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Sarcopenia prevalence has increased in proportion to the aging population in Japan. We aimed to investigate the association between sarcopenia and clinical outcomes and the prognostic factors of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC).This retrospective study involved patients aged ≥ 65 years who had undergone gastric ESD for EGC at our institution between January 2009 and December 2019. Patients were divided into two groups, namely, a sarcopenia group (109 patients) and a non-sarcopenia group (658 patients), based on the skeletal muscle index and intramuscular adipose tissue content (IMAC). Clinicopathological features, ESD-related adverse events, and outcomes were then compared.In the sarcopenia group, the mean age was higher, whereas performance and nutritional statuses were lower. There were no between-group differences in terms of treatment outcomes. Multivariate analyses (odds ratio [95% confidence interval (CI)]) indicated that a geriatric nutritional risk index score (GNRI) 92 (2.12 [1.09-4.11], p = 0.03), anticoagulant therapy (1.76 [1.13-2.76], p = 0.01), tumor size ≥ 30 mm (2.09 [1.23-3.55], p = 0.01), and sarcopenia (1.90 [1.05-3.45], p = 0.03) were significantly associated with ESD-related adverse events. High Charlson comorbidity index, low prognostic nutritional index, low GNRI, and high IMAC were significantly associated with poor overall survival (OS). OS was significantly shorter in the sarcopenia group even after matching.Patients with sarcopenia had significantly more adverse events and shorter OS; therefore, evaluation of a patient's general condition, including sarcopenia, before ESD is important.

Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated.We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) to evaluate transcriptional changes in its target genes.Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (P 0.05), while SCGB3A2 levels did not differ (P = 0.341). Transduction of NKX2-1/TTF-1 into AGS and NUGC4 cells induced transactivation of SFTPB and SFTPC, indicating that NKX2-1/TTF-1 can function as normally in gastric cells as it can in the lung cells.Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.

Background Postoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture. Methods This is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either “PGA shielding”, “steroid injection”, or “steroid injection + PGA shielding”. Additional steroid injection was performed for high-risk patients after 2019. Results The risk of refractory stricture was especially high in the cervical esophagus (OR 24.77, p = 0.002) and after total circumferential resection (OR 894.04, p p = 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10–1.28, p = 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14–0.98, p = 0.029). Conclusion Combining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture. Graphical abstract

Endoscopic submucosal dissection (ESD) is one of the main methods of treatments for early gastric cancer. Sarcopenia is a known risk factor for postoperative adverse events; however, the effect of sarcopenia on gastric ESD is unclear. We investigated the impact of sarcopenia on short-term prognosis after gastric ESD.This was a retrospective cohort study. We reviewed 832 patients who underwent gastric ESD between January 2015 and December 2019 and classified them into two groups: sarcopenia and non-sarcopenia groups. The curative resection rate, adverse events, and lengths of hospital stay were evaluated. We also evaluated risk factors associated with adverse events.700 patients were analyzed (239 in the sarcopenia group and 461 in the non-sarcopenia group). The curative resection rates were similar in both groups. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 (17% vs. 10%) were significantly more common, and the length of hospital stay was longer (8 vs. 7 days) in the sarcopenia group. Univariate analysis identified age ≥ 75 years, antithrombotic medication, history of gastric surgery, submucosal (SM) invasion, and sarcopenia as risk factors for CTCAE grade ≥ 2. Multivariate analysis showed that sarcopenia [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.11-2.89, p = 0.016], history of gastric surgery (OR 9.32, 95% CI 1.97-44.05, p = 0.005), and SM invasion (OR 2.14, 95% CI 1.24-3.70, p = 0.006) were significant independent risk factors.Sarcopenia significantly affected short-term prognosis and is a novel risk factor for gastric ESD.

Recently, covering materials for protecting post-endoscopic ulcers are being developed using hydrogels. Existing hydrogels are not ideal coating materials because it is difficult to control their physical properties. Therefore, we conducted an animal pilot study to investigate the protective effect of a novel ulcer coating material, whose physical properties can be easily controlled and designed. We applied the novel injectable hydrogel to artificial ulcers induced on the gastric mucosa of rats. Rats were assigned to the hydrogel or the control group. To measure the protective effect of hydrogel on ulcers, the perforation rate, ulcer diameter, and ulcer area were evaluated 48 h after gel application. As secondary endpoints, we assessed the residual rate of the hydrogel at the bottom of the ulcer, performed histological analysis, and analyzed adverse events associated with hydrogel. The perforation rate was significantly lower (16% vs. 75%) and the mean diameter of ulcers was significantly smaller (5.4 ± 1.8 mm vs. 7.8 ± 2.8 mm) in the hydrogel group. Histopathological findings revealed the inflammatory cell count was significantly higher in the control group. Our novel hydrogel showed a protective effect on artificial gastric ulcers in a rat model.

