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#33080435   2020/09/30 To Up

The role of Interleukin-4 in COVID-19 associated male infertility - A hypothesis.

COVID-19 is a present-day complex pandemic infection with unpredictable levels of morbidity and mortality in various global populations. COVID-19 is associated with the different comorbidities with its change in biological function such as causing heart dysfunction via deregulating ACE-2 receptor, gastrointestinal risk via causing vomiting, diarrhea, and abdominal pain, chronic kidney disease via proteinuria and hematuria, diabetes mellitus, liver injury via increasing ALT, AST and bilirubin level, lung injury, CNS risk, ocular risk, and cancer risk. In this, we are focused on the COVID-19 connected with male infertility. Some of the studies show that the patients of COVID-19 are associated with impaired spermatogenesis. Impaired spermatogenesis via COVID-19 decreases the level of testosterone by disturbing cytokines such as TNF-α, IL-4, IL-6, and IL-12 and further, attenuates the sperm count. COVID-19 is causing inflammation via TNF-α and interferons. IL-4 plays an eminent role in the activation of the JAK-STAT pathway and leads to the disturbing pro-inflammatory cytokine as well as further cause's male infertility. Th2 activates the IL-4 through IgG and IgE and mediates apoptosis with the triggering of STAT signaling. The activated STAT signaling augments Batf/Irf4, and the Bach2/Batf pathway. On the other hand, SARS-CoV-2 is activating the level of Th2 cells. So, we hypothesized that the augmented Th2 cells would disturb the level of IL-4, JAK-STAT signaling, Batf/Irf4, and Bach2/Batf pathway. The disturbed IL-4 decreases the level of the ACE-2 with the inflammation. This further leads to male infertility in COVID-19 patients. So, in this hypothesis, we focused on the role of IL-4 in COVID-19 patients associated with male infertility via Th2 cells and JAK-STAT signaling.
Kaviyarasi Renu, Mohana Devi Subramaniam, Rituraj Chakraborty, Haritha Myakala, Mahalaxmi Iyer, Geetha Bharathi, Kamalakannan Siva, Balachandar Vellingiri, Abilash Valsala Gopalakrishnan

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#33080272   2020/10/17 To Up

Complement activation induced by PEG enhances humoral immune responses against antigens encapsulated in PEG-modified liposomes.

Splenic marginal zone B (MZ-B) cells have attracted attention as alternative antigen-presenting cells. We recently developed an original delivery system, using PEGylated liposomes (PEG-Lip) to deliver antigens to MZ-B cells. In this system, to induce antigen-specific immunity, empty PEG-Lip and antigen-containing PEG-Lip were intravenously (i.v.) injected sequentially at 3 day intervals. Since complement activation by the second dose is required for the delivery of antigen-containing PEG-Lip to splenic MZ-B cells, we investigated the ability of liposomes, modified with various PEG derivatives having different functional terminal groups (methoxy PEG (CHO-PEG), hydroxy PEG (HO-PEG) or polyglycerol (PG), to activate the complement system and deliver a model antigen, ovalbumin (OVA), to splenic MZ-B cells in vitro and in vivo. Hydroxy PEG-modified liposomes (HO-PEG-Lip) both activated the complement system in vitro, and facilitated the preferential association of HO-PEG-lip with MZ-B cells in vitro. Manipulating HO-PEG density, in particular a density of 2 mol% in total lipids, significantly enhanced the association of HO-PEG-Lip with splenic MZ-B cells in vivo. Consequently, a single i.v. injection of HO-PEG-Lip (2% mol%) containing OVA induced OVA-specific IgG response. Our immunization system with HO-PEG-Lip, achieved efficient antigen delivery to MZ-B cells after a single intravenous injection, improving on our previous immunization system. This new delivery technique may be an improved, simple, antigen delivery system to MZ-B cells that induces meaningful levels of humoral immune response.
Taro Shimizu, Mizuki Awata, Amr S Abu Lila, Chihiro Yoshioka, Yoshino Kawaguchi, Hidenori Ando, Yu Ishima, Tatsuhiro Ishida

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#33080068   2020/10/20 To Up

Cell-mediated and humoral adaptive immune responses to SARS-CoV-2 are lower in asymptomatic than symptomatic COVID-19 patients.

