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1
Wickström, Erik, Karin Persson-Waller, Helena Lindmark-Månsson, Karin Östensson, and Åse Sternesjö. "Relationship between somatic cell count, polymorphonuclear leucocyte count and quality parameters in bovine bulk tank milk." Journal of Dairy Research 76, no. 2 (March 13, 2009): 195–201. http://dx.doi.org/10.1017/s0022029909003926.
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The somatic cell count (SCC) in bovine bulk tank milk is presently used as an indicator of raw milk quality, reflecting the udder health status of the herd. During mastitis, SCC increases, mostly owing to an influx of polymorphonuclear leucocytes (PMN) from blood into milk, with a concomitant change in milk composition. Bulk tank milk samples were categorized according to their SCC, as well as polymorphonuclear leucocyte count (PMNC), to study relationships between SCC, PMNC and various raw milk quality traits, i.e. contents of total protein, whey protein, casein, fat and lactose, casein number, proteolysis and rheological properties. The proportion of PMN, obtained by direct microscopy, was significantly higher in samples with high SCC compared with low SCC samples. SCC and PMNC were strongly correlated, yielding a correlation coefficient of 0·85. High SCC samples had lower lactose and casein contents, lower casein number and more proteolysis than low SCC samples. Samples with high PMNC had a lower casein number than low PMNC samples. Samples with high and low SCC or PMNC did not differ in respect to rheological properties. Our results do not indicate that PMNC is a better biomarker than SCC for raw bulk tank milk quality, as previously proposed.
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Miyamoto, Koji, Michael Lange, George McKinley, Christine Stavropoulos, Shin-ichi Moriya, Hirotaka Matsumoto, and Yoritaro Inada. "Effects of Sho-Saiko-To on Production of Prostaglandin E2 (PGE2), Leukotriene B4 (LTB4) and Superoxide from Peripheral Monocytes and Polymorphonuclear Cells Isolated from HIV Infected Individuals." American Journal of Chinese Medicine 24, no. 01 (January 1996): 1–10. http://dx.doi.org/10.1142/s0192415x96000025.
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The effects of Sho-saiko-to (SST), a traditional Chinese medicine, on the production of PGE2 from monocytes, LTB4 and superoxide from polymorphonuclear cells (PMNC) in HIY infected individuals were studied. SST inhibited the production of PGE2 from monocytes stimulated by opsonized zymosan in all groups including the healthy control group and also inhibited the production of superoxide from PMNC after stimulation with FMLP. On the other hand, SST enhanced the production of LTB4 when PMNC were stimulated by the calcium ionophore A23187. These results suggest that SST has different effects on the production of prostanoids or superoxide from monocytes and PMNC. Furthermore, our data indicates that inhibition of PGE2 or superoxide production will lead to indirect suppression of HIV, and enhancement of LTB4 will contribute to the upregulation of the immune reaction in my infected individuals.
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Weiss, Mauricio Andrade, and Adriano Vilela Sampaio. "Políticas monetárias não convencionais nos EUA: análise empírica do período 2007-2019." Revista de Economia 43, no. 80 (March 17, 2022): 241. http://dx.doi.org/10.5380/re.v43i80.75974.
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O objetivo do presente artigo é analisar a eficácia das políticas monetárias não convencionais (PMNC) adotadas nos EUA após a crise de 2008, considerando sua capacidade de criar condições acomodatícias nos mercados financeiros e promover o emprego, sem prejudicar a estabilidade de preços. A hipótese a ser testada é de que em uma situação de alta instabilidade e baixas taxas de juros, os instrumentos não convencionais se mostraram eficazes diante dos objetivos propostos. Foram empregados testes de causalidade de Granger para avaliar a relação entre os instrumentos de PMNC e os objetivos intermediários e finais de política monetária. Os resultados indicam que os instrumentos não convencionais se mostraram mais influentes que os convencionais (especialmente a taxa básica de juros) sobre as variáveis que representam os resultados de política monetária, o que corrobora a necessidade do uso de PMNC. Ademais, sugerem que o Fed logrou estabilizar o sistema financeiro nos momentos de maior instabilidade e manter condições acomodatícias nos mercados, criando um ambiente propício à retomada econômica.
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Aiboud, Kada. "politiques monétaires non conventionnelles et la relance économique : étude de la politique de l’assouplissement quantitatif en Algérie." les cahiers du cread 39, no. 4 (March 30, 2024): 175–203. http://dx.doi.org/10.4314/cread.v39i4.7.
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Le présent article traite des politiques monétaires non conventionnelles (PMNC) mises en œuvre par la Fed et la BCE, entre 2008 et 2014, face à la récession économique et la déflation engendrées par la crise financière de 2008. Il consiste à rendre compte, en suivant une approche descriptive fondée sur l'examen de nombreuses études sur les PMNC, des mesures d'assouplissement monétaires traditionnelles servant, d’une part, à influencer les conditions de financement dans les banques et les marchés financiers et, d’autre part, à favoriser la demande globale et à stimuler l'activité économique. Cette étude s’intéresse, également, à la politique de financement non conventionnel (FNC) mise en œuvre par la Banque d’Algérie de novembre 2017 à janvier 2019. Nous mettons l’accent sur les causes du recours à ce type de financement, sa conduite et les techniques mis en place pour contrôler l’inflation. Il ressort de cette étude que, contrairement au FNC en Algérie, les PMNC ont eu l’effet escompté sur la croissance économique et l’inflation, aux Etats-Unis et dans les pays de la zone euro.
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Löppönen, Pekka, Sina Hulkkonen, and Jorma Ryhänen. "Proximal Median Nerve Compression in the Differential Diagnosis of Carpal Tunnel Syndrome." Journal of Clinical Medicine 11, no. 14 (July 9, 2022): 3988. http://dx.doi.org/10.3390/jcm11143988.
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Carpal tunnel syndrome (CTS) is the most common median nerve compression neuropathy. Its symptoms and clinical presentation are well known. However, symptoms at median nerve distribution can also be caused by a proximal problem. Pronator syndrome (PS) and anterior interosseous nerve syndrome (AINS) with their typical characteristics have been thought to explain proximal median nerve problems. Still, the literature on proximal median nerve compressions (PMNCs) is conflicting, making this classic split too simple. This review clarifies that PMNCs should be understood as a spectrum of mild to severe nerve lesions along a branching median nerve, thus causing variable symptoms. Clear objective findings are not always present, and therefore, diagnosis should be based on a more thorough understanding of anatomy and clinical testing. Treatment should be planned according to each patient’s individual situation. To emphasize the complexity of causes and symptoms, PMNC should be named proximal median nerve syndrome.
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Reyna, Sara M., Puntip Tantiwong, Eugenio Cersosimo, Ralph A. DeFronzo, Apiradee Sriwijitkamol, and Nicolas Musi. "Short-Term Exercise Training Improves Insulin Sensitivity but Does Not Inhibit Inflammatory Pathways in Immune Cells from Insulin-Resistant Subjects." Journal of Diabetes Research 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/107805.
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Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells.Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC) were obtained for determination of Toll-like receptor (TLR) 2 and 4 protein content and mitogen-activated protein kinase phosphorylation.Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation.Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.
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Keizer-Garritsen, Jenneke J., Connie Brouwer, Lambert H. J. Lambooy, Patricia Ter Riet, Jos P. M. Bökkerink, Frans J. M. Trijbels, and Ronney A. De Abreu. "Measurement of thiopurine S-methyltransferase activity in human blood samples based on high-performance liquid chromatography: reference values in erythrocytes from children." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 40, no. 1 (January 1, 2003): 86–93. http://dx.doi.org/10.1258/000456303321016222.
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Background: Monitoring 6-thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) activity is especially important when patients are treated with 6-thiopurine drugs, since severe bone marrow toxicity may be induced if patients have deficient TPMT activity. Methods: We have developed a method based on high-performance liquid chromatography (HPLC) for the measurement of TPMT activity in various cell types: erythrocytes (RBC), human peripheral blood mononuclear cells (pMNC) and human malignant lymphoblasts (Molt-F4). The enzymatic activity is measured by the amount of 6-methylmercaptopurine formed, using 6-mercaptopurine (6MP) as substrate and S-adenosylmethionine as co-substrate. Results: The Km values calculated for 6MP were 0·54 (RBC), 0·85 (pMNC) and 0·65 (Molt-F4 cells) mmol/L. The Km values for S-adenosylmethionine were 11·9 (RBC), 16·4 (pMNC) and 6·65 (Molt-F4 cells) µmol/L. The assay variation was 8·2-17%. TPMT activity was determined in a control group of 103 children and young adults (44 female, 59 male). The values observed were (mean ± standard deviation): female children and young adults, 15·1 ± 4·8 pmol/107 cells per h ( n = 44); male children and young adults, 15·8 ± 6·4 pmol/107 cells per h ( n = 59). No gender or age differences were found. Conclusion: The HPLC-based method enables the rapid screening of TPMT activities in large groups of patients treated with 6-thiopurines.
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Wood, Paul, Jayesh Desai, Kelly Waldeck, Jason Cain, Nicholas Gottardo, Robyn Strong, Kathryn Kinross, et al. "ATRT-17. A phase II study of continuous low dose panobinostat in paediatric patients with malignant rhabdoid tumours and atypical teratoid rhabdoid tumours." Neuro-Oncology 24, Supplement_1 (June 1, 2022): i6—i7. http://dx.doi.org/10.1093/neuonc/noac079.016.
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Abstract BACKGROUND: Panobinostat treatment has been shown to terminally differentiate malignant rhabdoid tumours (MRT) and atypical teratoid rhabdoid tumours (ATRT) in pre-clinical models. We report results of the open label, phase II study of oral panobinostat in patients with newly diagnosed or relapsed MRT/ATRT. AIMS: To assess the anti-tumour activity of low dose, continuous oral panobinostat as well as its associated toxicities. To assess the biological activity of low dose panobinostat by measuring histone H4 acetylation status in peripheral mononuclear cells (PMNC), and differentiation markers. METHODS: Following primary institutional standard of care induction and consolidation chemotherapy and/or radiation treatment, patients were enrolled and commenced on panobinostat as a continuous daily oral dose starting at 10mg/m2/day, with a three-week wash out period between therapies. Real-time acetylation status, measuring acetylated H4 on PMNC, was performed to determine the pharmacodynamics of panobinostat at different dosing levels. Patients were monitored for toxicity; dose reductions were in decrements of 2mg/m2/day. RESULTS: A total of 13 patients with newly diagnosed ATRT/MRT and one patient with relapsed MRT have been enrolled. The average age at enrollment was 3.6 years (range 0.8-6.8 years). The mean treatment duration was 206 days (13-344 days). Currently, six patients (42.9%) remain on study with a mean study duration of 531 days (range 13-895 days). 6/14 patients (42.9%) were removed due to disease progression at a mean study duration of 245 days (44-560 days). 2/14 patients (14.3%) withdrew due to toxicity. 12/14 patients (85.7%) required dose reductions. The main toxicities were thrombocytopaenia and leukopaenia (Grade III-IV). Real-time pharmacodynamic assessment of panobinostat, at a dose as low as 6mg/m2/day resulted in significant acetylation of histone H4 in PMNC. CONCLUSIONS: Treatment with low dose panobinostat is well tolerated in infants and children with MRT/ATRT, with significant acetylation of histone H4 in PMNC.
