Influence of Organic Impurities on Fractional Crystallization of NaCl and Na2SO4 from High-Salinity Coal Chemical Wastewater: Thermodynamics and Nucleation Kinetics Analysis.

It is a valid path to realize the zero discharge of coal chemical wastewater by using the fractional crystallization method to recycle the miscellaneous salt in high-salinity wastewater. In this study, the thermodynamics and nucleation kinetics of sodium chloride (NaCl) and sodium sulfate (Na2SO4) crystallization in coal chemical wastewater were systematically studied. Through analyses of solubility, metastable zone width, and induction period, it was found that the impurity dimethoxymethane would increase the solid-liquid interface energy and critical crystal size during the nucleation of Na2SO4. Ternary phase diagrams of the pseudo-ternary Na2SO4-NaCl-H2O systems in simulated wastewater were plotted in the temperature range of 303.15 to 333.15 K, indicating that a co-ionization effect existed between NaCl and Na2SO4, and NaCl had a strong salting out effect on Na2SO4. Finally, the nucleation rate and growth rate of Na2SO4 crystals under simulated wastewater conditions were determined by the intermittent dynamic method, and the crystallization kinetic models of Na2SO4 were established. The crystallization nucleation of Na2SO4 crystals was found to be secondary nucleation controlled by surface reactions. The basic theoretical research of crystallization in this study is expected to fundamentally promote the application of fractional crystallization to realize the resource utilization of high-salinity wastewater in the coal chemical industry.

Copper-catalyzed cross-coupling and sequential allene-mediated cyclization for the synthesis of 1,2,3-triazolo[1,5-a]quinolines.

In this paper, a tandem reaction involving copper-catalyzed cross-coupling and allene-mediated cyclization of 1-(2-ethynylaryl)-1,4-disubstituted-1,2,3-triazole with N-tosylhydrazone has been developed. This method features operational simplicity, excellent functional group compatibility, broad substrate scope, and easily available feedstock, providing an efficient and practical strategy for the synthesis of highly functionalized 1,2,3-triazolo[1,5-a]quinolines.

Efficient electrochemical degradation of ceftazidime by Ti3+ self-doping TiO2 nanotube-based Sb-SnO2 nanoflowers as an intermediate layer on a modified PbO2 electrode.

Ceftazidime (CAZ) is an emerging organic pollutant with a long-lasting presence in the environment. Although some PbO2 materials exhibit degradation capabilities, inefficient electron transport in the substrate layer and the problem of electrode stability still limit their use. Here, an interfacial design in which TiO2 nanotube arrays generate Ti3+ self-doping oxide substrate layers and highly active 3D Sb-SnO2 nanoflowers-like interlayers was used to prepare PbO2 anodes for efficient degradation of CAZ. Interestingly, after implementing Ti3+ self-doping in the PbO2 anode base layer and introducing 3D nanoflowers-like structures, the capacity for •OH generation increased significantly. The modified electrode exhibited 5-fold greater •OH generation capacity compared to the unmodified electrode, and a 2.7-fold longer accelerated electrode lifetime. The results indicate that interfacial engineering of the base and intermediate layers of the electrodes can improve the electron transfer efficiency, promote the formation of •OH, and extend the anode lifetime of the activated CAZ system.

Simultaneous recycling of Si and Ti from diamond wire saw silicon powder and Ti-bearing blast furnace slag via reduction smelting: An investigation of the effects of refractories on recycling.

The industrial wastes diamond wire saw silicon powder (DWSSP) and Ti-bearing blast furnace slag (TBFS) are important Si and Ti secondary resources, respectively. During the industrial application of recycling DWSSP and TBFS via reduction smelting, the refractories can dissolve into the molten slag, which can change the composition of the slag and influence the extraction of Si and Ti. Unfortunately, few studies on the reduction smelting of DWSSP and TBFS related to refractories have been reported, making such studies urgently needed. Therefore, the main purpose of this work was to reveal the dissolution mechanism of refractories (alumina and magnesia bricks) and the effect of refractory dissolution on Si-Ti alloy preparation. The results show that during the reduction smelting, the dissolution of alumina and magnesia bricks changed from direct dissolution into the molten slag to indirect dissolution, and the amount of magnesia bricks dissolved was less than that of aluminum bricks. Al3+ (aluminum brick) entering the slag could replace Si4+ in [SinO2n] to form [AlxSin-xO2n]x-, increasing the viscosity of the slag. The O2- (magnesia brick) entering the slag could dissociate [AlxSin-xO2n]x-, decreasing the viscosity of the slag. Therefore, compared with alumina bricks, magnesia bricks can promote slag-alloy separation and improve the extraction ratios of Ti and Si. In the case of magnesia bricks, the maximum reduction ratio of TiO2 was 98.4 %, and the maximum extraction ratio of Si was 95.8 %. This work provides essential experimental data for the Si-Ti alloys prepared via recycling DWSSP and TBFS.