Objectives The natural history of sporadic non‐ampullary duodenal epithelial tumors (SNADETs) is poorly documented. The aim of this study was to evaluate the history of SNADETs in patients where immediate resection could not be performed. Methods This is a single‐center retrospective study of 86 consecutive cases of SNADETs who did not undergo immediate resection and were followed‐up with upper gastrointestinal endoscopy for more than 6 months. Results During a follow‐up period of 36.8 (6.0–613.0) months, macroscopic progression was admitted in eight (9.3%). Of these, the final histology in four was adenocarcinoma, and three cases demonstrated submucosal invasion. Rates of macroscopic progression at 150 months after detection were 11.1%, 16.7%, and 30.0% for SNADETs

Hepatitis B virus (HBV) infection is one of the serious health problems in the world as HBV causes severe liver diseases. Moreover, HBV reactivation has occasionally been observed in patients with resolved HBV infection and patients using immunosuppression and anticancer drugs. Large-scale hospital data focused on HBV infection and severe liver function were analyzed at our hospital, located in an urban area adjacent to Tokyo, the capital city of Japan. A total of 99,932 individuals whose blood samples were taken at 7,170,240 opportunities were analyzed. The HBV surface antigen (HBsAg)-positive group had a more frequent prevalence of patients with higher transaminase elevations than the HBsAg-negative group. However, among the HBsAg-negative group, patients who were positive for anti-HBV surface antibody and/or anti-HBV core antibody, had more severe liver conditions and fatal outcomes. More careful attention should be paid to alanine transaminase (ALT) elevations higher than 1000 IU/L in patients who had current and previous HBV infection.

Eosinophilic gastroenteritis is a rare disease that causes various abdominal symptoms that result from the infiltration of eosinophils in the digestive tract. However, this condition has been poorly explored, and the treatment criteria and prognosis after treatment are still unclear. A 20-year-old man with a refractory duodenal ulcer had been undergoing treatment since 14 years of age at another hospital. He was admitted to our hospital with abdominal pain and anemia (hemoglobin:6.3g/dL). His blood test showed elevated serum immunoglobulin E levels, considering that he was allergic to many foods. Furthermore, endoscopic biopsy detected the occurrence of eosinophilic gastroenteritis with gastritis, duodenal ulcer, and colitis. We treated him by avoiding allergenic foods and prescribing antihistamine and vonoprazan;however, duodenal ulcer and gastrointestinal tract inflammation did not show improvement. Thus, he was diagnosed with wide-ranging and refractory eosinophilic gastroenteritis and treated with 40mg/day of steroids. After 2 months, he recovered from gastritis and duodenal ulcer, and his eosinophil level decreased, as assessed using endoscopic biopsy. Eosinophilic gastroenteritis is poorly investigated, and its treatment standards have not yet been determined. Nonetheless, steroid treatment is often applied in severe cases.

Signet ring cell (SRC) gastric cancer at advanced stage has poor prognosis. While a recent study reported nearly one-third of SRC cases contain tumors with deficient mismatch repair (MMR) genes, other studies in SRC have been inconclusive. To re-analyze the results, we performed immunohistochemical staining of MLH1, MSH2, MSH6 and PMS2 proteins in 38 SRC gastric tumors compared with 109 non-SRC (NSRC) tumors from 94 patients. In contrast to the previous study, all SRC gastric tumors normally expressed MMR proteins, whereas 22 of 109 of NSRC (20%) showed deficient MMR proteins. To reinforce our results, we referred to the Cancer Genome Atlas (TCGA) genomic database and found that only 6 (6%) of 99 samples with diffuse gastric tumors showed deficient MMR, whereas 64 (21%) of 304 in intestinal gastric tumors showed deficient MMR. Our results as well as the TCGA database indicated that MMR genes are infrequently inactivated in SRC gastric cancer. These findings indicate that SRC patients may not be the best candidates for immuno-oncology therapy.

