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Oxidative stress and peritubular capillary (PTC) injury are involved in the progression of chronic kidney disease (CKD). We investigated protective effects of Shichimotsu-koka-To (SKT), a Japanese traditional Kampo prescription, against nephrosclerosis and hypertension on a CKD model due to irreversible nephritis. Six-week-old male Wistar rats were subjected to uninephrectomy, and to injection of rabbit anti-thymocyte serum. SKT treatment was continued for 15 weeks, blood pressure was measured, and then renal specimens were collected. PTC networks were detected by immunostaining for CD-31. And superoxide dismutase (SOD)-like activity in the tissue was evaluated. Blood pressure in the SKT group, as well as sham group, was significantly lower than with the vehicle. SKT markedly ameliorated renal function, which was evaluated with urea nitrogen clearance. Compared with the vehicle, SKT treatment lowered both the glomerular enlargement and hyper-cellularity by 80%, and decreased the extracellular matrix area by 75%. SKT treatment also suppressed tubular injury, and maintained PTC networks. Furthermore, SKT recovered SOD-like activity to the basal levels. These results suggest that SKT may be useful for the treatment of CKD during the progression to nephrosclerosis, through the mechanisms of anti-oxidative activity and maintenance of PTC networks.

Considering that fibrin deposition is observed in glomerulonephritis as well as in diabetic nephropathy, we performed studies to clarify the roles of the coagulation pathway and the active type of coagulation factor X (factor Xa) in the development of chronic kidney disease (CKD) using animal models. Factor Xa activates various cell types through protease-activated receptor 2 (PAR2). Several in vitro studies have demonstrated that PAR2 can mediate factor Xa signaling, but not thrombin signaling. Coagulation processes proceed together with the extracellular matrix (ECM) accumulation through factor V expression in rat Thy-1 nephritis. DX-9065a, a factor Xa inhibitor, suppresses this type of glomerulonephritis. The factor Xa inhibitor danaparoid ameliorated proteinuria, cellular proliferation, and fibrin deposition in lipopolysaccharide (LPS)-triggered activation of High IgA (HIGA) strain of ddY mice. Another factor Xa inhibitor, fondaparinux, suppressed urinary protein, glomerular hypertrophy, and connective tissue growth factor (CTGF), and ECM protein deposition together with angiogenesis in diabetic db/db mice. Finally, in the model of peritoneal fibrosis, fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue and angiogenesis. In consideration of the results to potential human therapy, factor Xa regulation may be promising for the treatment of the aggravation in glomerulonephritis and of the early phase of diabetic nephropathy. In the near future, novel factor Xa inhibitors with the characteristics of oral administration and biliary elimination may appear in the clinical use for treatment of cardiovascular diseases.

ネフローゼ症候群に柴苓湯が奏効した2症例を経験した。症例1は5.2g/日の多量の蛋白尿を呈し，柴苓湯の単独投与を開始し，その後の入院精査にて腎生検による組織型は微小変化型であったが，尿蛋白は入院中に減少し続け，投与開始の2ヵ月後に0.3g/日に至った。外来治療に移行して2.0g/日に増加したものの，再び減少し完全寛解に至った。症例2は8年前にネフローゼ症候群を呈し腎生検で特発性膜性腎症と診断され，少量プレドニゾロン，免疫抑制薬，アンジオテンシン受容体拮抗薬等の併用にて寛解していたが，経過中，4.4g/日の蛋白尿を呈して再発し，柴苓湯の併用にて4週間後1.3g/日となり，その後寛解した。身体所見および漢方医学的所見として症例1は軽度の胸脇苦満を認め，症例2は中等度の浮腫とともに胸脇苦満も明瞭であった。今回の症例におけるすみやかな寛解経過から，考えうる柴苓湯の作用機序を考察し報告する。

