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Surfer's myelopathy is non-traumatic spinal cord injury which develops in beginner surfers. The patient was a 17-year-old female who developed severe paraplegia with bilateral sensory dysfunction below the groin and bladder/rectal dysfunctions after her first surfing lesson. A spinal-cord MRI performed six hours after onset revealed an intramedullary hyperintensity area from T8 to the conus medullaris on the T2 weighted images. Expansion of this hyperintensity area was observed on Day 3 and showed a reduction on Day 8. After providing intravenous methylpredonisolone, intravenous glycerol and intravenous edaravone, motor function and bladder/rectal functions began to improve after approximately three weeks. In this study, the expansion of the lesion in the early stages of the disease course was observed by sequential spinal MRI. Furthermore, a time lag between improvement according to imaging and improvement in symptoms was also observed.

Multiple gastric cancers at the same time (synchronous) or recurrence after 1 year (metachronous) are frequently encountered. Since their genetic profiles were not well elucidated, we molecularly subtyped the genetic events of synchronous and metachronous early-stage gastric cancers. We studied mismatch repair (MMR) genes in 84 tumors from 31 patients (15 synchronous and 16 metachronous) by immunohistochemistry. We performed microsatellite instability analysis and targeted sequencing of 58 significantly mutated genes (SMGs) in 35 tumors from thirteen patients. Genomic data from TCGA were used for comparisons with advanced-stage cancers. Among the 31 patients, at least one deficient-MMR (dMMR) tumor was observed in eight (26%). Of eight patients, seven showed a mixture of proficient-MMR (pMMR) and dMMR tumors. The one case with only dMMR had six recurrent tumors within 2 years. To further subtype, we sequenced 58 SMGs in 35 samples (25 pMMR and 10 dMMR) from thirteen patients. In 35 samples, 163 mutations were identified, but none matched in almost cases, strongly indicating different clonal origins, whether synchronous or metachronous occurrences. Of the 25 pMMR cases, 1 belonged to Epstein–Barr virus (EBV), 24 belonged to chromosomal instability (CIN) subtypes. Of the thirteen cases, repetitive CIN, a mixture of CIN and MSI, a mixture of CIN and EBV, and repetitive MSI were observed in nine (70%), two (15%), one (8%) and one (8%), respectively. Despite multiple tumors occurring in the same patient simultaneously or several years apart, clonal origin was totally different. ‘Switching’ or ‘mixing’ of dMMR and pMMR, EBV or CIN occurred, which had clinical relevance with regard to immunotherapy.

Background: The Tokyo Guidelines (TG; 2013) indicated that emergency cholecystectomy is an important early treatment option for acute cholecystitis; however, surgical intervention is not necessarily indicated in patients with advanced age. We evaluated percutaneous transhepatic gallbladder aspiration (PTGBA), percutaneous transhepatic gallbladder drainage (PTGBD), and the administration of antibiotics alone as treatment options for acute ­cholecystitis. Methods: From January 2010 to December 2017, 159 patients with acute cholecystitis were treated at our institution. The data from these patients were retrospectively analyzed. Results: Of these 159 cases, 109 underwent PTGBA, 28 underwent PTGBD, and 22 were administered antibiotics alone. None of the 159 patients needed urgent (early) cholecystectomy, and all patients were discharged without mortality. PTGBA was unsuccessful in only 6 of 109 patients; PTGBD was performed in these 6 cases. Long-term follow-up was conducted in all cases. Of the 159 patients, 146 had gallbladder stones initially, while 13 had none at the time of presentation. Of these 146 patients with gallbladder stones, 84 underwent elective cholecystectomy, while 62 did not. Of the 84 patients who underwent elective cholecystectomy, 2 developed choledocholithiasis; of the 62 patients who did not undergo elective cholecystectomy, 5 developed choledocholithiasis and 2 developed acute cholecystitis. The incidences of choledocholithiasis and acute cholecystitis did not significantly differ between the 2 groups (p = 0.06). Conclusions: Despite the recommendations in the TG (2013), emergency cholecystectomy was not needed in any of the present patients with acute cholecystitis. Acute cholecystitis can be successfully treated with ­PTGBA or PTGBD, which are simple procedures with good short- and long-term safety. These procedures are highly recommended for patients with acute cholecystitis, especially in the elderly population.

Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines

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.

