Cardiolipin (CL) is a major membrane phospholipid specifically localized in mitochondria. At the cellular level, CL has been shown to have a role in mitochondrial energy production, mitochondrial ...membrane dynamics, and the triggering of apoptosis. However, the in vivo role of CL in multicellular organisms is largely unknown. In this study, by analyzing deletion mutants of a CL synthase gene (crls-1) in Caenorhabditis elegans, we demonstrated that CL depletion selectively caused abnormal mitochondrial function and morphology in germ cells but not in somatic cell types such as muscle cells. crls-1 mutants reached adulthood but were sterile with reduced germ cell proliferation and impaired oogenesis. In the gonad of crls-1 mutants, mitochondrial membrane potential was significantly decreased, and the structure of the mitochondrial cristae was disrupted. Contrary to the abnormalities in the gonad, somatic tissues in crls-1 mutants appeared normal with respect to cell proliferation, mitochondrial function, and mitochondrial morphology. Increased susceptibility to CL depletion in germ cells was also observed in mutants of phosphatidylglycerophosphate synthase, an enzyme responsible for producing phosphatidylglycerol, a precursor phospholipid of CL. We propose that the contribution of CL to mitochondrial function and morphology is different among the cell types in C. elegans.
Background: Cardiolipin is required for maintaining optimal mitochondrial function.
Results: Cardiolipin depletion selectively obstructed proliferation, mitochondrial function, and morphology in germ cells.
Conclusion: The contribution of cardiolipin to mitochondrial function and morphology varies among the different cell types in vivo.
Significance: This provides a biological basis for understanding the different sensitivities of organelles to changes in the lipid environment.
Background:There is a paucity of studies on whether early referral (ER) to nephrologist could reduce cardiovascular mortality on dialysis, and the length of pre-dialysis nephrological care needed to ...reduce mortality on dialysis.Methods and Results:A total of 604 consecutive patients who started dialysis between 2001 and 2009 in Senshu region, Osaka, Japan were analyzed. Non-linear associations between mortality and pre-dialysis duration of nephrological care were assessed using restricted cubic spline function, and predictors for death analyzed on Cox modeling. A total of 31.6%, 18.2%, 11.3% and 6.1% of patients had >12, 24, 36 and 48 months of pre-dialysis care, respectively. A total of 258 patients (42.7%) were categorized as ER (≥6 months pre-dialysis duration). During the follow-up period (median, 31.1 months), 218 patients died (cardiovascular, n=70; infection, n=69). Although patients with late referral (LR) had a proxy of inappropriate pre-dialysis care compared with the ER group, Cox multivariate analysis failed to show a favorable association between ER and cardiovascular outcome. In contrast, a deleterious effect of LR on overall survival was observed but was limited only to the first 12 months of dialysis (HR, 1.957; 95% CI: 1.104–3.469; P=0.021), but not observed thereafter.Conclusions:Current pre-dialysis nephrological care may reduce short-term mortality but may not improve cardiovascular mortality after dialysis initiation. (Circ J 2016; 80: 1008–1016)
Retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent antiproliferative and anti-inflammatory properties. Recently, retinoic acids were reported to inhibit Th1 cytokine ...production. We investigated the effects of retinoic acid on lupus nephritis in a model of NZB/NZW F(1) (NZB/W F(1)) mice. Three-month-old NZB/W F(1) mice were separated into two groups: one treated with all-trans-retinoic acid (ATRA; 0.5 mg i.p., three times weekly for 7 mo) and one with saline as a control. Compared with controls, ATRA-treated mice survived longer and exhibited a significant reduction of proteinuria, renal pathological findings including glomerular IgG deposits, and serum anti-DNA Abs. Splenomegaly was less marked in the treated mice than in controls. Transcripts encoding IFN-gamma, IL-2, and IL-10 in splenic CD4(+) T cells were significantly reduced in treated mice compared with controls. We conclude that treatment with ATRA in SLE-prone NZB/W F(1) mice significantly alleviates autoimmune renal disorder and prolongs survival; this may thus represent a novel approach to the treatment of patients with lupus nephritis.