A method for agricultural product quality and harvest amount prediction by using smartphone camera image is proposed. It is desired to predict agricultural product quality and harvest amount as soon as possible after the sowing. In order for that, satellite imagery data, UAV camera based images, ground based camera images are used and tried These methods do cost significantly and these do not work so well due to some reasons, in particular, most of farmers cannot use these properly. The proposed method uses just smartphone camera acquired images. Therefore, it is totally easy to use. If the results of prediction of product quality and harvest amount are not satisfied, then farmers have to add some additional fertilizer at the appropriate time. The experimental results with soy plantations show some possibility of the proposed method.

Lenvatinib (an inhibitor of vascular endothelial growth factor (GF) receptors 1–3, fibroblast GF receptors 1–4, platelet-derived GF receptor α, rearranged during transfection, and stem cell factor receptor) was non-inferior to sorafenib in a phase 3 (REFLECT) trial of advanced hepatocellular carcinoma. This study examined the efficacy and safety of lenvatinib in a real-world setting. This was a retrospective, multicenter, observational study. Inclusion and exclusion criteria were based on the phase 3 trial, and participants were observed for at least 12 weeks. Therapeutic effect was determined using the modified Response Evaluation Criteria In Solid Tumors (m-RECIST) at the 8th week. Patients received oral lenvatinib 12 mg/day (body weight > 60 kg) or 8 mg/day (body weight

Artificial Intelligence: AI based fertilizer control for improvement of rice quality and harvest amount is proposed together with intelligent drone based rice field monitoring system. Through experiments at the rice paddy fields which is situated at Saga Prefectural Research Institute of Agriculture: SPRIA in Saga city, Japan, it is found that the proposed system allows control rice crop quality and harvest amount by changing fertilizer type and supply amount. It, also, is found the most appropriate fertilizer supply management method which maximizing rice crop quality and harvest amount. Furthermore, these rice crop quality and harvest mount can be predicted in the early stage of rice leaf grow. Therefore, rice crop quality and harvest amount becomes controllable.

While the presentation mechanism of antigenic peptides derived from exogenous proteins by MHC class II molecules is well understood, relatively little is known about the presentation mechanism of endogenous MHC class II-restricted antigens. We therefore screened a chemical library of 200 compounds derived from natural products to identify inhibitors of the presentation of endogenous MHC class II-restricted antigens. We found that pyrenocine B, a compound derived from the fungus Pyrenochaeta terrestris, inhibits presentation of endogenous MHC class II-restricted minor histocompatibility antigen IL-4 inducible gene 1 (IL4I1) by primary dendritic cells (DCs). Phage display screening and surface plasmon resonance (SPR) analysis were used to investigate the mechanism of suppressive action by pyrenocine B. EpsinR, a target molecule for pyrenocine B, mediates endosomal trafficking through binding of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Lentiviral-mediated short hairpin (sh) RNA downregulation of EpsinR expression in DCs resulted in a decrease in the responsiveness of CD4+ T cells. Our data thus suggest that EpsinR plays a role in antigen presentation, which provides insight into the mechanism of presentation pathway of endogenous MHC class II-restricted antigen.

Method for Near Infrared: NIR reflectance estimation with visible camera data based on regression for Normalized Vegetation Index: NDVI estimation is proposed together with its application for insect damage detection of rice paddy fields. Through experiments at rice paddy fields which is situated at Saga Prefectural Agriculture Research Institute SPARI in Saga city, Kyushu, Japan, it is found that there is high correlation between NIR reflectance and Green color reflectance. Therefore, it is possible to estimate NIR reflectance with visible camera data which results in possibility of estimation of NDVI with drone mounted visible camera data. As is well known that the protein content in rice crops is highly correlated with NIR intensity, or reflectance of rice leaves, it is possible to estimate rice crop quality with drone based visible camera data.

CueO, a multi-copper oxidase (MCO) occurring in Escherichia coli, catalyses a four-electron reduction of O2 in a direct electron transfer (DET) mechanism with very high electrocatalytic activity on carbon aerogel electrodes. However, the overpotential of CueO is greater than that in other MCOs. By understanding the redox properties of CueO, we attempted to reduce this overpotential. Direct electrochemistry of CueO on carbon aerogel electrodes showed a pair of redox waves derived from the type I (T1) Cu site with a redox potential () of 0.28 V versus Ag|AgCl at pH 5.0. Dependence of on pH suggests the participation of proton transfer and acid–base equilibrium of some amino acid residue. The shape of the catalytic current is consistent with the T1 site being an inlet of electrons in the DET bioelectrocatalysis of O2, in which case the overpotential could be reduced by shifting towards the positive potential. To achieve this, we created mutants of CueO at M510, which is the axial ligand of the T1 Cu, and at D439, which forms a hydrogen bond with His443 coordinated with the T1 Cu. Two mutants, M510L and D439A, successfully reduced the overpotential.

