Effective magnetic hyperthermia induced by mitochondria-targeted nanoparticles modified with triphenylphosphonium-containing phospholipid polymers.

Magnetic hyperthermia (MHT) is a promising cancer treatment because tumor tissue can be specifically damaged by utilizing the heat generated by nano-heaters such as magnetite nanoparticles (MNPs) under an alternating magnetic field. MNPs are taken up by cancer cells, enabling intracellular MHT. Subcellular localization of MNPs can affect the efficiency of intracellular MHT. In this study, we attempted to improve the therapeutic efficacy of MHT by using mitochondria-targeting MNPs. Mitochondria-targeting MNPs were prepared by the modification of carboxyl phospholipid polymers containing triphenylphosphonium (TPP) moieties that accumulate in mitochondria. The mitochondrial localization of polymer-modified MNPs was supported by transmission electron microscopy observations of murine colon cancer CT26 cells treated with polymer-modified MNPs. In vitro and in vivo MHT using polymer-modified MNPs revealed that the therapeutic effects were enhanced by introducing TPP. Our results indicate the validity of mitochondria targeting in enhancing the therapeutic outcome of MHT. These findings will pave the way for developing a new strategy for the surface design of MNPs and therapeutic strategies for MHT.

Combination of magnetic hyperthermia and immunomodulators to drive complete tumor regression of poorly immunogenic melanoma.

Hyperthermia using magnetic nanoparticles enables tumor-specific heating and can destroy tumor tissues. This approach works as in situ vaccination with tumor antigens released from dying tumor cells. However, in situ vaccination caused by magnetic hyperthermia is often insufficient to induce complete regression of poorly immunogenic tumors surrounded by an immunosuppressive microenvironment. In this study, we explored a novel strategy for immunotherapy using magnetic hyperthermia to regress poorly immunogenic melanoma. Magnetic hyperthermia induced tumor cell death in a B16-F10 melanoma mouse model. After hyperthermia treatment, we found elevated levels of HMGB1, which is known to be released from dying cells to promote inflammation, and the proinflammatory cytokine TNF-α was increased in serum of the mice. Systemic administration of glycyrrhizin, an HMGB1 inhibitor, reduced the levels of TNF-α in serum and successfully delayed the regrowth of tumors after magnetic hyperthermia. To achieve complete tumor regression, TLR9 activation by intratumor injection of CpG was combined with systemic administration of anti-PD-1 antibody and anti-CTLA-4 antibody. The combination therapy of magnetic hyperthermia at 46°C with the immunomodulators (glycyrrhizin+CpG+anti-PD-1+anti-CTLA-4) achieved complete tumor regression in 80% of growing 5-mm B16-F10 tumors. These findings have important implications for the development of novel cancer immunotherapy using magnetic hyperthermia for poorly immunogenic tumors.

Mizoribine halts kidney fibrosis in childhood IgA nephropathy: association with modulation of M2-type macrophages.

BACKGROUND: The immunosuppressant mizoribine (Miz) can reduce progression of childhood IgA nephropathy (IgAN). This study examined whether Miz affects CD163+ M2-type macrophages which are associated with kidney fibrosis in childhood IgAN. METHODS: A retrospective cohort of 90 children with IgAN were divided into groups treated with prednisolone (PSL) alone (P group; n = 42) or PSL plus Miz (PM group; n = 48) for a 2-year period. Normal human monocyte-derived macrophages were stimulated with dexamethasone (Dex), or Dex plus Miz, and analyzed by DNA microarray. RESULTS: Clinical and histological findings at first biopsy were equivalent between patients entering the P and PM groups. Both treatments improved proteinuria and haematuria, and maintained normal kidney function over the 2-year course. The P group exhibited increased mesangial matrix expansion, increased glomerular segmental or global sclerosis, and increased interstitial fibrosis at 2-year biopsy; however, the PM group showed no progression of kidney fibrosis. These protective effects were associated with reduced numbers of glomerular and interstitial CD163+ macrophages in the PM versus P group. In cultured human macrophages, Dex induced upregulation of cytokines and growth factors, which was prevented by Miz. Miz also inhibited Dex-induced expression of CD300E, an activating receptor which can prevent monocyte apoptosis. CD300e expression by CD163+ macrophages was evident in the P group, which was reduced by Miz treatment. CONCLUSION: Miz halted the progression of kidney fibrosis in PSL-treated pediatric IgAN. This was associated with reduced CD163+ and CD163+CD300e+ macrophage populations, plus in vitro findings that Miz can suppress steroid-induced macrophage expression of pro-fibrotic molecules. A higher resolution version of the Graphical abstract is available as Supplementary information.

