Current treatment status of IgA nephropathy in Japan: a questionnaire survey.

BACKGROUND: In 2020, the Committee of Clinical Practical Guideline for IgA Nephropathy (IgAN) revised the clinical practice guidelines. Herein, we conducted a questionnaire survey to assess the potential discrepancies between clinical practice guidelines and real-world practice in Japan. METHODS: A web-based survey of members of the Japanese Society of Nephrology was conducted between November 15 and December 28, 2021. RESULTS: A total of 217 members (internal physicians: 203, pediatricians: 14) responded to the questionnaire. Of these respondents, 94.0% answered that the clinical practice guidelines were referred to "always" or "often." Approximately 66.4% respondents answered that histological grade (H-Grade) derived from the "Clinical Guidelines for IgA nephropathy in Japan, 3rd version" and the "Oxford classification" were used for pathological classification. Moreover, 73.7% respondents answered that the risk grade (R-grade) derived from the "Clinical Guidelines for IgA nephropathy in Japan, 3rd version" was referred to for risk stratification. The prescription rate of renin-angiotensin system blockers increased based on urinary protein levels (> 1.0 g/day: 88.6%, 0.5-1.0 g/day: 71.0%, < 0.5 g/day: 25.0%). Similarly, the prescription rate of corticosteroids increased according to proteinuria levels (> 1.0 g/day: 77.8%, 0.5-1.0 g/day: 52.8%, < 0.5 g/day: 11.9%). The respondents emphasized on hematuria when using corticosteroids. In cases of hematuria, the indication rate for corticosteroids was higher than in those without hematuria, even if the urinary protein level was 1 g/gCr or less. Few severe infectious diseases or serious deterioration in glycemic control were reported during corticosteroid use. CONCLUSION: Our questionnaire survey revealed real-world aspects of IgAN treatment in Japan.

Lifestyle behaviour patterns in the prevention of type 2 diabetes mellitus: the Fukushima Health Database 2015-2020.

OBJECTIVES: Lifestyle behaviours associated with the incidence of type 2 diabetes mellitus (T2DM) need further clarification using health insurance data. STUDY DESIGN: This is a cohort study. METHODS: In 2015, 193,246 participants aged 40-74 years attended the specific health checkups and were observed up to 2020 in Fukushima, Japan. Using the principal component analysis, we identified two patterns from ten lifestyle behaviour questions, namely, the "diet-smoking" pattern (including smoking, alcohol drinking, skipping breakfast, eating fast, late dinner, and snacking) and the "physical activity-sleep" pattern (including physical exercise, walking equivalent activity, walking fast, and sufficient sleep). Then, individual pattern scores were calculated; the higher the scores, the healthier the behaviours. RESULTS: The accumulative incidence rate of T2DM was 630.5 in men and 391.9 in women per 100,000 person-years in an average of 4 years of follow-up. Adjusted for the demographic and cardiometabolic factors at the baseline, the hazard ratio (95% confidence interval) of the highest versus lowest quartile scores of the "diet-smoking" pattern for T2DM risk was 0.82 (0.72, 0.92; P for trend = 0.002) in men and 0.87 (0.76, 1·00; P for trend = 0.034) in women; that of the "physical activity-sleep" pattern was 0.92 (0.82, 1·04; P for trend = 0.0996) in men and 0.92 (0.80, 1·06; P for trend = 0.372) in women. The "physical activity-sleep" pattern showed a significant inverse association in non-overweight men. CONCLUSIONS: Lifestyle behaviour associated with a healthy diet and lack of smoking may significantly lower the risk of T2DM in middle-aged Japanese adults.

Dermal anchoring structures: convex matrix structures at the bottom of the dermal layer that contribute to the maintenance of facial skin morphology.

BACKGROUND/PURPOSE: Facial skin must be linked to underlying structures to maintain facial morphology and prevent sagging, but the mechanism of facial skin retention is largely unknown. We aimed to elucidate this mechanism. METHODS: Twenty-two cheek skin specimens (age range: 10s-60s, both genders) were observed histologically. And 30 cheek of healthy Japanese volunteers (age range: 30s-50s, female) was photographed and the severity of sagging was graded. Dermal layer morphology was observed non-invasively with ultrasound. Skin-retaining force was measured with a Cutometer MPA 580(®) , and sagging severity was evaluated by grading criteria. RESULTS: Histological observation revealed characteristic convex structures at the bottom of the dermal layer. Non-invasive study showed that the depth of the convex structures, measured by ultrasonography, was significantly negatively related to the ratio of viscoelastic to elastic distention (Uv/Ue) and positively related to the ratio of elastic recovery to total deformation (Ur/Uf) at the cheek of female volunteers, measured by cutometer. It was also negatively related to sagging severity. Further, Ur/Uf was negatively and Uv/Ue was positively related to sagging severity. CONCLUSION: Characteristic convex structures at the bottom of the dermal layer serve as anchoring structures to maintain skin morphology.