Reticulated Polyamide Thin-Film Nanocomposite Membranes Incorporated with 2D Boron Nitride Nanosheets for High-Performance Nanofiltration.

Nanofiltration (NF) technology has been widely used in saline wastewater treatment due to its unique separation mechanism. However, the NF membrane, as the core of the nanofiltration technology, is restricted by the trade-off between permeability and selectivity, which greatly restricts the development of NF membranes. The interlamellar arrangement of 2D boron nitride nanosheets (BNNSs) can provide additional transport channels and selectivity, as well as strong adsorption capacity due to its high specific surface area, exhibiting significant potential for advanced membranes. In this work, BNNSs prepared by tannic acid (TA)-assisted exfoliation (TA@BNNSs) were successfully adopted to fabricate thin-film nanocomposite (TFN) membranes via interfacial polymerization (IP). The resultant TFN membranes' structure and properties were systematically characterized via various methods. The results demonstrated that the surface morphology of polyamide membranes evolved gradually from a nodular structure to a reticular topography, accompanied by the decrease of the thickness of the polyamide selective layer when incorporating TA@BNNSs into the membranes. This phenomenon can be mainly ascribed to that the uptake density and diffusion of piperazine (PIP) monomer were effectively regulated by BNNSs. This is validated by molecular dynamics and revealed by the adsorption of PIP in BN models, the diffusion coefficients, and interaction energies, respectively. In addition, the TFN membranes demonstrated improved permeance and stable solute rejection for the inorganic salts. Specifically, the water flux of PA-TA@BNNSs-10%/PMIA membrane could reach up to 109.1 ± 2.49 L·m-2·h-1 while keeping a high rejection of 97.5 ± 0.38% to Na2SO4, which was superior to most of the reported membranes in the literature. Besides, the PA-TA@BNNSs-10%/PMIA membrane exhibited an excellent stability in the long-term filtration process. The finding in this work provides a potential strategy for developing the next-generation 2D material-based membranes with high-performance for separation applications.

Heparanase plays a dual role in driving hepatocyte growth factor (HGF) signaling by enhancing HGF expression and activity.

Hepatocyte growth factor (HGF) is a heparin-binding cytokine that enhances growth, motility, and angiogenesis of many tumor types, including multiple myeloma where it is often highly expressed. However, little is known regarding what controls HGF level and activity in these tumors. Evaluation of bone marrow biopsies from myeloma patients revealed a strong positive correlation between the levels of HGF and heparanase, an endoglucuronidase known to promote aggressive tumor behavior. In vitro, addition of recombinant heparanase to myeloma cells or transfection of myeloma cell lines with the cDNA for heparanase significantly increased tumor cell expression and secretion of biologically active HGF. Shed syndecan-1, whose levels in myeloma are also enhanced by heparanase expression, binds to secreted HGF. This syndecan-1-HGF complex is active as shown by its ability to stimulate paracrine signaling via c-Met, the cell surface receptor for HGF. Surprisingly, heparanase enzyme activity was not required for up-regulation of HGF expression by the tumor cells. This is in contrast to the heparanase-mediated enhanced syndecan-1 shedding, which does require activity of the enzyme. This suggests that two different functional domains within the heparanase enzyme (the enzyme active site and a separate site) contribute to events leading to enhanced HGF signaling. These findings demonstrate a novel mechanism driving the HGF pathway whereby heparanase stimulates an increase in both HGF expression and syndecan-1 shedding to enhance HGF signaling. This work also provides further mechanistic insight into the dynamic role of heparanase in driving aggressive tumor progression.

