Search

Variations inWe present a Japanese family with a novelThe missense variation (c.265TC, p.Trp89Arg) inThis study might have revealed an example of a monogenic origin of atypical parkinsonism in females with

Splenomegaly severely compromises the quality of life of those affected. The aim of the present study was to describe the clinical characteristics of patients with haematological disorders who receive radiotherapy for splenomegaly, particularly focusing on the changes in spleen volume. The present study conducted a retrospective analysis of consecutive patients with haematological disorders who underwent splenic radiotherapy with palliative intent at the Department of Radiology of the University of Tokyo Hospital between June 2008 and June 2019. Pre- and post-radiotherapy spleen volumes were measured from computed tomography images. A total of 8 patients (5 men and 3 women) with a median age of 59 years (range, 46-76 years) were included. The median total prescription and fractional doses were 4.5 Gy (range, 1.5-10 Gy) and 0.78 Gy (range, 0.5-2.0 Gy), respectively. A total of 5 patients (62.5%) experienced a reduction in spleen volume. The mean ± SD spleen sizes pre- and post-radiotherapy were 1,887±1,011 and 1,368±577 ml, respectively. The mean variation rate in spleen volume was -19.1±24.7%, and the case with the most notable improvement in the present study exhibited a -52.4% change. Of the 5 patients who experienced pain prior to radiotherapy, 3 achieved pain relief, 1 did not experience any change and 1 patient was not assessed post-radiotherapy. Therefore, the findings of the present study revealed that palliative radiotherapy for splenomegaly may achieve symptom palliation and radiological volumetric effects in patients with haematological disorders.

Background and ObjectivesVariations in SLC9A6 cause the X-linked neurologic disorder Christianson syndrome in males. Meanwhile, female carriers with SLC9A6 variations may remain asymptomatic or develop intellectual disability, behavioral problems, and psychiatric illnesses. Only a few female carriers have been reported to have associated atypical parkinsonism in late life.MethodsWe present a Japanese family with a novel SLC9A6 variation identified by quad whole-exome sequencing analysis and a reverse phenotyping strategy. The molecular and cellular impacts of the W89R variation in vitro were examined.ResultsThe missense variation (c.265T>C, p.Trp89Arg) in SLC9A6 cosegregated with atypical parkinsonism and intellectual disability in female carriers of this family. The female carriers in this family presented with bradykinesia, rigidity, and tremor, predominately on the right side. We found that the W89R variation changed membrane traffic of NHE6-harboring vesicles, indicating potential involvement in the disease pathogenesis.DiscussionThis study might have revealed an example of a monogenic origin of atypical parkinsonism in females with SLC9A6 variations and draw attention to this understudied female-specific phenotype in clinical practice.

Harvesting energy from pedestrians can be used to power sensors in smart infrastructure, monitor structural health, and provide environmental sensing data. This paper presents a novel paver that efficiently harvests energy from human walking. Within the paver, a permanent magnetic motor is used as an electric generator. Racks, pinions, gears and a one-way-clutch are employed to convert the up-and-down motion of the paver’s top panel to the unidirectional rotational motion of the electric generator. A flywheel is attached to the electric generator to take full advantage of the theoretically available potential energy during human walking. A dynamic model is developed with the consideration of Coulomb friction, electrical damping and mechanical damping. Based on the model, parameters of the energy harvesting paver are analyzed to optimize the harvested energy from human walking. The experimental results show that, during typical human walking, the energy harvesting paver can produce an average electrical power of 3.6 W, with a peak value of 12 W. The average harvested energy is 1.8 J per step. The roles of the flywheel and electrical load in changing the amount of harvested energy are discussed. The flywheel’s influence to energy harvesting in walking, fast walking and running conditions are compared and discussed. The energy harvesting paver has potential applications in high-volume pedestrian paths and areas such as sport arenas, airports, railway stations, shopping malls, offices and apartment blocks.