Skin-to-Renal Pelvis Distance Predicts Costovertebral Angle Tenderness in Adult Patients with Acute Focal Bacterial Nephritis.

OBJECTIVES: The aim of this study was to examine whether the distance between the skin and the renal pelvis affects the detection of costovertebral angle (CVA) tenderness in patients with acute focal bacterial nephritis (AFBN). METHODS: We retrospectively reviewed the charts of our patients between April 2013 and June 2019 who were diagnosed as having AFBN. Diagnosis was based on ultrasound or computed tomography with contrast, revealing at least one wedge-shaped area of decreased vascularity and confirmation of fever not attributable to another condition. RESULTS: We extracted 23 cases, all Japanese (mean age 60.0 years old [range 45-81 years], 7 males, 16 females). CVA tenderness was present in 8 of these 23 patients. Receiver operating characteristic curves were drawn to evaluate the ability to differentiate skin-to-renal pelvis distance (SPD), body mass index, and age. Only SPD was a useful predictor of CVA tenderness, and 66 mm was determined as the optimal cutoff point (area under the receiver operating characteristic curve 0.858, 95% confidence interval 0.70-1.00). Logistic regression analysis was performed with CVA tenderness as a dependent variable, and SPD, body mass index, and age as explanatory variables. SPD was an independent predictive variable of CVA tenderness (P = 0.038, odds ratio 0.76, 95% confidence interval 0.590-0.986). CONCLUSIONS: CVA tenderness showed low yield in the diagnosis of AFBN in patients with longer SPD. Its use for diagnosis in obese patients may therefore be limited.

Induction of immunogenic cell death in murine colon cancer cells by ferrocene-containing redox phospholipid polymers.

Immunogenic cell death (ICD), activated by damage-associated molecular patterns (DAMPs), is an apoptotic cell death process that elicits antitumor immunity. Although anticancer drugs that can induce ICD are promising for cancer treatment, the design strategy for ICD inducers remains unclear. In this study, we demonstrated the cell-penetrating redox phospholipid polymer poly(2-methacryloyloxyethyl phosphorylcholine-co-vinyl ferrocene) (pMFc) inducing ICD in murine colon cancer CT26 cells. pMFc produced oxidative stress by extracting electrons from CT26 cells and induced the release of DAMPs, such as calreticulin, adenosine triphosphate, and high-mobility group box 1. Moreover, the injection of pMFc-treated CT26 cells inhibited tumor formation in subsequently challenged CT26 cells, indicating that pMFc elicited antitumor immunity through ICD. Using in vivo therapy, intratumoral injections of pMFc induced complete tumor regression in 20% (1/5) of mice. These results suggested that the redox phospholipid polymer provides a new option for ICD-inducing anticancer polymers.

Steroid treatment promotes an M2 anti-inflammatory macrophage phenotype in childhood lupus nephritis.

BACKGROUND: M1-type proinflammatory macrophages (MΦ) promote glomerular injury in lupus nephritis (LN). However, whether this phenotype is altered by steroid therapy is unclear. Therefore, we investigated the effect of steroid treatment on MΦ phenotype in LN. METHODS: Patients with LN (7-18 years old) were divided into 2 groups: those with no treatment (N) before biopsy (n = 17) and those who underwent steroid (S) treatment (3-73 days) before biopsy (n = 15). MΦ number and phenotype were assessed by immunofluorescence. In vitro studies used monocyte-derived MΦ from healthy volunteers. RESULTS: Age at biopsy, urine findings, and kidney function (eGFR) were comparable between the two groups. Biopsies in N group had higher levels of active lesions such as endocapillary hypercellularity, necrosis, and cellular crescent formation (p < 0.05). The total CD68+ MΦ infiltrate was comparable between N and S groups. However, N group had more M1 MΦ (CD68+ CD86+ cells) (p < 0.05) and fewer M2 MΦ (CD68+ CD163+ cells) (p < 0.05), giving a 6-fold increase in the M2/M1 ratio in S vs. N groups. Dexamethasone treatment of cultured MΦ induced upregulation of CD163 expression, increased production of anti-inflammatory (IL-10, IL-19) and profibrotic factors (FGF-22, PDGF), and upregulated the scavenger receptor, stabilin-1. Upregulation of stabilin-1 in CD163+ M2 MΦ was confirmed in biopsies from S group. CONCLUSIONS: Initial steroid treatment induces MΦ phenotypic change from proinflammatory M1 to anti-inflammatory or profibrotic M2 in LN with acute/active lesions. Although steroid treatment is effective for resolution of M1-medated injury, promotion of fibrotic lesions via M2 MΦ is a potential downside of steroid single therapy in LN.