Increased circulating myostatin in patients with type 2 diabetes mellitus.

The changes of plasma myostatin levels in patients with type 2 diabetes mellitus (T2D) and their clinical correlation were investigated. We recruited 43 T2D patients and 20 age-matched healthy subjects. Plasma myostatin, lipid and glucose, and serum insulin were determined. T2D patients showed significantly higher fasting plasma glucose (FPG), serum insulin and triglyceride levels, and lower high-density lipoprotein levels than normal control subjects (P<0.01). Mean plasma myostatin level in T2D patients and health controls was (66.5±17.8) and (46.2±13.8) ng/mL, respectively. An unpaired t test showed that the increase of myostatin in the T2D patients was significant (P<0.001). In both healthy control and T2D groups, the female subjects showed higher myostatin levels than the male subjects. In the T2D patients, plasma level of myostatin was negatively correlated with body mass index (BMI, r=-0.42, P<0.01) and FPG (r=-0.51, P[Symbol: see text]0.01), but positively correlated with insulin resistance index (HOMA-IR, r=0.48, P<0.01). Up-regulation of plasma myostatin in the T2D patients and its correlation with BMI, FPG and blood insulin sensitivity suggests that plasma myostatin may be implicated in the pathogenesis of T2D and thus presented as a therapeutic target for treating the disease. Furthermore, circulating myostatin levels may be used as a biomarker for the disease.

A novel approach for simultaneous recycling of Ti-bearing blast furnace slag, diamond wire saw Si powder, and Al alloy scrap for preparing TiSi2 and Al-Si alloys.

Large amounts of Ti-bearing blast furnace slag (TBFS), diamond wire saw Si powder (DWSSP), and Al alloy scrap (AAS) are generated annually. Although these are industrial waste, they contain valuable Ti, Si, and Al resources. In this work, a novel process is developed for the simultaneous recycling of Ti, Si, and Al from these three wastes to prepare TiSi2 and Al-Si alloys. TBFS, DWSSP, and CaO (flux) were mixed to form a mixed Ti-Si-slag, which was combined with AAS and underwent reduction smelting at 1823 K to prepare Si-Ti-Al alloys. Subsequently, TiSi2 (98.7%) and low-Fe Al-Si (0.64 wt% Fe) alloys were prepared sequentially by separating the molten Si-Ti-Al melt via electromagnetic directional crystallization with a pull-down rate of 3 µm/s. The impurities in the Si-Ti-Al alloy were removed during the separation process by segregation at the boundary of the solid-liquid phase and volatilization. Furthermore, the entire process produces no waste acid or waste gas. Therefore, this work has introduced an efficient and environmentally friendly method for the value-added recycling of Ti, Si, and Al resources from accumulated TBFS, DWSSP, and AAS.

Minimization and stabilization of smelting arsenic-containing hazardous wastewater and solid waste using strategy for stepwise phase-controlled and thermal-doped copper slags.

Minimization and stabilization of arsenic-containing smelting wastewater and residue is of crucial issue to resolve the arsenic contamination. Calcium arsenate is a typical precipitate produced from disposal of smelting acid wastewater. However, it suffers from poor stability and large quantity in the aqueous environment. Copper slags, as for rich-iron species materials, are disposed of in landfills or open-air tailing ponds, which are another waste material that have not been effectively utilized for reuse application. In this study, strategy for sequence of phase-controlled and thermal-doped copper slag technique was used as the efficient means of minimization and stabilization of arsenic-bearing resides. Detailed results were showed that stepwise phase precipitation significantly reduced the formation of hazardous solid waste; the total solid waste was reduced 47.0 wt% because the gypsum was separated from arsenic calcium residues through two-step methods. Subsequently, solid waste stabilization was achieved by using thermal-doped slag, and the high yield of magnetite (75.6 wt%) and fayalite (22.7 wt%) was produced from copper slags. It was proved that these iron-rich species displayed the remarkable performance to stabilize arsenic due to the formation of Fe-As-Ca-O complex; compared with the raw solid waste, the arsenic leachability was decreased from 280.75 to 1.05 mg/L via copper slag stabilization process. The immobilized arsenic content was 25.0 wt%. Overall, the proposed strategy for stepwise phase-controlled and thermal-doped copper slags was a potentially effective strategy for reducing emissions and pollution of arsenic-containing wastewater and residue.

