Auditory event-related potentials during stage 2 NREM sleep in humans

SUMMARY  Event-related potential (ERP) recordings were used to investigate the nature of auditory stimulus evaluation during stage 2 sleep. Frequent and rare stimuli, differing in intensity and frequency, were presented to six adult subjects while awake and asleep. The latency and voltage distribution of one of the long-latency components evoked during sleep resembled the P3 component evoked while awake. However, it was attenuated in voltage and superimposed on N3, a large late negative component, most probably the slow potential of the K complex. The identification of a P3-like potential during sleep suggests that the P3 potential is not solely a marker of active cognitive processes, but contains a small component which reflects automatic, pre-attentive evaluation of deviant stimuli.     

In vitro biosynthesis of plasma proteins under ischemic conditions of closed-circuit perfusion of healthy and intoxicated rabbit liver

We are elaborating on the kinetics and mechanisms of septic rabbit liver to de novo biosynthesize acute-phase response (APR) proteins under in vitro conditions of deepening ischemia in reference to their in vivo prevalence in serum and cerebrospinal fluids (CSF) collected at predetermined times. The significance of the data is interpreted as relevant to grafting cadaveric liver into end-stage liver diseased patients and APR-induced ischemic heart diseases (IHD). Hepatic APR was induced by CCl(4)-intubation, and the administration of cholera toxin (CT) or scorpion venom (SV), or both, to rabbits. Hepatic functional efficiency, in terms of biosynthesis of APR proteins in closed circuit perfusion of the isolated intoxicated liver with oxygenated saline or L-15 media paralleled the two-dimensional immunoelectrophoresis (2D-IEP) spectrum of APR serum proteins at time of liver isolation. We are suggesting: (a) in vitro biosynthesis of plasma proteins by isolated perfused liver is the result of in vivo decoded and retained APR inflammatory signals; and (b) decoded inflammatory signals are expressed not withstanding the perfusate's organic composition. Furthermore, 90 min of ischemic perfusion in saline or L-15 medium precipitated mitochondrial aberrations which resulted in further deterioration of de novo biosynthesis of APR plasma proteins. Regardless of the nature of the inflammatory stimuli, mitochondrial aberrations rendered the perfused organ a biologically inert tissue mass that was incapable of resuming biological function upon perfusion with oxygenated L-15 medium. This is most likely due to ischemia-induced irreversible hepatic necrosis. Thus, in vitro aberrations of mitochondrial function(s) critically limit the capability of the isolated liver to resume its organic function to sustain biosynthesis of de novo plasma proteins. Extrapolation of these results to the surgical management of end-stage liver diseases points to the importance of the status and the handling protocol(s) of the cadaver donor liver prior to successful grafting. We conclude that although histology of a cadaver liver may reveal well-preserved hepatic cellular organelles with at least minimal intra- and intercellular communication required for viable hepatic function, we deem it essential to further define acceptable minimal capabilities to de novo biosynthesize plasma proteins by a cadaver liver as a measure of its functional viability and suitability for transplantation. Ultimately, this measure may improve the success of liver transplants with minimal surgical and drug interventions.     

布氏显微镜活血分析: 细胞流变学研究的新方法

布氏显微镜活血分析：细胞流变学研究的新方法骆秉铨＊黄荣国＊陈兴新＊细胞流变学是研究血细胞流动变形的科学，在方法学上发展了一些比较成熟的方法，但多不能直接动态观察细胞水平的真实改变，有待完善和创新。我们采用布氏多功能显微镜的活血分析法［１］，在高放大倍...     

Participation of hematopoietic stem cells in formation of the immune response

The effect of different doses of sheep's red blood cells (SRBC) on endogenous colony formation and immunogenesis was studied in CBA and C57BL mice. The absolute and relative numbers of antibody-forming cells (AFC) was shown to increase with an increase in the dose of SRBC from 2×10⁷ to 2×10⁸, and to decrease with a dose of 2×10⁹ in mice of both lines. With an increase in the dose of antigen, the number of endogenous splenic colonies (ESC) of hematopoietic cells also increased. Interlinear differences in the number of ESC persisted. It is suggested that the mechanism of stimulation of the hematopoietic series is based on a unique type of blockade of the reticuloendothelial system by foreign red blood cells, leading to increased proliferative activity of the stem cells.Laboratory of Regulation of Immunopoiesis, Institute of Clinical and Experimental Medicien, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 4, pp. 330–332, April, 1979.     