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

AIM The single nucleotide polymorphism (SNP) c.415C>T in exon 3 of NUDT15 affects thiopurine-induced leukopenia in Asian patients with Crohn’s disease. Meanwhile, three additional genetic variants of NUDT15 were reported in patients with acute lymphoblastic leukemia. We evaluated the effects of these additional genetic variants of NUDT15 in patients with inflammatory bowel disease (IBD) treated with thiopurines. METHODS Ninety-six Japanese patients with IBD were enrolled. Genotyping for the NUDT15 and TPMT genes was performed using Custom TaqMan SNP genotyping assays or Sanger sequencing. The changes in white blood cell (WBC) count, mean corpuscular volume (MCV), platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT, and ESR were evaluated. RESULTS Genetic variants of exon 1 and exon 3 of NUDT15 were identified in 24 of 96 patients (25.0%). C.52G > A and c.36_37insGGAGTC in exon 1 were found in three patients each. All three patients with c.36_37insGGAGTC in exon 1 were heterozygotes of p.Arg139Cys in exon 3. Eighteen patients had p.Arg139Cys in exon 3 alone. The WBC count gradually decreased after initiation of thiopurine treatment in the mutated cases (n = 24), and was significantly lower at 6, 8, 10, and 16 wk (P = 0.0271, 0.0037, 0.0051, and 0.0185, respectively). The WBC counts were also evaluated in patients with and without prednisolone treatment. In the patients with prednisolone treatment, the WBC count tended to show a greater decrease in the mutated cases, with significant differences at 8 and 10 wk (P = 0.012 and 0.029, respectively). In the patients without prednisolone treatment, the WBC count was significantly lower at 2, 4, 8, and 14 wk in mutated cases (P = 0.0196, 0.0182, 0.0237 and 0.0241, respectively). MCV increased after starting thiopurine treatment in the mutated cases, and was significantly higher at 10 wk (P = 0.0085). Platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT and ESR did not differ significantly between the wild-type and mutated cases. TPMT mutations were not found in any of the patients. CONCLUSION Mutations in exon 1 of NUDT15 also affect thiopurine-induced leukopenia in patients with IBD. To discuss thiopurine-induced leukopenia in more detail, investigation of SNPs in both exon 1 and exon 3 of NUDT15 is needed.

AimsSTAT3 is a key modulator of activation and differentiation of macrophages. But it is still unknown if deficiency of STAT3 activates macrophages to destroy erythrocytes by phagocytosis. We generated STAT3 conditional knockout mice by crossing floxed STAT3 mice with Tie2 promoter-driven Cre-recombinase transgenic mice and clarified that Stat3 plays a critical role in the formation and activation of macrophages.Main methodsBlood cell count, reticulocyte count, serum lactate dehydrogenase, erythropoietin, iron and ferritin concentration, and life span of the erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice were analyzed. To explore the erythropoietic function of the mice, we subjected them to brief hemolytic anemia by injecting them intraperitoneally with phenylhydrazine. The fragility of erythrocytes was examined by scanning electron microscopy and osmotic tolerance test.Key findingsThe conditional knockout mice had mild normocytic anemia. They also displayed higher lactate dehydrogenase, ferritin and erythropoietin concentration, higher reticulocyte count, and a shorter lifespan of erythrocytes compared with wild-type controls. These data suggest that destruction of erythrocytes and secondary blood formation were accelerated in the STAT3 conditional knockout mice. It didn't appear due to the fragility of erythrocytes. A few of the conditional knockout mice suddenly developed acute severe anemia, high body temperature and massive splenomegaly, and died within 2weeks after the onset of anemia.SignificanceThis study provided evidence that STAT3 have a critical role in the destruction of erythrocytes by resident macrophages in the spleen.

A novel apparatus for polarization measurement in the soft X-ray region has been designed, constructed, and installed in the evaluation beamline for soft X-ray optical elements (BL-11) at the SR Center of Ritsumeikan University, Shiga, Japan. It allows us to perform conventional reflection and transmission measurements including rocking curve measurement as well as polarimetric and ellipsometric measurements based on the rotating-analyzer method by using six independently movable motorized stages. As a preliminary test of the apparatus, the reflection profile of a Mo/SiO 2 multilayer mirror prepared by an ion beam sputtering technique, which is designed as a reflection polarizer for use of 13.9 nm, has been measured by the apparatus. The result is compared with that by an existing reflectometer, and the azimuth angle dependence of the reflection intensity has been demonstrated. Consequently, it is shown that the apparatus has the capability to perform the rotating-analyzer ellipsometry.

The extract from Panax ginseng has been reported to improve the microcirculation in various organs. However, the mechanisms underlying this phenomenon are still poorly understood. In the present study, using the rheological properties of erythrocytes as an index, we have screened the components of Panax ginseng extract and identified Rg(2) and Rh(1) as the active ingredients. These two ginsenosides prevented the oxidative stress-induced elevation of erythrocyte suspension viscosity and the impairment of erythrocyte elongation in response to shear stress. Rg(2) and Rh(1) ginsenosides did not have antioxidant activity in an aqueous phase and did not inhibit the peroxidation of membrane lipids, either. However, they inhibited the oxidation-induced decrease of SH-groups in band 3 (anion exchanger-1), one of the important structural proteins of the erythrocyte membrane, but not in other structural proteins: bands 1 and 2 (spectrins), band 4.2 or band 5 (actin). These results suggest that ginsenosides Rg(2) and Rh(1) protect the rheological functions of erythrocytes against oxidative stress by preventing the oxidation of SH-groups in band 3 protein.

Patients with ulcerative colitis suffer from long term impairment of quality of life, especially when subjected to repeated hospitalization. We aimed to identify factors that may predict future hospitalization.We followed 139 consecutive patients with ulcerative colitis for average of 11.2 years (2.8 to 49.5 years) from the onset. Clinical and endoscopic stagings were determined by Japanese staging system, the extent of colitis by Montreal classification and endoscopic grading by Matts' grade.Overall hospitalization rate was 37% at 5 years, 47% at 10 years and 60% at 20 years from the onset. Of 5 parameters including demographic and staging scores, univariate analysis revealed clinical severity at onset (p = 0.003), total colonoscopic findings on severity (Matts' grade, p = 0.003), and total colonoscopic findings on sites of abnormality (p = 0.012) were significantly correlated with hospitalization. By multivariate analysis, total colonoscopic findings on sites of abnormality was the only baseline character significantly related to the need of hospitalization (p = 0.0007). In fact, 5/10/20 years hospitalization rates were only 18/26/33 percent for proctitis type, whereas those were 61/72/90 for total colitis type.The total colonoscopic finding on sites of abnormality at the onset is the only predictdr of hospitalization in patients with ulcerative colitis.