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Wood, Paul, Jayesh Desai, Kelly Waldeck, Jason Cain, Nick Gottardo, Robyn Strong, Kathryn Kinross, et al. "ATRT-08. A PHASE II STUDY OF CONTINUOUS LOW DOSE PANOBINOSTAT IN PAEDIATRIC PATIENTS WITH MALIGNANT RHABDOID TUMORS/ATYPICAL TERATOID RHABDOID TUMORS." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii277. http://dx.doi.org/10.1093/neuonc/noaa222.008.
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Abstract BACKGROUND Panobinostat treatment has been shown to terminally differentiate malignant rhabdoid tumor (MRT)/atypical teratoid rhabdoid tumors (ATRT) in pre-clinical models. This is an open label, phase II study of panobinostat in patients with newly diagnosed or relapsed MRT/ATRT. AIMS: To assess the anti-tumor activity of low dose, continuous panobinostat, its associated toxicities, the biological activity of low dose panobinostat by measuring histone acetylation status in peripheral mononuclear cells (PMNC), and markers of differentiation in fresh tumor tissue specimens. METHODS Following cycles of induction and consolidation chemotherapy and/or radiation treatment, patients were enrolled and commenced on panobinostat as a continuous daily oral dose starting at 10mg/m2 following a three-week wash out period between therapies. Real-time acetylation status, measuring acetylated H4 on PMNC, was performed to determine the pharmacodynamics of panobinostat. Patients were monitored for drug toxicities with the possibility of dose reductions in decrements of 2mg/m2. RESULTS Six patients with newly diagnosed ATRT/MRT and one patient with relapsed MRT have been enrolled to date. The average age at enrollment was 2.5 years. Currently, six patients (85.7%) remain on study with a mean treatment duration of 170 days (range 44–327 days). One patient was removed from study at day 44 due to disease progression. The main dose-limiting toxicity observed to date has been myelosuppression. Panobinostat, at a dose of 10mg/m2, caused significant acetylation of H4 in PMNC. CONCLUSIONS Treatment with panobinostat appears to be well tolerated in infants with MRT/ATRT, with successful real-time pharmacodynamic assessment of H4 acetylation.
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Diaz, Daphne, Gregory N. Prado, Patricia Neuman, Adriana Nieva, Manuel Torres-Grajales, Alicia Rivera, and Jose R. Romero. "Aldosterone Stimulates a Degranulation Response in Human Neutrophils: Role of Protein Disulfide Isomerase." Blood 120, no. 21 (November 16, 2012): 1034. http://dx.doi.org/10.1182/blood.v120.21.1034.1034.
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Abstract Abstract 1034 There is growing evidence for an important role of aldosterone (ALDO) in inflammatory responses in addition to its well-described effects on sodium homeostasis via activation of the mineralocorticoid receptor (MR). We studied the effects of ALDO on activation of ex vivo human polymorphonuclear leukocytes (PMNC). We isolated untouched circulating human PMNC by immunomagnetic isolation following density gradient sedimentation with PolymorphPrep from otherwise healthy subjects. Flow cytometric analyses showed greater than 97% of PMNC were positive for myeloid-neutrophil markers, CD45, CD16 and CD66b. We show that PMNC express MR by western blot and RT-PCR analyses and when incubated with ALDO (10−9 −10−7 M) showed a dose-dependent rise in cytosolic Ca2+ that peaked within 2 min using FURA-2AM fluorescence. We then studied the effect of ALDO on PMNC degranulation following incubations with ALDO (10−9 −10−7 M) for 30 min and observed a significant increase in β–glucuronidase release (P<0.001, n=3) by established fluorescent detection methods, an event that was blocked by pre-incubation of cells with 1μM canrenoic acid (CA), an MR antagonist (P<0.04, n=3). PMA and N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) were used as positive controls for PMNC activation. We then studied the effects of ALDO on HL-60, a human promyelocytic cell line, induced to differentiate into neutrophil-like cells by incubation for 5 days with 1.3% DMSO. We detected the presence of the mineralocorticoid receptor (MR), the receptor for ALDO, by western blot analyses and MR transcripts by quantitative RT-PCR using TaqMan detection probes in these cells and as reported in kidney and endothelial cells. Cells incubated with ALDO (10−8-10−7 M) showed a dose-dependent rise in cytosolic Ca2+ that peaked within 3 min using FURA-2AM fluorescence. To assess the degranulation response of these cells we quantified the in vitro release of myeloperoxidase (MPO) and observed that 10−8M ALDO was likewise associated with increased degranulation when compared to vehicle treated cells (AUC: 590±14 to 185±11, P<0.01, n=6). To characterize the mechanisms by which ALDO regulates the degranulation responses of these cells we studied the effects of Protein Disulfide Isomerase (PDI) on ALDO-stimulated cells. PDI catalyzes the oxidation or reduction of thiol/disulfide groups and modulates leukocyte function. Our results show that blockade of PDI, by bacitracin, led to a blunted ALDO-stimulated degranulation response in both cell types. Consistent with these observations, we show that in differentiated HL-60 cells, siRNA against PDI likewise led to reduced MPO responses (AUC: 590±14 to 290±13, P<0.01, n=6) that were associated with significantly reduced PDI mRNA levels but not with scrambled siRNA as determined by quantitative RT-PCR with ABI TaqMan detection probes and GAPDH and β2 microglobulin as endogenous controls (0.55 ± 0.02, ΔΔCT of PDI siRNA relative to scrambled transfected cells, P<0.01, n=6). These results suggest that ALDO stimulates MPO release. MPO has been shown to be one of the predominant granule proteins associated with Neutrophil Extracelullar Traps (NETs), extracellular structures that contain chromatin (DNA and histones) that can also trap microorganisms. We studied the effects of ALDO following digestion of the NETs by DNAse, and observed that 30–35% of the total cellular MPO was NET-associated. We also observed that incubation with 10−8 M ALDO led to increases in the oxidative-respiratory burst [superoxide production] (P<0.01, n=3), a responses that was blocked by pre-incubation of cells with 1 uM CA (P<0.03, n=3). Consistent with these results, we observed that ALDO likewise led to significant increases in the oxidative-respiratory burst in human PMNC (P<0.01, n=3). Thus our results suggest that activation of MR by ALDO leads to degranulation and NET production in neutrophils that may contribute to the inflammatory responses associated with MR activation in vivo. Furthermore, the association between degranulation and NET release implicates PDI as a novel regulator of MPO generated NET production. Disclosures: No relevant conflicts of interest to declare.
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Ramos-Rivera, Arelys, Alicia Rivera, Enrique D. Machado-Fiallo, Josue A. Benabe-Carlo, Gregory N. Prado, and Jose R. Romero. "Aldosterone Stimulates Neutrophils Leading To Increased β-Glucuronidase, Protein Disulfide Isomerase and Myeloperoxidase Secretion." Blood 122, no. 21 (November 15, 2013): 2271. http://dx.doi.org/10.1182/blood.v122.21.2271.2271.
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Abstract Aldosterone (ALDO) has been shown to play an important role in inflammatory responses in addition to its well described effects on sodium homeostasis via activation of the mineralocorticoid receptor (MR). However, its effects on polymorphonuclear leukocytes (PMNC) are not well described. We isolated untouched circulating human PMNC by immunomagnetic isolation following density gradient sedimentation with PolymorphPrep from otherwise healthy subjects. Flow cytometric analyses showed greater than 97% of PMNC were positive for the myeloid-neutrophil markers, CD45, CD16 and CD66b. We show that PMNC express MR by western blot and RT-PCR analyses. We incubated PMNC with ALDO (10–9–10–7M) for 30 min and observed a dose-dependent rise in β–glucuronidase release with an EC50 of 6.11 nM (P<0.001, n=3), an event that was blocked by pre-incubation of cells with 1μM canrenoic acid (CA), an MR antagonist (P<0.04, n=3). In addition, our results show that incubation of human PMNC with 10-8M ALDO likewise led to increases in myeloperoxidase ([MPO], P<0.05, n=3) and protein disulfide isomerase ([PDI], P<0.01, n=4), a multifunctional enzyme of the thioredoxin superfamily that mediates redox modifications, regulates KCNN4 channel and erythrocyte volume and is up-regulated under hypoxic conditions (Prado, 2013 FASEB J). We then studied the effects of ALDO on HL-60, a human promyelocytic cell line, induced to differentiate into neutrophil-like cells by incubation for 5 days with 1.3% DMSO. Our results likewise show an increase in MPO responses upon 10–8M ALDO stimulation as compared to vehicle (AUC: 1090±147 to 505±48, P<0.02, n=3). We have recently reported that aldosterone stimulates increases of striatin, a scaffolding protein that interacts with caveolin-1, and co-precipitates with striatin and as such may facilitate cross talk of signaling complexes. As there are no pharmacological inhibitors of striatin we used a molecular approach to reduce striatin levels. In differentiated HL-60 cells, siRNA against striatin led to reduced MPO responses (AUC: 590±14 to 528±13, P<0.05, n=3) that were associated with significantly reduced striatin mRNA levels but not when cells were transfected with scrambled siRNA as determined by quantitative RT-PCR with ABI TaqMan detection probes and β-microglobulin used as an endogenous control (P<0.01, n=3). These results suggest that striatin plays an important role in ALDO-stimulated degranulation responses. Of importance we also observed that incubation with ALDO (10–9–10–7M) in differentiated HL60 cells led to increases in the oxidative-respiratory burst [superoxide production] in a dose- and time-dependent manner (P<0.01, n=4). Consistent with these results, we observed that ALDO likewise led to significant increases in the oxidative-respiratory burst in human PMNC (P<0.01, n=3). As there is evidence that activated neutrophils, MPO and PDI are elevated in Sickle Cell Disease, we studied the in vivo effects of MR blockade in BERK sickle transgenic mice, a model of increased oxidative stress. Sickle mice were randomized to receive either normal rodent chow or chow containing eplerenone (156 mg/kg per day), an MR receptor antagonist, and tap water ad libitum for 14 days at which time the mice were sacrificed and blood collected. We observed that mice on eplerenone had significantly lower plasma PDI activity than mice on regular chow (63.7 ± 8.7 control diet to 47.9 ± 2.4 eplerenone, Relative Fluorescence Units [RFU]; P<0.005, n=6 and 9) and lower MPO levels (AUC: 214±11 to 73±20, P<0.03, n=3); events that were associated with increases in both erythrocyte MCV (41.3±2.5 vs 47.4±1.1 fL, P<0.03, n=7) and reticulocyte MCV (53.6.3±2.8 vs 60.1±0.6 fL, P<0.02, n=7). Thus, our results suggest that MR activation by ALDO is a novel mechanism for neutrophil stimulation and as such represents a novel therapeutic target aimed at ameliorating the vascular complications of Sickle Cell Disease. Supported by NIH R01HL090632 (AR) and R01HL096518 (JRR). Disclosures: No relevant conflicts of interest to declare.
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Al Mutoki, Sabah Mohammed Mlkat, Baydaa Abul Hassan Khalaf Al Ghzawi, Samir M. Abdul Amohsin, and Emad Abbas Jaffar Al-Mulla. "Raman shift of silicon rubber-nano titania PMNC." Epitoanyag - Journal of Silicate Based and Composite Materials 69, no. 1 (2017): 20–23. http://dx.doi.org/10.14382/epitoanyag-jsbcm.2017.4.
