in only three cases of diffuse lymphoma. In each of 3 cases of B-cell lymphoma, one of the genes, blc-2 mbr, bcl-2 mcr and c-myc, was rearranged respectively. The incidence of genetic abnormalities in diffuse lymphomas (6.3%) was lower than that in follicular lymphomas. None of diffuse lymphomas had double oncogene abnormality. No abnormalities were found in RB-1, bcl-1, and Ha-ras. These findings suggest that follicular lymphomas are associated with some abnormalities of oncogenes not restricted to bcl-2 that facilitate growth which may be associated with their clinical features.</p

Expression and intracellular localization of FKHRL1 in mammary gland neoplasms.

FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast.</p

Detection of Minute Duodenal Follicular Lymphoma Lesions Using Magnifying Endoscopy

Esophagogastroduodenoscopy revealed small duodenal lesions in a 56-year-old Japanese man and a 92-year-old Japanese woman with stage IV follicular lymphoma. Magnifying endoscopy examination revealed tiny white deposits in the second duodenal portion of the former patient and slightly enlarged duodenal villi in the latter. In both cases, biopsy revealed infiltration of follicular lymphoma cells and incipient formation of neoplastic follicles. Here, we discuss the usefulness of magnifying endoscopy and narrow-band imaging for the detection of small duodenal lesions in follicular lymphoma cases

Alteration of the size distributions and mixing states of black carbon through transport in the boundary layer in east Asia

Ground-based measurements of black carbon (BC) were performed near an industrial source region in the early summer of 2014 and at a remote island in Japan in the spring of 2015. Here, we report the temporal variations in the transport, size distributions, and mixing states of the BC-containing particles. These particles were characterized using a continuous soot monitoring system, a single particle soot photometer, and an aerosol chemical speciation monitor. The effects of aging on the growth of BC-containing particles were examined by comparing the ground-based observations between the near-source and remote island sites. Secondary formation of sulfate and organic aerosols strongly affected the increases in BC coating (i.e., enhancement of cloud condensation nuclei activity) with air mass aging from the source to the outflow regions. The effects of wet removal on BC microphysics were elucidated by classifying the continental outflow air masses depending on the enhancement ratios of BC to CO (ΔBC ∕ ΔCO), which were used as an indicator of the transport efficiency of BC. It was found that ΔBC ∕ ΔCO ratios were controlled mainly by the wet removal during transport in the planetary boundary layer (PBL) on the timescale of 1–2 days. The meteorological conditions and backward trajectory analyses suggested that air masses strongly affected by wet removal originated mainly from a region in southern China (20–35° N) in the spring of 2015. Removal of large and thickly coated BC-containing particles was detected in the air masses that were substantially affected by the wet removal in the PBL, as predicted by Köhler theory. The size and water solubility of BC-containing particles in the PBL can be altered by the wet removal as well as the condensation of non-BC materials

Risk assessments for broncho-pleural fistula and respiratory failure after lung cancer surgery by National Clinical Database Japan

BackgroundBroncho-pleural fistula (BPF) and respiratory failure (RF) are life-threatening complications after lung cancer surgery and can result in long-term hospitalization and decreased quality of life. Risk assessments for BPF and RF in addition to mortality and major morbidities are indispensable in surgical decision-making and perioperative care.MethodsThe characteristics and operative data of 80,095 patients who had undergone lung cancer surgery were derived from the 2014 and 2015 National Clinical Database (NCD) of Japan datasets. After excluding 1501 patients, risk models were developed from these data and validated by another dataset for 42,352 patients derived from the 2016 NCD dataset. Receiver operating characteristic curves were generated for postoperative BPF and RF development. The concordance-index was used to assess the discriminatory ability and validity of the model.ResultsBPF and RF occurred in 259 (0.3%) and 420 patients (0.5%), respectively, in the model development dataset and in 129 (0.3%) and 198 patients (0.5%), respectively, in the model validation dataset. Characteristic variables including types of surgery and comorbidities were identified as risk factors for BPF and RF, respectively. The concordance indexes of assessments for BPF and RF were 0.847 (p < 0.001) and 0.848 (p < 0.001), respectively, for the development dataset and 0.850 (p < 0.001) and 0.844 (p < 0.001), respectively, for the validation dataset.ConclusionsThese models are satisfactory for predicting BPF and RF after lung cancer surgery in Japan and could guide preoperative assessment and optimal measures for preventing BPF and RF

Zero-bias conductance peak splitting due to multiband effect in tunneling spectroscopy

We study how the multiplicity of the Fermi surface affects the zero-bias peak in conductance spectra of tunneling spectroscopy. As case studies, we consider models for organic superconductors $\kappa$-(BEDT-TTF)$_2$Cu(NCS)$_2$ and (TMTSF)$_2$ClO$_4$. We find that multiplicity of the Fermi surfaces can lead to a splitting of the zero-bias conductance peak (ZBCP). We propose that the presence/absence of the ZBCP splitting is used as a probe to distinguish the pairing symmetry in $\kappa$-(BEDT-TTF)$_2$Cu(NCS)$_2$.Comment: 7 pages, 7 figure

Low CD4/CD8 T-Cell Ratio Associated with Inflammatory Arthropathy in Human T-Cell Leukemia Virus Type I Tax Transgenic Mice

Human T-cell leukemia virus type I (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATL) as well as inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A transgenic mouse that expresses HTLV-1 Tax also develops T-cell leukemia/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. The aim of this study was to identify the primary T-cell subsets involved in the development of arthropathy in Tax transgenic mice. mRNA was strong in the spleen and joints of arthropathic mice, with a 40-fold increase compared with healthy transgenic mice.Our findings reveal that Tax transgenic mice develop rheumatoid-like arthritis with proliferating synovial cells in the joints; however, the proportion of different splenic T-cell subsets in these mice was completely different from other commonly used animal models of rheumatoid arthritis. The crucial T-cell subsets in arthropathic Tax transgenic mice appear to resemble those in HAM/TSP patients rather than those in rheumatoid arthritis patients

RANK, RANKL and osteoprotegerin in bone biology and disease

Upon the discovery of RANK, RANKL and OPG in the late 1990s, their importance in the maintenance of the skeletal structure and their dramatic role in bone disease were largely unexpected. In recent years the understanding of these proteins, in particular their regulation, has greatly increased. This review aims to bring the interested reader up to date with the latest news and views on the mechanisms controlling bone resorption in normal and pathological conditions