Epidemiological and clinical characteristics of infections with seasonal human coronavirus and respiratory syncytial virus in hospitalized children immediately before the coronavirus disease 2019 pandemic.

INTRODUCTION: Seasonal human coronavirus (HCoV)-229E, -NL63, -OC43, and -HKU1 are seasonal coronaviruses that cause colds in humans. However, the clinical characteristics of pediatric inpatients infected with HCoVs are unclear. This study aimed to compare and clarify the epidemiological and clinical features of HCoVs and respiratory syncytial virus (RSV), which commonly causes severe respiratory infections in children. METHODS: Nasopharyngeal swabs were collected from all pediatric inpatients with respiratory symptoms at two secondary medical institutions in Fukushima, Japan. Eighteen respiratory viruses, including RSV and four HCoVs, were detected via reverse transcription-polymerase chain reaction. RESULTS: Of the 1757 specimens tested, viruses were detected in 1272 specimens (72.4%), with 789 single (44.9%) and 483 multiple virus detections (27.5%). RSV was detected in 639 patients (36.4%) with no difference in clinical characteristics between RSV-A and RSV-B. HCoV was detected in 84 patients (4.7%): OC43, NL63, HKU1, and 229E in 25 (1.4%), 26 (1.5%), 23 (1.3%), and 16 patients (0.9%), respectively. Patients with HCoV monoinfection (n = 35) had a significantly shorter period from onset to hospitalization (median [interquartile range] days, 2 [1-4.5] vs. 4 [2-5]), significantly shorter hospitalization stays (4 [3-5] vs. 5 [4-6]), and more cases of upper respiratory infections (37.1% vs. 3.9%) and croup (17.1% vs. 0.3%) but less cases of lower respiratory infection (54.3% vs. 94.8%) than patients with RSV monoinfection (n = 362). CONCLUSION: Seasonal HCoV-infected patients account for approximately 5% of children hospitalized for respiratory tract infections and have fewer lower respiratory infections and shorter hospital stays than RSV-infected patients.

Structure of χ3-Borophene Studied by Total-Reflection High-Energy Positron Diffraction (TRHEPD).

We have investigated the structure of χ3-borophene on Ag(111), a monolayer material of boron atoms, via total-reflection high-energy positron diffraction (TRHEPD). By comparing the experimental rocking-curves with ones for several structures calculated by using dynamical diffraction theory, we confirmed that the χ3-borophene layer has a flat structure. The distance from the topmost layer of the metal crystal is 2.4 Å, which is consistent with results reported by X-ray standing wave-excited X-ray photoelectron spectroscopy. We also demonstrated that the in-plane structure of χ3-borophene is compatible with the theoretical predictions. These structural properties indicate that χ3-borophene belongs to a group of epitaxial monolayer sheets, such as graphene, which have weak interactions with the substrates.

[Management of healthy food environment improvement through restaurants and other settings by prefectures and cities of cabinet order].

Objectives　In Japanese nutrition policy, emphasis is placed on healthy food environment improvement through restaurants and other settings by prefectures and cities of cabinet order (cities). This study aimed to clarify the actual status of management implementation by prefectures and cities.Methods　A mail survey of 47 prefectures and 106 cities throughout Japan was conducted in October 2020. Management implementation, including the existence of a healthy food environment improvement system (system) for restaurants and other settings, was confirmed. Local governments that had implemented the system were asked about the scope, dissemination efforts, process evaluation, and improvement of the system.Results　Of the local governments that responded, 39/42 prefectures (92.9%) and 57/82 cities (69.5%) implementing the system were included in the study. A total of 84.6% of prefectures and 14.0% of cities assessed the nutrient intake of local residents within the past five years. The median number of dietitians in the main office of the department in charge of healthy food environment improvement was two in both prefectures and cities. A target for healthy food environment improvement was set by 69.2% of prefectures and 54.4% of cities. The scope of the system was restaurant meals for 94.9% of prefectures and 100.0% of cities as well as ready-made meals for 87.2% of prefectures and 93.0% of cities. A total of 69.2% of prefectures and 66.7% of cities collaborated internally or with other local governments, while 15.4% of prefectures and 15.8% of cities entrusted system dissemination to external organizations. A total of 87.2% of prefectures and 89.5% of cities assessed the number of registered stores/companies, while 17.6% of prefectures and 21.6% of cities assessed the number of restaurants and other settings in the entire jurisdiction. A total of 33.3% of prefectures and 40.4% of cities established a renewal system, while 71.8% of prefectures and 33.3% of cities improved the system.Conclusion　Although underreporting due to the COVID-19 pandemic is possible, in local governments that had implemented the system, few cities assessed nutrient intake, and approximately 50-70% of prefectures and cities set targets for healthy food environment improvement. While approximately 90% of each local government assessed the number of registered stores/companies, those that assessed the number of stores/companies in the entire jurisdiction as a population size were approximately 20%. Approximately 30-40% of each local government has established a renewal system.