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Bahramnia, Hamed, Hamidreza Mohammadian Semnani, Ali Habibolahzadeh, and Hassan Abdoos. "Epoxy/polyurethane nanocomposite coatings for anti-erosion/wear applications: A review." Journal of Composite Materials 54, no. 22 (March 12, 2020): 3189–203. http://dx.doi.org/10.1177/0021998320908299.
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Offshore pipelines are vulnerable against erosion/wear deterioration mechanisms that can be controlled through the use of proper surface coatings, such as polymer matrix nano-composite (PMNC) coatings that are well-known for their ease of production, availability and applicability. Epoxy, as a versatile rigid and brittle resin and polyurethane with proper chemical/mechanical properties, are potential candidates to make the matrix of these composites. A combination of these polymers can also enhance the mechanical behaviors, glass transition temperature and flexibility. In addition, the desired coating characteristics, such as adhesion to metal substrate, mechanical properties, erosion/wear resistivity and UV absorbance, can be further improved through the addition of appropriate nanoparticles within the polymer matrix. Especially, nanoparticles can improve the erosion/wear resistance of polymers because of establishing high strength bonds between the polymer chains and the reinforcements besides enhancing other required properties. The present work is a review on PMNC coatings that contain epoxy, polyurethane or EP/polyurethane as a polymer matrix along with the details of the nanoparticle reinforcements, such as alumina, silica, titanium oxide, zinc oxide, clay and carbon-based materials. The effect of these nanoparticles on the properties of composite coatings has also been investigated.
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Schmidt-Lucke, Caroline, Felicitas Escher, Sophie Van Linthout, Uwe Kühl, Kapka Miteva, Jochen Ringe, Thomas Zobel, Heinz-Peter Schultheiss, and Carsten Tschöpe. "Cardiac Migration of Endogenous Mesenchymal Stromal Cells in Patients with Inflammatory Cardiomyopathy." Mediators of Inflammation 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/308185.
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Introduction. Mesenchymal stromal cells (MSC) have immunomodulatory features. The aim of this study was to investigate the migration and homing potential of endogenous circulating MSC in virus negative inflammatory cardiomyopathy (CMi).Methods. In 29 patients withn=23or withoutn=6CMi undergoing endomyocardial biopsies (EMB), transcardiac gradients (TCGs) of circulating MSC were measured by flow cytometry from blood simultaneously sampled from aorta and coronary sinus. The presence of MSC in EMB, cardiac inflammation, and SDF-1αmRNA expression were detected via immunohistochemistry and real-time PCR.Results. MSC defined as CD45−CD34−CD11b−CD73+CD90+cells accounted for 0.010 [0.0025–0.048]%/peripheral mononuclear cell (PMNC) and as CD45−CD34−CD11b−CD73+CD105+cells for 0.019 [0.0026–0.067]%/PMNC, both with similar counts in patients with or without cardiac inflammation. There was a 29.9%P<0.01transcardiac reduction of circulating MSC in patients with CMi, correlating with the extent of cardiac inflammation (P<0.05, multivariate analysis). A strong correlation was found between the TCG of circulating MSC and numbers of MSC (CD45−CD34−CD90+CD105+) in EMB (r=-0.73,P<0.005). SDF-1αwas the strongest predictor for increased MSC in EMB (P<0.005, multivariate analysis).Conclusions. Endogenous MSC continuously migrate to the heart in patients with CMi triggered by cardiac inflammation.
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Marković, Maja D., Sanja I. Šešlija, Vesna V. Panić, and Pavle M. Spasojević. "Dual responsive hybrid hydrogels for controlled release of local anesthetic." Procesna tehnika 33, no. 2 (January 26, 2022): 18. http://dx.doi.org/10.24094/ptc.021.33.2.18.
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Inteligent hydrogels, such as pH sensitive hydrogels based on poly(methacrylic acid) (PMAA) are widely used for targeted drug delivery. Still, PMAA lack of good mechanical properties often limits its application. In order to overcome this limitation nanocellulose (NC) was extracted from wood waste material and then added to PMAA because NC is biocompatible, non-toxic and has excellent mechanical properties. Further, carboxymethyl cellulose (CMC) (cellulose derivate widely used for controlled release of drugs) was added. CMC can stabilize magnetite nanoparticles (MN) which is then also added. MN can significantly improve mechanical properties of hydrogels and also possess magnetic properties due to which MN can be used for targeted drug delivery. The as-prepared material can protect drug, deliver it to the site of action, control its release rate and enable in that way its efficient application with reduced side effects. Local anesthetic - lidocaine hydrochloride (LH) is often administrated by injection which can induce severe side effects. This problem is solved in present study by encapsulating LH into hydrogels based on PMAA, NC, CMC and MN (PMNC/MN-L). PMNC/MN-L hydrogels were characterized by FTIR and SEM spectroscopies and single compressive tests and then their swelling behavior and LH release were analyzed. Present study offers unique approach for green synthesis of dual responsive hydrogels with improves properties and their application for controlled release of local anesthetic with reduced side effects.
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Archuadze, Shorena, Elena Mikhailova, Elena Parovichnikova, Sergei Kulikov, and Valeri Savchenko. "IL-12 Producing Capacity of Cultivated Dendritic Cells of Aplastic Anemia Patients during Disease Manifestation and Immunosuppressive Treatment." Blood 110, no. 11 (November 16, 2007): 4084. http://dx.doi.org/10.1182/blood.v110.11.4084.4084.
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Abstract Dendritic cells (DCs) play principal role in the induction of antigen-specific T-cell immune response and in the development of antigen-specific self-tolerance. Moreover, they promote either Th1 or Th2 polarization of naive lymphocytes by production of immunoregulatory cytokines (IL-12 and IL-10). AA is characterized by increased Th1/Th2 ratio and by Th1 mediated antigen-specific suppression of hematopoiesis. DCs might be responsible for the activation of T-clone in AA patients. However, functional characteristics such as IL-12 production by DC in AA patients have not been studies yet. Therefore, IL-12 secretion capacity of DCs generated from peripheral mononuclear cells (PMNC) of 30 AA patients before and during the immunosuppressive therapy (IST) was compared to that of DCs of 7 donors. DC were derived from PMNC in the presence of GM-CSF and IL-4 for 5–7 days and further stimulated by exposition to 3T3-CD40L fibroblasts for 48 hours. Supernatants of DC cultures were subjected to ELISA for evaluation of IL-12 production. 70,8% of AA patients exhibited significantly (p=0,02) increased baseline level of IL-12 production by DCs compared to that of donors. Programmed IST resulted in the diminution of IL-12 production level in 67% of AA patients. Moreover, significant decrease in IL-12 production level correlated (Rs=0,79) with the achievement of independence from transfusions. Patients with high baseline level of IL-12 production by DCs required continuous (median - 24 months, p<0,05, see pict. 1) IST including repeated courses of antithymocyte globulin and cyclosporin-A. These data suggest that increase in IL-12 production by DCs of AA patients might contribute to cytotoxic T-clone expansion and consequently, to AA development. Patients that showed high initial levels of IL-12 secretion by DCs comprised the worst prognostic group. Figure Figure
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Al-Mutoki, Sabah Mohammed Mlkat, Ahmad Ghanim Wadday, Ali Abdulabbas Abdullah, Baydaa Abdul-Hassan Khalaf Al-Ghzawi, and Emad A. Jaffar Al-Mulla. "Effect of nanoTiO 2 dopant on electrical properties of SR8100/nanoTiO 2 PMNC." Results in Physics 6 (2016): 551–53. http://dx.doi.org/10.1016/j.rinp.2015.12.006.
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Eskinazi, Daniel P., John J. Perna, Abby G. Ershow, and R. Clifford Mihail. "Depressed PMNC Blastogenic Response in Patients with Cancer of the Head and Neck." Laryngoscope 99, no. 2 (February 1989): 151???157. http://dx.doi.org/10.1288/00005537-198902000-00006.
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Etienne, M. C., J. L. Lagrange, O. Dassonville, R. Fleming, A. Thyss, N. Renée, M. Schneider, F. Demard, and G. Milano. "Population study of dihydropyrimidine dehydrogenase in cancer patients." Journal of Clinical Oncology 12, no. 11 (November 1994): 2248–53. http://dx.doi.org/10.1200/jco.1994.12.11.2248.
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PURPOSE We conducted a prospective study on a large set of cancer patients in an attempt to evaluate the incidence of complete or partial dihydropyrimidine dehydrogenase (DPD) deficiency as found in peripheral mononuclear cells (PMNC). PATIENTS AND METHODS One hundred eighty-five unselected consecutive cancer patients were included. The population consisted of 152 men (mean age, 62.1 years; range, 35 to 90) and 33 women (mean age, 59.2 years; range, 36 to 77). Sixty-eight were head and neck patients treated by a 5-day continuous infusion of fluorouracil (FU; starting dose, 1 g/m2/d, with dose adaptation based on pharmacokinetics) for which DPD activity was measured 2 to 3 days before FU administration (94 cycles analyzed). PMNC-DPD activity was measured by a radio-enzymatic assay using carbon-14-FU. RESULTS DPD activity in the entire population showed a unimodal distribution, which globally fits a gaussian distribution. Mean and median DPD activity values were 0.222 and 0.211 nmol/min/mg protein, respectively (range, 0.065 to 0.559). No total DPD deficiency was found. Multifactor analysis of variance showed that liver function (biologic evaluation) and age did not influence DPD activity, but that DPD activity was, on average, 15% lower in women (0.194 nmol/min/mg protein) than in men (0.228 nmol/min/mg protein) (P = .03). No difference was demonstrated between premenopausal and postmenopausal women. In patients treated with FU, the risk of developing side effects was not linked to pretreatment DPD activity. FU-related toxicity was linked to FU systemic exposure. The correlation between pretreatment DPD activity and FU systemic clearance (CI) was weak (n = 90, linear regression r = .31, P = .002). Pretreatment DPD activity in patients who required a dose reduction was not significantly different from DPD activity in patients who did not require dose modification. CONCLUSION From the present study, it appears that total DPD deficiency is a rare event. Although pretreatment DPD activity cannot be a useful indicator for improving FU dose adaptation strategy, the identification of severe DPD deficiency (< 0.100 nmol/min/mg protein) could lead to starting the treatment with a markedly reduced FU dose or even to using an alternative chemotherapy regimen.
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Wang, Shuai, Zewei Sun, Wenting Zhao, Zhen Wang, Mingjie Wu, Yanyun Pan, Hui Yan, and Jianhua Zhu. "CD97/ADGRE5 Inhibits LPS Induced NF-κB Activation through PPAR-γUpregulation in Macrophages." Mediators of Inflammation 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/1605948.
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CD97/ADGRE5 protein is predominantly expressed on leukocytes and belongs to the EGF-TM7 receptors family. It mediates granulocytes accumulation in the inflammatory tissues and is involved in firm adhesion of PMNC on activated endothelial cells. There have not been any studies exploring the role of CD97 in LPS induced NF-κB activation in macrophages. Therefore, we first measured the CD97 expression in LPS treated human primary macrophages and subsequently analyzed the levels of inflammatory factor TNF-αand transcription factor NF-κB in these macrophages that have been manipulated with either CD97 knockdown or overexpression. We found that a reported anti-inflammatory transcription factor, PPAR-γ, was involved in the CD97 mediated NF-κB suppression. Furthermore, by immunofluorescence staining, we established that CD97 overexpression not only inhibited LPS induced p65 expression in the nucleus but also promoted the PPAR-γexpression. Moreover, using CD97 knockout THP-1 cells, we further demonstrated that CD97 promoted PPAR-γexpression and decreased LPS induced NF-κB activation. In conclusion, CD97 plays a negative role in LPS induced NF-κB activation and TNF-αsecretion, partly through PPAR-γupregulation.