Background: The Sousou area (Sousou) of Fukushima Prefecture, in which the Fukushima nuclear power plant is located, has a general population of 100,000, and approximately 200 hemodialysis (HD) patients. A substantial number of these patients are unable to receive HD at their local HD centers due to the serious shortage of medical staff worsened by the Great East Japan Earthquake and tsunami, and nuclear power plant accident. To receive HD, they must go to the Midorinosato Clinic (MC), a HD center in Miyagi Prefecture, located approximately 30-50 km north of Sousou. The number of such patients is now constantly increasing. Methods and findings: We collected detailed information on 30 consecutive HD patients living in Sousou who were referred to the MC between December 22, 2014 and October 31, 2016. Of them, 10 patients who received HD 53.7 ± 18.5 times on an outpatient basis at the MC were accepted by HD centers in Sousou when spaces became available (Group A). However, no fewer than 12 patients were still receiving HD at the MC as of the end of October 2016 (Group B). In three patients, chronic kidney disease (CKD) was conservatively managed with a view to introduce HD at the MC (Group C). Five patients followed different clinical courses (Group D). Group D included patients who were referred to but could not go to the MC to receive HD for medical reasons such as severe cardiac failure and visual impairment. Conclusions: A solution to the ongoing situation in Sousou where patients cannot receive HD at local facilities has yet to be found.

Installed during the Tohoku earthquake relief fundraising event, CONCERT FOR JAPAN, at Japan Society in New York City on April 2011, the Luminous Washi Lanterns was a meditation and celebration of renewal through light and impermanent materials. The paper examines the role of the ephemeral from the ancient to contemporary Japanese culture, collective experience during an ephemeral performance, and translation of traditional Japanese renewal rituals into a piece that engages a diverse range of people outside of Japan. How can designers instigate a process of renewal following a disaster in manners that engage people of all ages and backgrounds in a collective healing experience?

Background. Glomerular hypercellularity due to resident glomerular cell proliferation and leucocyte infiltration has been described in acute poststreptococcal glomerulonephritis (APSGN). APSGN usually resolves without progression. However, the mechanism of resolution remains to be determined. Methods. Renal biopsy tissues from 15 patients with APSGN (obtained 1–31 days after disease onset) and five control patients with minor glomerular abnormality were evaluated with respect to glomerular resolution. Apoptotic cells were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) as well as by immunostaining of single-stranded DNA (ssDNA). Results. The number of glomerular cells was high in the early-phase of APSGN and decreased over time. No TUNELþ glomerular cells were found in control subjects, whereas prominent glomerular TUNELþ cells were observed in APSGN patients, particularly in the early phase of the disease. The number of glomerular TUNELþ cells decreased exponentially but was still prominent in renal tissue biopsied at 31 days after disease onset. Double staining for ssDNA and glomerular cell markers showed that glomerular apoptotic cells were predominantly mesangium and endothelial cells, with some neutrophils and macrophages. Conclusions. These results suggest that apoptosis exists in the glomerulus in patients with APSGN from the early to the late stages of the disease and contributes to the resolution of glomerular hypercellularity.

The course of rapidly progressive glomerulonephritis (RPGN) caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is often life-threatening, especially in the elderly when pulmonary involvement and/or severely impaired renal function are present. Corticosteroids and cyclophosphamide are the first-line treatment, but ironically infection, not vascular events such as hemorrhage, caused by the vasculitis itself, is the most common cause of death of RPGN patients. Several new treatment strategies, such as leukocytapheresis (LCAP) and intravenous immunoglobulin (IVIg), have become available during the past decade and these treatments have made it possible to treat high-risk RPGN patients without inducing serious immunosuppressive states. In the present paper we review recent clinical trials of LCAP and IVIg therapy in patients with pauci-immune/ANCA-associated RPGN, and show improved clinical outcomes after using these new treatment strategies in our institution.