Endogenous sex hormone levels and breast cancer risk

Sex-steroid hormones are a major determinant of the risk of breast cancer. We evaluated the relationship between obesity and endogenous estrogen levels in 79 healthy, postmenopausal women. Thirty-nine of the women were siblings of patients with postmenopausal-onset breast cancer; the remaining women were age-matched (+/- 10 yr) controls. Our hypothesis was that the siblings of the breast cancer patients would weigh more and that this excess weight would lead to higher serum estrone levels. The choice of unaffected family members of breast cancer patients reduces the concern that results may have been influenced by the cancer rather than antecedent to its development. Our findings demonstrated a statistically significant excess estrone level in the siblings compared to the controls (58.9 vs 47.8 pg/ml, P = 0.005). The siblings weighed 4.3 kg more than the controls. Matched pairs analysis (sibling-control), adjusting for weight, also showed significant differences in serum estrone levels. These differences were observed despite comparability in dietary intake, medication use, and personal medical history. These findings represent the first time that higher estrogen levels have been measured in siblings of postmenopausal breast cancer patients. This observation may represent an important link in our understanding of the relationship between genetic and environmental risk factors of breast cancer. One approach to subsequent genetic studies of breast cancer may be to focus on the possible biological determinants such as sex-steroid hormone level receptors, oncogenes, and gene products and not on the "familial aggregation" of breast cancer.     

Actions of theβ-carboline ZK 93426 in an animal test of anxiety and the holeboard: Interactions with Ro 15-1788

Summary The effects of the-carboline ZK 93426, a putative benzodiazepine receptor antagonist, were investigated in the social interaction test of anxiety and in the holeboard. Like the receptor antagonist Ro 15-1788, ZK 93426 (2.5–10 mg/kg) caused a specific reduction in social interaction (interpreted as an anxiogenic effect) and caused a significant elevation in exploratory head-dipping (5 mg/kg). When low (ineffective) doses of both compounds (1 mg/kg ZK 93426; 4 mg/kg Ro 15-1788) were administered together they significantly reduced social interaction. No further reductions in social interaction were observed when effective doses of both compounds (5 mg/kg ZK 93426; 10 mg/kg Ro 15-1788) were tested in combination; it is likely that this is due to almost total benzodiazepine receptor occupancy at effective doses of either compound. When doses of each compound (5 mg/kg ZK 93426; 10 mg/kg Ro 15-1788) that resulted in stimulation of head-dipping were examined in combination, the elevation in exploration was no longer observed. Since at higher doses of both compounds there is an attenuation of the elevation in head-dipping, it is again likely that the effects of the two compounds are additive.     

CircCDR1as Suppresses Bone Microvascular Endothelial Cell Activity and Angiogenesis Through Targeting miR‐135b/ FIH‐1 Axis

ObjectiveThe current study investigated the role of CircCDR1as on angiogenesis of bone microvascular endothelial cells (BMECs) isolated from non‐traumatic ONFH.MethodsForty corticosteroid‐induced ONFH patients received THA were enrolled in our study. Expressions of CircCDR1as, miR‐135b, and FIH‐1 were detected by qRT‐PCR in affected necrosis tissue and non‐affected normal tissue. Bone microvascular endothelial cells (BMEC) were isolated from six patients and treated with 0.1 mg/mL hydrocortisone to establish a GC‐damaged model of BMECs. Circ CDR1as plasmid and miR‐135b mimic were transfected into BMECs. BMEC proliferation was assessed using MTT assays. The migration ability of cells was detected by scratch‐wound assays. Matrigel assay was performed to detect angiogenesis in vitro. Western blot assay was used to detect HIF‐1α, VEGF, and FIH‐1 expressions. FISH, RNA pull down, RIP, and luciferase assay were carried out to determine the interaction of CircCDR1as, miR‐135b, and FIH‐1.ResultsCircCDR1as was upregulated(2.02 ± 0.30 vs. 1.00 ± 0.10,P < 0.001) whereas miR‐135b was downregulated (0.55 ± 0.12 vs. 1.00 ± 0.10,P < 0.001) in affected tissues than in non‐affected tissues. Expression of CircCDR1as and FIH‐1 were negatively associated with miR‐135b in affected tissues (CircCDR1as with miR‐135b: r = −0.506, P < 0.001; FIH‐1 with miR‐135b r = −0.510, P < 0.001). Total blood tubule density was increased when CircCDR1as was silenced compared with NC (P < 0.01 vs. NC). The number of migrated BMECs were significantly increased in CircCDR1as silencing group compared with NC group (P < 0.05 vs. NC). In addition, CircCDR1as plasmids transfection increased the protein expressions of FIH‐1 (P < 0.05 vs. NC) and reduced the HIF‐1α as well as VEGF expression compared with NC group (P < 0.05 vs. NC). FISH, RNA pull down, RIP, and luciferase assay identified that FIH‐1 was a target of miR‐135b and could be modulated by CircCDR1as.ConclusionCircCDR1as decreases angiogenesis and proliferation of BMECs by sponging miR‐135b and upregulate FIH‐1.     