Saliva is the first body fluid to encounter exogenous materials or gases such as cigarette smoke (CS). The aim of this study was to examine whether smoking affects oral peroxidase (OPO) reactivity to mental stress. The subjects were 39 non-smokers and 10 smokers. In the experiment, the Kraepelin psychodiagnostic test as a psychological stressor and saliva was sampled 30 min before, just before, immediately after, and 30 min after the beginning of the test. OPO reactivity to the test between smokers and non-smokers was measured in addition to uric acid concentration, flow rate, IgA, thiocyanate (SCN-) concentration, amylase activity as a salivary stress marker, and ultra-weak chemiluminescence (UCL) level, which is indicative of salivary antioxidative and antibacterial abilities. Moreover, we studied the effect of smoking on the response of salivary peroxidase (SPO) and myeloperoxidase (MPO) activity to mental stress, respectively. The results showed that the IgA concentration, amylase activity, SCN(- concentration, and UCL level are higher in the non-smoking group than smoking group and the IgA concentration and UCL level increased in the non-smokers significantly just after the Kraepelin test. The levels of SCN-) were higher in smokers than in non-smokers and OPO activity was greater in the non-smoking group in all sessions. Furthermore, only the non-smokers had significantly increased MPO activity just after the test. MPO may play a crucial role in the response to acute psychological stress besides inflammation, and CS suppresses this response significantly.

An application of the loop transfer recovery (LTR) technique to critical control systems design is proposed for non-minimum phase plants. The controller structure is chosen as the Davison type integral controller with the Kalman filter. First, a critical control system is designed on the assumption that the state of the minimum phase part of the plant can be used for the feedback. A quadratic performance index with tuning parameters is used for determining the partial state feedback gain matrix. Second, the Kalman filter gain matrix is determined such that the output feedback controller performs as in the partial state feedback controller. The formal partial loop recovery procedure using the Riccati equation is adopted for this purpose. The proposed design method requires much simpler numerical search than the conventional one-step approach. An illustrative design example is presented.

Saliva sampling has the advantage of being noninvasive and stress free. Based on a recent study, salivary ultraweak chemiluminescence (UCL) is a new biomarker of psychologic stress. However, it is not clear what causes changes in the UCL level and whether the change is biologically significant. We investigated the candidates for salivary UCL induced by psychological stressors and discuss the physiologic function of these candidates. Vol unteers completed a questionnaire and then performed the Kraepelin test. Saliva was sampled just before, immediately after, and 30 min after the stress exposure. The UCL of saliva significantly increased just after stress exposure (1.56-fold) and returned to prestress levels after 30 min. The concentration of secretory immunoglobulin Aa lso increased significantly and the change in both biomarkers was rapid. Similar significant changes were observed in salivary peroxidase activity an dt he concentration of thiocyanate (SCN − ). On the other hand, the levels of amylase activity did not significantly increase and the concentration of cortisol increased slowly. Moreover, in the reconstitution experiment, UCL was generated at the same level by a mixture of peroxidase and SCN − at physiologic concentrations. In conclusion, we determined that the Kraepelin test as a mental arithmetic task elicited a significant response in the body and this response can be calculated using salivary UCL. Furthermore, SCN − and peroxidase in the saliva play a key role in salivary UCL.

In emergency transportation by ambulance, a patient receives acceleration in various direction. Particularly, longitudinal or lateral acceleration in braking and curve driving causes patient's stress such as blood pressure variation in brain, vomiting or feeling of discomfort. To reduce such patient's stress, we developed the 2-degree-of-freedom (2 DOF) actively-controlled bed (ACB) that reduces the acceleration acting on a patient by controlling posture of the bed. This paper reports its structure, control scheme and control performance. The effect is examined by experiment in terms of cancellation rate of acceleration and ride quality. Using the actual driving data of ambulance, the cancellation rate of acceleration in emergency transportation is also estimated by simulation.