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Freeh, Daniel M., and Mehmet Sarikaya. "Polymorphic Transition in Biogenic Calcium Carbonate: Nacre/Prismatic Interface in Abalone Shell." Microscopy and Microanalysis 3, S2 (August 1997): 753–54. http://dx.doi.org/10.1017/s1431927600010655.
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The research in biological hard tissues offers lessons for biomimetic (structure and processing) strategies, such as for the synthesis of hierarchical architectures tailored for specific engineering applications. These biocomposites, i.e., biogenic materials in which the major phase is an inorganic component associated with macromolecules (proteins and polysaccharides), include bones, dentin, sea-urchin skeletal units, bacterial and algal particles and molluscan shells. Here, a summary is given from a recent TEM study of the interfacial region of nacreous and prismatic sections of red abalone shell to understand the morphological and crystallographic correlations across this transition region.Many mollusk species have shells made of CaCO3 in various architectures that have evolved under different ecological conditions to produce structures that best protect the organism. The shells of many species contain both aragonite (orthorhombic, Pmnc) and calcite (Rhombohedral, R3m). In red abalone (Haliotis rufescens), the outer section, prismatic (P), is composed of columnar crystallites of calcite (1-5 μm base, 5-10 μm height), and the inner section, nacre (N), is composed of pseudo-hexagonal platelets of aragonite (side 2-5 μm), stacked as 0.25 μm layers, separated by a few nm-thick organic layer (Fig. 1).
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Gentile, D., A. Patel, and D. Skoner. "Association between Second-Hand Smoke Exposure (SSE) and enhanced peripheral blood mononuclear cell (PMNC) IL-13 production during infancy." Journal of Allergy and Clinical Immunology 115, no. 2 (February 2005): S116. http://dx.doi.org/10.1016/j.jaci.2004.12.475.
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ElKarim, Rihab, Carl Granert, Lars Lindquist, Hans Link, and Moiz Bakhiet. "Levels of Gamma Interferon and Interleukin-4 Are Inversely Related to the Levels of Their Corresponding Autoantibodies in Patients with Lower Respiratory Tract Infection." Infection and Immunity 67, no. 6 (June 1, 1999): 3051–54. http://dx.doi.org/10.1128/iai.67.6.3051-3054.1999.
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ABSTRACT To study the involvement of cytokines and their corresponding autoantibodies (Aabs) in inflammatory mechanisms in patients with lower respiratory tract infections, blood samples were taken from patients at the time of admission to the hospital and before treatment. Cell-released capturing enzyme-linked immunosorbent assay was used to measure the levels of gamma interferon (IFN-γ) and interleukin-4 (IL-4) produced spontaneously by peripheral mononuclear cells (PMNC). ELISA was used to measure Aabs to these cytokines in sera. The levels of both cytokines were inversely related to the levels of their corresponding Aabs. While a high level of IFN-γ was observed together with a low level of anti-IFN-γ Aab, decreased IL-4 levels were observed with increased levels of Aabs to IL-4. Immunoglobulins were purified, digested to obtain Fab fragments, and tested for specificity and cross-reactivity. The Aabs and their Fab fragments were tested in cytokine biological assays and showed neutralizing effects. Our data demonstrated increased levels of the proinflammatory cytokine IFN-γ and decreased release of the anti-inflammatory cytokine IL-4 during early presentation of lower respiratory tract infection. The levels of these cytokines were inversely related to the levels of their corresponding Aabs that exhibited regulatory effects on the cytokine biological function in vitro.
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Lima, Péricles Souza, and Fernando de Morais. "COMPARTIMENTAÇÃO GEOMORFOLÓGICA DO EXOCARSTE DE NATIVIDADE E CHAPADA DA NATIVIDADE – TO." Caminhos de Geografia 24, no. 91 (February 22, 2023): 346–65. http://dx.doi.org/10.14393/rcg249161623.
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O sudeste do Tocantins caracteriza-se, dentre outros aspectos geográficos, pela presença de um carste bem desenvolvido, o que motivou a realização da compartimentação geomorfológica do relevo cárstico localizado nos municípios de Natividade e Chapada da Natividade. Neste sentido, este artigo objetivou tecer considerações sobre a influência dos fatores endógenos e exógenos na configuração da paisagem, enquanto eram definidas cada porção do relevo. Para tanto, com o auxílio das imagens dos satélites ALOS/Palsar, Sentinel 2A e da carta topográfica (SC.23-Y-C-IV), foram feitos mapas da rede de drenagem local, de altimetria, declividade, assim como a confecção de perfis topográficos e bloco diagrama, para melhor detalhamento do exocarste. In loco, o software Avenza Maps e os pontos espacializados no Google Earth Pro tornaram a navegação rápida e objetiva. A partir de então, dividiu-se a área em três compartimentos: Compartimento dos Planaltos Metassedimentares Não-Carbonáticos (PMNC), Compartimento dos Planaltos Carbonáticos (CPC) e Superfícies com Ocorrência de Dolinas (SCOD). O trabalho resultou ainda na elaboração de um mapa exploratório de fenômenos cársticos em escala de semidetalhe (1:50.000). O trabalho pode contribuir para a elaboração de políticas ambientais e servir de referência às novas pesquisas, auxiliando na produção de conhecimento mais detalhado do carste da região estudada.
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Tiwari, U. P., B. Turano, and R. Jha. "Nutritional characteristics and in vitro digestibility by near-infrared spectroscopy of local and hybrid napiergrass varieties grown in rain-fed and irrigated conditions." Animal Production Science 54, no. 10 (2014): 1775. http://dx.doi.org/10.1071/an14289.
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Napiergrass can produce large amounts of biomass and its nutritive value has a significant effect on its effectiveness for animal production. However, temperature and drought stress limit its productivity. Drought-tolerant pearl millet × napiergrass hybrid (PMN) varieties were developed and produce high biomass yields. The nutritional content and digestibility of PMN is not well known, which limits its use in animal feeding. It was hypothesised that PMN hybrids are more drought tolerant and have higher nutritive value than napiergrass varieties. Four napiergrass varieties (Bana grass, Mott, MB4, and N51) and four PMN (PMN2, PMN3, 5344, 4604) were tested with or without irrigation treatment in a strip-plot design, with the objective of evaluating the nutritional value and in vitro digestibility of PMN hybrids and napiergrass. The forages were harvested on Day 110 of planting. Samples were hand chopped, oven-dried, ground to pass through a 1-mm screen and analysed for their nutrient content and in vitro digestibility using near-infrared spectroscopy. Dry matter (DM) content of PMN2 (24.3%) and PMN3 (22.9%) was significantly higher (P < 0.05) than 5344, Bana grass and N51 napiergrass varieties. No differences (P > 0.05) in acid detergent fibre, neutral detergent fibre, crude protein and metabolisable energy were found among napiergrass varieties. With no effect (P > 0.05) of irrigation, lignin content was highest (P < 0.08) in 4604 (8.2%) and lowest in 5344 (5.2%). Starch was highest (P < 0.05) in irrigated MB4 than both irrigated and non-irrigated 4604. Non-fibre carbohydrate content was highest (P < 0.05) in PMN2 (12.8%) than MB4 (8.7%). The in vitro true digestibility was significantly higher (P < 0.05) in 5344 and Bana grass (70.0% and 68.0% of DM, respectively), than PMN3 (54.5%). Rate of digestion was significantly higher (P < 0.05) in 5344 (4.9%/h) than PMN2 (2.7%/h), others were in between. Neutral detergent fibre digestibility (NDFD) of 5344 and Bana grass (56.7% and 53.2% of neutral detergent fibre, respectively) was significantly higher (P < 0.05) than PMN2 (38.0%). Although no effect of irrigation was observed, there was an interaction (P < 0.05) between variety and irrigation on neutral detergent fibre digestibility of napiergrass varieties. In conclusion, among four PMN varieties tested, PMN3 and 5344 has higher nutritional value and in vitro digestibility than PMN2 and 4604 even when grown in non-irrigated condition. Thus, PMN3 and 5344 is the preferred napiergrass variety for animal feeding, even in rain-fed farming conditions.
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Iqbal, Shazia Sarwat, Muhammad Jamaluddin, and Maria Saleem Mudassir. "Transformation of PMDC to PMC." ANNALS OF ABBASI SHAHEED HOSPITAL AND KARACHI MEDICAL & DENTAL COLLEGE 25, no. 3 (December 17, 2020): 122–23. http://dx.doi.org/10.58397/ashkmdc.v25i3.362.
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In Pakistan, medical professions are controlled and regulated by a body for proper function. Initially, it was Pakistan Medical and Dental Council (PMDC) but now it has become Pakistan Medical Commission (PMC). The Pakistan Medical Council Ordinance 1962 established the present-day Pakistan Medical and Dental Council as a statutory body in 1962 and all provincial councils were dissolved then. Three amendments were passed after the establishment of PMDC known as (Amendment)Act in 1973, 1999, and 20121. Now the PMC was established on 24th September 2020 for the regulation and control of the medical profession to increase the basic and higher medical education and practice in both medical and dental sections2.
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Ishikawa, K., S. Sadahiro, T. Suzuki, H. Makuuchi, and C. Murayama. "562 Dihydropyrimidine dehydrogenase (DPD) activity in peripheral mononuclear cells (PMNC-DPD) during long-term treatment with oral uracll/tegafur (UFT) as postoperative adjuvant chemotherapy for colorectal cancer (CRC)." European Journal of Cancer Supplements 1, no. 5 (September 2003): S170. http://dx.doi.org/10.1016/s1359-6349(03)90594-5.
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Abdelsalam, Mostafa, Mona M. Tawfik, Alaa Habib, Ahmed Abdel-Razik, Nahla Anber, Maysaa Zaki, and Mohammad S. Marie. "Occult hepatitis C virus infection among Egyptian hemodialysis patients and its potential effect on anemia management." Egyptian Journal of Internal Medicine 31, no. 4 (December 2019): 783–89. http://dx.doi.org/10.4103/ejim.ejim_94_19.
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Abstract Background Hepatitis C virus (HCV) infection is still a main health problem in hemodialysis (HD) patients. The prevalence of occult hepatitis C infection (OCI) in HD patients may be underestimated, and its possible influence on anemia management has not been studied. We aimed to determine the existence of OCI in Egyptian HD patients as well as its possible effect on anemia management. Patients and methods This cross-sectional multicenter study included 98 HCV-negative HD patients (negative for both anti-HCV antibody and HCV-RNA), 43 anti-HCV-positive HD patients, and 10 volunteer people matched for age and sex as a healthy control group. Serology test for anti-HCV antibody, reverse-transcription PCR for HCV-RNA (both serum and peripheral mononuclear cell (PMNC)), complete blood count (CBC), liver transaminases, serum iron, serum ferritin, and high-sensitivity C-reactive protein (hsCRP) were done. The average erythropoiesis-stimulating agent (ESA) doses were calculated over 6 months, and ESA resistance index was calculated. The frequency of packed red blood corpuscle (RBC) transfusion for each patient was recorded. Results Our HD patients had significant higher levels of serum ferritin (P=0.011), higher serum alanine aminotransferase and aspartate aminotransferase (P=0.002 and 0.006, respectively), higher hsCRP (P<0.0001), and significant lower level of hemoglobin (P<0.0001) compared with the healthy control group. The prevalence of OCI was 8.16% (8 of 98 patients). OCI patients had significant longer dialysis duration, higher transaminases, higher hsCRP, higher serum ferritin, and higher frequency of packed RBCs transfusion (P<0.0001), whereas mean hemoglobin levels and ESA resistance index showed insignificant differences compared with HCV-negative HD patients. Using logistic regression analysis, frequency of packed RBC transfusion and aspartate aminotransferase were the only independent predictors for OCI (P=0.012 and 0.049, respectively), and by multivariate analysis, no significant predictors were found to be associated with anemia in patients with OCI. Conclusion The prevalence of OCI in our study was 8.16%. OCI had no effect on anemia managements.
