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- Subclass-specific formation of perineuronal nets around parvalbumin-expressing GABAergic neurons in the Ammon's horn of the mouse hippocampus. [JOURNAL ARTICLE]
- J Comp Neurol 2014 Nov 25.
Perineuronal nets (PNNs) are closely associated with parvalbumin-positive (PV+) neurons, and play a major role in controlling developmental neural plasticity. Considering the recent advances in classification of PV+ neurons, here we aimed to clarify whether PNNs might be associated with specific subclasses of PV+ neurons in the hippocampus. In this study, we labeled PNNs by Wisteria floribunda agglutinin (WFA), and classified PV+ neurons based on the combination of cellular location, molecular expression (neuropeptide Y (NPY), somatostatin (SOM), special AT-rich sequence-binding protein-1 (SATB1)), and retrograde tracing through stereotaxic injection of Fluoro-Gold (FG) into the medial septum. The criteria of each subclass can be summarized as follows: axo-axonic cells, PV+/SATB1-/NPY- cells in the stratum pyramidale; basket cells, PV+/SATB1+/NPY- cells in the stratum pyramidale; bistratified cells, PV+/SATB1+/NPY+ cells in the stratum pyramidale; oriens-lacunosum-moleculare (O-LM) cells, PV+/ SOM+/FG- cells in the stratum oriens; hippocampo-septal projection (H-S) cells, PV+/SOM+/FG+ cells in the stratum oriens. The ratios of formation of WFA+ PNNs around each subclass of PV+ neurons were estimated according to the optical disector principle. The vast majority (over 90%) of putative PV+ basket cells were surrounded by PNNs, while only a minor population (less than 10%) of putative PV+ axo-axonic, O-LM and H-S cells were enwrapped with PNNs. The ratios of formation of PNNs around putative PV+ bistratified cells were intermediate (25-50%). These findings indicate that PNNs may be specifically associated with PV+ basket cells, and also provide some key to understand the functional significance of PNNs and PV+ neurons in the hippocampus. This article is protected by copyright. All rights reserved.
- Perineuronal nets affect parvalbumin expression in GABAergic neurons of the mouse hippocampus. [JOURNAL ARTICLE]
- Eur J Neurosci 2014 Nov 20.
Recent studies have suggested that the perineuronal net (PNN), a specialised extracellular matrix structure, and parvalbumin (PV), an EF-hand calcium-binding protein, are involved in the regulation of plasticity of neural circuits. Here, we aimed to quantitatively estimate the relationship between the two plasticity regulators, PV and PNNs, in the hippocampus of young adult mice. Dual fluorescence staining for PV and Wisteria floribunda agglutinin (a broad PNN marker) showed that a substantial population of PV-expressing (PV(+) ) GABAergic neurons lacked PNNs. Optical disector analysis demonstrated that there were fewer PNN(+) neurons than PV(+) neurons. The ratio of PNN expression in PV(+) neurons was generally lower in the dendritic layers than in the principal cell layers, whereas the ratio of PV expression in PNN(+) neurons was effectively 100%. The mean PV fluorescence was significantly higher in PNN(+) /PV(+) neurons than in PNN(-) /PV(+) neurons. Cumulative frequencies for single-cell PV fluorescence indicated that intensely stained PV(+) neurons tend to be enwrapped by PNNs, whereas weakly stained PV(+) neurons are likely to lack PNNs. We digested the PNNs by a unilateral injection of chondroitinase ABC (chABC) into the dorsal CA1 region. Although the densities of PV(+) neurons remained unchanged, the PV fluorescence declined 7 days after chABC injection. Quantitative real-time polymerase chain reaction analysis demonstrated a reduction in PV mRNA expression following chABC injection. These findings indicate that the presence or absence of PNNs affects the relative PV expression in GABAergic neurons in the hippocampus.
- Frequency of and predictive factors for vascular invasion after radiofrequency ablation for hepatocellular carcinoma. [Journal Article]
- PLoS One 2014; 9(11):e111662.
Vascular invasion in patients with hepatocellular carcinoma (HCC) is representative of advanced disease with an extremely poor prognosis. The detailed course of its development has not been fully elucidated.We enrolled 1057 consecutive patients with HCC who had been treated with curative intent by radiofrequency ablation (RFA) as an initial therapy from 1999 to 2008 at our department. We analyzed the incidence rate of and predictive factors for vascular invasion. The survival rate after detection of vascular invasion was also analyzed.During a mean follow-up period of 4.5 years, 6075 nodules including primary and recurrent lesions were treated by RFA. Vascular invasion was observed in 97 patients. The rate of vascular invasion associated with site of original RFA procedure was 0.66% on a nodule basis. The incidence rates of vascular invasion on a patient basis at 1, 3, and 5 years were 1.1%, 5.9%, and 10.4%, respectively. Univariate analysis revealed that tumor size, tumor number, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein were significant risk predictors of vascular invasion. In multivariate analysis, DCP was the most significant predictor for vascular invasion (compared with a DCP of ≤100 mAu/mL, the hazard ratio was 1.95 when DCP was 101-200 mAu/mL and 3.22 when DCP was >200 mAu/mL). The median survival time after development of vascular invasion was only 6 months.Vascular invasion occurs during the clinical course of patients initially treated with curative intent. High-risk patients may be identified using tumor markers.
- Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus. [JOURNAL ARTICLE]
- Lupus 2014 Nov 11.
In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the highest activity of systemic lupus erythematosus. Our results show that native circulating IgG complexes from active systemic lupus erythematosus patients expose fucosyl residues and their glycan core is accessible to soluble lectins. Two putative mechanisms may contribute to the increased exposure of these glycans: (1) the canonical N-glycosylation site of the IgG-CH2 domain; (2) an IgG binding non-IgG molecule, like complement or C-reactive protein. In both cases the complexed IgG may be alternatively targeted to lectin receptors of effector cells, e.g. dendritic cells.
- Glycoprotein Enrichment Method Using a Selective Magnetic Nano-Probe Platform (MNP) Functionalized with Lectins. [Journal Article]
- Methods Mol Biol 2015.:83-100.
Protein post-translational modifications (PTMs) have increasingly become a research field of incredible importance to fully understand the regulation of biological processes in health and disease. Among PTMs, glycosylation is one of the most studied for which contributed the development and improvement of enrichment techniques. Nowadays, glycoprotein enrichment methods are based on lectin affinity, covalent interactions, and hydrophilic interaction liquid chromatography (HILIC). Nonetheless, the nanotechnology era has fetched new methods to enrich glycoproteins from complex samples as human biological fluids. For instance, magnetic nanoparticles (MNPs) are being used as an interesting enrichment approach allowing a better characterization of glycoproteins and glycopeptides.In this chapter, we describe an enrichment method based on MNPs functionalized with lectins (Concavalin A, wheat germ agglutinin, and Maackia amurensis lectin) to enrich specific sets of glycoproteins from biological fluids. Moreover, it is proposed a bioinformatic strategy to deal with data retrieved from mass spectrometry analysis of enriched samples aiming the identification of relevant biological processes modulated by a given stimuli and, ultimately, of new biomarkers for disease screening/management.
- Synthesis and characterization of bioactive conjugated near-infrared fluorescent proteinoid-poly(L-lactic acid) hollow nanoparticles for optical detection of colon cancer. [Journal Article]
- Int J Nanomedicine 2014.:5041-53.
Colon cancer is one of the major causes of death in the Western world. Early detection significantly improves long-term survival for patients with colon cancer. Near-infrared (NIR) fluorescent nanoparticles are promising candidates for use as contrast agents for tumor detection. Using NIR offers several advantages for bioimaging compared with fluorescence in the visible spectrum: lower autofluorescence of biological tissues and lower absorbance and, consequently, deeper penetration into biomatrices. The present study describes the preparation of new NIR fluorescent proteinoid-poly(L-lactic acid) (PLLA) nanoparticles. For this purpose, a P(EF-PLLA) random copolymer was prepared by thermal copolymerization of L-glutamic acid (E) with L-phenylalanine (F) and PLLA. Under suitable conditions, this proteinoid-PLLA copolymer can self-assemble to nanosized hollow particles of relatively narrow size distribution. This self-assembly process was used for encapsulation of the NIR dye indocyanine green. The encapsulation process increases significantly the photostability of the dye. These NIR fluorescent nanoparticles were found to be stable and nontoxic. Leakage of the NIR dye from these nanoparticles into phosphate-buffered saline containing 4% human serum albumin was not detected. Tumor-targeting ligands such as peanut agglutinin and anticarcinoembryonic antigen antibodies were covalently conjugated to the surface of the NIR fluorescent P(EF-PLLA) nanoparticles, thereby increasing the fluorescent signal of tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent P(EF-PLLA) nanoparticles was demonstrated in a chicken embryo model. In future work, we plan to extend this study to a mouse model, as well as to encapsulate a cancer drug such as doxorubicin within these nanoparticles for therapeutic applications.
- Cold agglutinin disease-associated digital gangrene treated with plasmapheresis. [Letter]
- Indian J Dermatol Venereol Leprol 2014 Nov-Dec; 80(6):575-6.
- [Monoclonal gammopathy of undetermined significance and asymptomatic multiple myelom in the year 2014 ]. [English Abstract, Journal Article]
- Vnitr Lek 2014 Oct; 60(10):861-79.