Polymerization of IgA has been suggested as one of the causes of mesangial deposition in IgA nephropathy. HIGA mice are an inbred model of IgA nephropathy, established by selective mating of ddY mice. This strain is characterized by a unique profile of the IgA molecule that is dominantly polymeric and has high serum levels with intense IgA deposition on the mesangium. We carried out quantitative trait loci (QTL) analysis, using F2 generations by crossing HIGA with BALB/c mice. Significant linkage of polymeric IgA in serum samples was identified around D12Mit263, which is close to the gene of the immunoglobulin heavy chain on chromosome 12. The amino acid sequence of the alpha heavy chain revealed marked differences between BALB/c and HIGA mice. Furthermore, most differences were focussed on the hinge region. The DBA/2J strain, which has the same amino acid sequence in the hinge region as the HIGA strain, also showed polymeric IgA dominance but low IgA levels in sera. Size fraction analysis revealed that these polymeric IgA showed trimer dominance in both DBA/2J and HIGA mice. In conclusion, the hinge region plays a key role in trimeric IgA formation in HIGA mice.

In emergency transportation, a patient receives the acceleration of the right-and-left direction when an ambulance turns a corner or changes a lane. Such acceleration causes the feeling of discomfort or carsickness. With the aim of realizing safe and kind transportation for patients, we prototyped the actively-controlled bed for an ambulance which reduces the patient's discomfort by rotating the bed around the body axis. The bed is actuated by a DC servo motor. The desired angle of the bed is calculated in real time from the right-and-left acceleration acting on a car, which is measured with the accelerometer located beside a driver. The purpose of this paper is to examine the effect of the rotating-type actively-controlled bed in terms of ride quality. In experiment, the subjects evaluate a degree of ride quality on a scale of five for every second. Compared to the normal fixed bed, the ride quality improves when the bed is actively controlled.

Protective roles of thioredoxin, a redox-regulating protein, in renal ischemia/reperfusion injury. Background Thioredoxin (TRX) is a small protein with redox-regulating functions. Although TRX is known to be induced in response to various forms of oxidative stress, including ischemia/reperfusion injury, the induction and the specific role of this protein in the kidney have not been fully investigated. Methods Renal ischemia/reperfusion was induced by the clipping and release of renal arteries in C57BL/6 and human thioredoxin-overexpressing transgenic (hTRX-Tg) mice. TRX protein was detected by immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). TRX mRNA was detected by in situ hybridization and Northern blotting. Renal functions were evaluated by measuring the levels of blood urea nitrogen and serum creatinine in these mice. Results With ischemia/reperfusion, endogenous murine TRX was rapidly depleted from the cytosol in the cortical proximal tubuli and detected in the urinary lumen, whereas it was spread diffusely in all segments of the tubular epithelial cells in sham-operated mice. The urinary excretion of TRX increased transiently after ischemia/reperfusion and recovered to the control level in 72 hours. In the medullary thick ascending limb (mTAL), however, TRX was specifically retained in the cytosol. A similar distribution change of transgenic hTRX was observed in the kidney of hTRX-Tg. These hTRX-Tg mice were more resistant to the injury to the mTAL and functional deterioration caused by ischemia/reperfusion, compared with wild-type mice. Conclusion The present findings suggest that TRX is retained in mTAL and secreted from proximal tubuli into urine during renal ischemia/reperfusion. The mTAL-specific retention of TRX may have a protective effect against renal ischemia/reperfusion injury.

Background. Perilla frutescens (perilla) is a herbal medicine used in Japanese traditional Kampo medicine. The present study was conducted to evaluate the anti-nephritic effects of perilla in HIGA mice that spontaneously develop high levels of serum immunoglobulin A (IgA) along with mesangial IgA deposition. Methods. A perilla decoction and its major active constituent, rosmarinic acid (RsA), were orally administrated to 10-week-old HIGA mice for 16 weeks. At study completion, we measured proteinuria and serum IgA levels and generated histological scores from kidney specimens. In addition, we measured concentrations of IgA in culture media of intestinal Peyer’s patch cells and spleen cells obtained from the HIGA mice. Results. Perilla suppressed proteinuria, proliferation of glomerular cells, serum levels of IgA, glomerular IgA and IgG depositions in HIGA mice. Cultured Peyer’s patch cells and spleen cells from perilla-treated mice produced significantly less IgA than controls. Rosmarinic acid, by itself, suppressed serum IgA levels and glomerular IgA deposition in HIGA mice. Cultured spleen cells from RsA-treated mice produced less IgA than controls. Conclusions. The perilla decoction may suppress IgA nephropathy, in part, through modulation of the intestinal mucosal immune system. These effects were caused by RsA acting synergistically with other constituents.

