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Podocytes, which are susceptible to injury by various stimuli and stress, are critical regulators of proteinuric kidney diseases, regardless of the primary disease and pathogenesis. We further confirmed a significant correlation between urinary CD147/basigin (Bsg) levels and proteinuria in patients with focal segmental glomerulosclerosis. However, the molecular mechanism of podocyte injury involving Bsg is not fully understood. Here, the involvement of Bsg in the pathogenesis of podocyte injury was elucidated. Healthy podocytes rarely express Bsg protein. In two independent mouse models, including adriamycin-induced nephropathy and Nω-nitro-l-arginine methyl ester (l-name)-induced endothelial dysfunction, Bsg induction in injured podocytes caused podocyte effacement, which led to development of proteinuria. Bsg silencing in cultured podocytes exposed to transforming growth factor-β suppressed focal adhesion rearrangement and cellular motility via the activation of β1 integrin-focal adhesion kinase-matrix metallopeptidase signaling. In addition, induction of vascular endothelial growth factor and endothelin-1, which are implicated in podocyte-to-endothelial cross-communication, was lower in the supernatants of cultured Bsg-silenced podocytes stimulated with transforming growth factor-β. In this setting, Bsg may be involved in a physiological positive feedback loop that accelerates podocyte cell motility and depolarization. The current study thus suggests that Bsg silencing via suppression of β1 integrin-focal adhesion kinase-matrix metallopeptidase signaling may be an attractive therapeutic strategy for the maintenance of podocytes in patients with proteinuric kidney diseases.

Background: Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease. Methods: Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch–Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system. Results: In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients. Conclusion: Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases., ファイル公開：2019/08/01

Although the aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis remains unclear, it is generally believed that environmental factors such as infections contribute to its development of ANCA-associated vasculitis. Prior Epstein-Barr virus (EBV) infection is reported to be a trigger of systemic vasculitis. We herein report three cases of ANCA-associated vasculitis presenting with infectious mononucleosis due to primary EBV infection. The causal link between the two pathologies could not be proved, but primary EBV infection may play a role in the initiation or exacerbation of ANCA-associated vasculitis. Future studies are necessary to determine the interaction between these diseases conditions.

患者は74歳女性で，慢性腎不全にて保存的加療を行っていた．原疾患は腎硬化症が考えられていた．平成19年10月より吐気，食思不振を訴え，尿素窒素（BUN）64.1mg/dL，クレアチニン（Cr）5.14 mg/dL，重炭酸濃度（HCO3-）13.2 mmol/Lと腎不全の悪化を認めたため10月23日より入院となった．上部消化管内視鏡は慢性胃炎の所見であった．第3病日にはBUN 80.4mg/dL，Cr 6.38mg/dLと腎不全が進行し，尿毒症を考え第4病日より血液透析を開始した．しかし，その後も吐気が持続し，眼の焦点が合わない，頭がぼやけるなどの訴えが出現した．徐々に傾眠傾向となったため，第8病日に頭部MRIを撮影した．中脳水道周囲，乳頭体，視床内側に拡散強調像，T2強調像，fluid-attenuated inversion recovery（FLAIR）にて高信号域を認め，Wernicke脳症が疑われた．同日よりフルスルチアミンの投与を行ったところ意識レベルは速やかに改善した．後にビタミンB1は14（正常20～50）ng/mLと低値であったことが分かった．維持血液透析，リハビリを続け，第57病日にリハビリ目的にて他病院に転院となった．食事療法，尿毒症による栄養摂取不良と血液透析による水溶性ビタミンの喪失がWernicke脳症の原因と考えられた．

