Serum ferritin predicts prognosis in hemodialysis patients: the Nishinomiya study

Background  

The mortality in end-stage renal disease patients with dialysis remains high. Serum ferritin is a useful surrogated marker of iron storage. It has not been elucidated whether the ferritin level can predict the prognosis of patients with dialysis but without obvious inflammation. To clarify whether the ferritin level is involved in the prognosis in dialyzed patients, we investigated the relation between ferritin level and mortality in hemodialyzed patients during long-term follow-up.     

Immunohistochemical and Immunocytochemical Localization of Amylase in Rat Parotid Glands and von Ebner's Glands by Ion Etching-Immunoscanning Electron Microscopy

The distribution of amylase in rat parotid glands and von Ebner's glands was examined using ion etching-immunoscanning electron microscopy, which enables both light and electron microscopic observations of identical semi-thin resin sections immunolabeled with anti-α-amylase and immunogold in association with silver enhancement. At the light microscopic level, most acinar secretory granules (SG) and striated duct secretions of parotid glands were strongly stained dark brown. In von Ebner's glands, acinar SG and duct secretions were weakly to strongly stained light to dark brown. At the electron microscopic level, labeling was observed as bright gold-silver particles. The labeling intensity of acinar SG of parotid glands was higher than that of von Ebner's glands. In parotid glands, weak labeling of SG in transitional cells between acini and intercalated ducts, very weak labeling of SG in intercalated ducts, and strong labeling of striated duct secretions were observed. In von Ebner's glands, the secretions and some SG of interlobular ducts were strongly labeled compared to those of intralobular ducts and SG of acini. Less amylase was synthesized in von Ebner's acini compared to parotid acini, whereas von Ebner's ducts may secrete significantly more amylase to modify saliva than parotid ducts.     

Left main coronary trunk connecting into right atrium with an aneurysmal coronary artery fistula

Congenital coronary artery fistula (CAF) is an infrequent vascular anomaly that establishes a direct link between an epicardial coronary artery and a cardiac chamber, major vessels, or other vascular structures. In this case there was an aneurysmal-CAF between a left main trunk and the right atrium, which was initially diagnosed as a Kawasaki disease by transthoracic echocardiography and subsequently confirmed by coronary angiography and multi-slice CT angiography. A multi-slice CT angiography might well become the modality of choice for the characterization of these rare congenital anomalies.     

Antibody Fc Functional Activity of Intravenous Immunoglobulin Preparations Treated with Solvent-Detergent for Virus Inactivation

We report here results of in vitro comparisons of the Fc functional activity of a second-generation intravenous immunoglobulin (IGIV) preparation (Venoglobulin®-I) and a third-generation IGIV product that includes a deliberate virus-inactivation step (Venoglobulin®-S). Both formulations showed equivalent Fc-mediated function against viral antigens (rubella, influenza A, and influenza B) by single-radial hemolysis test, and against group B Streptococcus, Staphylococcus aureus and Escherichia coli by opsonophagocytosis assay. In addition, we showed by three different immunochemical reactions and by HPLC analysis that both preparations consisted of mostly monomeric IgG and contained very low levels of complement-fixing IgG aggregates. However, IgG aggregation induced by heating at 63°C markedly enhanced fixation of C1q and C3 and binding to Raji cells, indicating that the IgG molecules retained their complement-fixing capacity. Thus, the incorporation of a virus inactivation step in the manufacture of our third-generation IGIV did not alter the Fc functional activities of the IgG, as measured by these in vitro assay systems.     

Opposite response of lung adenocarcinoma and its choroidal metastases upon ramucirumab plus docetaxel therapy after immunotherapy: a case report

Angiogenesis - We report a unique case of advanced non-small cell lung cancer that exhibited the opposite response to its unilateral choroidal metastases upon ramucirumab plus docetaxel treatment....     