Dual effects of TGF-beta on ERalpha-mediated estrogenic transcriptional activity in breast cancer.

BACKGROUND: TGF-beta resistance often develops in breast cancer cells that in turn overproduce this cytokine to create a local immunosuppressive environment that fosters tumor growth and exacerbates the invasive and metastatic behavior of the tumor cells themselves. Smads-mediated cross-talk with the estrogen receptor has been implied to play an important role in development and/or progression of breast cancer. We investigated how TGF-beta regulates ERalpha-induced gene transcription and potential mechanisms of frequent TGF-beta resistance in breast cancer. METHODS: Effect of TGF-beta on ERalpha-mediated gene transcription was investigated in breast cancer cell lines using transient transfection, real-time PCR, sequential DNA precipitation, and small interfering RNA assays. The expression of Smads on both human breast cancer cell lines and ERalpha-positive human breast cancer tissue was evaluated by immunofluorescence and immunohistochemical assays. RESULTS: A complex of Smad3/4 mediates TGF-beta inhibition of ERalpha-mediated estrogenic activity of gene transcription in breast cancer cells, and Smad4 is essential and sufficient for such repression. Either overexpression of Smad3 or inhibition of Smad4 leads to the "switch" of TGF-beta from a repressor to an activator. Down-regulation and abnormal cellular distribution of Smad4 were associated with some ERalpha-positive infiltrating human breast carcinoma. There appears a dynamic change of Smad4 expression from benign breast ductal tissue to infiltrating ductal carcinoma. CONCLUSION: These results suggest that aberrant expression of Smad4 or disruption of Smad4 activity lead to the loss of TGF-beta suppression of ERalpha transactivity in breast cancer cells.

Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas.

Inhibitor of apoptosis proteins (IAPs) are upregulated in cancers and suppress cell death, in part, through their ability to directly inhibit caspases. Inhibitor of apoptosis proteins are differentially expressed in B-cell lymphomas. The functions of some IAPs are counteracted by the cell death inducer, second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO). In this study, we investigated the expression levels of Smac/DIABLO in 14 lymphoma cell lines by Western blot analysis. We also assessed 247 B-cell non-Hodgkin's lymphoma (NHL) and 40 Hodgkin's lymphoma (HL) tumors using immunohistochemical methods. Smac/DIABLO was expressed in most NHL and all HL cell lines. In NHL, Smac/DIABLO was expressed in 117 (47%) tumors and was differentially expressed in various NHL types. In most NHLs, from 29% to 68% of tumors were positive; however, Smac/DIABLO was not detected in small lymphocytic lymphoma/chronic lymphocytic leukemia and Burkitt lymphoma, and was rare in extranodal marginal zone B-cell lymphoma. In HL, Smac/DIABLO was positive in 25 (63%) tumors. Unlike NHL, all types of HL were positive for Smac/DIABLO, although nodular sclerosis was least often positive. The differential expression of Smac/DIABLO in NHLs suggests that apoptotic mechanisms are differentially involved in their pathogenesis. These results may also have implications for using Smac/DIABLO or its agonists as therapeutic agents.

Intermedin 1-53 in central nervous system elevates arterial blood pressure in rats.

Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CGRP) family identified from human and other vertebrate tissues. Preprointermedin can generate various mature peptides by proteolytic cleavage. Amino acid sequence analysis showed cleavage sites located between two basic amino acids at Arg93-Arg94 resulting in the production of prepro-IMD(95-147), namely IMD(1-53). The present study was designed to determine the effects of the IMD(1-53) fragment in the central nervous system (CNS) on mean arterial blood pressure and heart rate in normal rats and its possible mechanism. Rats were given doses of adrenomedullin (ADM) or IMD(1-53), intracerebroventricularly or intravenously, respectively, with continuous blood pressure and heart rate monitoring for 45min. Analysis with CGRP receptor antagonist CGRP(8-37), ADM receptor antagonist ADM(22-52), and anti-prepro-IMD antibody showed that 0.1, 0.5, and 1.0 nmol/kg IMD(1-53), caused a dose-dependent elevation in blood pressure, which was more prominent than the increase with equivalent IMD(1-47) or ADM. As well, IMD(1-53) caused a persistent increase in heart rate. The CNS action of IMD(1-53) could be blocked by ADM(22-52), CGRP(8-37), or prepro-IMD antibody. In contrast to the CNS action, intravenous administration of IMD(1-53) induced a depressor effect. These results suggest that IMD(1-53) is an important regulatory factor in mean arterial blood pressure and heart rate through its central and peripheral bioaction.