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Tuan, Dang Anh, Ngo Vo Thien Nhan, Pham Vu Nhat Uyen, Bui Thi Hong Loan, Jan Masak, and Tran Ngoc Dang. "Inhibitory effects of trans-cinnamaldehyde on candida spp. Biofilm and planktonic form compared to nystatin: A comparative analysis." Tạp chí Nghiên cứu Y học 173, no. 12E13 (December 31, 2023): 167–75. http://dx.doi.org/10.52852/tcncyh.v173i12e13.2178.
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Trans-Cinnamaldehyde, an α, β-unsaturated aromatic aldehyde, was a derivative of Cinnamonnum obtusifolium - Lauraceae; its bioavailability allows it to be used in the treatment of fungal infections as Candida species causing opportunistic fungal infections are common today. Antibiotic resistance in fungi is often due to their ability to form biofilm. Therefore, new substances with antibiofilm were being investigated as alternative treatment. Representatives of Candida spp. were used to determine the MIC, MBIC50, MBIC80, MBIC100, and MFC of trans-Cinnamaldehyde compared to Nystatin which is used for treatment of Candida infections in Vietnam. The most important antibiofilm effect of trans-Cinnamaldehyde was demonstrated by the CLSI M27-A2 method. Trans-Cinnamaldehyde was given MBIC100 higher than PMIC from 10 to 20 times, while Nystatin was given MBIC100 higher than PMIC from 5 to 20 times. In addition, PMFC of trans-Cinnamaldehyde was equivalent (Candida albicans and Candida tropicalis) or only twice (Candida glabrata) PMIC. The jump in Candida biofilm inhibitory activity was short, from MBIC50 to MBIC100 (no intermediate value, MBIC80). Trans-Cinnamaldehyde extract, compared to Nystatin, had a generally similar effect in preventing the growth and loss of Candida spp. both in biofilm and planktonic form and was somewhat more effective against Candida spp. in biofilm form.
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Korbling, M., YO Huh, A. Durett, N. Mirza, P. Miller, H. Engel, P. Anderlini, K. van Besien, M. Andreeff, and D. Przepiorka. "Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy- 1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease." Blood 86, no. 7 (October 1, 1995): 2842–48. http://dx.doi.org/10.1182/blood.v86.7.2842.2842.
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Abstract Apheresis-derived hematopoietic progenitor cells have recently been used for allogeneic transplantation. Forty-one normal donors were studied to assess the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (12 micrograms/kg/d) on the peripheralization of hematopoietic progenitor cells and lymphoid subsets. The white blood cell, polymorphonuclear cell (PMNC), and lymphocyte concentrations at the peak of rhG-CSF effect in the donor's peripheral blood (PB) exceeded baseline by 6.4-, 8.0-, and 2.2-fold, respectively. Corresponding concentrations of PB CD34+ cells and primitive subsets such as CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells increased by 16.3-fold, 24.2-fold, and 23.2-fold, respectively in eight normal donors. The percentage of CD34+ Thy-1dim and CD34+ Thy- 1dim CD38- cells among CD34+ cells increased as well, suggesting an additional peripheralization effect of rhG-CSF on primitive CD34+ subsets. The preapheresis PB CD34+ and CD34+ Thy-1dim cell concentrations were predictive of their corresponding apheresis yield per liter of donor blood processed PB lymphoid subsets were not significantly affected by rhG-CSF treatment. The mean apheresis-derived yield of CD34+, CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells per kilogram of recipient body weight and per liter of donor blood processed was 48.9 x 10(4) (n = 41), 27.2 x 10(4) (n = 10), and 1.9 x 10(4) (n = 10), respectively. As compared with 43 single bone marrow (BM) harvest, the CD34+ cell yield of peripheral blood progenitor cell allografts of 41 normal donors exceeded that of BM allografts by 3.7- fold and that of lymphoid subsets by 16.1-fold (CD3+), 13.3-fold (CD4+), 27.4-fold (CD8+), 11.0-fold (CD19+), and 19.4-fold (CD56+CD3-). All PBPC allografts were cryopreserved before transplantation. The mean recovery of CD34+ cells after freezing, thawing, and washing out dimethylsulfoxide was 86.6% (n = 31) and the recovery of lymphoid subsets was 115.5% (CD3+), 121.4% (CD4+), 105.6% (CD8+), 118.1% (CD19+), and 102.4% (CD56+CD3-). All donors were related to patients: 39 sibling-to-sibling, 1 parent-to-child, and 1 child-to-parent transplant. Thirty-eight transplants were HLA fully identical, two transplants differed in one and two antigens. Engraftment occurred in 38 recipients; two patients died too early to be evaluated, and one patient did not engraft. The lowest CD34+ cell dose transplanted and resulting in complete and sustained engraftment was 2.5 x 10(6)/kg of recipient body weight.(ABSTRACT TRUNCATED AT 400 WORDS)
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Korbling, M., YO Huh, A. Durett, N. Mirza, P. Miller, H. Engel, P. Anderlini, K. van Besien, M. Andreeff, and D. Przepiorka. "Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy- 1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease." Blood 86, no. 7 (October 1, 1995): 2842–48. http://dx.doi.org/10.1182/blood.v86.7.2842.bloodjournal8672842.
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Apheresis-derived hematopoietic progenitor cells have recently been used for allogeneic transplantation. Forty-one normal donors were studied to assess the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (12 micrograms/kg/d) on the peripheralization of hematopoietic progenitor cells and lymphoid subsets. The white blood cell, polymorphonuclear cell (PMNC), and lymphocyte concentrations at the peak of rhG-CSF effect in the donor's peripheral blood (PB) exceeded baseline by 6.4-, 8.0-, and 2.2-fold, respectively. Corresponding concentrations of PB CD34+ cells and primitive subsets such as CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells increased by 16.3-fold, 24.2-fold, and 23.2-fold, respectively in eight normal donors. The percentage of CD34+ Thy-1dim and CD34+ Thy- 1dim CD38- cells among CD34+ cells increased as well, suggesting an additional peripheralization effect of rhG-CSF on primitive CD34+ subsets. The preapheresis PB CD34+ and CD34+ Thy-1dim cell concentrations were predictive of their corresponding apheresis yield per liter of donor blood processed PB lymphoid subsets were not significantly affected by rhG-CSF treatment. The mean apheresis-derived yield of CD34+, CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells per kilogram of recipient body weight and per liter of donor blood processed was 48.9 x 10(4) (n = 41), 27.2 x 10(4) (n = 10), and 1.9 x 10(4) (n = 10), respectively. As compared with 43 single bone marrow (BM) harvest, the CD34+ cell yield of peripheral blood progenitor cell allografts of 41 normal donors exceeded that of BM allografts by 3.7- fold and that of lymphoid subsets by 16.1-fold (CD3+), 13.3-fold (CD4+), 27.4-fold (CD8+), 11.0-fold (CD19+), and 19.4-fold (CD56+CD3-). All PBPC allografts were cryopreserved before transplantation. The mean recovery of CD34+ cells after freezing, thawing, and washing out dimethylsulfoxide was 86.6% (n = 31) and the recovery of lymphoid subsets was 115.5% (CD3+), 121.4% (CD4+), 105.6% (CD8+), 118.1% (CD19+), and 102.4% (CD56+CD3-). All donors were related to patients: 39 sibling-to-sibling, 1 parent-to-child, and 1 child-to-parent transplant. Thirty-eight transplants were HLA fully identical, two transplants differed in one and two antigens. Engraftment occurred in 38 recipients; two patients died too early to be evaluated, and one patient did not engraft. The lowest CD34+ cell dose transplanted and resulting in complete and sustained engraftment was 2.5 x 10(6)/kg of recipient body weight.(ABSTRACT TRUNCATED AT 400 WORDS)
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Slavutskaya, M., I. Lebedeva, M. Omelchenko, E. Abdullina, and S. Karelin. "EEG correlates of impaired anticipation processes in the early stages of schizophrenia." European Psychiatry 65, S1 (June 2022): S315—S316. http://dx.doi.org/10.1192/j.eurpsy.2022.804.
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Introduction An impairment of anticipation processes is considered as a common deficiency in schizophrenia (Kveraga et al., 2007), however its neural mechanisms remain poorly understood. Objectives The aim of the study was to analyze CNV-like slow negative waves during the pre-target stimuli waiting period in patients with the first episode of the disease. Methods 32-channels EEGs during “Go / No go delay” saccadic paradigm have been recorded in 16 young male patients with illness duration less than 2 years and 18 age and sex matched healthy subjects. The delay period between fixation and target (“Go” or “No go”) visual stimulus was 2800-3000 ms. The early and late components of CNV - like slow negative waves (PMN1 and 2) have been studied in 1 sec pre-stimulus interval of delay period. Results As compared to norm, the patients showed significantly increased latencies of saccades to correctly discriminated stimuli and higher percent of “errors saccades”. The amplitudes of No go-PMN1 and Go-PMN2 waves were also increased in patients. The amplitude foci of these waves were diffusely distributed in patients and mostly localized in frontal leads in norm. Conclusions The findings assume some violation of anticipation for action (motor or inhibitory response) processes as well as an increase of presumably cortical activation during stimulus anticipation in the “Go/No go delay” saccadic paradigm in the early stage of schizophrenia. Disclosure No significant relationships.
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S. Kashan, Jenan,, and Saad M. Ali. "3D Model of Bone Scaffolds Based on the Mechanical Behaviour for a Hybrid Nano Bio-composites." journal of Mechanical Engineering 17, no. 2 (July 15, 2020): 45–67. http://dx.doi.org/10.24191/jmeche.v17i2.15300.