症例は56歳男性. 44歳時慢性糸球体腎炎と診断され50歳時に血液透析に導入された. 透析導入5年目頃より, 透析後に38度台の発熱を呈するようになり, その後, 透析以外の日にも発熱をきたすようになった. CRP上昇 (4.6mg/dL), 白血球増加 (10,700/μL), 好酸球増加 (36%), 抗核抗体陽性を認め, 透析膜アレルギーによる発熱, 透析液中の発熱物質の存在, 感染症, 膠原病, 悪性腫瘍, 薬剤熱等が疑われたが, 精査の結果いずれも否定的であった. Myeloperoxidase (MPO)-ANCA, proteinase 3 (PR3)-ANCAが陽性であり, ANCA-related vasculitisが強く疑われprednisolone 40mgを開始したところ発熱は軽快し, CRPの陰性化, 好酸球の減少を認めた. 血液透析患者の不明熱の原因としてこれまで指摘されてきたもの以外にANCA-related vasculitisも考慮する必要があると考えられた.

Background We recently developed a ddY mouse strain having high IgA levels (HIGA) that provided a murine model of IgA nephropathy. We additionally showed that administration of interleukin (IL)-12, a potent helper T (Th)1-inducing cytokine, induced an apparent reduction in serum IgA levels. In the present study, we assessed the influence of IL-12 administration on several physicochemical characteristics of nephritogenic IgA molecules in HIGA mice. Methods HIGA mice received daily intraperitoneal injections of IL-12 or control injections of phosphate-buffered saline for 3 weeks. Crescent formation and levels of circulating and glomerular IgA were analysed. Moreover, potential changes in charge, size, and glycosylation of serum and glomerular IgA were investigated. Results In the IL-12 group, glomerular IgA deposition was faint, although crescent formation was more marked than in the control group. Serum IgA levels in IL-12 mice were significantly lower than in controls. IL-12-treated mice also showed markedly decreased acidic and polymeric IgA both in sera and in glomerular eluate. A lectin-binding study revealed a markedly reduced ratio of sialylated and galactosylated IgA in the sera and in glomerular eluate from HIGA mice kidneys. IL-12 treatment significantly increased sialylation and galactosylation of circulating IgA, although glycosylation of IgA in glomerular eluate remained low. Conclusions In HIGA mice showing under-glycosylation, IL-12 administration may lead to changes in the physicochemical characteristics of IgA, and this may occur through a shift to Th1. These results suggest that the Th1 and Th2 balance might play a role in the development of immunopathologic lesions in this model of IgA nephropathy.

Oxidative stress is a major determinant of acute kidney injury (AKI); however, the effects of an AKI on renal redox system are unclear, and few existing AKI markers are suitable for evaluating oxidative stress. We measured urinary levels of the redox-regulatory protein thioredoxin 1 (TRX1) in patients with various kinds of kidney disease and in mice with renal ischemia-reperfusion injury. Urinary TRX1 levels were markedly higher in patients with AKI than in those with chronic kidney disease or in healthy subjects. In a receiver operating characteristic curve analysis to differentiate between AKI and other renal diseases, the area under the curve for urinary TRX1 was 0.94 (95% confidence interval, 0.90–0.98), and the sensitivity and specificity were 0.88 and 0.88, respectively, at the optimal cutoff value of 43.0 μg/g creatinine. Immunostaining revealed TRX1 to be diffusely distributed in the tubules of normal kidneys, but to be shifted to the brush borders or urinary lumen in injured tubules in both mice and humans with AKI. Urinary TRX1 in AKI was predominantly in the oxidized form. In cultured human proximal tubular epithelial cells, hydrogen peroxide specifically and dose dependently increased TRX1 levels in the culture supernatant, while reducing intracellular levels. These findings suggest that urinary TRX1 is an oxidative stress-specific biomarker useful for distinguishing AKI from chronic kidney disease and healthy kidneys.