Reelin plays an important role in the migration of embryonic neurons, but its continuing presence suggests additional functions in the brain. We now report a novel function where reelin protects P19 embryonal cells from apoptosis during retinoic acid-induced neuronal differentiation. This increased survival is associated with reelin activation of the phosphatidyl-inositol-3-kinase (PI3 K)/Akt pathway. When PI3 K was inhibited with LY294002, reelin failed to protect against this retinoic acid-induced apoptosis. The protective effect of reelin includes activating the Src-family kinases/PI3 K/Akt pathway which then led to selective phosphorylation of Bcl-2/Bcl-XL associated death promoter (BAD) at serine-136, while the phosphorylation-incompetent mutation of BAD (S136A) suppressed this protection. These and additional studies define a novel pathway where reelin binds apoE receptors, significantly activates the PI3 K/Akt pathway causing phosphorylation of BAD which helps to protect cells from apoptosing, thus serving an important role in promoting the survival of maturing neurons in the brain.

In order to perform transmission measurement of metallic sodium in the mm thickness range, we made the sample using a glove box which is quite different technique compared with the previous works. Using a CW source, we have made direct measurement of actual transmittance of a sodium sample with a thickness of 1 ~ 8 mm in the spectral range > 115 nm which is restricted by magnesium fluoride (MgF2) windows, resulting in, for example, ~ 50 % transmittance of a 3 mm thick solid sodium sample including the transmittance of the windows and the reflection losses at each interface at the wavelength of ~ 120 nm, with a very weak temperature dependence up to 150 °C which is beyond the melting point of 97 °C. To confirm the high transmittance, we set up a simple transmission imaging configuration with a 8-mm thick sodium sample, resulting in clear images composed of 100 µm diameter tungsten bars recorded on a Charge Coupled Device detector. The results show that a short pulse intense source such as high order harmonics as well as short pulse EUV plasma source opens a new technique for investigating dynamics of phase transitions as well as hydrodynamics of molten metal.

Electrostatic repulsive force among human red blood cells (RBCs) was observed by macromolecules-induced RBC aggregation and RBC flow behavior in narrow tube, by reducing the sialic acid content of RBCs with neuraminidase. The electrophoretic mobility of the RBCs was proportional to the sialic acid content. (1) When the sialic acid content was reduced, the RBC aggregation observed with a low shear rheoscope was enhanced with fibrinogen (MW=340,000), Ig G (MW=160,000) or Dextran T-70 (MW=70,400), but did not without the macromolecules. In coexistence of normal cells, sialic acid-reduced cells settled significantly faster, possibly due to their preferential aggregation by the macromolecules. (2) Sialic acid-reduced RBCs accumulated more to flow axis in narrow tube (20-50 μm in inner diameter), especially at acidic pH, as evaluated by the thickness of marginal cell-free layer using an image processor. The thickness was further increased with Dextran T-70 due to the RBC aggregation. Conclusively, electrostatic repulsive force among RBCs provided by sialic acid is important for understanding hemorheological behavior of the RBCs and circulatory disturbances in various diseases.

Previously, we reported that males with mental retardation (MR) (MR group) expended more energy than males without MR (control group) at a given work load. The precise physiological mechanisms for this difference remain unclear. Using the same set of subjects (23 age-, height-, and weight-matched male pairs, mean age: 36.3 y), we examined possible causes for the observed metabolic difference by monitoring physical movements and evaluating the metabolic capability of the skeletal muscles. In the supine position when no body movements were detected for any subjects, oxygen consumption (VO2) and heart rate (HR) were not markedly different between the MR and the control groups. By contrast, in the sitting and standing positions and during walking at 30 and 50 m/min, when significantly larger body movements were monitored in the MR group, VO2 and HR were significantly higher in this group than in the control group. Linear regression analyses, performed separately in the MR and control groups, revealed that the slope of the regression line of HR on relative exercise intensity (%VO2max) during walking, that of VO2 on walking speeds, and that of VO2 on the number of steps in the MR group were almost identical with those in the control group. These results suggest that the capability of skeletal muscles was not so different between the two groups. Thus, the high energy expenditure in the MR group was suggested to be a result of excessive body movements rather than an intrinsic incapability of skeletal muscles.