Roles of different peptide fragments derived from proadrenomedullin in the regulation of vascular tone in isolated rat aorta.

The effects of proadrenomedullin N-terminal 20 peptide (PAMP) and adrenotensin (ADT) on adrenomedullin (ADM)-induced vasodilation were investigated in aortic rings from rat. ADM (10(-9) to 10(-7)M) relaxed the aorta preconstricted with phenylephrine in a concentration-dependent manner. Denudation of endothelium or pretreatment with nitric oxide synthase (NOS) inhibitor, L-NAME, attenuated the vasodilatory action of ADM. ADM-induced vasorelaxation in the aortic rings with endothelium was converted to contraction by PAMP, but not by ADT. The ADM-induced vasodilation was not affected by PAMP in aorta rings without endothelium or in intact aortic rings pretreated with L-NAME. ADM-stimulated nitrite production and NOS activity of the aortas, which was inhibited by PAMP, ADT or PAMP plus ADT. ADM, PAMP, and ADT increased the cyclic adenosine monophosphate (cAMP) contents in vascular tissue. The combination of ADM with PAMP or ADT caused a smaller increase in cAMP level as compared with that of PAMP or ADT alone. These results show that ADM-induced endothelium-dependent vasodilation could be converted to vasoconstriction in the presence of PAMP, probably through a NO-dependent pathway. There was no indication that cAMP was involved in the converting effect of PAMP on ADM vasodilator action.

[Effects of adrenomedullin and proadrenomedullin N-terminal 20 peptide, alone or in combination, on the rat hearts in vitro].

OBJECTIVE: To study the effects of adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) alone or in combinations on the isolated rat hearts as well as the possible signaling pathways involved in their actions. METHODS: In isolated rat hearts the left ventricular pressure (LVP), LVP+/-dp/dtmax, coronary fluid (CF) and heart rate(HR) of the hearts infused at different concentrations of ADM and/or PAMP were determined by a 4-cannal physiological recorder, then the cAMP contents were assayed in myocardium. RESULTS: After being infused with ADM from 10(-11) to 10(-8) mol x L(-1) or PAMP from 10(-11) to 10(-8)mol x L(-1), the LVP and LVP+/-dp/dtmax of the isolated hearts decreased gradually in a concentration-dependent manner, and at the same concentration, the effects of PAMP were more potent than those of the ADM. When ADM and PAMP were co-administrated with both concentrations as low as from 10(-11) to 10(-10) mol x L(-1), the cardiac parameters were decreased more than either ADM or PAMP administrated alone. However, the inhibitory effects of ADM and PAMP were attenuated when they were in combination at higher concentrations as from 10(-9) to 10(-8) mol x L(-1). When the rat hearts were infused with ADM PAMP and ADM plus PAMP, the CF were always higher than those of the controls and decreased when co-administrated with L-NAME, an inhibitor of NOS, but the decreased degree of LVP and LVP+/-dp/dtmax were attenuated by L-NAME. The cAMP contents in the left cardiac ventricle were increased significantly by ADM infusions but not changed obviously by PAMP, and were of no statistical difference in rat hearts with ADM administrated alone from those combinated with ADM and PAMP. CONCLUSION: These results showed that ADM and PAMP infused alone or in combinations inhibited the function of rat hearts in vitro, which might be partly involved with the NOS/NO pathway.

[Involvement of endothelin in the proliferative effect of lysophosphatidic acid on vascular smooth muscle cells in rats].