Programming of donor T cells using allogeneic δ-like ligand 4-positive dendritic cells to reduce GVHD in mice.

Alloreactive T cells play a critical role in eliminating hematopoietic malignant cells but are also the mediators of graft-versus-host disease (GVHD), a major complication that subverts the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, induction of alloreactive T cells does not necessarily lead to GVHD. Here we report the development of a cellular programming approach to render alloreactive T cells incapable of causing severe GVHD in both major histocompatibility complex (MHC)-mismatched and MHC-identical but minor histocompatibility antigen-mismatched mouse models. We established a novel platform that produced δ-like ligand 4-positive dendritic cells (Dll4(hi)DCs) from murine bone marrow using Flt3 ligand and Toll-like receptor agonists. Upon allogeneic Dll4(hi)DC stimulation, CD4(+) naïve T cells underwent effector differentiation and produced high levels of interferon γ (IFN-γ) and interleukin-17 in vitro, depending on Dll4 activation of Notch signaling. Following transfer, allogeneic Dll4(hi)DC-induced T cells were unable to mediate severe GVHD but preserved antileukemic activity, significantly improving the survival of leukemic mice undergoing allogeneic HSCT. This effect of Dll4(hi)DC-induced T cells was associated with their impaired expansion in GVHD target tissues. IFN-γ was important for Dll4(hi)DC programming to reduce GVHD toxicities of alloreactive T cells. Absence of T-cell IFN-γ led to improved survival and expansion of Dll4(hi)DC-induced CD4(+) T cells in transplant recipients and caused lethal GVHD. Our findings demonstrate that Dll4(hi)DC programming can overcome GVHD toxicity of donor T cells and produce leukemia-reactive T cells for effective immunotherapy.

Surgery and imatinib therapy for liver oligometastasis of GIST: a study of Japanese Study Group on GIST.

We conducted a multicenter prospective study to clarify the efficacy and safety of surgery and imatinib for liver oligometastasis of gastrointestinal stromal tumors. Eligible gastrointestinal stromal tumor patients were enrolled in the surgery trial or the imatinib trial. Primary endpoints were recurrence-free survival and progression-free survival, respectively. The trials were prematurely terminated due to amendment of guidelines for adjuvant imatinib therapy and low patient accrual. In the surgery trial, all the six patients showed hepatic recurrence: median recurrence-free survival was 145 days (range: 62-1366 days). Of the five patients receiving salvage imatinib therapy, two showed progressive disease although no death was observed. Of the five patients enrolled in the imatinib trial, one died of pneumonia after progressive disease, and four had not shown progressive disease as of last visit. The results suggest that liver oligometastasis of gastrointestinal stromal tumor may not be controllable by surgery alone and require concomitant imatinib therapy.

Ezh2 regulates transcriptional and posttranslational expression of T-bet and promotes Th1 cell responses mediating aplastic anemia in mice.

Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome. IFN-γ-producing Th1 CD4(+) T cells mediate the immune destruction of hematopoietic cells, and they are central to the pathogenesis. However, the molecular events that control the development of BM-destructive Th1 cells remain largely unknown. Ezh2 is a chromatin-modifying enzyme that regulates multiple cellular processes primarily by silencing gene expression. We recently reported that Ezh2 is crucial for inflammatory T cell responses after allogeneic BM transplantation. To elucidate whether Ezh2 mediates pathogenic Th1 responses in AA and the mechanism of Ezh2 action in regulating Th1 cells, we studied the effects of Ezh2 inhibition in CD4(+) T cells using a mouse model of human AA. Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure. Ezh2 inhibition resulted in significant decrease in the expression of Tbx21 and Stat4, which encode transcription factors T-bet and STAT4, respectively. Introduction of T-bet but not STAT4 into Ezh2-deficient T cells fully rescued their differentiation into Th1 cells mediating AA. Ezh2 bound to the Tbx21 promoter in Th1 cells and directly activated Tbx21 transcription. Unexpectedly, Ezh2 was also required to prevent proteasome-mediated degradation of T-bet protein in Th1 cells. Our results demonstrate that Ezh2 promotes the generation of BM-destructive Th1 cells through a mechanism of transcriptional and posttranscriptional regulation of T-bet. These results also highlight the therapeutic potential of Ezh2 inhibition in reducing AA and other autoimmune diseases.

A multicenter phase II trial of mFOLFOX6 plus bevacizumab to treat liver-only metastases of colorectal cancer that are unsuitable for upfront resection (TRICC0808).

BACKGROUND: A phase II clinical trial was conducted on colorectal cancer patients with only liver metastases (focal diameter exceeds 5 cm or the number of liver metastases is ≥5; H2·H3) to evaluate the liver resection rate and safety after 6 cycles of mFOLFOX6+bevacizumab (BV) therapy. METHODS: mFOLFOX6+BV therapy was applied for 6 cycles to the patients with H2·H3 liver only metastasis. Hepatectomy was considered after the sixth cycle as a rule, and was performed if possible. The primary endpoint was the curative hepatectomy rate (R0 resection rate). RESULTS: Forty-six patients were registered and 45 patients were included in the efficacy analysis. Of the 19 patients rated as unresectable before therapy, 18 completed 6 cycles of mFOLFOX6+BV therapy and subsequently underwent hepatectomy (16 were R0-resected). Of the 26 initially unresectable patients, 6 underwent hepatectomy (4 were RO-resected). The overall R0 resection rate was 44.4% (20/45). Chemotherapy-associated grade 3 or higher adverse events included neutrophil decreased (17.4%) and leukocyte decreased (8.7%), fatigue (6.5%) etc. Only hypertension (6.5%) and venous thromboembolism (2.2%) were BV-associated grade 3 or higher adverse events. Among the 25 patients who underwent hepatectomy, intraoperative/postoperative complications included grade 3 wound infections (2 cases), biloma, delayed wound healing and intraperitoneal abscess (each 1 case). CONCLUSIONS: In colorectal cancer patients with liver-only metastases, mFOLFOX6+ BV therapy yielded a high hepatectomy rate and a high percentage of initially unresectable and subsequently resectable cases. The chemotherapy associated adverse events and hepatectomy complications were both within acceptable ranges.

The histone methyltransferase Ezh2 is a crucial epigenetic regulator of allogeneic T-cell responses mediating graft-versus-host disease.