The effects of the oxygenation-deoxygenation process on red blood cell (RBC) aggregation were examined in relation to morphological changes in RBCs and the contribution of CO2. A low-shear rheoscope was used to measure the rate of rouleaux (one-dimensional aggregate) formation in diluted autologous plasma exposed to gas mixtures with different Po2and Pco2. RBC indexes and RBC suspension pH were measured for the oxygenated or the deoxygenated condition, and the cell shape was observed with a scanning electron microscope. In the oxygenation-deoxygenation process, the rate of rouleaux formation increased with rising pH of the RBC suspension, which was lowered in the presence of CO2. The rate increased with increasing mean corpuscular hemoglobin concentration (thus the cells shrank), which increased with rising pH and decreased in the presence of CO2. With rising pH, cell diameter increased and cell thickness decreased (thus the cell flattened). In addition, slight echinocytosis was induced in the presence of CO2, and the aggregation was reduced by the morphological change. In conclusion, RBC aggregation in the oxygenation-deoxygenation process is mainly influenced by the pH-dependent change in the surface area-to-volume ratio of the cells, and the aggregation is modified by CO2-induced acidification and the accompanying changes in mean corpuscular hemoglobin concentration and cell shape.

Unsteady forces acting on a square cylinder in oscillating flow with nonzero mean velocity are measured. The oscillating air flows are generated by a unique AC servomotor wind tunnel. The generated velocity histories are almost exact sinusoidal waves. The measured unsteady forces are examined in relation with the Morison equation and the contribution of the inertia term. It is confirmed that the Morison equation is applicable to explain the present experimental results. The fluid force coefficients, including the inertia coefficients, are evaluated for both in-line and transverse forces.

The effects of erythrocyte aggregation on O2release were examined using O2-permeable fluorinated ethylenepropylene copolymer tubes (inner diameter, 25 μm; outer diameter, 100 μm). Measurements were performed using an apparatus built on an inverted microscope that contained a scanning-grating spectrophotometer with a photon count detector connected to two photomultipliers and an image processor through a video camera. The rate of O2release from the cells flowing in the narrow tube was determined based on the visible absorption spectrum and the flow velocity of the cells as well as the tube size. When the tube was exposed to nitrogen-saturated deoxygenated saline containing 10 mM sodium dithionite, the flowing erythrocytes were deoxygenated in proportion to the traveling distance, and the deoxygenation at a given distance increased with decreasing flow velocity and cell concentration (hematocrit). Adding Dextran T-70 to the cell suspension increased erythrocyte aggregation in the tube, which resulted in suppressed cell deoxygenation and increased marginal cell-free-layer thickness. The deoxygenation was inversely proportional to the cell-free-layer thickness. The relation was not essentially altered even when the medium viscosity was adjusted with Dextran T-40 to remain constant. The rate of O2release from erythrocytes in the tube was discussed in relation to the O2diffusion process. We conclude that the diffusion of O2from erythrocytes flowing in narrow tubes is inhibited primarily by erythrocyte aggregation itself and partly by thickening of the cell-free layer.

To evaluate the rheological properties and the oxidative susceptibility of gamma-ray-irradiated red blood cells (RBCs).RBCs in mannitol-adenine-phosphate (MAP) medium were irradiated with 35 Gy and stored at 4 degrees C for 4 weeks. The deformability of the RBCs was examined under shear flow in relation to the morphological and biochemical changes. The RBCs were further exposed to 1 mM FeSO(4) and 5 mM ascorbate to examine the oxidative susceptibility.The RBC deformability was decreased during storage, and the impairment was further enhanced by the irradiation, which promoted cell shrinkage and intracellular hemoglobin condensation accompanying potassium loss. Lipid peroxidation and protein aggregation of the RBC membrane as well as echinocytosis were not enhanced by the irradiation. The exposure to free iron did not stimulate the oxidation of the irradiated RBC membrane.The decreased deformability of gamma-ray-irradiated RBCs in MAP medium was mainly induced by dehydration due to potassium loss, and the membrane lipids and proteins were stably preserved against oxidative stress.

Adult T-cell leukemia (ATL) is characterized by infiltration of various tissues by circulating ATL cells, a finding often associated with a poor prognosis. Leukocyte migration from the circulation into tissues depends on integrin-mediated adhesion to the endothelium, and integrins are tightly regulated by several factors, such as chemokines. In this study, we focused on the interaction between chemokines and chemokine receptors on ATL cells to understand factors involved in ATL cell infiltration of lymphoid organs. We compared freshly isolated ATL cells from patients with and without lymphoid organ involvement for the expression of the chemokine receptor CCR7/EBI1, the functional receptor for secondary lymphoid-tissue chemokine (SLC), which is expressed at high levels by high endothelial venules of lymph nodes and Peyer's patches. Reverse transcriptase-polymerase chain reaction and flow cytometric analysis, using anti-CCR7 monoclonal antibody (CCR7.6B3), revealed that ATL cells from patients with lymphoid organ involvement expressed significantly more CCR7/EBI1 than control CD4+CD45RO+ T cells and ATL cells from patients without lymphoid organ involvement. Consequently, significantly more ATL cells from patients with lymphoid organ involvement than control CD4+CD45RO+ T cells and ATL cells from patients without lymphoid organ involvement adhered to surfaces coated with ICAM-1 and SLC or EBI1-ligand chemokine (ELC), another ligand for CCR7/EBI1, under static and flow conditions and migrated toward SLC or ELC at a low concentration (30 ng/ml). These findings suggest that increased CCR7/EBI1 expression plays a role in lymphoid organ infiltration of ATL cells. (Blood. 2000; 30-38)