Phosphorylation of Smad2/3 at the specific linker threonine residue indicates slow-cycling esophageal stem-like cells before re-entry to the cell cycle.

UNLABELLED: The stem cell compartment in the esophageal epithelium is possibly located in the basal layer. We have identified significant expression of Smad2/3, phosphorylated at specific linker threonine residues (pSmad2/3L-Thr), in the epithelial cells of murine stomach and intestine, and have suggested that these cells are epithelial stem cells. In this study, we explore whether pSmad2/3L-Thr could serve as a biomarker for esophageal stem cells. We examined esophageal tissues from normal C57BL/6 mice and those with esophagitis. Double immunofluorescent staining of pSmad2/3L-Thr with Ki67, CDK4, p63, or CK14 was performed. After immunofluorescent staining, we stained the same sections with hematoxylin-eosin and observed these cells under a light microscope. We used the 5-bromo-2-deoxyuridine (BrdU) labeling assay to examine label retention of pSmad2/3L-Thr immunostaining-positive cells. We collected specimens 5, 10, 15 and 20 days after repeated BrdU administrations and observed double immunofluorescent staining of pSmad2/3L-Thr with BrdU. In the esophagus, pSmad2/3L-Thr immunostaining-positive cells were detected in the basal layer. These cells were detected between Ki67 immunostaining-positive cells, but they were not co-localized with Ki67. pSmad2/3L-Thr immunostaining-positive cells showed co-localization with CDK4, p63, and CK14. Under a light microscope, pSmad2/3L-Thr immunostaining-positive cells indicated undifferentiated morphological features. Until 20 days follow-up period, pSmad2/3L-Thr immunostaining-positive cells were co-localized with BrdU. pSmad2/3L-Thr immunostaining-positive cells significantly increased in the regeneration phase of esophagitis mucosae, as compared with control mice (esophagitis vs. CONTROL: 6.889 ± 0.676/cm vs. 4.293 ± 0.659/cm; P < 0.001). We have identified significant expression of pSmad2/3L-Thr in the specific epithelial cells of murine esophagi. We suggest that these cells are slow-cycling epithelial stem-like cells before re-entry to the cell cycle.

A hybridisation-dependent membrane-insertable amphiphilic DNA.

We synthesised a novel membrane-insertable amphiphilic DNA. The amphiphilic DNA had a nine-nucleotide hydrophobic region at one end consisting of octyl phosphotriester linkages. The amphiphilic DNA bound to the lipid membrane by inserting the hydrophobic region; this process was facilitated by the presence of the complementary DNA strand.

Investigating the pressure-reducing effect of wound dressings.

OBJECTIVE: Currently, polyurethane foam dressings are commercially available from many manufacturers. However, the pressure-reducing effect is expected to differ by the formulation and combination of the main and secondary ingredients and by manufacturing method. In this study, we investigated the effects of pressure reduction using dressing materials with various structural characteristics, including polyurethane foam dressings based on the engineering point of view, focusing on the dry state. METHOD: Pressure was measured in a model that simulated compression on the sacral region in a decubitus position. Pressure was measured for different dressings: ten products, consisting of five types of material (polyurethane foam, hydropolymeric, Hydrofiber, hydrocolloid, and low-adherent absorbent). RESULTS: All dressings used in this study showed significantly reduced pressure. ALLEVYN Non-Adhesive had the lowest pressure at 35.833 ± 1.155 mmHg, and DuoDERM Extra Thin CGF had the highest pressure at 66.867 ± 1.060 mmHg. The pressure of the control was 74.667 ± 1.405 mmHg. The other dressings were: ALLEVYN Adhesive: 44.233 ± 0.777 mmHg; ALLEVYN Gentle Border: 46.967 ± 1.537mmHg; Mepilex Border: 53.867 ± 0.231 mmHg; Biatain Silicone: 56.000 ± 0.520 mmHg; TIELLE: 57.267 ± 3.403 mmHg;Versiva XC: 65.900 ± 0.800 mmHg; DuoDERM CGF: 57.267 ± 1.007 mmHg; and Melolin: 53.433 ± 1.973 mmHg. CONCLUSION: The pressure-reducing effect of dressing differs not only by material type but also by product. That is, the pressure-reducing effect can differ even if the dressings are of the same material type, such as polyurethane foam. Our study investigated only the effect of materials and structural characteristics on the cushion of dressings in the dry state. Therefore, further investigation is needed to confirm the effect of pressure reduction by dressing to meet the conditions in the clinic.