Replacement of Met510, the axial ligand to the type I Cu in a cuprous oxidase CueO, with Leu afforded the three-coordinated type I Cu, while Gln, Ala, and Thr mutations led to the replacement of the thioether ligand with oxygen ligands (amide carbonyl group and water), and characteristic properties of absorption, circular dichroism, and electron paramagnetic resonance spectra of a variety of Met510 mutants were correlated with the changes in redox potential and enzyme activities.

We report the electro-enzymatic reduction of O 2 to water at a current density controlled by the diffusion of the dissolved O 2 in rotating disk electrode experiments under a broad pH range between 2 and 8. The electrocatalyst is CueO from Escherichia coli , which belongs to the family of multi-copper oxidases, immobilized on mesoporous carbon supports. The electrons are transferred from the electrode to CueO without an electron transfer mediator. The current density reached a value as high as 12 mA cm −2 at 1 atm O 2 , 25 °C, and 10,000 rpm on the CueO-modified electrodes. The CueO-modified mesoporous carbon cathode is quite superior to the smooth CueO cathode in the current density, electrode kinetics, pH tolerance, and thermal stability.

Estimation of rice crop quality and harvest amount in paddy fields with the different rice stump density derived from helicopter mounted NIR camera and remote sensing satellite data is made. Using the intensive study site of rice paddy fields with managing, estimation of protein content in rice crop and nitrogen content in rice leaves through regression analysis with Normalized Difference Vegetation Index: NDVI derived from camera mounted on a radio-control helicopter is made together with harvest amount of rice crops. Through experiments at rice paddy fields which is situated at Saga Prefectural Agriculture Research Institute SPRIA in Saga city, Japan, it is found that protein content in rice crops is highly correlated with NDVI which is acquired with visible and Near Infrared: NIR camera mounted on radio-control helicopter. It also is found that nitrogen content in rice leaves is correlated to NDVI as well. Protein content in rice crop is negatively proportional to rice taste. Therefore rice crop quality can be evaluated through NDVI observation of rice paddy field.

Relation between protein content in rice crops and fertilizer amount as well as rice stump density is clarified with a multi-spectral camera data mounted on a radio-wave controlled helicopter. Estimation of protein content in rice crop and total nitrogen content in rice leaves through regression analysis with Normalized Difference Vegetation Index: NDVI derived from camera mounted radio-controlled helicopter is already proposed. Through experiments at rice paddy fields which is situated at Saga Prefectural Research Institute of Agriculture: SPRIA in Saga city, Japan, it is found that total nitrogen content in rice leaves is linearly proportional to fertilizer amount and NDVI. Also, it is found that protein content in rice crops is positively proportional to fertilizer amount for lower fertilizer amount while protein content in rice crop is negatively proportional to fertilizer amount for relatively high fertilizer amount.

Bulk BaTiO3 ceramics with 〈111〉-texture have been prepared by the modified templated grain growth method, using platelike Ba6Ti17O40 particles as templates, and the mechanism of texture development is examined. The Ba6Ti17O40 particles induce the abnormal growth of BaTiO3 grains, and a structure similarity between {001} of Ba6Ti17O40 and {111} of BaTiO3 gives 〈111〉-texture to abnormally grown BaTiO3 grains. Thus, the 〈111〉-texture develops in the BaTiO3 matrix. The use of platelike Ba6Ti17O40 particles has been extended to a 0.65Pb(Mg1/3Nb2/3)O3–0.35PbTiO3 matrix, but the matrix phase is decomposed by extensive chemical reactions between the matrix and template phases.

Background and Purpose— Angiotensin-converting enzyme (ACE) inhibitor-based therapy reduces the recurrence of stroke. The present study assessed the effects of long-term ACE inhibitor therapy on cerebral circulation in patients with previous minor stroke. Methods— After a run-in period, 19 patients were randomized to ACE inhibitor therapy (n=9; 4 mg of perindopril daily; mean age, 64±8 years; mean systolic/diastolic blood pressure [BP]±SD, 133±12/77±9 mm Hg) or placebo therapy (n=10; mean age, 66±9 years; mean BP, 139±10/78±8 mm Hg). Cerebral blood flow (CBF) was measured during hypercapnia, normocapnia, and hypocapnia using a positron emission tomography with H 2 15 O at entry into the study and after 3 to 12 months. Cerebral perfusion reserve (CPR) was defined as percent CBF response to a 1 mm Hg change in arterial partial pressure of CO 2 between hypercapnia and hypocapnia. Results— Systolic/diastolic BP and CBF during normocapnia showed no significant changes between entry and completion of the trial in the perindopril and placebo groups. Mean value of CPR showed a significant increase in the perindopril group (from 3.7±1.7%/mm Hg to 4.8±1.7%/mm Hg; P P Conclusions— Long-term ACE inhibitor-based therapy had a beneficial effect on the cerebral circulation by improving CPR in patients with previous minor stroke.