The combustion behavior of a methane hydrate sphere under normal gravity is experimentally investigated. The initial diameter of the sphere is 20 mm. Variation in temperature at the center of the sphere (T c) is measured with a K-type thermocouple at ignition temperatures (T c,i) from 193 to 253 K at 20 K intervals. Variation in the near-surface temperature of the sphere (T s) is measured at ignition temperatures (T s,i) from 233 to 263 K at 10 K intervals. Two combustion phases are observed. When the hydrate is ignited, a stable flame envelope is formed around the sphere (phase 1). In phase 1, the surface of the sphere is dry. After a few seconds, water formed by dissociation of the methane hydrate appears on the surface and methane bubbles are formed by methane ejected from inside the sphere (phase 2), thus destabilizing the flame and causing local extinction. Methane bubbles move down along the surface and merge into a large methane bubble at the bottom of the sphere. This bubble bursts, releasing methane to form a temporary flame, and the water drops from the hydrate sphere. Water on the surface is cooled by the hydrate inside, and an ice shell confines the methane gas that dissociated inside the sphere. Because the dissociation occurs continuously inside the hydrate, the inner pressure gradually increases and at some instant, the ice cracks and methane gas is ejected from the cracks, which results in a micro-explosion with a flame. In phase 1, the surface temperature is below the freezing point of water, and so the surface remains dry and a stable flame envelope is formed; in phase 2, the surface temperature is above the freezing point, and so water appears on the surface. When the temperature at the center of the sphere is lower (193, 213, or 233 K), some methane hydrate remains even after flame extinction because heat transfer from the flame decreases in phase 2 as a result of local extinction. The diameter of the sphere decreases during combustion in accordance with the d-square law, which indicates that the heat of dissociation is supplied by the flame and methane is supplied by the dissociation of methane hydrate in the sphere, as in single-droplet combustion.

To prevent delays in transfusion and the development of hemolytic transfusion reactions at the emergency room of a local hospital, we implemented a Type O blood usage program for life-threatening bleeding patients in August 2001 according to Japanese government guidelines for transfusion. To better understand actual conditions for urgent blood transfusion before and after implementation of this program, we surveyed the time between ordering to the start of transfusion, shock index at the start of transfusion, total volume of transfused blood, causes of death, irradiation of blood, side effects, and reasonable adaptation of transfusion. Results showed the time between ordering to the start of transfusion shortened to 9.3 minutes from 62.2 minutes after implementation. There was no case in which non-irradiated blood unit, was transfused, nor of incompatible blood transfusion following cross matching. Further, there was no increase in workload following implementation of the Type O blood usage program. In conclusion, Type O blood usage programs can dramatically save time between ordering to the start of transfusion. However, they carry risks such as Rh-positive blood transfusion to Rh-negative patients (about 0.5%) and antigen-positive blood transfusion to patients positive for irregular antibodies (about 1.3%). Adaptation of this transfusion must be carefully controlled. All patients receiving type O blood transfusion should be investigated for suitability after transfusion.

A 19-year-old man was transferred to our hospital after sustaining multiple injuries in a motor vehicle crash. He had no history of previous blood transfusion. On arrival, he became hemodynamically unstable and required a splenectomy. Because of his hemodynamic status, he received several units of blood in the operating room and during his postoperative course. All together, a total of 75 units of blood was required. On the 28th postoperative day, he was noted to have acute hemoglobinemia and hemoglobinuria. A diagnosis of delayed hemolytic transfusion reaction (DHTR) was made because of the presence of anti-E antibody in the patient's plasma. DHTR is usually the result of extravascular hemolysis, and occurs within three weeks of blood transfusion. Since a splenectomy had been performed, we believe that hemolysis occurred in the blood vessels. Although the exact mechanisms of DHTR are not clear, potential sequelae such as hemoglobinuria and subsequent renal failure can be clinically devastating. For this reason, we should always be aware of the potential for developing DHTR when transfusing splenectomized patients.

The patient is a 41-year-old man diagnosed with uveitis in 2004. Although the patient was positive for HLA-B51, the primary disease could not be identified, and oral administration of prednisolone (PSL) was initiated. A subsequent gradual decrease in the PSL dose was accompanied by the development of recurrent spasmodic chorioretinopathy and hypopyon. In November 2007, the patient was diagnosed with Behçet's disease based on the findings of erythema nodosum, acneiform eruption, and oral aphtha. In order to control the ocular symptoms, infliximab was administered. However, the patient's renal function began to deteriorate in November 2011, and he was transferred to our department after 6 months. At that time, his creatinine level was 8.56 mg/dL. Renal biopsy examination revealed granulomatous interstitial nephritis. Moreover, only infliximab yielded a positive result in a drug-induced lymphocyte stimulation test (DLST). Following initiation of PSL administration at 60 mg/day, his renal function improved. His creatinine level remained constant at approximately 3 mg/dL. In the present case, Behçet's disease, sarcoidosis, and infection were excluded as the underlying disease causing granulomatous interstitial nephritis. Moreover, infliximab is reportedly involved in the development of granulomas. Recent reports have stated that administration of TNF-alpha inhibitors occasionally results in the development of granulomas in the lungs and skin, and sometimes, in the kidneys as well. When renal dysfunction occurs in patients receiving TNF-alpha inhibitors, we believe that it is essential to include adverse events associated with TNF-alpha inhibitors in the differential diagnoses.