The present study was designed to evaluate the effects of free iron on normal red blood cells (RBCs) and possible mechanisms responsible for the alteration of the RBC rheological properties. Human RBCs (Ht 5%) were incubated for 1 h at 37°C with 0–2 mM FeSO 4 in the presence of ascorbate. Thiobarbituric acid reactive substances assay was employed to estimate lipid peroxidation and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate to analyze membrane proteins. A cone-plate viscometer, and low-shear and high-shear rheoscopes were used to compare the rheological parameters in Fe 2+ /ascorbate-treated RBCs with those of diamide-treated ones. The incubation of RBCs with free iron caused a dose-dependent increase in lipid peroxidation, enhanced binding of hemoglobin to the cell membrane, diminishing of band 3 content and the concomitant increase in lower molecular weight peptides (approximately 60 and 35 kDa), while the incubation with diamide resulted in spectrin crosslinking. Both diamide and Fe 2+ /ascorbate treatment impaired RBC deformability and aggregation. The suspensions of Fe 2+ -treated RBCs manifested increased viscosity, presumably due to enhanced formation of three-dimensional aggregates. In conclusion, although in both these cases of oxidative stress the ultimate result was the deterioration of membrane structure and functions, the mechanisms of oxidative changes of the RBCs rheological properties were apparently dissimilar.

Thiol-compounds, dithiothreitol (DTT) and N -acetylcysteine (NAC), were examined for their antioxidant effects on Fe 2+ /ascorbate-treated and diamide-treated red blood cells (RBCs). Both of the compounds protected RBCs against diamide-induced spectrin crosslinking; they also prevented loss of deformability and aggregation impairment in diamide-treated cells. Neither DTT nor NAC were effective in suppressing lipid peroxidation induced by Fe 2+ /ascorbate treatment. DTT showed a limited protective effect on iron-mediated band 3 fragmentation and RBC deformability, but it was capable of preventing the decrease of rouleaux formation rate to some extent. NAC exhibited a dose-dependent band 3 protective activity, partially prevented Fe 2+ /ascorbate-induced deformability impairment and the decrease of rouleux formation rate. These findings suggest that thiol compounds are effective in modulating diamide-induced oxidative alterations of RBCs membrane constituents and rheological properties. NAC is more efficacious than DTT in protecting RBCs against iron-mediated oxidative injury, which can be attributed to its potent reductant and radical scavenging abilities.

The effects of supplemental night lighting and nitrate exclusion in the nutrient solution on the growth, nitrate concentration, and nitrate reductase activity (NRA) in the leaf of spinach plants grown under NFT and natural light in the greenhouse were studied. When the plants became of marketable size, they were grown in a nutrient solution without nitrate and exposed to artificial lighting of different light intensities and qualities from 23 : 00 to 6 : 00 1. Two days after treatments, top fresh weight was not affected by nitrate exclusion, whereas 7 days after treatments, plant growth was markedly reduced by nitrate exclusion. However, supplemental night lighting after nitrate exclusion on the subsequent growth of spinach were ineffective. 2. After nitrate exclusion, sap nitrate concentrations of leaf blades and petioles under supplemental night lighting decreased more rapidly than that without the treatment. The decrease of sap nitrate concentrations was unaffected with light quality. However, light intensities affected markedly, and the sap nitrate concentrations of leaf blade at two days after treatment were 1, 059, 799, 612 and 531 ppm under 0 (without lighting), 50, 150 and 250 m mol m-2s-1 (PPFD), respectively. 3. NRA of the plants with supplemental night lighting was higher than that without lighting.

Zinc finger protein 521 (ZFP521) regulates a number of cellular processes in a wide range of tissues, such as osteoblast formation and adipose commitment and differentiation. In the field of neurobiology, it is reported to be an essential factor for transition of epiblast stem cells into neural progenitors in vitro. However, the role of ZFP521 in the brain in vivo still remains elusive. To elucidate the role of ZFP521 in the mouse brain, we generated mice lacking exon 4 of the ZFP521 gene. The birth ratio of our ZFP521 Δ/Δ mice was consistent with Mendel's laws. Although ZFP521 Δ/Δ pups had no apparent defect in the body and were indistinguishable from ZFP521+/+ and ZFP521 +/Δ littermates at the time of birth, ZFP521 Δ/Δ mice displayed significant weight reduction as they grew, and most of them died before 10 weeks of age. They displayed abnormal behavior, such as hyper-locomotion, lower anxiety and impaired learning, which correspond to the symptoms of schizophrenia. The border of the granular cell layer of the dentate gyrus in the hippocampus of the mice was indistinct and granular neurons were reduced in number. Furthermore, Sox1-positive neural progenitor cells in the dentate gyrus and cerebellum were significantly reduced in number. Taken together, these findings indicate that ZFP521 directly or indirectly affects the formation of the neuronal cell layers of the dentate gyrus in the hippocampus, and thus ZFP521 Δ/Δ mice displayed schizophrenia-relevant symptoms. ZFP521 Δ/Δ mice may be a useful research tool as an animal model of schizophrenia.

