The Role of Cytokine in the Lupus Nephritis

Lupus nephritis (LN) is a major clinical manifestation of systemic lupus erythematosus (SLE). Although numerous abnormalities of immune system have been proposed, cytokine overexpression plays an essential role in the pathogenesis of LN. In the initial phase of the disease, the immune deposits and/or autoantibodies induce cytokine production in renal resident cells, leading to further inflammatory cytokine/chemokine expression and leukocyte infiltration and activation. Then, infiltrate leukocytes, such as macrophages (Mφ) and dendritic cells (DCs), secrete a variety of cytokines and activate naïve T cells, leading the cytokine profile towards T helper (Th)1, Th2, and/or Th17. Recent studies revealed these inflammatory processes in experimental animal models as well as human LN. The cytokine targeted intervention may have the therapeutic potentials for LN. This paper focuses on the expression of cytokine and its functional role in the pathogenesis of LN

乳腺由来のPTHrPは牛の骨吸収を刺激するか？ : 血清オステオカルシン濃度による評価の試み

オステオカルシン(OC)は骨形成と骨吸収のどちらにも関与することが知られているが，ウシにおいては泌乳量や加齢に伴う血清OC濃度の変動は不明である。またそれらを加味した周産期に関する情報は少ない。そこでカルシウムの不均衡が生じやすい周産期の乳牛において，その骨代謝の指標としてOCが有効であるかを検討した。まず，ウシ血清OC濃度は新生子期が最も高く，その後急激に低下し，初産以降は月齢とともに緩やかに低下することが明らかとなった。周産期のみならず，血清OC濃度を評価する際には月齢を考慮する必要があることがわかった。周産期においては，月齢による影響を加味しても，初産牛と経産牛は共に分娩前からすでに骨代謝回転が強く抑制されていることがわかった。しかしながら，経産牛ではこの時期の血清OC濃度は基本的に低いため，骨代謝マーカーとしての血清OC濃度の変動を観察することは困難であった。Age-related changes in serum osteocalcin concentration in nonperiparturient cows and periparturient variations in serum osteocalcin concentrations in primiparous and multiparous cows were evaluated. Levels were evaluated in 104 nonperiparturient female Holstein dairy cows, ranging in age from 11 days to 10 years; these levels were highest in the youngest animals and gradually decreased with age. Serum osteocalcin levels from 14 days pre-calving to 21 days post-calving in primiparous cows were statistically higher than those in multiparous cows. A comparison of osteocalcin levels between nonperiparturient and periparturient cows of a similar age showed that gestation significantly lowered the serum osteocalcin levels in both primiparous and multiparous cows. These results suggest that although serum osteocalcin is one of the markers reflecting bone metabolism, it is not as effective for detection of abnormalities in cows at the time of parturition, especially in high parity cows that are more susceptible to periparturient hypocalcemia

獣医学分野における形態学教育の充実

本事業は獣医学部における形態学教育に必要な設備機器を充実させ，さらには実習において使用する標本整備及び実習方法を充実することによって，優れた獣医師及び高い技術を有する学生を育成することを目的としている。具体的には学生用顕微鏡管理・整備委員会が主体となって，①顕微鏡が設置されている全ての実習室に，デジタルカメラを装備したディスカッション顕微鏡を整備し，顕微鏡映像を液晶プロジェクターを介してスクリーンへ投影できるようにする，②全ての顕微鏡実習で双眼顕微鏡を使用できるようにする，③多様なニーズに対応できる顕微鏡の設置，④実習に使用する顕微鏡標本の充実，を4 カ年計画で行う。平成20 年度は，デジタルカメラ装備の2 人ディスカッション顕微鏡及び培養倒立型顕微鏡（実習室に設置されている液晶プロジェクターに連結し，画像をスクリーンに投影可能）を実習室1 に設置した。また（34 台）を整備した。さらに，実体顕微鏡実の購入，及び実習標本および実習方法の充実を実施した

Lateral–Medial Dissociation in Orbitofrontal Cortex–Hypothalamus Connectivity

The orbitofrontal cortex (OFC) is involved in cognitive functions, and is also closely related to autonomic functions. The OFC is densely connected with the hypothalamus, a heterogeneous structure controlling autonomic functions that can be divided into two major parts: the lateral and the medial. Resting-state functional connectivity has allowed us to parcellate the cerebral cortex into putative functional areas based on the changes in the spatial pattern of connectivity in the cerebral cortex when a seed point is moved from one voxel to another. In the present high spatial-resolution fMRI study, we investigate the connectivity-based organization of the OFC with reference to the hypothalamus. The OFC was parcellated using resting-state functional connectivity in an individual subject approach, and then the functional connectivity was examined between the parcellated areas in the OFC and the lateral/medial hypothalamus. We found a functional double dissociation in the OFC: the lateral OFC (the lateral orbital gyrus) was more likely connected with the lateral hypothalamus, whereas the medial OFC (the medial orbital and rectal gyri) was more likely connected with the medial hypothalamus. These results demonstrate the fundamental heterogeneity of the OFC, and suggest a potential neural basis of the OFC-hypothalamic functional interaction