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Ceramic/polymer Nano composites in the view of possessing design uniqueness and property combinations have gained a great attention and reported to be the materials of the 21st century that are not found in conventional composites. In the present work, an attempt has been made to study, develop and improve the bio-mechanic for a designed and fabricated Ceramic/polymer bio-composite for a human natural bone repair and replacement in the case of complex fracture and bone diseases by adding the Nano fillers ceramic particles to the Polymer Matrix Nano composites (PMNC) for fabricated a hybrid Titanium dioxide and yttria stabilized zirconia reinforced high density polyethylene (HDPE) matrix bio-composites properties. These bioactive composites have been investigated by using hot pressing technique at different compression pressures of (30, 60, and 90 MPa) at a compounding temperature of (180, 190, and 200 °C). The SOLIDWORKS 17.0 and the finite element ANSYS 15.7 software programs were used to the simulation, modelling and analysing of femur bone biomechanics that can withstand the highest stresses and strains. The response surface methodology (RSM) technique was used to improve and verify the results. For all the fabricated Nano bio-composites systems, the results showed that the obtained output parameters values were increased with increasing the process input parameters, also the vice versa for the strain energy and equivalent elastic strain values, also the Nano ceramic compositions represented the main factor influenced the results. The main investigates results of the current research deduced that for the increase of the Nano ceramic powder (TiO2) contain from 1% to 10%, the compression fracture strength and the micro-Vickers hardness values increased by 50% and by 8.45%, respectively, and when adding 2% of zirconia (ZrO2), an additional increase in the compression fracture strength and micro hardness by 28.21% and 40.19% achieved, respectively. When using 10% TiO2 + 2% ZrO2/HDPE bio-composite at highest compact temperature of 200 °C and compounding pressure of 90 MPa, the strain energy and the equivalent elastic strain reduced by 82.69% and 14.53% when compared with using of 1% TiO2 content. While when increasing the nano ceramic content from 1% to 10% without adding the ZrO2 nano filler, they reduced by 142.25% and 67.81%, respectively. The maximum equivalent von Misses stress obtained is equal to 39.957MPa and when increasing the nano ceramic content from 1% to 10%, the stress safety factors and fatigue live values increased by 58.38% and by 46.28%, respectively and when adding 2% of zirconia (ZrO2), the stress safety factor reached its maximum values, with an additional increase in its values by 21.42% and 69.40%, respectively. These results give great choices to use successful in vivo tests and for a better life performance with any age, patient status and degree of injury.
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Lipton, Brian P., Abraham P. Bautista, Joseph B. Delcarpio, and Kathleen H. McDonough. "Effects of endotoxin on neutrophil-mediated I/R injury in isolated perfused rat hearts." American Journal of Physiology-Heart and Circulatory Physiology 280, no. 2 (February 1, 2001): H802—H811. http://dx.doi.org/10.1152/ajpheart.2001.280.2.h802.
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With the use of a syngeneic model, we demonstrate that rat polymorphonuclear neutrophils (PMNs) exacerbate ischemia-reperfusion injury in the isolated rat heart. However, PMNs (19 × 106cells) from lipopolysaccharide (LPS)-treated rats (LPS-PMNs; 100 mg/kg administered 7 h before exsanguination) induce less reperfusion injury in the isolated heart. Average recovery of left ventricular developed pressure after 20 min of ischemia and 60 min of reperfusion was 51 ± 4% in hearts receiving PMNs from saline-treated control rats (saline-PMNs) versus 78 ± 2% in hearts receiving LPS-PMNs. Ischemic hearts reperfused with LPS-PMNs recovered to the same extent as did hearts reperfused with Krebs buffer only. LPS-PMNs and saline-PMNs showed no difference in basal or phorbol ester-induced superoxide production. Whereas twice the number of LPS-PMNs was positive for nitroblue tetrazolium, the percent positive for L-selectin, a receptor integral in PMN-adhesion to endothelium, was 50% less in LPS-PMNs than in controls. After reperfusion, three-fourths of the saline-PMNs remained within the hearts, whereas only one-fourth of LPS-PMNs were trapped. These data suggest that PMNs from LPS-treated rats do not exacerbate ischemia-reperfusion injury as do control PMNs, possibly, due to impaired PMN adhesion to endothelium as a result of decreased L-selectin receptors.
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Hannon, Connor, Patrick L. Quinn, Stephanie Iacono, Rachel Konik, Angela Sarna, Gennaro Di Tosto, Krista Maxey-Kohn, et al. "The impact of a pancreatic cancer multi-disciplinary clinic on patient-centric outcomes." Journal of Clinical Oncology 42, no. 3_suppl (January 20, 2024): 641. http://dx.doi.org/10.1200/jco.2024.42.3_suppl.641.
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641 Background: A one-day multi-disciplinary clinic allows for a comprehensive evaluation of patients in a single-visit format. This study aims to evaluate the impact of a one-day pancreatic cancer multi-disciplinary clinic (PMDC) on patient-centric outcomes. Methods: Patients with pancreatic cancer who were seen at The Ohio State University PMDC from January 2021 to March 2023 were identified. Patient-centric outcomes were evaluated including time from diagnosis to first evaluation and treatment, number of supportive care referrals completed, and number of physical trips to the medical center leading up to the first treatment. Outcomes were compared to pancreatic cancer patients seen in the year prior to the opening of the PMDC (non-PMDC). Results: Among the 139 PMDC and 141 non-PMDC patients, the median number of days between referral and treatment initiation was similar (PMDC: 33 days (IQR: 22, 44) vs. non-PMDC: 32 days (IQR: 23, 42); p >0.9). The median time between diagnosis and treatment initiation was also similar (PMDC: 28 days (IQR: 19, 37) vs. non-PMDC: 30 days (IQR: 21, 37); p=0.4). Of note, PMDC patients received more supportive care visits within 30 days of diagnosis (PMDC: 2 (IQR: 1, 2) vs. non-PMDC: 0 (IQR: 0, 1) ; p <0.001) and completed more visits with cancer providers (PMDC: 7 (IQR: 6, 8) vs. non-PMDC: 5 (IQR: 4, 7); p <0.001) compared with non-PMDC patients. In addition, PMDC patients also required fewer physical trips to the medical center (PMDC: 4 (IQR: 3, 5) vs. non-PMDC: 4 (IQR: 3, 6); p <0.001). Conclusions: Pancreatic cancer patients seen in a one-day multi-disciplinary clinic attend a greater number of coordinated appointments and receive more supportive care services with fewer physical trips to the medical center compared with patients not seen in a PMDC clinic. Future studies should focus on the long-term patient-centric benefits of a multi-disciplinary approach for cancer patients.
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Lawrence, MB, LV McIntire, and SG Eskin. "Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion." Blood 70, no. 5 (November 1, 1987): 1284–90. http://dx.doi.org/10.1182/blood.v70.5.1284.1284.
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Abstract The effect of flow on the adhesion of polymorphonuclear leukocytes (PMNL) to vascular endothelium was investigated using a parallel plate chamber with a well-defined flow field. Washed PMNL were perfused over a monolayer of primary human umbilical vein endothelial cells (HUVEC) pretreated with formyl-methionyl-leucyl-phenylalanine (FMLP, 1 X 10(-7) mol/L) for five minutes. In other experiments HUVEC were pretreated with interleukin 1 (IL1,2 U/mL) for four hours. PMNL adhesion to stimulated and control HUVEC was measured over a physiologic range of wall shear stresses. PMNL adhesion to nylon-coated surface was also studied. At a wall shear stress of 0.98 dynes/cm2,283 +/- 37.3 PMNL/mm2 (mean +/- SEM) adhered to FMLP-treated HUVEC while 195 +/- 20.3 PMNL/mm2 adhered to control HUVEC. At 1.96 dynes/cm2, 68 +/- 14.1 PMNL/mm2 adhered to FMLP-treated HUVEC and 42 +/- 6.0 PMNL/mm2 adhered to control HUVEC. At 3.92 dynes/cm2, virtually no PMNL adherence was noted on either control or FMLP-treated HUVEC. On IL 1-treated HUVEC at 1.96 dynes/cm2, 371 +/- 25.8 PMNL/mm2 adhered while 28 +/- 2.9 PMNL/mm2 adhered to control HUVEC. PMNL adhesion to IL 1-treated and control HUVEC dropped to 10.2 +/- 3.8 and 6.8 +/- 3.5 PMNL/mm2, respectively, at 3.01 dynes/cm2. The effect of flow on PMNL adhesion appears to be an important factor in determining the outcome of the PMNL/HUVEC adhesive interaction under these experimental conditions.
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Lawrence, MB, LV McIntire, and SG Eskin. "Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion." Blood 70, no. 5 (November 1, 1987): 1284–90. http://dx.doi.org/10.1182/blood.v70.5.1284.bloodjournal7051284.
Full textAbstract:
The effect of flow on the adhesion of polymorphonuclear leukocytes (PMNL) to vascular endothelium was investigated using a parallel plate chamber with a well-defined flow field. Washed PMNL were perfused over a monolayer of primary human umbilical vein endothelial cells (HUVEC) pretreated with formyl-methionyl-leucyl-phenylalanine (FMLP, 1 X 10(-7) mol/L) for five minutes. In other experiments HUVEC were pretreated with interleukin 1 (IL1,2 U/mL) for four hours. PMNL adhesion to stimulated and control HUVEC was measured over a physiologic range of wall shear stresses. PMNL adhesion to nylon-coated surface was also studied. At a wall shear stress of 0.98 dynes/cm2,283 +/- 37.3 PMNL/mm2 (mean +/- SEM) adhered to FMLP-treated HUVEC while 195 +/- 20.3 PMNL/mm2 adhered to control HUVEC. At 1.96 dynes/cm2, 68 +/- 14.1 PMNL/mm2 adhered to FMLP-treated HUVEC and 42 +/- 6.0 PMNL/mm2 adhered to control HUVEC. At 3.92 dynes/cm2, virtually no PMNL adherence was noted on either control or FMLP-treated HUVEC. On IL 1-treated HUVEC at 1.96 dynes/cm2, 371 +/- 25.8 PMNL/mm2 adhered while 28 +/- 2.9 PMNL/mm2 adhered to control HUVEC. PMNL adhesion to IL 1-treated and control HUVEC dropped to 10.2 +/- 3.8 and 6.8 +/- 3.5 PMNL/mm2, respectively, at 3.01 dynes/cm2. The effect of flow on PMNL adhesion appears to be an important factor in determining the outcome of the PMNL/HUVEC adhesive interaction under these experimental conditions.
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Minamino, T., M. Kitakaze, K. Node, H. Funaya, M. Inoue, M. Hori, and T. Kamada. "Adenosine inhibits leukocyte-induced vasoconstriction." American Journal of Physiology-Heart and Circulatory Physiology 271, no. 6 (December 1, 1996): H2622—H2628. http://dx.doi.org/10.1152/ajpheart.1996.271.6.h2622.
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Polymorphonuclear leukocytes (PMNs) can induce endothelium-dependent constriction of vascular rings. Because adenosine inhibits the function of PMNs, we examined the effects of adenosine on the PMN-induced coronary vasoconstriction. We measured changes in the isometric tension of isolated rings of canine coronary arteries suspended in an organ chamber filled with Krebs-Henseleit solution after the addition of autologous PMNs. N-formyl-L-methionyl-leucyl-phenylalanine (FMLP)-stimulated PMNs increased the tension of the coronary artery with the endothelium in a concentration-dependent manner. Treatment of FMLP-stimulated PMNs with adenosine inhibited both the adhesion of PMNs to the endothelium and the PMN-induced vasoconstriction. Stimulation of PMNs with CGS-21680C, but not with cyclohexyladenosine, inhibited both the adhesion of PMNs to the endothelium and the PMN-induced vasoconstriction. However, treatment of coronary arteries with adenosine had no effect on the adherence of PMNs to the endothelium and the PMN-induced constriction. These results suggest that stimulation of adenosine A2a receptors on PMNs may inhibit the PMN-induced vasoconstriction by inhibiting the adhesion of PMNs to the endothelium.
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Bass, D. A., P. Olbrantz, P. Szejda, M. C. Seeds, and C. E. McCall. "Subpopulations of neutrophils with increased oxidative product formation in blood of patients with infection." Journal of Immunology 136, no. 3 (February 1, 1986): 860–66. http://dx.doi.org/10.4049/jimmunol.136.3.860.