Coagulation process proceeds on cultured human mesangial cells via expression of factor V.BackgroundIn a previous clinicopathological study, we observed mesangial factor V expression accompanied by the intact form of cross-linked fibrin deposition in the active type of IgA nephropathy. The conversion of prothrombin to thrombin by factor Xa is potently accelerated more than 104-fold by the presence of factor V, which is a membrane-bound cofactor. Another membrane-bound cofactor, tissue factor, is known to play an initiating role in the coagulation cascade and to be synthesized in mesangial cells (MCs) by the stimulation of tumor necrosis factor-α (TNF-α). However, the synthesis of factor V, which plays on the terminating stage of prothrombin activation, has not been reported previously in MCs by in vitro study. Our current study tested the coagulation process via expression of factor V by the stimulation of proinflammatory cytokine, TNF-α, in cultured human MCs.MethodsTo evaluate factor V protein expression, immunoperoxidase staining with densitometric evaluation and Western blot analysis were conducted after stimulation of TNF-α. To test factor V activity, stimulated MCs were incubated in combination with factor Xa, prothrombin, fibrinogen and factor XIII, and fibrin production on MCs was assessed after immunoperoxidase staining on the cell surface. In a blocking test using an antibody against factor V, suppression of fibrin production was evaluated to clarify the role of factor V activity. For the evaluation of factor V mRNA expression in cultured human MCs, in situ hybridization and Northern blot analysis were performed.ResultsFactor V protein expression in MCs after TNF-α stimulation increased both time- and dose-dependently. As a marker of factor V activity with exogenous factor Xa, fibrin production on TNF-α–stimulated MCs was increased in a time-dependent manner and was inhibited by the addition of anti-factor V antibody. Factor V mRNA was identified in MCs by in situ hybridization and showed an increase after stimulation with TNF-α on Northern blot analysis.ConclusionsOur data suggest that the coagulation process proceeds on MCs as the result of increased expression of endogenous factor V activity on its cell surface in cooperation with exogenous factor Xa.

For the loss factor measurement, the half-power-width method and curve fitting method are used. In this paper, two curve fitting methods based on pole-zero models are proposed. The first method is to express the measured and model frequency response functions in decibels and the parameters of the model are changed so that the model response gets close enough to the measured response by the differential iteration method. The second method is to take the distance of the two responses on the complex plane and normalize it to the amplitude of the measured frequency response function. Then, the normalized distance is minimized by the differential iteration method. These two methods have the following features: (1) They can fit the resonance and anti-resonance characteristics simultaneously. (2) They can fit frequency response functions with large loss factors to which the half-power-width method are not applicable. (3) The minimum required numbers of measurement points within the half-power-width for these methods are roughly 1/30 of the number necessary for the half-power-width method.

Leaves of Perilla frutescens var. crispa DECNE. (perilla, Labiatae) are used as a garnishing vegetable in East Asian countries as well as an herbal medicine prescribed in Kampo medicines such as Saiboku-to. A previous in vitro study revealed that a decoction of perilla leaves inhibits the proliferation of murine-cultured mesangial cells. In the present study, we evaluated the in vivo anti-proliferative effects of a perilla decoction using rat mesangio-proliferative glomerulonephritis induced by an intravenous injection of rabbit anti-rat thymocyte serum (ATS). Leaves of perilla were boiled, and the decoction was orally administered to the rats as drinking water at doses of 100 and 500 mg/kg/d from the day of ATS-injection (day 0) to day 8, when rats were sacrificed. In the histological evaluation, the total number of glomerular cells, proliferating cell nuclear antigen (PCNA) positive cells, and macrophage/monocyte antigen-positive cells in the glomerulus, was significantly decreased in perilla-treated rats. A significantly lower level of proliferation was induced by the serum of the perilla-treated rats than by that of the controls. These results suggest that the perilla decoction suppresses the proliferation of mesangial cells in vivo by an inhibition of the glomerular infiltration of macrophage/monocytes and of the production of circulating growth factors.