Posttranscriptional modification of histones by methylation plays an important role in regulating Ag-driven T-cell responses. We have recently drawn correlations between allogeneic T-cell responses and the histone methyltransferase Ezh2, which catalyzes histone H3 lysine 27 trimethylation. The functional relevance of Ezh2 in T-cell alloimmunity remains unclear. Here, we identify a central role of Ezh2 in regulating allogeneic T-cell proliferation, differentiation, and function. Conditional loss of Ezh2 in donor T cells inhibited graft-versus-host disease (GVHD) in mice after allogeneic bone marrow (BM) transplantation. Although Ezh2-deficient T cells were initially activated to proliferate upon alloantigenic priming, their ability to undergo continual proliferation and expansion was defective during late stages of GVHD induction. This effect of Ezh2 ablation was largely independent of the proapoptotic molecule Bim. Unexpectedly, as a gene silencer, Ezh2 was required to promote the expression of transcription factors Tbx21 and Stat4. Loss of Ezh2 in T cells specifically impaired their differentiation into interferon (IFN)-γ-producing effector cells. However, Ezh2 ablation retained antileukemia activity in alloreactive T cells, leading to improved overall survival of the recipients. Our findings justify investigation of modulating Ezh2 as a therapeutic strategy for the treatment of GVHD and other T cell-mediated inflammatory disorders.

Delta-like ligand 4 identifies a previously uncharacterized population of inflammatory dendritic cells that plays important roles in eliciting allogeneic T cell responses in mice.

Graft-versus-host disease (GVHD) reflects an exaggerated inflammatory allogeneic T cell response in hosts receiving allogeneic hematopoietic stem cell transplantation (HSCT). Inhibition of pan-Notch receptor signaling in donor T cells causes reduction of GVHD. However, which Notch ligand(s) in what APCs is important for priming graft-versus-host reaction remains unknown. We demonstrate that δ-like ligand-4 (Dll4) and Dll4-positive (Dll4(high)) inflammatory dendritic cells (i-DCs) play important roles in eliciting allogeneic T cell responses. Host-type Dll4(high) i-DCs occurred in the spleen and intestine of HSCT mice during GVHD induction phase. These Dll4(high) i-DCs were CD11c(+)B220(+)PDCA-1(+), resembling plasmacytoid dentritic cells (pDCs) of naive mice. However, as compared with unstimulated pDCs, Dll4(high) i-DCs expressed higher levels of costimulatory molecules, Notch ligands Jagged1 and Jagged2, and CD11b, and produced more Ifnb and Il23 but less Il12. In contrast, Dll4-negative (Dll4(low)) i-DCs were CD11c(+)B220(-)PDCA-1(-), and had low levels of Jagged1. In vitro assays showed that Dll4(high) i-DCs induced significantly more IFN-γ- and IL-17-producing effector T cells (3- and 10-fold, respectively) than Dll4(low) i-DCs. This effect could be blocked by anti-Dll4 Ab. In vivo administration of Dll4 Ab reduced donor-alloreactive effector T cells producing IFN-γ and IL-17 in GVHD target organs, leading to reduction of GVHD and improved survival of mice after allogeneic HSCT. Our findings indicate that Dll4(high) i-DCs represent a previously uncharacterized i-DC population distinctive from steady state DCs and Dll4(low) i-DCs. Furthermore, Dll4 and Dll4(high) i-DCs may be beneficial targets for modulating allogeneic T cell responses, and could facilitate the discovery of human counterparts of mouse Dll4(high) i-DCs.

Occurrence of cardiovascular events after the 2011 Great East Japan Earthquake and tsunami disaster.

There are conflicting reports regarding the occurrence of cardiovascular events after a major earthquake. To understand the impact of the Great East Japan Earthquake on cardiovascular events, we retrospectively examined the clinical records prepared by emergency room physicians between 2009 and 2011 (n = 66,244), and compared the occurrence of these events between 2011 and 2009, and 2011 and 2010. There was a significant increase in the number of patients with cardiovascular events during the 3 week period after the earthquake in 2011 (n = 106) compared with that during the same period in 2009 (n = 72) or 2010 (n = 65) (P = 0.002). The number of patients with acute coronary syndrome or congestive heart failure in March 2011 was significantly increased compared with 2009 or 2010, however, there were no significant increases in 2011 in other cardiovascular events including stroke, aortic dissection, pulmonary thromboembolism, or out-of-hospital cardiac arrest compared with 2009 or 2010. These findings suggest that the incidence of cardiovascular events may have been heterogeneous after the disaster.