Inhibition Effect of Eucommia ulmoides Leaf Extract on Interleukin 8 Production by A549 Cells.

Asthma is characterized by chronic inflammation of the airway mucosa. As Eucommia ulmoides Oliv. leaf extract (ELE) has been known to have anti-inflammatory properties, herein, we investigated the effect of ELE on interleukin (IL-) 8 production in A549 cells, a human airway epithelial cell line. The addition of ELE 1 h before tumor necrosis factor-alpha (TNFα) stimulation inhibited IL-8 production by A549 cells in a concentration-dependent manner. The addition of geniposidic acid, the main component of ELE, also inhibited IL-8 production. To further investigate the mechanism by which ELE inhibits IL-8 production, the effect of ELE or geniposidic acid on TNFα-stimulated p38 phosphorylation was examined by Western blotting. After 30 min of TNFα stimulation, p38 phosphorylation was inhibited by the addition of ELE or geniposidic acid, suggesting that ELE inhibited IL-8 production in TNFα-stimulated A549 cells by suppressing one of the signal transducers of p38 phosphorylation. These results indicate that ELE can be used as an effective measure against asthma, particularly neutrophilic asthma.

Quantitative Ultrasound Image Analysis Helps in the Differentiation of Hepatocellular Carcinoma (HCC) From Borderline Lesions and Predicting the Histologic Grade of HCC and Microvascular Invasion.

OBJECTIVES: Quantitative image analysis is one of the methods to overcome the lack of objectivity of ultrasound (US). The aim of this study was to clarify the correlation between the features from a US image analysis and the histologic grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and differentiation of HCC smaller than 2 cm from borderline lesions. METHODS: We retrospectively analyzed grayscale US images with histopathologic evidence of HCC or a precancerous lesion using ImageJ version 1.47 software (National Institutes of Health, Bethesda, MD). RESULTS: A total of 148 nodules were included (borderline lesion, n = 31; early HCC [eHCC], n = 3; well-differentiated HCC [wHCC], n = 16; moderately differentiated HCC [mHCC], n = 79; and poorly differentiated HCC [pHCC], n = 19). A multivariate analysis selected lower minimum gray values (odds ratio [OR], 0.431; P = .003) and a higher standard deviation (OR, 1.880; P = .019) as predictors of HCC smaller than 2 cm. Median (range) minimum gray values of borderline lesions, eHCC, wHCC, mHCC, and pHCC were 29 (0-103), 7 (0-47), 6 (0-60), 10 (0-53), and 2 (0-38), respectively, and gradually decreased from borderline lesions to pHCC (P < 0.001). The multivariate analysis showed a higher aspect ratio (OR, 2.170; P = .001) and lower minimum gray value (OR, 0.475; P = .043) as predictors of MVI. An anechoic area diagnosed by a subjective evaluation was correlated with the minimum gray value (P < .0001). The proportion of the anechoic area gradually increased from eHCC to pHCC (P = .031). CONCLUSIONS: In a US image analysis, HCC smaller than 2 cm had features of greater heterogeneity and a lower minimum gray value than borderline lesions. Moderately differentiated HCC was smoother than borderline lesions, and the anechoic area correlated with histologic grading. Microvascular invasion was correlated with a slender shape and a lower minimum gray value.

[Total Arch Replacement Using Bilateral Axillary Artery Perfusion].

OBJECTIVES: The selection of arterial cannulation site is an important decision to avoid cerebral complication for total arch replacement(TAR). We report the surgical outcome of TAR using bilateral axillary artery perfusion in our hospital. METHODS: Between January 2012 and June 2020, 97 patients who underwent elective TAR for atherosclerotic aneurysms were enrolled in this study. Among them, bilateral axillary artery perfusion was used for 81 patients, and frozen elephant trunk( FET) procedure were used for 34 patients. In the case of FET procedure, translocated TAR was performed with distal anastomosis between the left common carotid artery and the left subclavian artery. The left subclavian artery was reconstructed by rerouting the graft used for the left axillary artery perfusion. RESULTS: There were no perioperative cerebral infarction and no hospital deaths. The mean operation time was 420 minutes. Compared to the conventional elephant trunk method, the FET method significantly reduced the operation time to 381 minutes. CONCLUSIONS: Bilateral axillary artery perfusion could contribute to reduce the cerebral infarction in TAR and facilitate the FET procedure.