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Abstract Stimulated human polymorphonuclear leukocytes (PMNL) have a marked increase in oxidative metabolism, producing reduced oxygen species (e.g., H2O2) that mediate bacterial killing. Previously, quantitation of metabolic responses of PMNL from patients with acute infections employed assays that measure mean activity of the entire PMNL population; such studies reported a modest and highly variable increase in oxidative metabolic responses of such "toxic" PMNL compared with normal cells. To assess metabolic capability of PMNL from 51 patients with acute bacterial infection, we employed a quantitative flow cytometric assay of H2O2-dependent oxidative product formation, the intracellular oxidation of 2',7'-dichlorofluorescin (DCFH). After stimulation by phorbol myristate acetate, the PMNL of patients demonstrated an increase in mean DCFH oxidation (315 +/- 14 and 180 +/- 4.5 amol/cell, patients and controls). Hexose monophosphate shunt activation was similarly increased in stimulated PMNL from bacteremic patients. These data are comparable with previous studies of mean metabolic activities of toxic PMNL. However, these mean values underestimate the quantitative responses of the hyperresponsive ("primed") PMNL within a mixture of normal and primed PMNL in the patients' blood. The flow cytometric assay demonstrated that the PMNL of the patients were composed of two populations. One population of PMNL had normal oxidative responses; the other "primed" population had up to 4.6 times the oxidative product formation of normal cells. Similar priming of circulating PMNL was caused by infection with gram-positive or gram-negative staining bacteria or by Candida species. The proportion and oxidative ability of the primed PMNL occurred independently of the number of juvenile neutrophil forms and independently of "toxic" morphologic changes of Wright's-stained PMNL. On the average, 40% of the PMNL of patients were primed, but the size of the primed PMNL population varied widely between patients (range 0 to 80%). This variable subpopulation may explain the variability of mean responsiveness of the PMNL of patients reported previously. Moreover, the marked increase in oxidative metabolic capability of the primed PMNL may be a significant component of the host response to acute infection. It could also contribute to the damage to host tissues such as pulmonary vascular endothelium during bacteremia.
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Patel, Roshal R., Rose Parisi, Vivek Verma, Ramez Kouzy, Joseph Abi Jaoude, Timothy A. Lin, Clifton David Fuller, et al. "Association between Prior Malignancy Exclusion Criteria and Age Disparities in Cancer Clinical Trials." Cancers 14, no. 4 (February 18, 2022): 1048. http://dx.doi.org/10.3390/cancers14041048.
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Prior malignancy exclusion criteria (PMEC) are often utilized in cancer clinical trials; however, the incidence of PMEC and the association of PMEC with trial participant age disparities remain poorly understood. This study aimed to identify age disparities in oncologic randomized clinical trials as a result of PMEC. Using a comprehensive collection of modern phase III cancer clinical trials obtained via ClinicalTrials.gov, we assessed the incidence and covariates associated with trials excluding patients with prior cancers within 5+ years from registration (PMEC-5). Using the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, we further sought to determine the correlation between PMEC-5 and age disparities. PMEC-5 were used in 41% of all trials, with higher PMEC-5 utilization among industry-supported trials as well as trials evaluating a targeted therapy. Comparing trial patient median ages with population-matched median ages by disease site and time-period, we assessed the association between PMEC-5 and age disparities among trial participants. PMEC-5 were independently associated with heightened age disparities, which further worsened with longer exclusionary timeframes. Together, PMEC likely contribute to age disparities, suggesting that eligibility criteria modernization through narrower PMEC timeframes may work toward reducing such disparities in cancer clinical trial enrollment.
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Ren, Yunjia, Li Hua, Xiuping Meng, Yue Xiao, Xu Hao, Sheng Guo, Peiyan Zhao, et al. "Correlation of Surface Toll-Like Receptor 9 Expression with IL-17 Production in Neutrophils during Septic Peritonitis in Mice Induced byE. coli." Mediators of Inflammation 2016 (2016): 1–17. http://dx.doi.org/10.1155/2016/3296307.
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IL-17 is a proinflammatory cytokine produced by various immune cells. Polymorphonuclear neutrophils (PMNs) are the first line of defense in bacterial infection and express surface Toll-like receptor 9 (sTLR9). To study the relationship of sTLR9 and IL-17 in PMNs during bacterial infection, we infected mice withE. coliintraperitoneally to establish a septic peritonitis model for studying the PMNs response in peritoneal cavity. We found that PMNs and some of “giant cells” were massively accumulated in the peritoneal cavity of mice with fatal septic peritonitis induced byE. coli. Kinetically, the CD11b+PMNs were increased from 20–40% at 18 hours to >80% at 72 hours after infection. AfterE. coliinfection, sTLR9 expression on CD11b+and CD11b−PMNs and macrophages in the PLCs were increased at early stage and deceased at late stage; IL-17 expression was also increased in CD11b+PMNs, CD11b−PMNs, macrophages, and CD3+T cells. Using experiments ofin vitroblockage, qRT-PCR and cell sorting, we confirmed that PMNs in the PLCs did increase their IL-17 expression duringE. coliinfection. Interestingly, sTLR9−CD11b+Ly6G+PMNs, not sTLR9+CD11b+Ly6G+PMNs, were found to be able to increase their IL-17 expression. Together, the data may help understand novel roles of PMNs in septic peritonitis.
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van Spriel, Annemiek B., Jeanette H. W. Leusen, Marjolein van Egmond, Henry B. P. M. Dijkman, Karel J. M. Assmann, Tanya N. Mayadas, and Jan G. J. van de Winkel. "Mac-1 (CD11b/CD18) is essential for Fc receptor–mediated neutrophil cytotoxicity and immunologic synapse formation." Blood 97, no. 8 (April 15, 2001): 2478–86. http://dx.doi.org/10.1182/blood.v97.8.2478.
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Abstract Receptors for human immunoglobulin (Ig)G and IgA initiate potent cytolysis of antibody (Ab)-coated targets by polymorphonuclear leukocytes (PMNs). Mac-1 (complement receptor type 3, CD11b/CD18) has previously been implicated in receptor cooperation with Fc receptors (FcRs). The role of Mac-1 in FcR-mediated lysis of tumor cells was characterized by studying normal human PMNs, Mac-1–deficient mouse PMNs, and mouse PMNs transgenic for human FcR. All PMNs efficiently phagocytosed Ab-coated particles. However, antibody-dependent cellular cytotoxicity (ADCC) was abrogated in Mac-1−/− PMNs and in human PMNs blocked with anti–Mac-1 monoclonal Ab (mAb). Mac-1−/− PMNs were unable to spread on Ab-opsonized target cells and other Ab-coated surfaces. Confocal laser scanning and electron microscopy revealed a striking difference in immunologic synapse formation between Mac-1−/− and wild-type PMNs. Also, respiratory burst activity could be measured outside membrane-enclosed compartments by using Mac-1−/− PMNs bound to Ab-coated tumor cells, in contrast to wild-type PMNs. In summary, these data document an absolute requirement of Mac-1 for FcR-mediated PMN cytotoxicity toward tumor targets. Mac-1−/− PMNs exhibit defective spreading on Ab-coated targets, impaired formation of immunologic synapses, and absent tumor cytolysis.
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Lawrence, MB, CW Smith, SG Eskin, and LV McIntire. "Effect of venous shear stress on CD18-mediated neutrophil adhesion to cultured endothelium." Blood 75, no. 1 (January 1, 1990): 227–37. http://dx.doi.org/10.1182/blood.v75.1.227.227.
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Abstract The CD11/CD18 family of glycoproteins has been identified as a mediator of a number of adhesive interactions crucial to inflammatory responses. Using a monoclonal antibody (MoAb) against CD18 (TS1/18), the role of these molecules in polymorphonuclear neutrophil (PMNL) adhesion to cultured primary human umbilical vein endothelial cells (HUVEC) was examined under venous flow conditions. Incubation of PMNL with TS1/18 (anti-CD18) did not inhibit PMNL adhesion to interleukin-1 (IL-1)- treated HUVEC at 2.0 dynes/cm2 (TS1/18-treated 305 +/- 58 PMNL/mm2 v 334 +/- 63 PMNL/mm2 on control). Furthermore, incubation of HUVEC with R6.5.D6, an MoAb against intercellular adhesion molecule-1 (ICAM-1) did not significantly inhibit PMNL adhesion to IL-1-treated HUVEC at 2.0 dynes/cm2 (P greater than .3). In contrast to the lack of inhibition of adhesion under conditions of flow, incubation of PMNL with TS1/18 reduced PMNL adherence in static adhesion assays. PMNL migration beneath HUVEC monolayers has been shown to be stimulated by 4-hour IL-1 treatment. TS1/18 and R6.5.D6 significantly inhibited migration of PMNL beneath IL-1-treated HUVEC monolayers under flow conditions by slightly more than 80% (P less than .005). In flow experiments with CD18- deficient PMNL, virtually no transendothelial migration was observed. The effect of FMLP (10(-8) mol/L) on PMNL adhesion to untreated HUVEC at wall shear stresses ranging from 0.25 to 2.0 dynes/cm2 was also investigated. FMLP had little effect on PMNL adherence at shear stresses above 0.5 dynes/cm2 (P greater than .45). In response to FMLP exposure at lower wall shear stresses, PMNL adherence to untreated HUVEC increased 6.9-fold at 0.5 dynes/cm2 (P less than .001). At 0.25 dynes/cm2, FMLP stimulation increased PMNL adherence to untreated HUVEC 6.5-fold compared with controls (P less than .005), and FMLP failed to make CD18-deficient PMNL more adherent. In experiments with PMNL pretreated with TS1/18 (anti-CD18), there was a 67% inhibition of FMLP- stimulated adhesion at 0.5 dynes/cm2 (P less than .025). The upper threshold of CD18-mediated PMNL adhesion appears to be between 0.5 and 1.0 dyne/cm2. Above these wall shear stresses, the initial attachment of PMNL to cultured endothelium was mediated almost exclusively by CD18- independent mechanisms. By simulating some of the flow parameters in the microcirculation with well-characterized shear forces, PMNL adhesion by CD18-independent and dependent mechanisms can be differentiated. These data also indicate that CD18 is an important mediator of transendothelial migration by PMNL, which have attached to the endothelium by a CD18-independent mechanism.
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Lawrence, MB, CW Smith, SG Eskin, and LV McIntire. "Effect of venous shear stress on CD18-mediated neutrophil adhesion to cultured endothelium." Blood 75, no. 1 (January 1, 1990): 227–37. http://dx.doi.org/10.1182/blood.v75.1.227.bloodjournal751227.