To determine whether indocyanine green clearance is an early indicator of hepatocellular injury in septic shock and to assess its predictive value.Observational study with prospective data collection.Traumatology and critical care unit in a city hospital, staffed by traumatology and intensive care clinicians.Twelve patients in septic shock who survived at least 2 months (group S) and nine patients who died within 2 wks (group N).Routine resuscitation from septic shock (surgery, fluid loading, and administration of catecholamines and antibiotic drugs).Pulmonary artery occlusion pressure, cardiac index, oxygen delivery index, oxygen consumption index, and the indocyanine green elimination rate constant (KICG; or the slope of the loge [indocyanine green concentration] vs. time curve) 3-9 mins after injection were measured within 12 hrs of the onset of hypotension, then at 24 hrs, and every 24 hrs thereafter. Alanine aminotransferase and total bilirubin were measured on day 0 and day 1. Volume of fluid administered and duration of shock were the same in survivors and nonsurvivors. The oxygen consumption index was higher in survivors at 12 hrs, but no intergroup difference in pulmonary artery occlusion pressure, cardiac index, or oxygen delivery index was significant at any time point. KICG in nonsurvivors was lower than in survivors both initially and after 24 hrs, and it was subnormal in all patients except one survivor (p.05). The KICG increased between 24 and 120 hrs in 11 survivors but progressively decreased and remained below 0.05 in seven nonsurvivors. The remaining two nonsurvivors died within 24 hrs of the initial measurement of KICG, which was0.05. Alanine aminotransferase and total bilirubin were less sensitive measures of hepatic dysfunction in the first 24 hrs than the KICG.The KICG can identify reversible liver injury in septic shock, suggesting good prognosis. Either failure to increase the KICG within 120 hrs or an extremely low KICG is a poor prognostic sign.

背景:低体温下では低心拍出量,循環血液量の減少,多尿がみられ,著しい体液変動が予想されるが,体液量測定はほとんど行われていない。目的:軽度低体温療法下の重症頭部外傷例における体液量の推移を知ること。対象:GCS 5～8点の頭部外傷7例(男5例,女2例,平均44歳)。ブランケットを用い体表冷却により,直腸温を33.5～34.5℃まで低下させ,その体温を48時間維持したのち,24時間に1℃ずつ36.5℃まで復温した。復温後も最低2日間は,直腸温を37.5℃未満に維持した。方法:インドシアニングリーンの分布容積を循環血漿量(PV, l)とした。生体電気インピーダンス法により測定した全身抵抗値(Resis., Ω)と身長(H, cm)から求めた,H2/resis.を体水分量指標(TBWI)とした。PV/TBWI ratioを用いて,体水分に占める血管内水分の割合をみた。測定は,冷却中(C) (33.5～34.5℃),復温前期(R1) (34.5～35.5℃),復温後期(R2) (35.5～36.5℃),復温後(P) (36.5～37.5℃)の4点で行った。冷却から96時間,8時間ごとの尿量,水分バランスを測定した。結果:浸透圧利尿剤は6例に,チオペンタールは6例に用い,減圧開頭術は5例に行った。PVは,C, R1, R2の各時点でPに比して減少した。TBWIは,R2ではCよりも増加し,PではR2よりも減少した。PV/TBWI ratioは,C, R1, R2の各時点でPに比して低下した。尿量,水分バランスともに有意な変化はなかった。考察:PVの低下とTBWIの増加は血管外水分の異常増加を表し,復温完了後のPVの増加とTBWIの減少は,血管透過性の改善を反映する。結語:軽度低体温療法下の頭部外傷例では,血管内から血管外への水分の移動により血漿量が減少する。