Classification of Imbalanced Data Represented as Binary Features

Typically, classification is conducted on a dataset that consists of numerical features and target classes. For instance, a grayscale image, which is usually represented as a matrix of integers varying from 0 to 255, enables one to apply various classification algorithms to image classification tasks. However, datasets represented as binary features cannot use many standard machine learning algorithms optimally, yet their amount is not negligible. On the other hand, oversampling algorithms such as synthetic minority oversampling technique (SMOTE) and its variants are often used if the dataset for classification is imbalanced. However, since SMOTE and its variants synthesize new minority samples based on the original samples, the diversity of the samples synthesized from binary features is highly limited due to the poor representation of original features. To solve this problem, a preprocessing approach is studied. By converting binary features into numerical ones using feature extraction methods, succeeding oversampling methods can fully display their potential in improving the classifiers’ performances. Through comprehensive experiments using benchmark datasets and real medical datasets, it was observed that a converted dataset consisting of numerical features is better for oversampling methods (maximum improvements of accuracy and F1-score were 35.11% and 42.17%, respectively). In addition, it is confirmed that feature extraction and oversampling synergistically contribute to the improvement of classification performance

Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Δ12,14-Prostaglandin J2

15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-γ ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ2 can suppress interleukin (IL)-1β-induced prostaglandin E2 (PGE2) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE2 synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ2 led to a significant increase in IL-1α-induced COX-2 expression and PGE2 production in a dose dependent manner. The effect of 15d-PGJ2 was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ2 exerts a positive feedback regulation of the arachidonate cascade of PGE2 in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis

The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese

The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese.BackgroundA considerable diversity in prognosis is seen with lupus glomerulonephritis (LGN). Hence, the clinical usefulness of a recent International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification to judge the long-term outcome of human LGN has been investigated.MethodsWe studied retrospectively 60 subjects with LGN (7 males, 53 females, mean age of 33 years old) who underwent renal biopsies and were followed from 1 to 366 months, with a mean of 187 months. We diagnosed renal pathology as classes, active and sclerosing lesions, according to the new and WHO1995 classification of LGN, and analyzed the clinicopathologic factors affecting to the prognosis of LGN.ResultsNew classification got much higher consensus in the judgment of classes (98% vs. 83%, P = 0.0084). The group of Class IV-S (N = 6) or IV-G (N = 17) at initial biopsies showed higher rate of end-stage renal failure (ESRF) compared with that of Class I, II, III or V (40.9% vs. 2.6%, P < 0.001). The mean 50% renal survival time of Class IV was 189 ± 29 months, and patients with Class IV-S tended to have a poorer prognosis (95 ± 22 months for IV-S vs. 214 ± 35 months for IV-G, P = 0.1495). Class IV was also selected as the most significant risk factor for ESRF by stepwise model (P = 0.002). In subanalysis for ESRF in Class IV (-S or –G), treatment including methylprednisolone pulse therapy was only selected as a significant improving factor for primary outcome (P = 0.034). In addition, activity index was the significant risk factor of death and/or ESRF after initial renal biopsies (P = 0.043). As for actuarial patient death during all follow-up periods, complications with anti-phospholipid syndrome or nephrotic syndrome were significant risk factors (P = 0.013, P = 0.041, respectively).ConclusionNew ISN/RPS 2003 classification provided beneficial pathologic information relevant to the long-term renal outcome and the optimal therapy preventing ESRF and/or death in patients with LGN

The Impacts of Albuminuria and Low eGFR on the Risk of Cardiovascular Death, All-Cause Mortality, and Renal Events in Diabetic Patients: Meta-Analysis

Background:Precise effects of albuminuria and low estimated glomerular filtration rate (eGFR) on cardiovascular mortality, all-cause mortality, and renal events in diabetic patients are uncertain.Materials and Methods:A systematic review was conducted of the literature through MEDLINE, EMBASE, and CINHAL from 1950 to December 2010. Cohort studies of diabetic patients providing adjusted relative risk (RR) of albuminuria and eGFR for risks of cardiovascular mortality, all-cause mortality, and renal events were selected. Two reviewers screened abstracts and full papers of each study using standardized protocol.Results:We identified 31 studies fulfilling the criteria from 6546 abstracts. With regard to the risk of cardiovascular mortality, microalbuminuria (RR 1.76, 95%CI 1.38-2.25) and macroalbuminuria (RR 2.96 95%CI 2.44-3.60) were significant risk factors compared to normoalbuminuria. The same trends were seen in microalbuminuria (RR 1.60, 95%CI 1.42-1.81), and macroalbuminuria (RR 2.64, 95%CI 2.13-3.27) for the risk of all-cause mortality, and also in microalbuminuria (RR 3.21, 95%CI 2.05-5.02) and macroalbuminuria (RR 11.63, 95%CI 5.68-23.83) for the risk of renal events. The magnitudes of relative risks associated with low eGFR along with albuminuria were almost equal to multiplying each risk rate of low eGFR and albuminuria. No significant factors were found by investigating potential sources of heterogeneity using subgroup analysis.Conclusions:High albuminuria and low eGFR are relevant risk factors in diabetic patients. Albuminuria and low eGFR may be independent of each other. To evaluate the effects of low eGFR, intervention, or race, appropriately designed studies are needed. © 2013 Toyama et al

Noninvasive prediction of shunt operation outcome in idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, cognitive deterioration and urinary incontinence in elderly individuals. These symptoms can be improved by shunt operation in some but not all patients. Therefore, discovering predictive factors for the surgical outcome is of great clinical importance. We used normalized power variance (NPV) of electroencephalography (EEG) waves, a sensitive measure of the instability of cortical electrical activity, and found significantly higher NPV in beta frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2) in shunt responders compared to non-responders. By utilizing these differences, we were able to correctly identify responders and non-responders to shunt operation with a positive predictive value of 80% and a negative predictive value of 88%. Our findings indicate that NPV can be useful in noninvasively predicting the clinical outcome of shunt operation in patients with iNPH