Full textAbstract:
The CD11/CD18 family of glycoproteins has been identified as a mediator of a number of adhesive interactions crucial to inflammatory responses. Using a monoclonal antibody (MoAb) against CD18 (TS1/18), the role of these molecules in polymorphonuclear neutrophil (PMNL) adhesion to cultured primary human umbilical vein endothelial cells (HUVEC) was examined under venous flow conditions. Incubation of PMNL with TS1/18 (anti-CD18) did not inhibit PMNL adhesion to interleukin-1 (IL-1)- treated HUVEC at 2.0 dynes/cm2 (TS1/18-treated 305 +/- 58 PMNL/mm2 v 334 +/- 63 PMNL/mm2 on control). Furthermore, incubation of HUVEC with R6.5.D6, an MoAb against intercellular adhesion molecule-1 (ICAM-1) did not significantly inhibit PMNL adhesion to IL-1-treated HUVEC at 2.0 dynes/cm2 (P greater than .3). In contrast to the lack of inhibition of adhesion under conditions of flow, incubation of PMNL with TS1/18 reduced PMNL adherence in static adhesion assays. PMNL migration beneath HUVEC monolayers has been shown to be stimulated by 4-hour IL-1 treatment. TS1/18 and R6.5.D6 significantly inhibited migration of PMNL beneath IL-1-treated HUVEC monolayers under flow conditions by slightly more than 80% (P less than .005). In flow experiments with CD18- deficient PMNL, virtually no transendothelial migration was observed. The effect of FMLP (10(-8) mol/L) on PMNL adhesion to untreated HUVEC at wall shear stresses ranging from 0.25 to 2.0 dynes/cm2 was also investigated. FMLP had little effect on PMNL adherence at shear stresses above 0.5 dynes/cm2 (P greater than .45). In response to FMLP exposure at lower wall shear stresses, PMNL adherence to untreated HUVEC increased 6.9-fold at 0.5 dynes/cm2 (P less than .001). At 0.25 dynes/cm2, FMLP stimulation increased PMNL adherence to untreated HUVEC 6.5-fold compared with controls (P less than .005), and FMLP failed to make CD18-deficient PMNL more adherent. In experiments with PMNL pretreated with TS1/18 (anti-CD18), there was a 67% inhibition of FMLP- stimulated adhesion at 0.5 dynes/cm2 (P less than .025). The upper threshold of CD18-mediated PMNL adhesion appears to be between 0.5 and 1.0 dyne/cm2. Above these wall shear stresses, the initial attachment of PMNL to cultured endothelium was mediated almost exclusively by CD18- independent mechanisms. By simulating some of the flow parameters in the microcirculation with well-characterized shear forces, PMNL adhesion by CD18-independent and dependent mechanisms can be differentiated. These data also indicate that CD18 is an important mediator of transendothelial migration by PMNL, which have attached to the endothelium by a CD18-independent mechanism.
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Sykulev, Yuri, Nadia Anikeeva, and Dimitry Gakamsky. "The role of peptide-MHC ligand density in stimulating T-cell receptor signaling (58.21)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 58.21. http://dx.doi.org/10.4049/jimmunol.188.supp.58.21.
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Abstract Cell surface MHC proteins form clusters on the cell membrane. The MHC density within clusters could affect recognition of noncognate (self) and cognate peptide-MHC (pMHC) ligands and influence the kinetics of TCR-mediate signaling and quality of T cell responses. To evaluate the role of density, orientation and valency of pMHC ligands we utilized different scaffolds to assemble pMHC oligomers modeling MHC clusters. We systematically investigated how these parameters influence the binding of the pMHC oligomers to live CD8+ cytotoxic T lymphocytes (CTL) and the kinetics of TCR-mediated signaling. We have found that the recognition of noncognate or self pMHC strongly depends on the pMHC density and architecture and size of the scaffolds. In contrast, the valency but not the pMHC density mostly determined the recognition of strong agonist pMHC ligands. In addition, the pMHC density significantly influences the ability of cognate and noncognate pMHC to cooperate and to induce robust and rapid TCR signaling. The latter regulates the kinetics of target cell destruction by CTL that is essential for successful anti-virus immunity.
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Cho, Kyung-Jin, Even Walseng, Satoshi Ishido, and Paul A. Roche. "Ubiquitination by March-I prevents MHC class II recycling and promotes MHC class II turnover in antigen-presenting cells." Proceedings of the National Academy of Sciences 112, no. 33 (August 3, 2015): 10449–54. http://dx.doi.org/10.1073/pnas.1507981112.
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MHC class II (MHC-II)-dependent antigen presentation by antigen-presenting cells (APCs) is carefully controlled to achieve specificity of immune responses; the regulated assembly and degradation of antigenic peptide–MHC-II complexes (pMHC-II) is one aspect of such control. In this study, we have examined the role of ubiquitination in regulating pMHC-II biosynthesis, endocytosis, recycling, and turnover in APCs. By using APCs obtained from MHC-II ubiquitination mutant mice, we find that whereas ubiquitination does not affect pMHC-II formation in dendritic cells (DCs), it does promote the subsequent degradation of newly synthesized pMHC-II. Acute activation of DCs or B cells terminates expression of the MHC-II E3 ubiquitin ligase March-I and prevents pMHC-II ubiquitination. Most importantly, this change results in very efficient pMHC-II recycling from the surface of DCs and B cells, thereby preventing targeting of internalized pMHC-II to lysosomes for degradation. Biochemical and functional assays confirmed that pMHC-II turnover is suppressed in MHC-II ubiquitin mutant DCs or by acute activation of wild-type DCs. These studies demonstrate that acute APC activation blocks the ubiquitin-dependent turnover of pMHC-II by promoting efficient pMHC-II recycling and preventing lysosomal targeting of internalized pMHC-II, thereby enhancing pMHC-II stability for efficient antigen presentation to CD4 T cells.
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Cacchillo, David A., and John D. Walters. "Effect of Ciprofloxacin on Killing of Actinobacillus actinomycetemcomitans by Polymorphonuclear Leukocytes." Antimicrobial Agents and Chemotherapy 46, no. 6 (June 2002): 1980–84. http://dx.doi.org/10.1128/aac.46.6.1980-1984.2002.
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ABSTRACT Actinobacillus actinomycetemcomitans, a pathogen associated with aggressive periodontitis, resists phagocytic killing by polymorphonuclear leukocytes (PMNs). It is susceptible to ciprofloxacin, which PMNs actively accumulate. This study tested the hypothesis that ciprofloxacin-loaded PMNs are more effective at killing A. actinomycetemcomitans than control PMNs. Isolated human PMNs were loaded by brief incubation with 0.5 μg of ciprofloxacin/ml. Opsonized bacteria (ATCC 43718) were incubated at 37°C with control and ciprofloxacin-loaded PMNs and in the presence and absence of 0.5 μg of ciprofloxacin/ml. When assayed at bacteria-to-PMN ratios of 30:1 and 90:1, ciprofloxacin-loaded PMNs killed significantly more bacteria and achieved significantly shorter half times for killing than control PMNs (P < 0.05; Tukey's test). At ratios of 3:1 and 10:1, these differences were not significant.
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Jin, Yutong, Brian Dixon, Lyndon Jones, and Maud Gorbet. "The Differential Reactive Oxygen Species Production of Tear Neutrophils in Response to Various Stimuli In Vitro." International Journal of Molecular Sciences 22, no. 23 (November 29, 2021): 12899. http://dx.doi.org/10.3390/ijms222312899.
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A large number of polymorphonuclear neutrophils (PMNs) invade the ocular surface during prolonged eye closure (sleep); these leukocytes are commonly referred as tear PMNs. PMNs contribute to homeostasis and possess an arsenal of inflammatory mediators to protect against pathogens and foreign materials. This study examined the ability of tear PMNs to generate reactive oxygen species (ROS), an essential killing mechanism for PMNs which can lead to oxidative stress and imbalance. Cells were collected after sleep from healthy participants using a gentle eye wash. ROS production in stimulated (phorbol-12-myristate-13-acetate (PMA), lipopolysaccharides (LPS) or N-Formylmethionyl-leucyl-phenylalanine (fMLP)) and unstimulated tear PMNs was measured using luminol-enhanced chemiluminescence for 60 min. A high level of constitutive/spontaneous ROS production was observed in tear PMNs in the absence of any stimulus. While tear PMNs were able to produce ROS in response to PMA, they failed to appropriately respond to LPS and fMLP, although fMLP-stimulated tear PMNs generated ROS extracellularly in the first three minutes. Higher ROS generation was observed in isolated tear PMNs which may be due to priming from the magnetic bead cell separation system. The differential responses of tear PMNs in ROS generation provide further evidence of their potential inflammatory roles in ocular complications involving oxidative stress.
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Aruna, Adimoolam, Chien-Ju Lin, Ganesan Nagarajan, and Ching-Fong Chang. "Neurohypophysial Hormones Associated with Osmotic Challenges in the Brain and Pituitary of the Euryhaline Black Porgy, Acanthopagrus schlegelii." Cells 10, no. 11 (November 9, 2021): 3086. http://dx.doi.org/10.3390/cells10113086.
Full textAbstract:
Our study showed differential expression of the arginine vasotocin (avt)/isotocin (it) in the brain and pituitary gland of the euryhaline black porgy (Acanthopagrus schlegelii) during osmotic stress. A decrease in serum osmolality and increased cortisol levels were observed after acute transfer from seawater (SW) to freshwater (FW). The increased expressions of avt, avt receptor (avtr: v1a), and isotocin receptor (itr: itr1) transcripts on day 1 and it and itr transcripts on days 7 and 30 were found in the brains and pituitary glands of FW fish. Increased levels of avt mRNA in the diencephalon and avtr mRNA in the pituitary together with serum cortisol on day 1 of FW exposure indicated activation of the hypothalamic–pituitary–interrenal (HPI) axis. The expression levels of avtr and itr after FW transfer were increased in the pituitary on days 7 and 30. Furthermore, in situ hybridization demonstrated spatially differential expression of avt and itr transcripts in nucleus preopticus parvocellularis of pars gigantocellularis (PMgc), magnocellularis (PMmc), and parvocellularis (PMpc) of the preoptic area (POA). Positive signals for avt and it were highly abundant in PMpc after FW exposure. The data suggest involvement of neurohypophysial hormones in the brain (telencephalon and diencephalon) and pituitary for osmotic stress.
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Cassidy, L. F., D. S. Lyles, and J. S. Abramson. "Depression of polymorphonuclear leukocyte functions by purified influenza virus hemagglutinin and sialic acid-binding lectins." Journal of Immunology 142, no. 12 (June 15, 1989): 4401–6. http://dx.doi.org/10.4049/jimmunol.142.12.4401.
Full textAbstract:
Abstract Infection of polymorphonuclear leukocytes (PMNL) with influenza virus causes depression of PMNL metabolic and bactericidal activities. The studies reported here were undertaken to determine whether the hemagglutinin (HA) glycoprotein of influenza virus mediates this depression. PMNL were incubated with purified HA and the oxidative responses to exogenous stimuli were measured. The results indicate that HA, in either liposomes or protein aggregates referred to as rosettes, depressed PMNL oxidative responses. Depression was observed within 2 min of initial interaction of HA with PMNL and lasted more than 2 h. The membrane fusion activity of HA requires proteolytic cleavage of the HA, whereas the receptor binding activity does not. There was no difference in the ability of virions with cleaved or uncleaved HA to depress PMNL responses suggesting that the fusion event is not required for PMNL dysfunction. Inasmuch as the HA glycoprotein binds to sialic acid-containing receptors on the surface of the PMNL, we tested whether other sialic acid-specific binding proteins can mediate the reduction of PMNL responses. Sialic acid-specific lectins from Limulus polyphemus or Limax flavus were incubated with PMNL before measuring their responses to secondary stimulus. Depression was observed upon incubation with the lectins similar to that seen upon incubation with the HA or influenza virus. These results suggest that attachment of influenza virus to sialic acid-containing receptors is responsible at least in part, for suppressing PMNL oxidative responses.