We investigate a single impurity Anderson model in superconducting state focusing on the localized excited states induced around the impurity site with use of the numerical renormalization group method. Using this model, we present a unified treatment of electronic states around various kinds of impurities embedded in conventional s -wave superconductivity that have been investigated independently so far: (1) magnetic impurity, (2) nonmagnetic impurity with potential scattering, and (3) nonmagnetic impurity with resonance scattering. In the case of the symmetric Anderson model, we clarify how the localized excited state induced around (1) is transformed into the one induced around (3) with a decrease of the strength of the on-site Coulomb repulsion at the impurity site. On the other hand, in the case of the asymmetric Anderson model, we show how the bound state induced by the magnetic impurity disappears when the impurity is gradually transformed from (1) into (2) with an increase of the energy of the imp...

We investigate the electronic state around a magnetic impurity in the superconductivity in order to clarify how the anisotropy of the s - d interaction works in the presence of the superconducting energy gap. Using the numerical renormalization group method, we obtain regions induced by the anisotropy where two localized excited states with different energies appear at the same time; they cannot obtain as far as the isotropic interaction is considered. This means that the anisotropy of the s - d interaction works relevantly in some cases in the superconducting state. We also examine whether or not the bound state energy for the anisotropic and antiferromagnetic s - d interaction is scaled by T K /Δ ( T K : Kondo temperature, Δ: superconducting order parameter), and find that it does not hold in the regions with two bound states.

Three cases of necrotizing fasciitis are presented. In all cases aggressive antibiotic therapy were performed soon after admission, and fever up, leucocytosis and elevation of CRP improved. However, a follow-up CT scan taken several days after admission revealed severe aggravation of lesions; surgical treatment was performed immediately. The amount of gas production was small compared with the area of necrosis in two cases. It was suggested during the follow-up, that X-ray's nor inflammatory findings such as body temperature, leucocyte and CRP do not necessarily reflect aggravation of the lesions, and that frequent CT scan is essential.

目的:出血性ショックの臨床例で,インドシアニングリーン(ICG)を用いた色素希釈法により血漿容積(plasma volume; PV)と肝灌流を評価し,その有用性を検討する。対象:出血性ショック14例(外傷12,出血性胃潰瘍2)。12例は蘇生に成功し(蘇生例)2例は死亡した(非蘇生例)。方法:ICG (indocyanine green)の排泄速度定数(KICG)を肝灌流の指標とした。そしてICGの分布容積すなわちPVとKICGをショック発症後2～72時間に連続的に測定した。ICG 25mgを静脈内投与し,3, 5, 7, 9分の血漿ICG濃度から血漿濃度曲線を求め,時間0のICG濃度C0からPVを算出した(PV=25/C0/体重ml/kg)。KICG (/min)は,時間-濃度の対数の直線の傾きから求めた。結果:蘇生例中9例では,測定期間中,PVは40ml/kg以上を維持し,KICGも正常(0.18/min以上)を保った。蘇生例の残り3例では,PVとKICGが6時間目に減少し,12～48時間後には同時に回復した。これらの症例では,PVの増減は血圧や尿量の推移と並行しなかった。一方非蘇生例では,PVは40ml/kg未満に低下したが,KICGの低下はより一層顕著であった。またPVとKICGとは正の相関(r=0.445, p