Redox-Active Polymers Connecting Living Microbial Cells to an Extracellular Electrical Circuit.

Microbial electrochemical systems in which metabolic electrons in living microbes have been extracted to or injected from an extracellular electrical circuit have attracted considerable attention as environmentally-friendly energy conversion systems. Since general microbes cannot exchange electrons with extracellular solids, electron mediators are needed to connect living cells to an extracellular electrode. Although hydrophobic small molecules that can penetrate cell membranes are commonly used as electron mediators, they cannot be dissolved at high concentrations in aqueous media. The use of hydrophobic mediators in combination with small hydrophilic redox molecules can substantially increase the efficiency of the extracellular electron transfer process, but this method has side effects, in some cases, such as cytotoxicity and environmental pollution. In this Review, recently-developed redox-active polymers are highlighted as a new type of electron mediator that has less cytotoxicity than many conventional electron mediators. Owing to the design flexibility of polymer structures, important parameters that affect electron transport properties, such as redox potential, the balance of hydrophobicity and hydrophilicity, and electron conductivity, can be systematically regulated.

Hepatic hemangioma supplied by abnormal portal vein: A case report.

Hepatic hemangioma is the most common hepatic tumor with a prevalence of approximately 3%. It is typically supplied by the hepatic artery as evident from findings of abdominal angiography, contrast-enhanced ultrasonography (CEUS), contrast-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance imaging. However, few cases of hepatic hemangioma supplied by the portal vein have been reported. In this paper, we report a rare case of hepatic hemangioma supplied by the portal vein as shown on CEUS and CT arterioportography.

The endogenous redox rhythm is controlled by a central circadian oscillator in cyanobacterium Synechococcus elongatus PCC7942.

The intracellular redox and the circadian clock in photosynthetic organisms are two major regulators globally affecting various biological functions. Both of the global control systems have evolved as systems to adapt to regularly or irregularly changing light environments. Here, we report that the two global regulators mutually interact in cyanobacterium Synechococcus elongatus PCC7942, a model photosynthetic organism whose clock molecular mechanism is well known. Electrochemical assay using a transmembrane electron mediator revealed that intracellular redox of S. elongatus PCC7942 cell exhibited circadian rhythms under constant light conditions. The redox rhythm disappeared when transcription/translation of clock genes is defunctionalized, indicating that the transcription/translation controlled by a core KaiABC oscillator generates the circadian redox rhythm. Importantly, the amplitude of the redox rhythm at a constant light condition was large enough to affect the KaiABC oscillator. The findings indicated that the intracellular redox state is actively controlled to change in a 24-h cycle under constant light conditions by the circadian clock system.

Cell-Membrane Permeable Redox Phospholipid Polymers Induce Apoptosis in MDA-MB-231 Human Breast Cancer Cells.

Induction of oxidative stress is an effective approach to causing apoptotic death of cancer cells. Since oxidative stress is generally caused by an intracellular redox imbalance, altering the intracellular redox is a promising strategy toward the growth suppression of cancer cells. Here, we attempted to induce apoptosis in MDA-MB-231 human breast cancer cells by adding a cell-membrane permeable redox phospholipid polymer that can alter the intracellular redox. We found that apoptosis and the deactivation of oxidative phosphorylation were induced in the MDA-MB-231 cells in the presence of the oxidized form of the redox polymer. Remarkably, such phenomena were not observed in the presence of the reduced form of the redox polymer that cannot intercept metabolic electrons. These results indicate that the redox polymer that mediates extracellular electron transfer (EET) generates oxidative stress, leading to the apoptosis of the cancer cells.

Assessment of factors associated with mizoribine responsiveness in children with steroid-dependent nephrotic syndrome.