Molecular Diversity of Human Respiratory Syncytial Virus before and during the COVID-19 Pandemic in Two Neighboring Japanese Cities.

Human respiratory syncytial viruses (HRSVs) are divided into subgroups A and B, which are further divided based on the nucleotide sequence of the second hypervariable region (HVR) of the attachment glycoprotein (G) gene. Understanding the molecular diversity of HRSV before and during the coronavirus disease 2019 (COVID-19) pandemic can provide insights into the effects of the pandemic on HRSV dissemination and guide vaccine development. Here, we analyzed HRSVs isolated in Fukushima Prefecture from September 2017 to December 2021. Specimens from pediatric patients were collected at two medical institutions in neighboring cities. A phylogenetic tree based on the second HVR nucleotide sequences was constructed using the Bayesian Markov chain Monte Carlo method. HRSV-A (ON1 genotype) and HRSV-B (BA9 genotype) were detected in 183 and 108 specimens, respectively. There were differences in the number of HRSV strains within clusters prevalent at the same time between the two hospitals. The genetic characteristics of HRSVs in 2021 after the COVID-19 outbreak were similar to those in 2019. HRSVs within a cluster may circulate within a region for several years, causing an epidemic cycle. Our findings add to the existing knowledge of the molecular epidemiology of HRSV in Japan. IMPORTANCE Understanding the molecular diversity of human respiratory syncytial viruses during pandemics caused by different viruses can provide insights that can guide public health decisions and vaccine development.

Outcome of fetal echocardiography: a 17 year single-institution experience in Japan.

BACKGROUND: The aim of this retrospective study was to evaluate the influence of prenatal diagnosis on perinatal outcomes of congenital heart disease (CHD) over a 17 year period at a single center. METHODS: The perinatal outcome of CHD in 146 patients diagnosed on fetal echocardiography between 1994 and 2010 were reviewed. The characteristics of 193 neonatal inpatients with CHD treated at the authors' department between 2001 and 2010 were also analyzed; among the inpatients, 61 were diagnosed before birth (prenatal group) and 132 were diagnosed after birth (postnatal group). RESULTS: Among the 146 patients prenatally diagnosed with CHD, the prenatal mortality, including abortion and stillbirth, decreased from 1994 to 2010. Among the 193 neonatal inpatients, the prenatal group had lower gestational age and bodyweight than the postnatal group. Further, the prenatal group had lower blood pH at admission, but no patient in that group experienced ductal shock, although six patients in the postnatal group did. The average dose of prostaglandin E1 used in duct-dependent CHD was significantly lower in the prenatal group than in the postnatal group (3.4 vs. 4.6 ng/kg per min; P = 0.015). CONCLUSIONS: Prenatal diagnosis of CHD enables planned labor, prevents ductal shock, and reduces prostaglandin E1 side-effects and medical expenditure.

Changes in virus detection in hospitalized children before and after the severe acute respiratory syndrome coronavirus 2 pandemic.

The impact of strengthening preventive measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the prevalence of respiratory viruses in children was examined. After the SARS-CoV-2 pandemic, the rate of multiple virus detection among hospitalized children decreased. Immediately after the SARS-CoV-2 pandemic, respiratory syncytial and parainfluenza viruses were rarely detected and subsequently reemerged. Human metapneumovirus and influenza virus were not consistently detected. Non-enveloped viruses (bocavirus, rhinovirus, and adenovirus) were detected to some extent even after the pandemic. Epidemic-suppressed infectious diseases may reemerge as susceptibility accumulates in the population and should continue to be monitored.

[Questionnaire survey of efficacy of patient support in outpatient chemotherapy by pharmacist].