OBJECTIVE: To observe the effects of lysophosphatidic acid (LPA) on production of endothelin (ET) in rat aorta vascular smooth muscle cells (VSMCs). METHODS: Cultured VSMCs were used in the study. DNA synthesis of VSMCs was measured by 3H-TdR incorporation. The amount of ET mRNA of VSMCs was determined by competitive quantitative RT-PCR. The levels of synthesis and release of ET in VSMCs were determined by radioimmunoassay (RIA). RESULTS: 5-20 mumol.L-1 of LPA promoted VSMCs 3H-TdR incorporation in a concentration dependent manner. The amount of ET mRNA in VSMCs treated by 5-20 mumol.L-1 of LPA was increased by 16%, 21%, and 23%, respectively, compared with the control. After 8 hours of incubation, 5-20 mumol.L-1 of LPA elevated the ET production in a concentration dependent manner. After 8 hours of VSMCs incubated with LPA (5-20 mumol.L-1), the content of ET in medium was increased by 140%-200%, respectively, compared with the control. In addition, it was found that BQ123, a non-selective ET receptor antagonist, greatly decreased the VSMCs DNA synthesis induced by LPA. CONCLUSION: LPA stimulated the ET mRNA expression and ET production in VSMCs. The effects of LPA on VSMCs DNA synthesis were partly mediated by ET/ETA receptor pathway. It suggests that LPA and ET interact and exert biological effects as endogenous active peptides.

[Effects of peptides originated from the proadrenomedullin on the production of nitric oxide in rat aorta].

OBJECTIVE: To observe the effect of adrenomedullin (ADM) on the production of nitric oxide (NO) in rat aorta and the effect of Proadrenomedullin N-terminal 20 peptide (PAMP) and adrenotensin (ADT) on the ADM-induced NO production. METHODS: Isolated aortic tissues were exposed to ADM, PAMP and ADT for 2 h. The NO production, indicated by nitrite content in the incubated media, and the nitric oxide synthase (NOS) activity in the incubated tissues were assayed. RESULTS: Nitrite productions and NOS activities of the aortic tissues were significantly increased by ADM in a concentration-dependent manner. The nitrite production and NOS activity of the aortic tissues stimulated by ADM (10(-8) mol.L-1) incubation were (0.282 +/- 0.046) mumol per mg protein and (0.323 +/- 0.056) pmol.min-1 per mg protein, respectively, which were greater than those of the control (0.173 +/- 0.026) mumol per mg protein and (0.110 +/- 0.028) pmol.min-1 per mg protein (P < 0.01), respectively. The nitrite production and NOS activity were (0.204 +/- 0.049) mumol per mg protein and(0.178 +/- 0.023) pmol.min-1 per mg protein when the tissues were treated with ADM (10(-8) mol.L-1) and PAMP (10(-8) mol.L-1) in combination, and were (0.150 +/- 0.036) mumol per mg protein and (0.123 +/- 0.031) pmol.min-1 per mg protein when ADM (10(-8) mol.L-1) and ADT (10(-8) mol.L-1) were used in combination, which were significantly less than those in ADM (10(-8) mol.L-1) group. After incubation of the aortic tissues with the same concentrations(10(-8) mol.L-1) of ADM, PAMP and ADT in combination, the nitrite production and NOS activity were (0.162 +/- 0.029) mumol per mg protein and (0.110 +/- 0.024) pmol.min-1 per mg protein, which were also greatly reduced as compared with those of the ADM group (10(-8) mol.L-1, P < 0.01). However, neither PAMP nor ADT had effect on the production of nitrite and NOS activity in the aortic tissues. CONCLUSION: ADM enhanced the NO production in rat aorta, which was antagonized by PAMP and ADT alone or in combination through influencing the NOS activity.

Cytoplasmic expression of nucleophosmin 1 as a marker for diagnosing residual disease of acute myeloid leukemia.