This paper proposes a simplified design method for sampled-data critical control systems with rate-limited exogenous inputs. Fast-discretization technique is used to obtain the input-output relationship with intersample behavior. From the input-output relationship, we derive an approximate condition for the critical specification. It is given as the inequality constraint on the step response, which can be calculated recursively. Controller parameters are determined by a numerical search. A design example is presented to show the validity of the proposed method.

This paper gives a matching condition for sampled-data critical control systems with persistent and/or transient inputs by using the lifting technique. The obtained condition is given as a set of inequality constraints on the impulse and/or step responses. A computational method for evaluating it is also discussed.

The upper frequency limit of a p-p type sound intensity probe is mostly determined by the sensitivity reduction of the probe.The sensitivity reduction is caused by obtaining the pressure from the average of the two pressure signals including the phase, and by obtaining the particle velocity from the finite difference of the two pressure signals.This is a systematic error suggesting a possibility of correction.In order to compensate or correct the sensitivity reduction, the direction of energy flow must be known.If a one-dimensional intensity probe is used, the probe direction must be varied to find the direction of the energy flow.If a three-dimensional intensity probe is used, the direction of the energy flow can be at least roughly estimated from a single measurement and then the sensitivity reduction can be corrected.This paper proposes a method of sensitivity reduction correction in the high frequency region for a three-dimensional(3-D)intensity probe.A theory of the method is described first and then numerical results that validate the theory will be given.This method works even for a probe with some amount of phase mismatch among microphones and for a sound field with reflections.

Direct inhibitory effects of simvastatin on matrix accumulation in cultured murine mesangial cells Background 3-Hydroxy-3-methylglutarylcoenzymeA(HMG-CoA) reductase inhibitors have been demonstrated to suppress glomerular injuries in various renal diseases. These agents inhibit in vitro proliferation of several cell types, including mesangial cells. This effect indicates the ability to ameliorate mesangioproliferative lesions, independent of the improvement of hypercholesterolemia. On the other hand, it is not clear whether HMG-CoA reductase inhibitors directly regulate extracellular matrix (ECM) accumulation from mesangial cells. Methods In this study, to examine the in vitro effects of simvastatin, an HMG-CoA reductase inhibitor, on mRNA expressions of matrix proteins, growth factors, and matrix turnover proteins, we incubated cultured murine mesangial cells stimulated by fetal calf serum (FCS) with or without simvastatin for 24 hours, and Northern analysis was performed. Results Simvastatin showed a slightly suppressive effect on mRNA expression of type IV collagen and fibronectin and a slightly up-regulative effect on that of type I collagen, whereas mRNA expression of type III collagen was markedly up-regulated. mRNA expression of platelet-derived growth factor (PDGF)-B chain and PDGF receptor β-subunit was suppressed, whereas that of transforming growth factor-β (TGF-β) was not affected by simvastatin. Concerning matrix turnover proteins, simvastatin markedly reduced mRNA expression of plasminogen activator inhibitor-1 (PAI-1) without affecting the expression of tissue-type plasminogen activator (tPA). Conclusion These results suggest type-specific modulation of matrix protein production independent of TGF-β and the suppressive effects of autocrine PDGF by administration of HMG-CoA reductase inhibitors in mesangial cells. Moreover, the beneficial effects of these agents on matrix protein accumulation may be through promoting ECM degradation derived from PAI-1 suppression.