Pathological hyperphosphorylated tau is the principal component of paired helical filaments, a pathological hallmark of Alzheimer disease (AD) and a strong candidate for a neurotoxic role in AD and other neurodegenerative disorders. Here we show that heat shock protein 27 (Hsp27) preferentially binds pathological hyperphosphorylated tau and paired helical filaments tau directly but not non-phosphorylated tau. The formation of this complex altered the conformation of pathological hyperphosphorylated tau and reduced its concentration by facilitating its degradation and dephosphorylation. Moreover, Hsp27 rescues pathological hyperphosphorylated tau-mediated cell death. Therefore, Hsp27 is likely to provide a neuroprotective effect in AD and other tauopathies.

While the presentation mechanism of antigenic peptides derived from exogenous proteins by MHC class II molecules is well understood, relatively little is known about the presentation mechanism of endogenous MHC class II-restricted antigens. We therefore screened a chemical library of 200 compounds derived from natural products to identify inhibitors of the presentation of endogenous MHC class II-restricted antigens. We found that pyrenocine B, a compound derived from the fungus Pyrenochaeta terrestris, inhibits presentation of endogenous MHC class II-restricted minor histocompatibility antigen IL-4 inducible gene 1 (IL4I1) by primary dendritic cells (DCs). Phage display screening and surface plasmon resonance (SPR) analysis were used to investigate the mechanism of suppressive action by pyrenocine B. EpsinR, a target molecule for pyrenocine B, mediates endosomal trafficking through binding of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Lentiviral-mediated short hairpin (sh) RNA downregulation of EpsinR expression in DCs resulted in a decrease in the responsiveness of CD4+ T cells. Our data thus suggest that EpsinR plays a role in antigen presentation, which provides insight into the mechanism of presentation pathway of endogenous MHC class II-restricted antigen.

Estimation of protein content in rice crop and nitrogen content in rice leaves through regression analysis with Normalized Difference Vegetation Index: NDVI derived from camera mounted radio-control helicopter is proposed. Through experiments at rice paddy fields which is situated at Saga Prefectural Research Institute of Agriculture: SPRIA in Saga city, Japan, it is found that protein content in rice crops is highly correlated with NDVI which is acquired with visible and Near Infrared: NIR camera mounted on radio-control helicopter. It also is found that nitrogen content in rice leaves is correlated to NDVI as well. Protein content in rice crop is negatively proportional to rice taste. Therefore rice crop quality can be evaluated through NDVI observation of rice paddy field.

In a subset of patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome characterized by thrombocytopenia, thrombosis, recurrent abortion and antiphospholipid antibodies develops. Male (NZW x BXSB) F1 mice are widely used as a model for SLE-associated antiphospholipid syndrome. Our earlier genetic studies showed that one susceptibility allele for thrombocytopenia and associated IgG platelet-binding autoantibodies in male (NZW x BXSB) F1 mice was linked to the BXSB-type polymorphic microsatellite D8Mit96, located in proximity to the gene Plat for tissue-type plasminogen activator (t-PA). In the present studies, sequence analyses for structural and promoter regions of Plat revealed a single nucleotide polymorphism encoding a catalytic domain of t-PA, with an amino acid substitution of anionic Glu366 in NZW for a cationic Lys in BXSB. Progeny studies using NZW x (NZW x BXSB) F1 male backcross mice showed that the BXSB Plat allele was significantly associated with high levels of both platelet-binding antibodies and thrombocytopenia. Furthermore, these two traits appeared to be regulated by a complementary effect of two BXSB alleles; one is linked to Plat and the other to the H-2 complex and the gene for plasminogen. Thus, the BXSB-type Plat may be one susceptibility allele for the multigenic antiphospholipid syndrome seen in (NZW x BXSB) F1 mice. Potential mechanisms are discussed.