Galectin-3, a multifunctional β-galactoside-binding lectin, is known to participate in development, oncogenesis, cell-to-cell attachment, and inflammation. We studied to determine whether galectin-3 is associated with cell injury and regeneration in two types of acute renal failure (ARF), namely ischemic and toxic ARF. In ischemia/reperfusion renal injury in rats (bilateral renal pedicles clamped for 40 minutes), galectin-3 mRNA began to increase at 2 hours and extended by 6.2-fold at 48 hours (P < 0.01 versus normal control rats), and then decreased by 28 days after injury. In addition, a significant negative correlation between galectin-3 mRNA expression and serum reciprocal creatinine was shown at 48 hours after injury (n = 13, r = −0.94, P < 0.0001). In folic acid-induced ARF, galectin-3 mRNA was found to be up-regulated at 2 hours after injury and increased levels continued until at least 7 days post-injury. In immunohistochemistry, at 2 hours following reperfusion, galectin-3 began to develop in proximal convoluted tubules. From 6 hours up to 48 hours, galectin-3 was also found in proximal straight tubules, distal tubules, thick ascending limbs, and collecting ducts. In later stages of regeneration, galectin-3 expressions were found in macrophages. In conclusion, we demonstrated that galectin-3 expressions were markedly up-regulated in both ischemic and toxic types of ARF. Galectin-3 may play an important role in acute tubular injury and the following regeneration stage.

Regulation of GH-releasing hormone receptor (GHRH-R) messenger RNA (mRNA) expression was studied, with the ribonuclease protection assay, in the fetal rat pituitary gland and in MtT-S clonal cells. GHRH-R mRNA was first detected on embryonic day (E)19 and increased rapidly thereafter, to reach a maximum at E21. Incubation of E17 or E18 pituitaries with 50 nM dexamethasone (DEX), a synthetic glucocorticoid, induced GHRH-R mRNA expression, suggesting that glucocorticoids play a pivotal role in the developmental expression of this mRNA. In E19 pituitaries, 24 h treatment with DEX increased GHRH-R mRNA by 60%, and GH mRNA by 76%, but did not affect pit-1 mRNA level, suggesting that the effect of DEX is specific for expressions of GH mRNA and GHRH-R mRNA. The accumulation of GHRH-R mRNA by DEX was time dependent, and it was slightly enhanced by the protein synthesis inhibitor, puromycin (100 microM). In MtT-S cells (a pituitary cell line established from an estrogen-induced tumor), DEX induced GHRH-R mRNA expression within 2 h in a dose-dependent manner. This induction was augmented by puromycin (100 microM) or cycloheximide (3.5 microM). However, the RNA synthesis inhibitor Actinomycin D (1 microM) completely inhibited GHRH-R mRNA accumulation in response to either DEX or DEX plus puromycin, suggesting that glucocorticoids induce GHRH-R mRNA mainly through stimulation of mRNA transcription. These results suggest: that GHRH-R mRNA accumulation in the fetal pituitary gland of rats normally occurs at E19, probably because of the direct action of glucocorticoids on the pituitary gland, to stimulate GHRH-R mRNA transcription; and that the expression of glucocorticoid receptors is an important event in GH cell development in rats. Accordingly, immunocytochemical results suggest an increase in glucocorticoid receptors in immature GH cells between E17 and E18. The present results also imply that MtT-S cells may be a good model in which to further study the molecular mechanisms of the regulation of GHRH-R gene expression.

The liquid-phase oxygenation of benzene was studied using supported vanadium(V) catalysts. Molecular oxygen and ascorbic acid were used as the oxidant and reducing reagent, respectively. The reduced vanadium species is suggested to be the active catalytic species in this reaction system. The catalytic activity of the supported V catalysts for phenol formation was found to be somewhat higher than those of supported Cu counterparts. The addition of Cu ions to the supported V catalyst caused an increase in the yield of phenol. The leaching of the catalytically active V species from the support during the liquid-phase oxidation was also inhibited by the addition of Cu ions to the supported V catalysts. The concentration of acetic acid in the aqueous solvent was found to have an optimum value for the phenol production. The formation of hydrogen peroxide was observed during the benzene oxidation catalyzed by the supported V catalyst, and the accumulated amount of the formed hydrogen peroxide was quantitatively detected by iodometry. The electronic absorption spectra of the reaction solution including the V species also indicated the formation of hydrogen peroxide during the benzene oxidation. The produced hydrogen peroxide was suggested to directly participate in the phenol formation from benzene.