Metallic sodium (Na) was proposed as a transparent material in the vacuum ultra-violet (VUV) spectral range in 1930s and in 1960s. However no clear transmission has ever been demonstrated. In this paper we describe firstly the direct measurement of actual transmittance of a sodium samples in a spectral range longer than 115 nm which corresponds to the shortest transmission wavelength of magnesium fluoride (MgF 2 ) windows, resulting in several tens of % transmittance of a 3 mm-thick solid sodium sample including MgF 2 windows at the wavelength of ~120 nm. We also find very weak temperature dependency of the transmittance up to 150 degrees centigrade where the solid sample is melted at 97 degrees. The measured transmittance pushes us to make a simple imaging experiment illuminated by the VUV light through a 2-mm thick sodium sample, resulting in obtaining a clear image composed of 100 μm diameter tungsten mesh recorded on a two dimensional Charge Coupled Device detector. The result also opens a way to construct an optical imaging device for objects inside or through a solid or a liquid sodium medium. According to the present experiment, we can make a continuous real time transmission imaging for a liquid sodium sample if we use proper optical setup including an intense continuous VUV source or high repetition rated intense coherent source for holographic data acquisition. Such an experiment opens up a way to perform transmission imaging through or inside a sodium medium for characterization of hydrodynamic and material properties.

Microglia transform from ameboid to ramified cells during development and display an ameboid appearance again under certain pathological conditions. Some cytokines produced by astrocytes may be responsible for the microglial transformation. In the present study, we compared the effects of cytokines, granulocyte/macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3) on the morphology of rat cultured microglia. For quantitative evaluation, we employed "transformation index" as calculated by (perimeter of cell)2/4 pi (cell area). GM-CSF facilitated the ramification of cultured rat microglia, which was effectively induced in a serum-free medium. However, M-CSF and IL-3 did not induce the ramification. A certain serum adhesion protein (possibly vitronectin) as well as other high molecular weight substances in fetal calf serum inhibited the GM-CSF-induced microglial ramification. Among ordinary supplements for a chemically defined medium, progesterone, insulin, and a high concentration of glucose suppressed the ramification. These findings suggest that GM-CSF may be involved in microglial ramification and that many kinds of supplements that are added to culture media profoundly affect the morphology of microglial cells.

The deformation of erythrocytes in microvessels less than 15 microns in inner diameter was analyzed using a microvascular bed isolated from rabbit mesentery. The deformation was compared with that found in glass capillaries.Human erythrocytes were perfused through two media: first, a microvascular-bed section isolated from rabbit mesentery; and second, a set of glass capillaries. Images of deformed erythrocytes were recorded on videotape under strobe light and analyzed with an image processor. The flow velocity of the erythrocytes was determined from the difference of their positions between video frames or by a dual-spot cross-correlation technique. Erythrocyte deformability was modified with diamide, diazene dicarboxylic acid bis[N,N-dimethylamide], by crosslinking spectrins.Symmetrical (parachute-like or slipper-like) deformation of erythrocytes was observed only in microvessels smaller than 13 microns in inner diameter. Erythrocytes in microvessels were less deformed than those in glass capillaries with corresponding diameters, and the marginal cell-free layer was narrower. The deformation increased by increasing the flow velocity of erythrocytes, and the cell-free layer became wider. Diamide-treated cells in microvessels were less deformed than normal cells and showed slightly narrower cell-free layers. Stronger stress in narrower microvessels induced further deformation of cells.Erythrocyte deformation in microvessels was essentially different from that in glass capillaries, and the effect of erythrocyte deformability on the flow dynamics of erythrocytes in microvessels was properly evaluated using an isolated microvascular bed.

Rheological characteristics of red cells in two patients with refractory anemia (with single chromosomal abnormality of 20q- or 13q-, respectively) were investigated with the hematological and biochemical properties. (1) Whole blood viscosity was remarkably increased, and the red cell deformability was greatly impaired (the impairments were prominent in patient with 20q-). (2) The hematocrit of both patients was about half of the normal value. Remarkable anisocytosis with elliptocytes and poikilocytes was observed in the patient with 20q-, but the anisocytosis was not so prominent in the patient with 13q-. (3) 2,3-diphosphoglycerate content in red cells was markedly increased in both patients, but adenylate content was not. (4) The red cells were slightly resistant to osmotic hemolysis, but they were not heat-labile. (5) Structural abnormality of spectrin was suggested from the impaired dimer-dimer association in red cell membrane and from the different susceptibility of spectrin to tryptic digestion. In conclusion, the rheological impairments and the abnormal shape of red cells in refractory anemia probably originated from the structural abnormality of cytoskeletal proteins in membrane, and the functional and structural abnormality may be different among patients.

In an attempt to explore the process of naturally occurring secretory leukoprotease inhibitor (SLPI) fragmentation, the cleavage profile of SLPI, which had been prepared by recombinant techniques, was investigated biochemically. Restricted fragments of SLPI were detected using SDS-PAGE after treatment with human neutrophil elastase (NE) or normal saliva and sequenced at their cleavage sites. Among these restricted fragments, two species of nearly half-length SLPIs that contained the C-terminal domain, (Arg58-Ala107)SLPI and (Arg59-Ala107SLPI, were detected. They were both as active at inhibiting NE as the parent SLPI. These results suggest that functional SLPI derivatives may be generated physiologically in the respiratory tract under inflammatory and healthy conditions.