It has been reported that anti-phospholipid antibodies are detected in some patients with idiopathic thrombocytopenic purpura (ITP). To study the significance of determination of antiphospholipid ...antibodies in patients with ITP, clinical and laboratory findings were compared between patients whose sera were positive for these antibodies (Group A) and non-positive patients (Group B). Anti-cardiolipin antibody (aCL) was determined by enzyme-linked immunosorbent assay and lupus anticoagulant (LA) was determined by activated partial thromboplastin time (aPTT) and thromboplastin time inhibition test. Seven out of 27 cases of ITP belonged to Group A and 3 of the 7 were confirmed to have anti-phospholipid antibody syndrome (APS). There was a tendency for habitual abortion, and thrombosis, megakaryocytes in the bone marrow and plateletassociated IgG (PAIgG)-positive cells were more frequent in Group A than in Group B. However, it was difficult to discriminate APS from ITP alone, when there were no symptoms or signs of APS. Therefore, measurement of anti-phospholipid antibodies in ITP was thought to be useful for the differential diagnosis of APS and subsequently for the prevention of thrombosis. (Internal Medicine 36: 882-885, 1997)
Anti-DNA antibody, especially high-affinity anti-DNA antibody (ADNA), is thought to have an important role in the pathogenesis of lupus nephritis. In this study, ADNA which binds to double-stranded ...DNA under a high concentration of sodium chloride was measured in patients who had received immunoadsorption (IA) therapy with a dextran-sulfate column. Titers of high-affinity ADNA in the cases with renal dysfunction tended to be higher than in those without renal dysfunction. The change in the titer of high-affinity ADNA paralleled the clinical course. These findings suggest that measurement of high-affinity ADNA is useful for follow-up of the clinical course of patients who have undergone IA therapy. (Internal Medicine 35: 367-372, 1996)
We examined the effects of gamma-interferon (γ-IFN) and the new immunosuppressant FK506 on resting B cell proliferation of New Zealand black/white F1 hybrid (B/W F1) mice, an animal model of human ...systemic lupus erythematosus (SLE). γ-IFN and FK506 inhibited in a dose-dependent manner both B cell proliferation and autoantibody production of resting B cells respectively. There was a synergistic interaction between γ-IFN and FK506 in their inhibition and they did not exhibit cell cytotoxicity. This in vitro synergism of γ-IFN and FK506 may have clinical application in that low doses of γ-IFN and FK506 combinations may be effective to correct polyclonal B cell activation of patients with SLE.
Environmental effect of acid deposition on the acidity and chemical properties of soils was investigated using soil samples collected from Mt. Hiei and its surrounding mountains, in Kyoto city. The ...average soil pH(H2O) of A0 and its lower horizons for samples from 15 mountains were 3.96 and 4.26, respectively. These mountains were classified into two types. One type is represented by Mt. Hiei, where the soil pH was distributed in a wide pH range from acidic to neutral, the other by Mt. Daimonji, where the soil pH was distributed in a narrow acidic pH range . Almost all mountains in Kyoto city belongs to Mt. Daimonji type. The average chloride, nitrate and sulfate concentrations in water extracts of soils from 15 mountains were 0 .046, 0.0064 and 0.0322 cmolkg-1, respectively. Chloride and sulfate concentrations in soils tended to increase with decreasing soil pH, nitrate ion concentration remaining generally very low. The exchangeable Al in soils was soluble below pH 5.5. Based on the acidity and chemical properties of soils, it is suggested that the acid buffering capacities of soils of the mountains on three sides of Kyoto basin will decrease considerably in the near future, because soil pH, as well as exchangeable Ca and Mg, exchangeable Al and sulfate concentrations in the soils support this conclusion.
Abstract
We examined the effects of gamma‐interferon (γ‐IFN) and the new immunosuppressant FK506 on resting B cell proliferation of New Zealand black/white F
1
hybrid (B/W F
1
) mice, an animal model ...of human systemic lupus erythematosus (SLE). γ‐IFN and FK506 inhibited in a dose‐dependent manner both B cell proliferation and autoantibody production of resting B cells respectively. There was a synergistic interaction between γ‐IFN and FK506 in their inhibition and they did not exhibit cell cytotoxicity. This
in vitro
synergism of γ‐IFN and FK506 may have clinical application in that low doses of γ‐IFN and FK506 combinations may be effective to correct polyclonal B cell activation of patients with SLE.
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