Increased carotid artery plaque score is an independent predictor of the presence and severity of coronary artery disease

OBJECTIVES: Carotid ultrasonography is noninvasive and effective for the assessment of atherosclerotic lesions. The relationship between carotid ultrasound findings and presence and severity of coronary artery disease (CAD) was examined in Japanese patients. METHODS AND RESULTS: Subjects were 116 patients who underwent carotid ultrasonography and coronary angiography. In carotid ultrasonography, mean-intima-media thickness (IMT), common carotid artery max IMT, bifurcation max IMT, plaque number, and plaque score (PS). The coronary angiographic data was obtained in the same period as carotid ultrasonography was performed. Patients were divided into two groups based on the presence or absence of coronary artery stenosis (CAS and non-CAS) and CAS group was further categorized into three groups, 1 vessel disease (1VD), 2VD, and 3VD. Physical findings, biochemical data, and carotid ultrasonogram data between the groups were compared. Items showing a significant difference between CAS and non-CAS were age, gender (male), incidence of diabetes and dyslipidemia, fasting blood sugar (FBS), triglyceride, HDL-cholesterol (HDL-C), high-sensitivity C-reactive protein, and all carotid ultrasound findings. All of the above parameters also showed a significant difference between four different severity groups. Stepwise logistic regression analysis was performed to determine which factors predict the presence and/or severity of CAS. High PS showed the strongest predictive value for both and followed by low HDL-C and high FBS. The cut-off value of PS obtained by receiver operating characteristic curve for predicting the presence of CAS was 1.9. CONCLUSIONS: Assessment of PS by carotid ultrasonography together with other risk factor assessment was clinically relevant to predict the presence and severity of CAS.     

DAP1, a Negative Regulator of Autophagy,Controls SubAB-Mediated Apoptosis and Autophagy

Autophagy and apoptosis play critical roles in cellular homeostasis and survival. Subtilase cytotoxin (SubAB), produced by non-O157 type Shiga-toxigenic Escherichia coli (STEC), is an important virulence factor in disease. SubAB, a protease, cleaves a specific site on the endoplasmic reticulum (ER) chaperone protein BiP/GRP78, leading to ER stress, and induces apoptosis. Here we report that in HeLa cells, activation of a PERK (RNA-dependent protein kinase [PKR]-like ER kinase)-eIF2α (α subunit of eukaryotic initiation factor 2)-dependent pathway by SubAB-mediated BiP cleavage negatively regulates autophagy and induces apoptosis through death-associated protein 1 (DAP1). We found that SubAB treatment decreased the amounts of autophagy markers LC3-II and p62 as well as those of mTOR (mammalian target of rapamycin) signaling proteins ULK1 and S6K. These proteins showed increased expression levels in PERK knockdown or DAP1 knockdown cells. In addition, depletion of DAP1 in HeLa cells dramatically inhibited the SubAB-stimulated apoptotic pathway: SubAB-induced Bax/Bak conformational changes, Bax/Bak oligomerization, cytochrome c release, activation of caspases, and poly(ADP-ribose) polymerase (PARP) cleavage. These results show that DAP1 is a key regulator, through PERK-eIF2α-dependent pathways, of the induction of apoptosis and reduction of autophagy by SubAB.     

Effects of acetate-free citrate-containing dialysate on metabolic acidosis, anemia, and malnutrition in hemodialysis patients

Previously, dialysate contained small amounts of acetate as an alkaline buffer. Recently, acetate‐free dialysate (A[?]D) has been available. We evaluated the clinical effect of A(?)D over acetate‐containing dialysate (A(+)D) on acid–base balance, anemia, and nutritional status in maintenance hemodialysis (MHD) patients. Twenty‐nine patients on MHD were treated with A(+)D for 4 months (first A(+)D), switched to A(?)D for 4 months, and returned to A(+)D for the next 4‐month period (second A(+)D). Metabolic acidosis: Serum bicarbonate (HCO3^‐) levels did not change in patients with normal HCO3^‐ levels (≥20 mEq/L) throughout the study. Meanwhile, in patients with initially low HCO3^‐ levels, it was significantly increased during the A(?)D period only. Anemia: In patients with target hemoglobin (Hb) ≥10 g/dL, Hb levels were maintained during the study period, even if the dose of erythropoiesis‐stimulating agents (ESAs) decreased. In patients with low Hb levels, it was significantly increased in the A(?)D period without increasing ESA or iron doses. Nutritional Condition: In patients with normal albumin levels (≥3.8 g/dL), albumin did not change throughout the study period. However, in patients with lower albumin levels, it was significantly increased during the A(?)D period. These improvements in metabolic acidosis, anemia, and nutrition in the A(?)D period completely dissipated during the second A(+)D period. Hemodialysis (HD) with A(?)D may improve a patient's clinical status with intractable metabolic acidosis, hyporesponsiveness to ESA, and malnutrition that were not normalized in HD with A(+)D.