Systemic lupus erythematosus (SLE) is a multigenic disease associated with IgG hypergammaglobulinemia, IgG anti-nuclear antibodies and immune complex (IC)-type glomerulonephritis. In both human and murine SLE, one susceptibility allele has been mapped to the interval linked to the IgG Fc receptor II (FcgammaRII) gene on chromosome 1. In spontaneous SLE models of NZB and (NZB x NZW) F(1) mice, expression of FcgammaRIIB1, which acts as a negative regulator for B cells, was abnormally down-regulated in follicular germinal center B cells from aged mice, compared to findings in non-SLE NZW, while levels in non-germinal center B cells were practically identical. Such strain differences were also evident in young mice upon in vivo stimulation with foreign antigens. In the FcgammaRIIB promoter region, the NZB allele has two deletion sites, including transcription factor-binding sites. Analyses using (NZB x NZW) F(1) x NZW backcross mice showed that this NZB allele was significantly linked to hyper-IgG, irrespective of the MHC haplotype, while high levels of IgG antibodies specific for DNA were regulated by a combinatorial effect of the F(1)-unique MHC haplotype and the NZB FcgammaRIIB allele. Therefore, the FcgammaRIIB promoter polymorphism may possibly predispose to SLE through germinal center B cells abnormally down-regulating FcgammaRIIB1 expression upon autoantigen stimulations and thus escaping negative signals for IgG production.

Stearoyl-coenzyme A desaturase 1 (SCD1) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. However, the impact of SCD1 on atherosclerosis remains unclear. The aim of this study was to determine whether SCD1 affects macrophage reverse cholesterol transport (RCT) in mice. Compared to the control, adenoviral-mediated SCD1 overexpression in RAW264.7 macrophages increased cholesterol efflux to HDL, but not to apoA-I, without clear changes in ABCA1, ABCG1 and SR-BI expressions. While knockdown of ABCG1 and SR-BI did not affect the SCD1-induced cholesterol efflux to HDL, SCD1-overexpressing macrophages promoted the formation of both normal- and large-sized HDL in media, accompanying increased apolipoprotein A-I levels in HDL fractions. Transformation to larger particles of HDL was independently confirmed by nuclear magnetic resonance-based lipoprotein analysis. Interestingly, media transfer assays revealed that HDL generated by SCD1 had enhanced cholesterol efflux potential, indicating that SCD1 transformed HDL to a more anti-atherogenic phenotype. To study macrophage RCT in vivo, (3)H-cholesterol-labeled RAW264.7 cells overexpressing SCD1 or the control were intraperitoneally injected into mice. Supporting the in vitro data, injection of SCD1-macrophages resulted in significant increases in (3)H-tracer in plasma, liver, and feces compared to the control. Moreover, there was a shift towards larger particles in the (3)H-tracer distribution of HDL fractions obtained from the mice. In conclusion, macrophage-specific SCD1 overexpression promotes overall RCT through increased cholesterol efflux to HDL, suggesting that macrophage SCD1 achieves an anti-atherogenic effect by enhancing RCT.

The ubiquity of an organic arsenic compound, arsenobetaine [(CH3)3As+CH2COO−], in marine animals is wellknown. On the other hand, the fate of it is not well known in vivo. The degradation of arsenobetaine accumulated in a shark to inorganic arsenic was shown to occur in a natural environment. This means that arsenobetaine bioconverted from inorganic arsenic from sea-water is degraded to original inorganic arsenic.

Experimental results revealed that although [ 3 H]thymidine uptake in the hair bulb increased time dependently for 12 days under normal culture conditions (95% air-5% CO 2 at 37°C), striking morphological changes occurred in the hair bulb cells as demonstrated by histological findings. As such, organ culture conditions applicable to human hair follicles were studied utilizing observations from both histology and DNA synthesis. We found that culture conditions of 95% O 2 -5% CO 2 at 31°C were superior when compared to normal culture conditions for cultures of human hair follicles when attempting to maintain the normal morphology of hair germinative cells. The hair bulb and the germinative cells successfully maintained their normal morphology throughout the 96 and 48 h culture period, respectively. Autoradiographs of [ 3 H]thymidine-labeled follicles showed localization in the germinative cells below Auber's critical line. Hair bulb DNA synthesis increased time dependently for 96 h after culture initiation. Under conditions of 95% O 2 -5% CO 2 at 31°C, the synthesis of DNA in hair germinative cells was observed. Such an organ culture method may prove useful for studies on the human hair growth mechanism.