Nemaline myopathy is a representative form of congenital myopathy, and is characterized by nemaline bodies in muscle fibers. Here we report a 47-year-old man with congenital nemaline myopathy complicated with dilated cardiomyopathy-related heart failure, and restrictive respiratory failure. The complication of dilated cardiomyopathy in nemaline myopathy has rarely been reported. In this case, nemaline bodies were detected in the cardiac muscle fibers, demonstrating the presence of underlying disease-related myocardial degeneration. The patient responded to the combination of conventional therapy for heart failure including β-blocker and noninvasive continuous positive-pressure ventilation for respiratory failure. His general condition has been stable during a 10-month follow up period.

With use of photon techniques including visible light, soft and hard x-rays, precise fundamental laser welding processes in the repair and maintenance of nuclear plant engineering were reviewed mechanistically. We make discussions centered on the usefulness of an intense soft x-ray beams for evaluations of spatial residual strain distribution and welded metal convection behavior including the surface morphology. Numerical results obtained with a general purpose three-dimensional code SPLICE for the simulation of the welding and solidifying phenomena. Then it is concluded that the x-ray beam would be useful as one of the powerful tools for understanding the mechanisms of various complex phenomena with higher accuracy and higher resolution.

Hypertension is one of the risk factors of cardiovascular diseases, which are widely prevalent maladies that result in burdensome medical expenditures. Therefore, it is important to explore primary preventive measures for hypertension. Until recently, it was thought that exercise was a risk factor for hypertension, but recent reports have suggested that low-intensity physical training actually lowers blood pressure. However, habitual physical exercise has still not been clearly proven to prevent the development of hypertension. To clarify this point, one must first establish a method for predicting hypertension and second examine the possibility of preventing the development of hypertension by changing the subject's environment. In this study we have investigated a method for predicting hypertension by classifying blood pressure responses to increasing exercise intensity and the effect of habitual exercise on blood pressure response.This study was composed of three experiments. Experiment one involved female students (n=42) and experiment two, male students (n=38), in whom blood pressure response rates during exercise were recorded. In experiment three, the same group of female students (n=23) was subjected to training in order to chart its effects on blood pressure response, both while exercising and while at rest. The exercises were performed with a bicycle ergometer in an upright position. There were four different degrees of work intensity. Blood pressure was measured using the auscultation method, with Riva-Rocci mercury measured by the same investigator.High blood pressure responses at rest were noted among some normotensive female and male students. The systolic blood pressure responses during the peddling exercise showed significant individual differences at the lowest work load; the distribution of the increment of the systolic blood pressure ratio at the lowest work load against the increment while resting showed two peaks. This result suggests that this increment ratio is an important variable related to the prediction of hypertension. The increment ratio showed no significant change in female students after three months of aerobic exercise.The high-response group showed high readings of the TPR indicator (MBP/VO2). Aerobic training was shown to be effective in significantly lowering the TPR indicator both at rest and during exercise. This result suggests that habitual exercise may contribute to preventing the development of hypertension.

CPD blood, in glass containers and polyvinyl chloride (PVC) bags, was X-irradiated with 50 Gy (n = 4), and then stored for up to 4 weeks. Rheological, hematological and biochemical changes of the red cells during storage were examined. Changes in blood viscosity and various properties of red cells (deformability, shape, hematological indices and concentrations of 2,3-diphosphoglycerate and nucleotides) during storage at 4 degrees C were not altered by the irradiation. The rheological, biochemical and morphological properties of red cells were as well preserved in PVC bags as in glass containers. No abnormal and/or cross-linked proteins in red-cell membranes were induced by the irradiation. Irradiation of PVC bags did not affect the above properties of red cells through any changes in the bag constituents. In conclusion, X-ray irradiation with 50 Gy to CPD blood in PVC bags does not affect the rheological functions of red cells.

Linear polarization measurements were carried out using a newly developed soft x‐ray polarimeter and ellipsometer (SXPE) for complete polarization analysis at a soft x‐ray beamline (BL‐11) of the SR Center, Ritsumeikan University, Japan. A Mo/Si multilayer mirror (period: 10.36 nm, ratio of Mo layer to period: 0.64, and 23 bilayers with topmost Si layer) was deposited on the surface of a commercial Si(111) substrate by an ion beam sputtering method. It was cut into two pieces which were then used as reflection‐type polarizers. When the incident wavelength was scanned from 12.4 nm to 14.8 nm by a Monk‐Gillieson type varied‐line‐spacing grating monochromator of the BL‐11, the angles of incidence of both the Mo/Si multilayer polarizers in the SXPE were also varied from 37.5° to 52.3°. The polarizances depended strongly on the wavelength, and the best performance of over 99% was obtained in the vicinity of 14 nm. Using these polarizers, we assessed that the degree of linear polarization of the BL‐11 was almost constant at 85–88% in the measured wavelength range.

In pneumonia in the elderly, one occasionally encounters difficulties in evaluation with respect to both clinical observation and treatment. Thus a simple serum indicator is indicated. We measured secretory leukoprotease inhibitor (SLPI) concentrations in sera to see whether this can provide a useful indicator for pneumonia, especially in the elderly. Serum samples from patients over 65 yr of age, with (n = 54) or without (n = 87) pneumonia, and from healthy, young (n = 16) and aged (n = 188) control subjects were assayed using ELISA for human SLPI. Comparisons were made between groups with clinical diagnoses of either definite or probable pneumonia and among cases with various other respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease, and lung cancer. The mean SLPI concentration in patients with pneumonia was significantly higher than in patients without pneumonia or in healthy controls. The data suggest that the measurement of SLPI can provide a useful indicator for pneumonia to be used in clinical evaluation.