Two cases of rapidly progressive glomerulonephritis (RPGN) with skin vasculitis-associated anti-neutrophil cytoplasmic antibody (ANCA) are examined. Both cases showed purpura on the lower legs on admission and subsequently revealed renal or pulmonary vasculitis. One case responded positively to oral prednisolone alone, but the other case showed high ANCA titer and renal—pulmonary vasculitis. We discuss the diversity of clinical symptoms and the titer of antibody-associated vasculitis.

It is known that growth hormone (GH) contributes to glomerulosclerosis and that this probably occurs via insulin-like growth factor-I (IGF-I). However, the manner by which GH and nephrectomy (Nx) alter IGF-binding protein (IGFBP) mRNA in the kidney has not been fully explained. The effects of GH on renal IGF-I and IGFBP-1, 2, 3, 4, and 5 following Nx were examined in spontaneous dwarf rats (SDRs) which have a complete and specific lack of GH among pituitary hormones. In normal Sprague-Dawley rats (SDs), Nx resulted in significant decreases in levels of IGFBP-1 mRNA and IGFBP-5 mRNA to 62.7 ± 4.9 and 56.5 ± 5.0% those of sham-operated kidneys, respectively. Nx did not alter the IGF-I mRNA level in SDs. The levels of IGFBP-2, IGFBP-3, and IGFBP-4 mRNAs were likewise unchanged following nephrectomy. In SDRs, Nx significantly decreased the levels of IGFBP-1, IGFBP-4, and IGFBP-5 mRNA, to 57 ± 2.6, 46 ± 12, and 64 ± 8.1% of sham-operated animals. However, Nx did not alter the levels of IGF-I, IGFBP-2, and IGFBP-3 mRNA. GH injections of nephrectomized SDRs fully normalized the decreased IGFBP-4 mRNA levels, whereas levels of IGFBP-1 and IGFBP-5 mRNA were not reversed. The altered expression of IGFBP-4 mRNA following Nx of SDRs compared to that of SDs appears highly significant since it is known that, unlike SDs, glomerulosclerosis does not fully develop in SDRs following renal ablation. The change in the IGFBP-4 mRNA level might be related to the development of glomerulosclerosis in SDs.

To investigate the time sequence of glomerular cell proliferation in acute human glomerulonephritis, renal biopsy tissues were examined from 15 acute post-streptococcal glomerulonephritis (APSGN) patients (who were biopsied 1-31 days after onset), using an immunoperoxidase technique with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) and various cell surface markers. Few, if any, PCNA+ cells were observed in normal glomeruli, but many cells were positive for PCNA in the acute phase of APSGN. Glomerular PCNA+ cells were observed either within glomerular tufts, or lining Bowman's capsule (parietal epithelial cells); the number of positive cells tended to decrease exponentially as the disease duration increased (r = -0.91, P < 0.0001). PCNA+ cells within glomerular tufts were further identified by double immunostaining. PCNA was not found in PMN or T cells, but a small proportion of macrophages were PCNA+. Most of the remaining PCNA+ cells were resident glomerular cells; the proportion of PCNA+ endothelial cells (CD31+) was over 80 per cent in the early phase, but as the disease continued the proportion of mesangial cells (alpha-smooth muscle actin+) increased to about half of the total PCNA+ cells within the tuft. These data indicate that the hypercellular glomeruli in APSGN are due not only to immune cell infiltration, but also to resident glomerular cell proliferation, probably induced by locally produced growth factors.