Nucleophosmin 1 (NPM1) is a nuclear protein and in approximately 50% to 60% of cytogenetically normal acute myeloid leukemia (AML), NPM1 is mutated and localized in the cytoplasm. Both wild type and mutant NPM1 can be detected by immunohistochemistry (IHC). We set out to evaluate whether subcellular localization of NPM1, as detected by IHC, is stable during disease course in AML, and whether cytoplasmic expression of NPM1 (NPMc+) can be used to differentiate recovery versus residual disease in formalin-fixed and hydrochloric acid/EDTA decalcified specimens. IHC against NPM1 was performed on bone marrow biopsies of 31 patients with AML at initial diagnosis and on 40 follow-up biopsies. Immunostaining patterns of NPM1, defined as NPMc+, NPMc-, and indeterminate, were correlated with morphology, ancillary tests, and clinical follow-up information. Of the 20 (64.5%) cases with NPMc- at initial diagnosis, none of the 27 follow-up biopsies showed NPMc+, regardless of disease status. Of the 11 cases (35.5%) with NPMc+ at initial diagnosis, all of the 3 biopsies with persistent/relapsed disease, and none of the 7 benign biopsies had NPMc+ at follow-up. For the 3 biopsies with indeterminate follow-up pathologic diagnoses of recovery versus residual disease, all were NPMc- at follow-up, which was consistent with remission and was supported by clinical follow-up. Therefore, subcellular localization of NPM1 as detected by IHC is stable during the course of the disease, and NPMc+ at follow-up supports residual disease in cases with NPMc+ at initial diagnosis.

Extracavitary KSHV-associated large B-Cell lymphoma: a distinct entity or a subtype of primary effusion lymphoma? Study of 9 cases and review of an additional 43 cases.

Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma in HIV patients, which typically presents with lymphomatous effusions in the body cavities without forming mass lesions. PEL is associated with Kaposi sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus-8) with distinct clinical and pathologic features. Rare cases of KSHV-associated large B-cell lymphoma (KSHV-LBL) have been observed in the lymph nodes or extranodal sites without lymphomatous effusions during the course of disease. KSHV-LBL is generally similar to classic PEL on the basis of the clinical presentation (HIV(+) male), morphology (immunoblastic, plasmablastic, or anaplastic), immunophenotype (CD45(+), CD20(-), CD79a(-), CD30(+), CD138(+), and EMA(+)), presence of Epstein-Barr virus infection, and clonal immunoglobulin gene rearrangements. However, it is not clear whether KSHV-LBL is a distinct entity or represents part of the spectrum of classic PEL; in particular, there is no consensus diagnostic term for KSHV-LBL. In this study, we investigated the clinicopathologic features of 9 cases of KSHV-LBL from our files. An additional 43 such cases and 84 cases of classic PEL from the English literature were reviewed and compared with each other. In contrast to the classic PEL, KSHV-LBL had a very significant lower expression of CD45 (74% vs. 94%, P=0.004) but significant higher expression of CD20 (17% vs. 5%, P=0.04) and CD138 (70% vs. 38%, P=0.05). KSHV-LBL also had slightly higher positivity of CD79a (23% vs. 5%, P=0.13) and immunoglobulin light chain expression, although the difference was not statistically significant [κ chain (12% vs. 0%) and λ chain (31% vs. 21%)]. The expressions of EMA and CD30 were slightly lower in KSHV-LBL compared with those observed in PEL (57% vs. 75% and 63% vs. 76%, respectively). Interestingly, 29% (10/34) of cases of KSHV-LBL revealed aberrant CD3 expression, which may mislead to a diagnosis of T-cell lymphoma, particularly anaplastic large cell lymphoma in combination with the anaplastic morphology and expression of CD30 and EMA. Although KSHV-LBL shows different clinical presentations and some variations in immunophenotype from classic PEL, it is still uncertain, on the basis of our findings, whether it is justifiable to separate them as 2 distinct entities. Nevertheless, we feel it is necessary to have a consensus diagnostic term, and we recommend a tentative one as "KSHV-associated large B-cell lymphoma (KSHV-LBL)" to replace many different names previously used.

Expression of AIF and HtrA2/Omi in small lymphocytic lymphoma and diffuse large B-cell lymphoma.