The aim of this study is evaluation of the efficacy of the pharmacist in providing support at the ambulatory therapy center (ATC), especially in connection with chemotherapy side effects in patients. The unsigned questionnaire survey was conducted for patients receiving chemotherapy in ATC. 108 patients were enrolled, and 78 patients answered questions. Patients were asked which kind of specialists provide the most ideal support in the ATC, and what do patients suffer in the ATC. Interestingly, more patients chose pharmacists than nurses and doctors. Many of patients suffer hair loss, nausea and peripheral neuropathy, and many people feel time spent in the ATC is not so meaningful.

Planned Safety Analysis of the ACTS-CC 02 Trial: A Randomized Phase III Trial of S-1 With Oxaliplatin Versus Tegafur and Uracil With Leucovorin as Adjuvant Chemotherapy for High-Risk Stage III Colon Cancer.

BACKGROUND: This trial was designed to verify the superiority of 6 months of postoperative adjuvant chemotherapy with SOX (S-1 with oxaliplatin) with UFT (tegafur and uracil) with LV (leucovorin) in terms of disease-free survival in patients with high-risk stage III colon cancer. We report the results of a planned safety analysis. PATIENTS AND METHODS: Patients who underwent curative resection for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries) were randomly assigned to receive either UFT/LV (300-600 mg/d UFT with 75 mg/d LV on days 1-28, every 35 days, for 5 cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 with 80-120 mg/d S-1 on days 1-14, every 21 days, for 8 cycles). Treatment status and safety were evaluated. RESULTS: A total of 966 patients were enrolled, and 932 patients were included in safety analyses. The planned 6-month protocol treatment was received by 76.9% of the patients in the UFT/LV group and 65.8% of those in the SOX group. The overall incidence of any Grade adverse events (AEs) were 91.3% in the UFT/LV group and 98.7% in the SOX group, and those of Grade ≥ 3 AEs were 16.1% and 36.1%, respectively. As for Grade ≥ 3 AEs, leukopenia, neutropenia, thrombocytopenia, and sensory neuropathy were more common in the SOX group. The incidence of Grade ≥ 3 sensory peripheral neuropathy was 4.6% in the SOX group. CONCLUSION: The completion rate of adjuvant SOX and its incidence of AEs were acceptable in patients with colon cancer.

A case of gastrointestinal bleeding due to right hepatic artery pseudoaneurysm following total remnant pancreatectomy: A case report.

INTRODUCTION: Pseudoaneurysm is a serious complication after pancreatic surgery, which mainly depends on the presence of a preceding pancreatic fistula. Postpancreatectomy hemorrhage following total pancreatectomy is a rare complication due to the absence of a pancreatic fistula. Here we report an unusual case of massive gastrointestinal bleeding due to right hepatic artery (RHA) pseudoaneurysm following total remnant pancreatectomy. PRESENTATION OF CASE: A 75-year-old man was diagnosed with intraductal papillary mucinous carcinoma recurrence following distal pancreatectomy and underwent total remnant pancreatectomy. After discharge, he was readmitted to our hospital with melena because of the diagnosis of gastrointestinal bleeding. Gastrointestinal endoscopy was performed to detect the origin of bleeding, but an obvious bleeding point could not be detected. Abdominal computed tomography demonstrated an expansive growth, which indicated RHA pseudoaneurysm. Emergency angiography revealed gastrointestinal bleeding into the jejunum from the ruptured RHA pseudoaneurysm. Transcatheter arterial embolization was performed; subsequently, bleeding was successfully stopped for a short duration. Because of improvements in his general condition, the patient was discharged. DISCUSSION: To date, very few cases have described postpancreatectomy hemorrhage following total remnant pancreatectomy. We suspect that the aneurysm ruptured into the jejunum, possibly because of the scarring and inflammation associated with his two complex surgeries. CONCLUSION: Pseudoaneurysm should be considered when the fragility of blood vessels is suspected, despite no history of anastomotic leak and intra-abdominal abscess. Our case also highlighted that detecting gastrointestinal bleeding is necessary to recognize sentinel bleeding if the origin of bleeding is undetectable.

Observation of a shape resonance of the positronium negative ion.