This study was performed to investigate the role of cell-mediated immunity in lupus nephritis (LN). Frozen sections from 38 patients with LN were examined by indirect immunoalkaline-phosphatase labeling using monoclonal antibodies to identify the immune cells infiltrating into the interstitium and glomerulus. 14 patients showed minor glomerular abnormality (MGA), 9 had mesangial LN (MesLN), 12 had diffuse proliferative LN (DPLN) and 3 had membranous LN (MLN). Monocyte/macrophage and helper/inducer T cells infiltrated in the interstitium predominantly, but intraglomerular infiltration of these cells was rare. Monocyte/macrophage and suppressor/cytotoxic T cell levels were significantly higher (p < 0.05) in the interstitium in DPLN patients and monocyte/macrophage level was significantly higher (p < 0.05) in MesLN patients than in MGA patients. In the interstitium, serum creatinine level was highly correlated with infiltrations of suppressor/cytotoxic T cell, monocyte/macrophage (p < 0.01), pan T cell and total leucocyte (p < 0.05). Clinical activity score was correlated with suppressor/cytotoxic T cell (p < 0.001), monocyte/macrophage and pan T cell (p < 0.01). These results suggest that suppressor/cytotoxic T cell and and monocyte/macrophage may play an important role in the progression of lupus nephritis.

We present a case of a 25-year-old woman with a renin-secreting juxtaglomerular cell tumor, retroperitoneal fibrosis associated with glomerular hypertrophy, glomerulonephritis, and marked tubulointerstitial alterations. Myofibroblasts, as shown by positive immunostaining for α-smooth muscle actin, were found along with transforming growth factor-beta (TGF-β) in the interstitium of the tumor-free kidney. Regarding the pathogenesis of renal fibrosis and glomerular hypertrophy, this case may provide evidence not only experimentally but also clinically that the renin-angiotensin system plays an important role because angiotensin II is known to induce renal fibrosis associated with increased TGF-β and the appearance of myofibroblasts.

Recent evidence indicates that tubulointerstitial injury plays an important role in hypertensive kidney injury and that phenotypic changes contribute to this pathology. Moreover, angiotensin II is known to be actively involved in the pathogenesis of progressive kidney injury induced by hypertension. The present study was undertaken to see the effect of a newly developed angiotensin II type I receptor (AT1 receptor) antagonist on hypertension-induced kidney injury and to determine the contribution of phenotypic changes to morphologic alterations. Two-kidney, one-clip (2K1C), Goldblatt hypertensive rats (n = 27) were made by clipping the left renal artery. These animals were orally administered 57G709 (a selective non-peptide AT1 receptor antagonist)(10 mg/kg/day), captopril (20 mg/kg/day), or vehicle alone for 23 days beginning 4 weeks after clipping. In the non-clipped kidney of vehicle-treated 2K1C rats, marked tubulointerstitial injury as well as glomerular sclerosis and/or hyalinosis was found in association with phenotypic changes, as shown by the neoexpression of vimentin in periglomeruli, perivascular walls, distal tubuli, and injured interstitium. Renin expression was markedly suppressed in the non-clipped kidneys of vehicle-treated 2K1C rats as compared with renin expression in normotensive control kidneys of sham-operated rats. Both 57G709 and captopril markedly ameliorated hypertensive kidney injury as reflected by the glomerular sclerosing index and by the tubulointerstitial index as determined by the point-counting method, and this improvement was accompanied by a significant decrease in blood pressure, urinary protein excretion, kidney/body weight ratio, and heart/body weight ratio. In addition, the vimentin neoexpression mentioned above was also suppressed with an inhibition of angiotensin II. These results suggest that in 2K1C Goldblatt hypertensive kidney injury, the AT1 receptor antagonist 57G709 exerts a potent renal protective effect associated with the inhibition of phenotypic changes. (J Lab Clin Med 1999;133:134-43)