BACKGROUND: Several immunosuppressants have been used to treat children with steroid-dependent nephrotic syndrome (SDNS). Mizoribine (MZR) is an immunosuppressant used to maintain remission in children with SDNS, although its effectiveness for treating SDNS remains controversial. Therefore, in this study, we assessed the clinical factors associated with children having SDNS who were successfully treated with MZR. METHODS: A total of 47 children with SDNS who underwent MZR treatment were retrospectively evaluated. Clinical features including pharmacokinetics after MZR administration were compared between MZR responders and non-responders. RESULTS: The comparison of the two groups revealed no significant differences in age, body weight (BW), daily dose of MZR per BW, serum concentration 2 h after administration (C2), peak serum concentration (Cmax), and area under the concentration curve 0-4 h after administration (AUC0-4). C2/(single dose/BW), Cmax/(single dose/BW), and AUC0-4/(single dose/BW) were significantly higher in the MZR responders than in the non-responders (all p < 0.01). Receiver operating characteristic analysis revealed that the cutoff values of C2 (single dose/kg), Cmax/(single dose/BW), and AUC0-4/(single dose/BW) were 0.55, 0.58, and 1.37, respectively. CONCLUSIONS: MZR is a useful immunosuppressant for treating frequent-relapse NS in children who are susceptible to the drug. The efficacy of MZR may be associated with not only serum concentrations defined by the dosage or absorption efficiency through MZR transporters, but also the susceptibility defined by the expression level and performance of MZR transporters on the target cells.

Functional assessment of improvement of myocardial ischemia using coronary flow velocity reserve after coronary artery bypass surgery in hemodialysis.

BACKGROUND: In patients with end-stage renal disease requiring hemodialysis (HD patients), myocardial ischemia after coronary artery disease is a major cause of mortality. Coronary pathophysiology, namely myocardial microvascular dysfunction, appears to differ from patients not requiring HD (non-HD patients). OBJECTIVES: We compared functional improvement of myocardial ischemia after coronary artery bypass surgery (CABG) between HD and non-HD patients by transthoracic coronary flow velocity reserve (CFVR). METHODS: We retrospectively reviewed isolated CABG patients from between 2008 and 2017. Finally, 161 patients were enrolled; each underwent pre- and postoperative CFVR assessment, and left anterior descending (LAD) artery revascularization with "in-situ" internal mammary artery (IMA). Graft patency was confirmed, and after successful CABG, postoperative CFVR improvement between the two groups was compared. RESULTS: Preoperative CFVR value in group H was 1.81 ± 0.52, group N was 1.93 ± 0.66. There was no significant difference between the groups. IMA to LAD grafts were patent in postoperative evaluation in all patients. Postoperative CFVR in group H was 2.48 ± 0.72 and group N was 2.83 ± 0.73 (P = .042). Significant difference was observed. CONCLUSION: In both groups, CFVR values improved after successful CABG, but postoperative CFVR values were significant different. In younger populations CFVR values are generally higher. Our HD group was significantly younger than the non-HD group, but CFVR values were postoperatively significantly lower. CFVR values are reportedly affected by both epicardial and microcoronary circulation. In this study population, as all grafts to the LAD were patent, the lower CFVR value in the HD group was considered to have resulted in microvascular disorders.

Blood reservoir function in patients with Fontan circulation and asplenia syndrome.

Splanchnic circulation constitutes a major portion of the vasculature capacitance and plays an important role in maintaining blood perfusion. Because patients with asplenia syndrome lack this vascular bed as a blood reservoir, they may have a unique blood volume and distribution, which may be related to their vulnerability to the haemodynamic changes often observed in clinical practice. During cardiac catheterisation, the mean circulatory filling pressure was calculated with the Valsalva manoeuvre in 19 patients with Fontan circulation, including 5 patients with asplenia syndrome. We also measured the cardiac output index and circulatory blood volume by using a dye dilution technique. The blood volume and the mean circulatory filling pressure and the venous capacitance in patients with asplenia syndrome were similar to those in the remaining patients with Fontan circulation (85 ± 14 versus 77 ± 18 ml/kg, p = 0.43, 31 ± 8 versus 27 ± 5 mmHg, p = 0.19, 2.8 ± 0.6 versus 2.9 ± 0.9 ml/kg/mmHg, p = 0.86). Unexpectedly, our data indicated that patients with asplenia syndrome, who lack splanchnic capacitance circulation, have blood volume and venous capacitance comparable to those in patients with splanchnic circulation. These data suggest that (1) there is a blood reservoir other than the spleen even in patients with asplenia; (2) considering the large blood pool of the spleen, the presence of a symmetrical liver may represent the possible organ functioning as a blood reservoir in asplenia syndrome; and (3) if this is indeed the case, there may be a higher risk of hepatic congestion in patients with Fontan circulation with asplenia syndrome than in those without.

Comparison of respiratory system impedance in asthma and COPD: A prospective observational study.