When an electron binds to its anti-matter counterpart, the positron, it forms the exotic atom positronium (Ps). Ps can further bind to another electron to form the positronium negative ion, Ps(-) (e(-)e(+)e(-)). Since its constituents are solely point-like particles with the same mass, this system provides an excellent testing ground for the three-body problem in quantum mechanics. While theoretical works on its energy level and dynamics have been performed extensively, experimental investigations of its characteristics have been hampered by the weak ion yield and short annihilation lifetime. Here we report on the laser spectroscopy study of Ps(-), using a source of efficiently produced ions, generated from the bombardment of slow positrons onto a Na-coated W surface. A strong shape resonance of (1)P(o) symmetry has been observed near the Ps (n=2) formation threshold. The resonance energy and width measured are in good agreement with the result of three-body calculations.

One-dimensional metallic surface states of Pt-induced atomic nanowires on Ge(0 0 1).

Surface states of platinum-induced atomic nanowires on a germanium (0 0 1) surface, which shows a structural phase transition at 80 K, were studied by angle-resolved photoelectron spectroscopy (ARPES). We observed four one-dimensional metallic surface states, among which, two bands were reported in our previous study (Yaji et al 2013 Phys. Rev. B 87 241413). One of the newly-found two bands is a quasi-one-dimensional state and is split into two due to the Rashba effect. Photoelectron intensity from one of the spin-polarized branches is reduced at a boundary of the surface Brillouin zone below the phase transition temperature. The reduction of the photoelectron intensity in the low temperature phase is interpreted as the interference of photoelectrons, not as the Peierls instability. We also discuss the low energy properties of the metallic surface states and their spin splitting using high-resolution ARPES with a vacuum ultraviolet laser.

Effect of uni-adrenalectomy on blood pressure in a patient with excessive adrenal 18-hydroxy-11-deoxycorticosterone production bilaterally.

A 46-year-old woman was presented with mineralocorticoid excess syndrome and a large mass originating from the right adrenal gland. Clinical examination before right adrenalectomy revealed elevated serum concentrations of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) both systemically and in the adrenal veins bilaterally. Histopathological and immunohistochemical analyses of the surgical specimen demonstrated adrenal hyperplasia of outer fasciculata cells, and the presence of cystic mass. The adrenalectomy ameliorated her blood pressure (BP) from 156/96 mmHg to 148/87 mmHg with a concomitant increase of serum potassium concentration from 3.1 mEq/l to 3.5 mEq/l. These results suggest that uni-adrenalectomy is, at least in part, effective in ameliorating not only BP but also potassium concentration in a patient of adrenal hyperplasia with excessive bilateral 18-OH-DOC production.

Suppression of immunoglobulin production by a novel dihydroorotate dehydrogenase inhibitor, S-2678.

We discovered a novel dihydroorotate dehydrogenase (DHO-DH) inhibitor, S-2678 ([2-fluoro-2',5'-dimethyl-4'-[6-(3-methyl-2-butenyloxy) pyridin-3-yl] biphenyl-4-yl]-(3-methyl-2-butenyl) amine). Its inhibitory activity against DHO-DH was more potent than that of A77 1726, an active metabolite of the anti-rheumatic drug leflunomide. S-2678 suppressed immunoglobulin production in mouse B cells and human peripheral blood mononuclear cells in vitro, with little or no inhibition of cell proliferation, probably through inhibition of class switch recombination in the immunoglobulin heavy chain loci in B cells. In vivo antibody production induced by systemic immunization with ovalbumin was dramatically suppressed by oral administration of S-2678, without any toxicological signs. However, S-2678 did not affect T-cell activation in vitro, and cytokine production induced by intravenous anti-CD3 antibody in mice. S-2678 did not affect host defense in a mouse model of Candida infection, whereas leflunomide severely impaired it. In conclusion, S-2678 selectively acts on B cells, resulting in antibody production, which suggests that it is useful for the treatment of humoral immunity-related diseases.