Ion extraction from a cold plasma produced by laser multiphoton ionization has been enhanced by using radio-frequency (140 MHz) dielectric plasma heating. When 10 W in heating power is applied to a plasma of ion density around 3×1010 cm−3, it is observed that the peak ion flux extracted with an electrostatic voltage of 20 V increases by a factor of more than 2. The time for extracting all the ions becomes short by a factor of 3 without any production of radio-frequency discharged plasma. It is considered that these results are due to the increase in the electron temperature of the plasma. This method will be very useful for the process of ion extraction in atomic vapor laser isotope separation.

An experimental study of the enhancement of the electron temperature of a laser-induced plasma by use of radio-frequency dielectric heating has been carried out. A radio-frequency electric field of 140 MHz is used to heat the plasma produced by multistep resonant photoinization. It is clearly observed that the electron temperature increases from 0.3 to 1.0 eV when a radio-frequency input power of 1.0 W is applied. Also, applying heating induces a plasma oscillation. This is due to the generation of ion waves in the plasma, and therefore, means that the enhanced electron temperature is higher than the ion temperature. It is expected that this method will improve the efficiency for extracting ions rapidly from a laser-induced plasma in atomic vapor laser isotope separation.

A new apparatus for polarimetric and ellipsometric measurements based on the rotating-analyzer method in the soft x-ray region has been designed, constructed, and installed in the soft x-ray beamline (BL-11) at the SR Center of Ritsumeikan University, Shiga, Japan. It can realize the optical configurations for the complete polarization analysis by using six independently movable drive shafts. A demonstration of the capabilities of the apparatus has been performed using Mo/Si multilayer polarizers deposited by an ion beam sputtering method. It is for the first time shown that the degree of linear polarization of monochromatized light from the BL-11 is approximately 87% at 92 eV since the beamline has been constructed.

On the basis of actual data on the frequency response (FR) of CH{sub 4}, C{sub 2}H{sub 6}, and C{sub 3}H{sub 8}/5A zeolite systems it is shown that various transport processes of diffusion and also adsorption-desorption occurring simultaneously can be separately investigated by the present method. The FR data of the light hydrocarbons reveal that (1) in the higher equilibrium temperature (T{sub e}) range the overall sorption kinetics is partially blocked by the surface resistance, (2) in the lower T{sub e} range the overall kinetics is explained well by the dual-mode sorption model involving mobile and immobile adspecies, and (3) only in the intermediate narrow T{sub e} range is the transport controlled by a single intracrystalline diffusion process. The Fickian diffusivities deduced from the FR data of the complex system involving a number of the additional phenomena were 1 order of magnitude higher than the values obtained from classical sorption-rate measurements and 4 orders of magnitude lower than those by the NMR method. The advantages of the present new method are discussed.

A 73-year-old woman was diagnosed with diffuse large B-cell lymphoma of the uterus (Stage IVB). After 3 courses of CHOP therapy, right abducens nerve paralysis appeared and was diagnosed as central nervous system infiltration with lymphoma cells. Although partial remission was obtained by chemotherapy with methotrexate, numbness and muscle weakness of all four limbs appeared asymmetrically and progressed subacutely. Nerve conduction velocity examination revealed mononeuritis multiplex, but we could not reach a final diagnosis. Steroid pulse therapy, chemotherapy including high-dose methotrexate, and radiation therapy were ineffective. On autopsy, histological examination of the peripheral nerves revealed systemic neurolymphomatosis.

Effect of 2,3-diphosphoglycerate (2,3-DPG) on the deformability of human erythrocytes was examined with a rheoscope under shear stress of 8-82 dyn/cm2. With increasing 2,3-DPG in erythrocytes (from 5 to 15 mM/l cells) by incubating with inosine and pyruvate in isotonic 50 mM phosphate-buffered saline, erythrocyte deformability under uniform shear stress was remarkably impaired. But reduction of 2,3-DPG (from 5 to 2.2 mM/l cells) did not affect the deformability. In 2,3-DPG-enriched erythrocytes, increased intracellular hemoglobin concentration (MCHC), decreased intracellular pH, and increased contents of ATP and IMP (and ITP) were observed. (1) When the MCHC (i.e., the internal viscosity) was normalized by suspending in hypotonic medium, the deformability of 2,3-DPG-enriched erythrocytes was greatly improved, but still decreased. (2) The change of intracellular pH between 6.5 and 7.5 (as compared adjusting to same MCHC) did not alter the deformability. (3) The changes of purine nucleotides, ATP (0.6-2.1 mM/l cells), IMP (0-0.9 mM/l cells) and ITP (0-0.5 mM/l cells) did not alter the erythrocyte deformability. In conclusion, decreased deformability of erythrocytes induced by augmentation of 2,3-DPG is due mainly to the increased internal viscosity and due partly to the increased membrane viscoelasticity.