BACKGROUND AND OBJECTIVE: A single assessment of within-breath variations of respiratory system reactance (Xrs) at 5 Hz (ΔX5) measured by the forced oscillation technique (FOT) has been reported to be useful for the detection of pathophysiological changes in chronic obstructive pulmonary disease (COPD) and asthma. We examined longitudinal changes in respiratory system resistance (Rrs) and Xrs during tidal breathing between stable asthma and COPD patients in order to clarify the features of changes of respiratory system impedance and airflow limitation for these conditions. METHODS: Between April 2013 and September 2013, outpatients with a COPD or asthma diagnosis were recruited. We examined forced expiratory volume in 1 s (FEV1 ) and FOT every 6 months until September 2015. Annual changes were estimated from the linear regression curve slope. RESULTS: We included 57 and 93 subjects with COPD and asthma, respectively. The median follow-up period was 26 months (range: 24-29 months). Within-breath analysis showed that the difference between mean Rrs at 5 Hz and 20 Hz was significantly lower, and ΔX5 more negative, in COPD than in asthma patients. With regard to annual changes, only ΔX5 was significantly different, more negative, in COPD than in asthma patients. Comparing between COPD subjects of Global Initiative Chronic Obstructive Lung Disease (GOLD) stage I/II and those with asthma, there were no significant differences in respiratory system impedance at enrolment, while annual change in ΔX5 was significantly more negative in mild COPD than in asthma patients. CONCLUSION: ΔX5 may be useful for long-term assessment of airflow limitation in COPD.

Significance of blood cultures in nursing home-acquired pneumonia.

The significance of blood cultures in nursing home-acquired pneumonia (NHAP) is incompletely understood. We retrospectively analyzed the clinical and laboratory features of 515 patients with NHAP admitted to our hospital over an 11-year period. Blood cultures were obtained from 336 patients (65.2%). We compared 13 and 323 patients with positive and negative blood cultures, respectively. The former showed lower systolic blood pressure and higher blood urea nitrogen (BUN), creatinine, C-reactive protein (CRP), and A-DROP scores than the latter. With regard to A-DROP parameters, patients with positive blood cultures showed significantly higher rates of dehydration (BUN ≥ 21 mg/dL) and low blood pressure (systolic blood pressure ≤ 90 mmHg). Multivariate analysis identified CRP values and low blood pressure as independent predictors of bacteremia: CRP (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.04-1.19, P = 0.003) and low blood pressure (OR 6.03; 95% CI 1.06-34.25, P = 0.04). A receiver operating characteristic curve indicated that CRP was of moderate accuracy (area under the curve = 0.75), and its diagnostic accuracy was optimal at a cut-off point of 19.2 mg/dL (sensitivity 69%, specificity 87%). Since the probability of true bacteremia is very low in NHAP, obtaining blood cultures from all patients with NHAP is unnecessary. However, our results suggest blood cultures are warranted from patients with high CRP values (≥20 mg/dL) or low blood pressure.

Specific Interaction between Redox Phospholipid Polymers and Plastoquinone in Photosynthetic Electron Transport Chain.

Redox phospholipid polymers added in culture media are known to be capable of extracting electrons from living photosynthetic cells across bacterial cell membranes with high cytocompatibility. In the present study, we identify the intracellular redox species that transfers electrons to the polymers. The open-circuit electrochemical potential of an electrolyte containing the redox polymer and extracted thylakoid membranes shift to positive (or negative) under light irradiation, when an electron transport inhibitor specific to plastoquinone is added upstream (or downstream) in the photosynthetic electron transport chain. The same trend is also observed for a medium containing living photosynthetic cells of Synechococcus elongatus PCC7942. These results clearly indicate that the phospholipid redox polymers extract photosynthetic electrons mainly from plastoquinone.

Local leukocyte proliferation as a target for cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis grade VI.

Henoch-Schönlein purpura nephritis (HSPN) is one of the most common types of chronic glomerulonephritis in children; however, there have been few reports on the pathogenesis and management of grade VI HSPN. We present the case of a 6-year-old boy with grade VI HSPN accompanied by severe nephrotic syndrome and hypocomplementaemia. Immunohistological studies revealed profound glomerular accumulation of CD45- and CD68-positive inflammatory cells. Moreover, some cells expressed the proliferating marker proliferating cell nuclear antigen. His proteinuria and general oedema persisted despite repeated high-dose steroid therapy; however, these clinical symptoms immediately improved after beginning treatment with cyclophosphamide (CyP). Grade VI HSPN was successfully treated with steroids and immunosuppressants. Among immunosuppressive drugs, CyP was considered the most effective.