The impact of hypothermia on reperfusion-associated oxidative stress in postischemic skeletal muscle was evaluated in a small animal model of high-grade partial ischemia. The infrarenal aorta of heparinized Sprague-Dawley rats was clamped for 90 min, declamped, and then reperfused for 60 min. Previous characterization of this model with 51Cr-tagged microspheres revealed that hindlimb perfusion during aortic clamping continued at 16.6% of baseline values. Resting transmembrane potential difference (Em) and tissue malondialdehyde (MDA), lactate and high-energy phosphate content were determined in hindlimb skeletal muscle at baseline, during ischemia, and upon reperfusion. Four experimental groups (N = 7 in each group) were studied: control animals underwent aortic clamping and declamping; hypothermia animals underwent topical cooling of hindlimbs prior to aortic clamping, with muscle temperatures maintained between 5 and 15°C during ischemia; sham animals underwent midline laparotomy only; and hypothermia-sham animals underwent cooling and midline laparotomy only. During ischemia, resting Em(−mV) was significantly depolarized (P < 0.05 versus baseline) in control (74.9 ± 0.8 from 91.0 ± 0.1), hypothermia (64.4 ± 1.1 from 90.9 ± 0.3), and hypothermia-sham (67.2 ± 1.4 from 90.9 ± 0.4) animals. Upon reperfusion, resting Em remained depolarized in control animals (74.7 ± 1.6), while repolarization occurred in hypothermia (74.7 ± 1.6), while repolarization occurred in hypothermia (88.8 ± 1.1) and hypothermia-sham (90.7 ± 0.3) animals. Tissue MDA content (nmol/g wet tissue), a marker of phospholipid peroxidation, was markedly elevated (P < 0.05 versus baseline) during ischemia in control (121.5 ± 18.4 from 67.1 ± 7.2) and hypothermia (118.5 ± 18.7 from 66.8 ± 7.5) animals, and continued to increase upon reperfusion in control animals (190.5 ± 14.0; P < 0.05 versus ischemia), while returning to baseline values in hypothermia animals (77.0 ± 12.8; P = NS versus baseline). These data indicate that high-grade partial ischemia in skeletal muscle is accompanied by significant phospholipid peroxidation, and that antecedent regional hypothermia markedly attenuates subsequent and further reperfusion-associated oxidative injury.

We report a case of late presentation of traumatic rupture of the diaphragm discovered incidentally on chest radiography (CXR) during an annual medical checkup. A 60-year-old man suffered severe blunt trauma from heavy steel frames collapsing against his back, resulting in pelvic and femoral fractures as well as pulmonary contusions. The patient recovered, but 10 months later CXR performed for lung cancer surveillance during an annual medical checkup revealed a traumatic rupture of the diaphragm. Video-assisted thoracic surgery was performed with reduction of the intestine and primary closure of the diaphragmatic defect. The patient recovered uneventfully. This report serves as a useful reminder that a medical history of severe blunt trauma should provoke a high index of suspicion for diaphragmatic rupture during annual medical surveillance.

A 17-year-old woman presented to the Emergency Department of our hospital following a suicide attempt. She reported having ingested 340 tablets of caffeine, each of which contained 200mg of caffeine, about 3 hours earlier. Soon after arrival, her blood pressure dropped, and electrocardiography revealed sinus tachycardia and ventricular tachycardia (VT). Subsequently, she developed ventricular fibrillation (VF), and VF was resistant to pharmaceutical interventions and even to cardioversion. Therefore, we performed percutaneous cardiopulmonary support (PCPS). This resulted in disappearance of VF and tachycardia, symptoms of caffeine poisoning, and improvement was observed 16 hours after the start of PCPS. In our case, caffeine poisoning symptoms disappeared without blood purification, after PCPS had stabilized her circulation. Based on our observations in this case, stabilization of the circulation using PCPS in severe caffeine poisoning with VF, a potentially fatal arrhythmia, is a significantly beneficial strategy.

To elucidate the mechanism of persistent dyspnea after blunt chest trauma, we prospectively studied the pulmonary function of 18 patients with blunt chest trauma for 6 months. Nine of the patients had flail chest and 12 had pulmonary contusion (PC). Pulmonary function was evaluated using spirometry, arterial blood gas analysis, chest x-ray studies and CT scans. Functional residual capacity (FRC) remained significantly reduced throughout the 6 months in patients with PC. Such patients experienced a fall in Pao2 when changed from a sitting position to a supine position and they had fibrous changes in the contused lung as demonstrated by CT scans at 6 months after injury. These findings were supported in an additional study of another 20 patients who had suffered PC 1 to 4 years previously. This study demonstrated that pulmonary function recovered within 6 months in patients without PC even with a residual deformity of the thoracic wall caused by flail chest, while patients with PC had decreased FRC and a fall in Pao2 when moved to the supine position even several years after injury. This might be related to the persistent dyspnea seen after blunt chest trauma.