Reversible phospho-Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection.

Transforming growth factor (TGF)-ß, type I receptor (TßRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1-4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients.

The effect of IL-17 on the production of proinflammatory cytokines and matrix metalloproteinase-1 by human periodontal ligament fibroblasts.

OBJECTIVES: To investigate the effects of IL-17 on IL-6, IL-1ß, and matrix metalloproteinase (MMP-1) production, and to compare the MMP-1 production between the individual and combined effects of IL-1ß and IL-6 in human periodontal ligament fibroblasts (HPDLF). MATERIALS AND METHODS: Human periodontal ligament fibroblasts were cultured with IL-17 for 0.5, 1, 4, 24, 48, and 72 h, and were cultured with IL-1ß, IL-6/sIL-6R, or a combination of IL-1ß and IL-6/sIL-6R for 24 h. To measure the mRNA levels of IL-6, IL-1ß, and MMP-1, total RNA was extracted from the cultured HPDLF, and a real-time PCR analysis was performed. The protein levels of IL-6, IL-1ß, and MMP-1 in supernatants were measured using enzyme-linked immunosorbent assays (ELISAs). RESULTS: IL-17 significantly increased the expression of IL-6 and MMP-1 mRNA and protein, while IL-17 transiently increased the expression of IL-1ß mRNA. The combination of IL-1ß and IL-6/sIL-6R induced significantly higher levels of MMP-1 protein than IL-1ß alone. CONCLUSIONS: IL-17 upregulated the production of IL-6 and MMP-1 sequentially in HPDLF. IL-6/sIL-6R may enhance the effects of IL-1ß on MMP-1 production. The present results suggest that IL-17 induces MMP-1 production not only directly, but also indirectly by promoting IL-6 production, thus resulting in the degradation of collagens in the PDL.

Parallel comparison of apheresis-collected platelet concentrates stored in four different additive solutions.

BACKGROUND AND OBJECTIVES: Partially replacing plasma with additive solutions in platelet (PLT) concentrates (PCs) may help to reduce transfusion reactions. Constituents of PLT additive solutions (PASs) have been revealed to affect the quality of PCs. Previous studies involved pairwise comparison of identical PLTs with two different PASs or multicomparison using random PLTs with three or more PASs. In this study, we performed parallel comparison using PCs from identical donors with four PASs. In addition to traditional parameters, the release of bioactive substances and plasma proteins was assessed. MATERIALS AND METHODS: Platelets collected four times by apheresis from three donors were suspended in Intersol, SSP+, Composol or M-sol with 35% autologous plasma. The PC parameters, including PLT activation markers, glucose consumption, chemokines and plasma proteins, were assessed during 5-day storage. RESULTS: Mean PLT volumes were decreased in SSP+, Composol and M-sol after 5-day storage, with significant differences, whereas the hypertonic shock response (HSR) was decreased only in Intersol. Glucose consumption was faster in Intersol and M-sol than in SSP+ or Composol. PLT activation, determined as CD62P, sCD62P, sCD40L and RANTES, was significantly higher in Intersol than the other three PASs. No marked change was observed in fibrinopeptide A and C3a in any PASs. CONCLUSIONS: M-sol, SSP+ and Composol effectively preserved the quality of PCs. PLT activation was significantly enhanced in Intersol compared with the other three PASs. These effects seem to depend on magnesium and potassium as a constituent. Parallel comparison further verified that the PC quality largely depended on PASs but not donors.

Analysis of a questionnaire on adverse reactions to blood donation in Japan.

In 2007, the Japanese Red Cross Blood Center performed a large-scale questionnaire study of post-donation adverse reactions. The questionnaire was distributed to 98,389 donors, and the answers were returned by 55,231 (56.1%). In total, 2,877 (5.2%) complained of an adverse reaction. Assuming that there were no adverse reactions for the 46,150 donors who did not reply, the rate of adverse reaction can be speculated to be 2.8%. Our study strongly suggests that blood centers have long underestimated the risks of vaso-vagal reactions. Taking at least 6h of careful rest after donation would be a helpful counter measure.