Mesangiolytic glomerulopathy in severe congestive heart failure. To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

It is well known that a discrete-time variable structure observer can be designed by reducing the design problem to an output feedback control problem. This approach, however, is valid only for a restricted class of plants. Considering the computation delay, we propose a new method for direct design of a discrete-time variable structure observer. The proposed design method reduces an observer design problem to a state feedback control problem after a coordinate transformation. A numerical example is presented to show that proposed method can be applied to a problem that cannot be designed by reducing to an output feedback control problem.

disorder resulting from clonal expansion of a transwith stage III hypertension and stage II arteriolosclerformed haematopoietic stem cell associated with prominent overproduction of erythrocytes, and to a lesser otic retinopathy by Scheie’s classification. Cardiac ausextent expansion of granulocytic and megakaryocytic cultation revealed accentuated second and fourth heart elements. Previous reports presented three cases of sounds. There was neither splenomegaly nor abdompolycythaemia vera associated with diffuse mesangiop- inal bruit. Both lower extremities had pruritus and the

A three dimensional intensity probe using four microphones is proposed. Four microphones are placed at apexes of a regular tetrahedron. One is placed in the front and three others consisting a vertical regular triangle are in the back. The microphones are attached at the tips of parallel thin tubes. The microphone arrangement is not the conventional face to face type. The aim of this type of microphone arrangement is to design a sound intensity probe with a simple structure, which is essential for reducing the diffraction problem. Algorithms for three dimensional intensity components from cross spectra are given as well as for leakage components. Measurements of sensitivity characteristics in an anechoic room using two types of probes with 60mm and 20mm microphone separations show that sensitivity fluctuations are small enough (less than 1dB) for the practical application of the sound intensity method. The leakage errors of approximately 5%(-13dB) seem also acceptable. The measurement results indicate that sensitivity and leakage errors will become smaller if a more ideal plane wave field in an anechoic room is achieved.

The active type of coagulation factor X (factor Xa) activates various cell-types through protease-activated receptor 2 (PAR2). We previously reported that a factor Xa inhibitor could suppress Thy-1 nephritis. Considering that fibrin deposition is observed in diabetic nephropathy as well as in glomerulonephritis, this study examined the roles of the coagulation pathway and factor Xa in the development of diabetic nephropathy using type 2 diabetic model mice. Diabetic (db/db) and normoglycemic (m+/m+) mice were immunohistochemically evaluated for their expression/deposition of PAR2, transforming growth factor (TGF)-β, fibrin, extracellular matrix (ECM) proteins, and CD31 at week 20. Significantly greater numbers of PAR2-positive cells and larger amounts of fibronectin, and collagen IV depositions were observed in the glomeruli of db/db mice than those in m+/m+ mice. Next, expression of PAR2 versus deposition of collagen IV and fibronectin was compared between week 20 and week 30, and the number of PAR2-positive cells in the glomeruli decreased in contrast with the increased accumulation of ECM proteins. In an intervention study, fondaparinux, a factor Xa inhibitor, was subcutaneously administered for ten weeks from week 10 to 20. Fondaparinux treatment significantly suppressed urinary protein, glomerular hypertrophy, fibrin deposition, expression of connective tissue growth factor, and ECM proteins deposition together with CD31-positive capillaries. These results suggest that coagulation pathway and glomerular PAR2 expression are upregulated in the early phase of diabetes, together with the increase of profibrotic cytokines expression, ECM proteins deposition and CD-31-positive vessels. Factor Xa inhibition may ameliorate glomerular neoangiogenesis and ECM accumulation in diabetic nephropathy.

透析中の異常高血圧は重篤な合併症の原因となりうる. 今回我々は経口降圧剤およびニフェジピンの舌下投与では調節不良の, 透析中に異常高血圧 (収縮期血圧200mmHg以上) を呈する慢性腎不全患者6症例に対し, 塩酸ニカルジピン注射薬の透析中持続静注を試みその降圧効果および副作用について検討した. その結果6症例中全症例において収縮期血圧 (mean±SD) 216.2±17.2mmHgから1時間後152.5±26.6mmHgへと有意な血圧低下 (P