Presence of monoclonal immunoglobulin in serum or urine is a relatively common event affecting about 3.2 % of people over 50. Isolated increase of only one type of free light chain, either κ or λ, is detected in 0.7-0.8 % of people over 50. Most people with monoclonal immunoglobulin meet the criteria of the so-called "mono-clonal gammopathy of undetermined significance (MGUS)". MGUS is defined by concentration of monoclonal immunoglobulin in serum < 30 g/l, number of plasma cells in the bone marrow < 10 % and the absence of symptoms of multiple myeloma and other lymphoproliferative diseases. A proportion of people with MGUS gradually progresses from asymptomatic into symptomatic myeloma or other malignant lymphoproliferative disease requiring treatment. Therefore, MGUS is considered to be one of the most common premalignant conditions with an average risk of transformation into malignant disease of 1 % per year. Monoclonal gammopathy of IgG and IgA subtype can develop into multiple myeloma. Light chain monoclonal gammopathy can develop not only into light chain multiple myeloma but also into AL-amyloidosis and light chain deposition disease (amorphous deposits of light chains damaging organs). IgM monoclonal gammopathy may develop into Waldenstrom macroglobulinemia or other lymphoproliferative disorder, or into rare IgM subtype of multiple myeloma. Unfortunately, people with MGUS are threatened by more than an increased risk of transformation into multiple myeloma or other severe hematologic disease. Pre-malignant clone of plasma cells in the bone marrow causes changes in the bone marrow that directly affect the person. For people with MGUS, there is an increased incidence of osteoporosis and increased fracture risk when compared to the general population. People with MGUS also have an increased risk of bacterial infections and thromboembolic complications compared with the same age population without MGUS. Clonal plasma cells, which are the basis of MGUS, may in some cases produce toxic monoclonal immunoglobulin which can damage the bodys own antibody activity by binding to specific antigens (such as cold agglutinin disease), or their deposits in organs (e.g. kidney damage) or physical properties (e.g. cryoglobulinemia). Therefore, it is recommended that this group of people is regularly checked with the aim to capture not only transformation into symptomatic multiple myeloma or another malignant disease, but also the formation of the above-mentioned complications. Moreover, it is recommended to monitor patients with asymptomatic myeloma and to initiate treatment only after symptoms of multiple myeloma are observed. In 2014, discussion of subdivision of subgroups of patients with asymptomatic myeloma with high ( 80 %) probability of early (within 2 years) transformation in multiple myeloma which would be beneficial for early initiation of treatment is ongoing. According to first proposals, patients with asymptomatic myeloma that meet at least one of the three conditions: more than 60 % of plasma cells in the bone marrow, ratio of free light kappa and lambda chains is greater than 100 or less than 0.01, or multiple focal lesions on whole-body MRI of the skelet. The review contains current opinions on prognostic classification and appropriate intervals and extent of control examinations.Key words: asymptomatic myeloma - monoclonal gammopathy of undetermined significance - PET/CT - symptomatic multiple myeloma - Waldenström macroglobulinemia.
- The life of phi: the development of phi thickenings in roots of the orchids of the genus Miltoniopsis. [JOURNAL ARTICLE]
- Planta 2014 Nov 7.
Phi thickenings, bands of secondary wall thickenings that reinforce the primary wall of root cortical cells in a wide range of species, are described for the first time in the epiphytic orchid Miltoniopsis. As with phi thickenings found in other plants, the phi thickenings in Miltoniopsis contain highly aligned cellulose running along the lengths of the thickenings, and are lignified but not suberized. Using a combination of histological and immunocytochemical techniques, thickening development can be categorized into three different stages. Microtubules align lengthwise along the thickening during early and intermediate stages of development, and callose is deposited within the thickening in a pattern similar to the microtubules. These developing thickenings also label with the fluorescently tagged lectin wheat germ agglutinin (WGA). These associations with microtubules and callose, and the WGA labeling, all disappear when the phi thickenings are mature. This pattern of callose and WGA deposition show changes in the thickened cell wall composition and may shed light on the function of phi thickenings in plant roots, a role for which has yet to be established.
- Validation of Three Staging Systems for Hepatocellular Carcinoma (JIS Score, Biomarker-Combined JIS Score and BCLC System) in 4,649 Cases from a Japanese Nationwide Survey. [Journal Article]
- Dig Dis 2014; 32(6):717-24.
Clinical staging is very important for optimal therapeutic strategy and prognostic prediction in patients with hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used and best-validated method for HCC. Similarly, the conventional Japan Integrated Staging (c-JIS) score and the biomarker-combined JIS (bm-JIS) score have also been reported to effectively stratify HCC patients. The aim of this study was to evaluate the performance of these three staging systems for prognostic prediction.A total of 4,649 HCC patients were included in this study. A multivariate analysis identified the independent risk factors associated with overall survival. The stratification ability and the suitability as a prognostic model of the three staging systems were compared.Multivariate analysis revealed that male sex, higher Child-Pugh score, tumor size >2.0 cm, multiple tumors, vascular invasion, higher alpha-fetoprotein (AFP) level, higher des-gamma-carboxyprothrombin level, higher Lens culinaris agglutinin-reactive AFP level, and a performance status of 3-4 were independent risk factors in HCC. The independent homogenizing ability and stratification value of the bm-JIS score were higher than those of the c-JIS score and the BCLC system (χ(2) = 972.7581, 758.1041 and 679.6832, respectively). Moreover, the bm-JIS score had the lowest Akaike Information Criteria value, followed by the c-JIS score and the BCLC system (9,844.278, 10,054.93 and 10,131.35, respectively).Our results suggest that the bm-JIS score offers good stratification ability and is a better prognostic predictor than the c-JIS score and the BCLC system. © 2014 S. Karger AG, Basel.