CONTEXT: The pathogenesis of non-Hodgkin lymphoma may involve deregulation of apoptosis. In response to apoptotic stimuli, several proapoptotic proteins are released into the cytoplasm from the mitochondria, including second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein binding protein with low p I (Smac/DIABLO), apoptosis-inducing factor (AIF), and high temperature requirement protein A2 (HtrA2/Omi). Apoptosis-inducing factor promotes apoptosis through a caspase-independent pathway, while Smac/DIABLO and HtrA2/Omi do so through both caspase-dependent and caspase-independent pathways. Smac/DIABLO was reported to be strongly positive in diffuse large B-cell lymphoma (DLBCL) and virtually absent in small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). Little is known about the expression of AIF and HtrA2/Omi in lymphomas. OBJECTIVE: To evaluate the expression of AIF and HtrA2/Omi in SLL and DLBCL. DESIGN: Twenty-three DLBCLs, 20 SLLs/CLLs, and 10 benign lymph nodes were evaluated for AIF and HtrA2/Omi expression by immunohistochemical staining. RESULTS: Apoptosis-inducing factor was strongly and diffusely expressed in 19 of 23 (83%) cases of DLBCL with comparable expression pattern between germinal center-like and non-germinal center-like subgroups. Apoptosis-inducing factor was weakly positive in 15 of 20 (75%) cases of SLL/CLL with increased intensity in pseudofollicles. In contrast, HtrA2/Omi was weakly expressed in SLL/CLL (17 of 20; 85%) and DLBCL (18 of 23; 78%). CONCLUSIONS: The different expression level and pattern of AIF and HtrA2/Omi in SLL/CLL and DLBCL may suggest different apoptotic mechanisms involved in the pathogenesis and prognosis of these diseases. HtrA2/Omi does not appear to be a major player in the regulation of apoptosis of DLBCL and SLL/CLL.

Multiple hemodynamic effects of endogenous hydrogen sulfide on central nervous system in rats.

BACKGROUND: Endogenous hydrogen sulfide is a new neuromodulator which takes part in the regulation of central nervous system physiology and diseases. Whether endogenous hydrogen sulfide in the central nervous system regulates cardiovascular activity is not known. In the present study, we observed the hemodynamic changes of hydrogen sulfide or its precursor by intracerebroventricular injection, and investigate the possible roles of endogenous digitalis like factors and sympathetic activity in the regulation. METHODS: Ninety-four Sprague-Dawley rats underwent a right cerebroventricular puncture, then the hydrogen sulfide saturation buffer or its precursor injected by intrcerebroventricular catheter. A heperin-filled catheter was inserted into the right femoral artery or into the left ventricle, and changes of blood pressure or cardiac function recorded by a Powerlab/4S instrument. Phentolamine or metoprolol were pre-injected to observe the possible role in autonomic nerve activity. After rats were sacrificed, plasma was collected and endogenous digitalis-like factors were measured with a commercial radioimmunoassay kit. The aortic, cardiac sarcolemmal vesicles were isolated and the activity of Na(+)-K(+)-ATPase was measured as ouabain-sensitive ATP hydrolysis under maximal velocity conditions by measuring the release of inorganic phosphate from ATP. Unpaired Student's t test for two groups or analysis of variances (ANOVA) for multiple groups were used to compare the differences of the changes. RESULTS: Intracerebroventricular injection of hydrogen sulfide induced a transient hypotension, then dramatic hypertenive effects in a dose-dependent manner. Bolus injection of L-cysteine or beta- mercaptopyruvate also increased mean arterial pressure (P < 0.01), whereas hydroxylamine-a cystathionine beta synthase inhibitor decreased the arterial pressure (P < 0.01). Hydrogen sulfide and L-cysteine increased mean arterial pressure, left ventricular develop pressure and left-ventricle maximal rate of systolic and diastolic pressure; these functions were decreased by hydroxylamine (P < 0.01). Glibenclamide (a K(ATP) channel blocker) blocked the transient hypotensive effect, phentolamine (an alpha-adrenergic receptor blocker) blocked the hypertensive effect, and metoprolol (a selective beta 1 receptor blocker) blocked the positive inoptropic effect of central nervous system hydrogen sulfide. The endogenous digitalis-like factors in plasma were elevated (P < 0.01) after treatment with L-cysteine, association with decreasing Na(+)-K(+)-ATPase activity in cardiac or aortic sarcolemmal vesicles (P < 0.01). Hydroxylamine injection reduced the endogenous digitalis-like factors level in plasma association with increasing Na(+)-K(+)-ATPase activity in cardiac and aortic sarcolemmal vesicles. CONCLUSION: Central nervous system endogenous hydrogen sulfide upregulated mean arterial pressure and cardiac systolic function by activation of sympathetic nerves or release of endogenous digitalis-like factors.