Diffusion-weighted magnetic resonance imaging of endometrial cancer: differentiation from benign endometrial lesions and preoperative assessment of myometrial invasion.

BACKGROUND: Uterine endometrial cancer is the most common gynecologic malignancy, and benign endometrial hyperplasia or polyps should be differentiated from endometrial cancer. In evaluating endometrial cancer on magnetic resonance imaging (MRI), the assessment of the depth of myometrial invasion is important because it closely correlates with the patient's prognosis. PURPOSE: To verify the feasibility of diffusion-weighted magnetic resonance imaging (DWI) to distinguish benign and malignant endometrial lesions, and to evaluate myometrial invasion of endometrial cancer. MATERIAL AND METHODS: Sixty-seven endometrial lesions including 45 cancers and 22 benign lesions (hyperplasia and polyps) were evaluated by DWI with apparent diffusion coefficient (ADC) measurement. The staging accuracies of DWI and gadolinium-enhanced T1-weighted images in the assessment of myometrial invasion were evaluated in 33 patients with endometrial cancer. RESULTS: The ADC values (x10(-3) mm(2)/s) in cancer and benign lesions were 0.84+/-0.19 and 1.58+/-0.36, respectively (P<0.01). The staging accuracy (superficial or deep myometrial invasion) was 94% for DWI and 88% for gadolinium-enhanced T1-weighted images. Coexisting adenomyosis and infiltrative myometrial invasion caused staging errors on gadolinium-enhanced T1-weighted images, whereas DWI could demonstrate the tumor extent correctly. CONCLUSION: DWI provides helpful information in evaluating benign and malignant endometrial lesions.

Highly c-axis orientated superconducting core and large critical current density in Ba0.6Na0.4Fe2As2 powder-in-tube tape.

Improvement of the critical current density (Jc) of superconducting wires/tapes is one of the key issues in the field of superconductivity applications. Here we report the fabrication of a silver-sheathed Ba1-xNaxFe2As2 (BaNa-122) superconducting tape by using a powder-in-tube technique and its superconducting properties, in particular transport Jc, as well as the tape-core texture. The optimally-doped BaNa-122 tape with Na concentration x = 0.4 exhibits the superconducting critical temperature (Tc) of 33.7 K and high transport Jc of 4 × 104 A/cm2 at 4.2 K in a magnetic field of 4 T. Patterns of x-ray diffraction for the superconducting core show that the degree of c-axis orientation is significantly enhanced through the tape fabrication process. The tendency of c-axis orientation is advantageous for achieving higher Jc, suggesting the high potential of BaNa-122 for superconducting wire/tape applications.

Diffusion-weighted magnetic resonance imaging of urinary epithelial cancer with upper urinary tract obstruction: preliminary results.

BACKGROUND: Various malignant tumors of the body show high signal intensity on diffusion-weighted magnetic resonance imaging (DWI). In the genitourinary region, DWI is expected to have a role in detecting urinary epithelial cancer noninvasively. PURPOSE: To demonstrate the feasibility of DWI for the diagnosis of urinary epithelial cancer with upper urinary tract obstruction. MATERIAL AND METHODS: Twenty upper urinary tract cancers in 16 patients were evaluated by high-b-value DWI (b=800 s/mm(2)). The signal intensity was visually evaluated, and the apparent diffusion coefficients (ADCs) were measured. RESULTS: All urinary epithelial cancers showed high signal intensity on DWI. The ADC in cancerous lesions was 1.31+/-0.27 x 10(-3) mm(2)/s, which was significantly lower than that of the lumens of the ureter or renal pelvis (3.32+/-0.44 x 10(-3) mm(2)/s; P<0.001). Maximum intensity projection images of DWI in combination with static-fluid MR urography provided three-dimensional entire urinary tract imaging with the extension of tumors. CONCLUSION: DWI is useful in the tumor detection and in evaluating the tumor extension of urinary epithelial cancer in patients with upper urinary tract obstruction.

High-b-value diffusion-weighted magnetic resonance imaging of pancreatic cancer and mass-forming chronic pancreatitis: preliminary results.