Comprehensive analysis of the lncRNA-miRNA-mRNA regulatory network for bladder cancer

BackgroundLong non-coding RNAs (lncRNAs) are essential regulators for various human cancers. However, these lncRNAs need to be further classified for cancer. In the present study, we identified novel competing endogenous RNA (ceRNA) network for bladder cancer (BC) and explored the gene functions of the ceRNA regulatory network.MethodsDifferential gene expression analysis were performed on The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) datasets to identify differentially expressed messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs). Based on the competing endogenous RNA (ceRNA) hypothesis, a lncRNA-miRNA-mRNA network was constructed using the StarBase database and visualization by Cytoscape software. Functional enrichment analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed via R package ClusterProfiler. The protein-protein interaction network was constructed by STRING database and visualization by Cytoscape. Finally, we used CIBERSORT and the TIMER database to analyze the immune infiltrations for BC.ResultsThe regulatory network was constructed via TCGA BLCA cohort. The differential expressions of lncRNA, miRNA, and mRNA were 186, 200, and 2,661, respectively. There were 106 lncRNA, miRNA, and mRNA included in the ceRNA network. In this network, Calcium Voltage-gated Channel Auxiliary Subunit Alpha2delta1 (CACNA2D1, P<0.001), domain containing engulfment adaptor1 (GULP1, P=0.001), latent transforming growth factor beta binding protein 1 (LTBP1, P=0.006), myosin light chain kinase (MYLK, P=0.001), serpin family E member 2 (SERPINE2, P=0.002), spectrin beta non-erythrocytic 2 (SPTBN2, P=0.047), and hsa-miR-590-3p (P<0.001) significantly affected the prognosis of BC patients. Functional enrichment analyses showed that the biological functions included negative regulation of protein phosphorylation, cell morphogenesis, and sensory organ morphogenesis. Important cancer pathways of KEGG included parathyroid hormone synthesis secretion action, the notch signaling pathway, MAPK signaling pathway, the Rap1 signaling pathway, signaling pathways regulating the pluripotency of stem cells, and the transforming growth factor-β signaling pathway. Our findings demonstrated that the ceRNA network has important biological functions and a significant influence on the prognosis of BC.ConclusionsThe lncRNA-miRNA-mRNA network constructed in the present study could provide useful insight into the underlying tumorigenesis of BC, and can determine new molecular biomarkers for the diagnosis and therapeutical treatment of BC.     

Combination of Methods for <Emphasis Type="Italic">in Vitro</Emphasis> Study of Antioxidant Properties of Chemical Compounds

Blood ammonia concentration increased in the portal vein (by 1.4 times) and inferior vena cava (caudal to the renal vein inflow, by 2.2 times; and cranial to the hepatic vein inflow, by 2.5 times) of rats 3 h after intragastric administration of 16.57 M ethanol solution (446 mmol/kg, ≈ 1.4 LD_{50/48 h}). Ammonia concentration in mixed blood samples (post-decapitation) increased by 39%. The rate of ammonia accumulation was 3-fold higher in an intraperitoneal lavage solution. Three-hour exposure of ethanol-treated animals to atmospheric ammonia (0.84–1.07 mg/liter, i.e. ≈ 1/8LC₅₀ for intact rats) was followed by a 2.4-fold increase in blood ammonia concentration as compared to specimens of the ethanol group. Ammonia inhalation potentiated the lethal effect of ethanol (dose variation factor 0.81), suppressed external respiration, and decreased oxygen consumption. Our results indicate that kinetic changes in endogenous ammonia have an adverse effect on the outcome of alcohol intoxication in rats. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 688–690, June, 2008