BACKGROUND: Mass-forming chronic pancreatitis may mimic a pancreatic cancer on dynamic computed tomography (CT) and magnetic resonance (MR) imaging, and preoperative differential diagnosis is often difficult. Recently, the usefulness of diffusion-weighted MR imaging (DWI) in the diagnosis of pancreatic cancer has been reported in several studies. PURPOSE: To determine whether high-b-value DWI can distinguish pancreatic cancer from benign mass-forming chronic pancreatitis. MATERIAL AND METHODS: Twenty pancreatic cancers and four cases of mass-forming chronic pancreatitis were evaluated by high-b-value DWI (b=800 s/mm(2)). The signal intensity on DWI was visually evaluated, and the isotropic apparent diffusion coefficients (ADCs) were measured. RESULTS: All twenty pancreatic cancers showed high signal intensity (18 showed very high, two showed slightly high) on DWI. None of the mass-forming chronic pancreatitis cases showed very high intensity (three showed iso to low, one showed slightly high) on DWI. The ADCs in the pancreatic cancer and mass-forming chronic pancreatitis were 1.38 +/- 0.32 x 10(-3) mm(2)/s and 1.00 +/- 0.18 x 10(-3) mm(2)/s, respectively (P < 0.05). CONCLUSION: On high-b-value DWI, most pancreatic cancers showed very high signal intensity, and may hence be distinguished from benign mass-forming chronic pancreatitis based on our preliminary results.

[Effect of sivelestat sodium on acute lung injury after acute aortic dissection].

Acute lung injury is a frequent and serious complication in patients with acute aortic dissection (AAD). Elevated neutrophil elastase has been reported to be one of the major determinants occurring in AAD. On admission, we administered sivelestat sodium hydrate, a neutrophil elastase inhibitor, to 11 patients with AAD who were medically treated to prevent lung injury. We compared their clinical course with that of 12 patients of control group in which sivelestat was not used prophylacticaly. Although there were 5 patients (42%) who suffered from respiratory failure and needed mechanical ventilation in the control group, no one needed intubation in the sivelestat group. Our study suggested that sivelestat sodium hydrate could be effective in preventing intubation due to respiratory failure. Further prospective study is necessary to evaluate prophylactic administration of sivelestat sodium hydrate in AAD.

Inhibition of cortical collecting tubule chloride transport by organic acids.

Cl self-exchange by the rabbit cortical collecting tubule (CCT) occurs via an apical anion exchanger in series with a basolateral Cl conductance. We studied the effects of organic acids on CCT Cl self-exchange. We found no evidence for transport of acid anions by the self-exchange system. Rather, Cl self-exchange was inhibited by a variety of organic acids. The degree of inhibition correlated with the chloroform/water partition coefficient and was enhanced by lowering pH, indicating inhibition by the lipid-soluble, protonated species. Inhibition by the representative acid iso-butyrate was dose-dependent and showed sidedness (basolateral greater than apical). Iso-butyrate also reversibly reduced transepithelial conductance without altering K permeability, suggesting inhibition of the principal cell basolateral Cl conductance. Because small organic compounds with similar lipid solubilities but no carboxyl group had no effect, both the carboxyl group and the lipid-solubility of organic acids appear to be important. The results are consistent with blockade of chloride channels by organic acids.

IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis.

IL-17 is a newly discovered T cell-derived cytokine whose role in osteoclast development has not been fully elucidated. Treatment of cocultures of mouse hemopoietic cells and primary osteoblasts with recombinant human IL-17 induced the formation of multinucleated cells, which satisfied major criteria of osteoclasts, including tartrate-resistant acid phosphatase activity, calcitonin receptors, and pit formation on dentine slices. Direct interaction between osteoclast progenitors and osteoblasts was required for IL-17-induced osteoclastogenesis, which was completely inhibited by adding indomethacin or NS398, a selective inhibitor of cyclooxgenase-2 (COX-2). Adding IL-17 increased prostaglandin E2 (PGE2) synthesis in cocultures of bone marrow cells and osteoblasts and in single cultures of osteoblasts, but not in single cultures of bone marrow cells. In addition, IL-17 dose-dependently induced expression of osteoclast differentiation factor (ODF) mRNA in osteoblasts. ODF is a membrane-associated protein that transduces an essential signal(s) to osteoclast progenitors for differentiation into osteoclasts. Osteoclastogenesis inhibitory factor (OCIF), a decoy receptor of ODF, completely inhibited IL-17-induced osteoclast differentiation in the cocultures. Levels of IL-17 in synovial fluids were significantly higher in rheumatoid arthritis (RA) patients than osteoarthritis (OA) patients. Anti-IL-17 antibody significantly inhibited osteoclast formation induced by culture media of RA synovial tissues. These findings suggest that IL-17 first acts on osteoblasts, which stimulates both COX-2-dependent PGE2 synthesis and ODF gene expression, which in turn induce differentiation of osteoclast progenitors into mature osteoclasts, and that IL-17 is a crucial cytokine for osteoclastic bone resorption in RA patients.

Autocrine stimulatory mechanism by transforming growth factor beta in human hepatocellular carcinoma.

The serum concentration of transforming growth factor beta (TGF-beta) is elevated as tumors progress in hepatocellular carcinoma (HCC) patients. In this study, we examined whether modulation of tumor-derived TGF-beta signal transduction contributes to malignant progression. We investigated the production of TGF-beta1, the biological effects of TGF-beta and neutralizing antibody on HCC cells, activation of Smad 2, Smad 3, and Smad 4, induction of antagonistic Smads (Smad 6 and Smad 7), and promoter activities of two target genes, plasminogen activator inhibitor type 1 (PAI-1) and p15INK4B. In human cell lines HCC-M and HCC-T, TGF-beta accelerates their proliferation. Smad 2 was activated constitutively by an autocrine mechanism, because in the absence of exogenous TGF-beta, a high level of Smad 2 phosphorylation, induction of PAI-1 transcripts, and nuclear localization of Smad 2 were observed. This constitutive activation of Smad 2 was, at least in part, attributable to the lack of induction of antagonistic Smads by TGF-beta. However, Smads activated by tumor-derived TGF-beta constantly suppressed p151NK4B expression. In addition, 3 of 10 human HCC tissues showed nuclear localization of Smad 2 and low mRNA levels of p15INK4B and antagonistic Smads but a high level of PAI-1. Our observations suggest that this constant suppression of the p15INK4B gene could be involved in the malignant progression of HCC.

Evaluating remediation of radionuclide contaminated forest near Iwaki, Japan, using radiometric methods.

Radiometric surveys have been conducted in support of a project investigating the potential of biofuel power generation coupled with remediation of forests contaminated with radionuclides following the Fukushima Daiichi accident. Surveys conducted in 2013 and 2014 were used to determine the distribution and time dependence of radionuclides in a cedar plantation and adjacent deciduous forestry subject to downslope radionuclide migration, and a test area where litter removal was conducted. The radiocaesium results confirmed enhanced deposition levels in the evergreen areas compared with adjacent areas of deciduous forestry, implying significant differences in depositional processes during the initial interception period in 2011. Surveys were conducted both with and without a collimator on both occasions, which modified the angular response of the detector to separate radiation signals from above and below the detector. The combined data have been used to define the influence of radionuclides in the forest canopy on dose rate at 1 m, indicating that, in evergreen areas, the activity retained within the canopy even by 2013 contributed less than 5% of ground level dose rate. The time dependent changes observed allow the effect of remediation by litter removal in reducing radionuclide inventories and dose rates to be appraised relative natural redistribution processes on adjacent control areas. A 15 × 45 m area of cedar forest was remediated in September 2013. The work involved five people in a total of 160 person hours. It incurred a total dose of 40-50 µSv, and generated 2.1 t of waste comprising forest litter and understory. Average dose rates were reduced from 0.31 µSv h-1 to 0.22 µSv h-1, with nuclide specific analyses indicating removal of 30 ± 3% of the local radiocaesium inventory. This compares with annual removal rates of 10-15% where radionuclide migration down-slope over ranges of 10-50 m could be observed within adjacent areas. Local increases were also observed in areas identified as sinks. The results confirm the utility of time-series, collimated, radiometric survey methods to account for the distribution and changes in radionuclide inventory within contaminated forests. The data on litter removal imply that significant activity transfer from canopy to soil had taken place, and provide benchmark results against which such remediation actions can be appraised.

Magainins as paradigm for the mode of action of pore forming polypeptides.

Magainins are a class of antimicrobial peptides discovered in the skin of Xenopus laevis. The peptides kill bacteria by permeabilizing the cell membranes without exhibiting significant toxicity against mammalian cells, and are a promising candidate for a new antibiotic of therapeutic value. The main target of the peptides are considered to be the lipid matrix of the membranes. This review summarizes studies on magainin-lipid interactions in comparison with other pore forming peptides. The selective toxicity can be at least partly explained by preferential interactions of magainins with anionic phospholipids abundant in bacterial membranes. A novel mode of action is discussed in detail, i.e., the formation of a dynamic peptide-lipid supramolecular pore, which allows the mutually coupled transbilayer transport of ions, lipids, and peptides per se.