The characterization of cell-mediated and humoral adaptive immune responses to SARS-CoV-2 is fundamental to understand COVID-19 progression and the development of immunological memory to the virus. In this study, we detected T cells reactive to SARS-CoV-2 proteins M, S and N, as well as serum virus-specific IgM, IgA, IgG, in nearly all SARS-CoV-2 infected individuals, but not in healthy donors. Virus-reactive T cells exhibited signs of in vivo activation, as suggested by the surface expression of immune-checkpoint molecules PD1 and TIGIT. Of note, we detected antigen-specific adaptive immune response both in asymptomatic and symptomatic SARS-CoV-2 infected subjects. More importantly, symptomatic patients displayed a significantly higher magnitude of both cell-mediated and humoral adaptive immune response to the virus, as compared to asymptomatic individuals. These findings suggest that an uncontrolled adaptive immune response contribute to the development of the life threatening inflammatory phase of the disease. Finally, this study might open the way to develop effective vaccination strategies. This article is protected by copyright. All rights reserved.
Alessio Mazzoni, Laura Maggi, Manuela Capone, Michele Spinicci, Lorenzo Salvati, Maria Grazia Colao, Anna Vanni, Seble Tekle Kiros, Jessica Mencarini, Lorenzo Zammarchi, Elisabetta Mantengoli, Lorenzo Menicacci, Eleonora Caldini, Sergio Romagnani, Francesco Liotta, Alessandro Morettini, Gian Maria Rossolini, Alessandro Bartoloni, Lorenzo Cosmi, Francesco Annunziato

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#33079389   2020/10/20 To Up

Interpretive discrepancies caused by target values inter-batch variations in chemiluminescence immunoassay for SARS-CoV-2 IgM/IgG by MAGLUMI™.

Plasma specimens from COVID-19 patients were double-tested for anti-SARS-CoV-2 antibodies by two different batches of MAGLUMI™ 2019-nCov IgM/IgG assays to evaluate IgM/IgG levels, qualitative interpretation, antibody kinetics and linearity of diluted specimen. Here we show that (i) high-level IgM specimens need to be diluted with negative human plasma but not kit diluents and (ii) measured anti-SARS-CoV-2 IgM/IgG concentrations are substantially higher with later marketed immunoassay batch leading to (iii) the change of qualitative interpretation (positive vs. negative) in 12.3 % of specimens measured for IgM, (iv) the informative time-course pattern of antibody production only when data from different immunoassay batches are not combined. This article is protected by copyright. All rights reserved.
Iveta Selingerova, Dalibor Valik, Lenka Gescheidtova, Vladimir Sramek, Zdenka Cermakova, Lenka Zdrazilova-Dubska

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#33079366   // To Up

Treatment of Necrotizing Soft Tissue Infections: IVIG.

Immunoglobulins are key effector molecules in the humoral immune response. Intravenous polyspecific immunoglobulin (IVIG) is a preparation of polyclonal serum immunoglobulins, typically IgG, from thousands of donors. It has been used as adjunctive therapy in critically ill patients with severe infections, i.e. sepsis, septic shock, and necrotizing soft tissue infections. IVIG has been used for patients with severe invasive group A streptococcal infection since the early nineties and off-label use of IVIG for necrotizing soft tissue infections is common. It is also used for a variety of autoimmune, inflammatory, and immunodeficiency diseases. A meta-analysis of the clinical studies available for IVIG use in group A streptococcal toxic shock syndrome indicates a survival benefit. A blinded, placebo-controlled clinical trial (INSTINCT) assessed the effect of IVIG in 100 intensive care unit patients with necrotizing soft tissue infections, including all bacterial etiologies. The study did not demonstrate any effect on self-reported physical functioning at 6 months. In this chapter, we review the mechanisms of action of IVIG and the clinical studies that are available for necrotizing soft tissue infections as well as severe group A streptococcal infections.
Martin Bruun Madsen, Helena Bergsten, Anna Norrby-Teglund

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#33079269   2020/10/20 To Up

Trypanosomatid species in Didelphis albiventris from urban forest fragments.

Urbanization results in loss of natural habitats and, consequently, reduction of richness and abundance of specialist to the detriment of generalist species. We hypothesized that a greater richness of trypanosomatid in Didelphis albiventris would be found in fragments of urban forests in Campo Grande, Mato Grosso do Sul, Brazil, that presented a larger richness of small mammals. We used parasitological, molecular, and serological methods to detect Trypanosoma spp. infection in D. albiventris (n = 43) from forest fragments. PCR was performed with primers specific for 18S rDNA, 24Sα rDNA, mini-chromosome satellites, and mini-exon genes. IFAT was used to detect anti-Trypanosoma cruzi IgG. All hemoculture was negative. We detected trypanosomatid DNA in blood of 35% of opossum. Two opossums were seropositive for T. cruzi. The trypanosomatid species number infecting D. albiventris was higher in the areas with greater abundance, rather than richness of small mammals. We found D. albiventris parasitized by T. cruzi in single and co-infections with Leishmania spp., recently described molecular operational taxonomic unit (MOTU) named DID, and Trypanosoma lainsoni. We concluded that (i) trypanosome richness may be determined by small mammal abundance, (ii) D. albiventris confirmed to be bio-accumulators of trypanosomatids, and (iii) T. lainsoni demonstrated a higher host range than described up to the present.
Wesley Arruda Gimenes Nantes, Filipe Martins Santos, Gabriel Carvalho de Macedo, Wanessa Texeira Gomes Barreto, Luiz Ricardo Gonçalves, Marina Silva Rodrigues, Jenyfer Valesca Monteiro Chulli, Andreza Castro Rucco, William de Oliveira Assis, Grasiela Edith de Oliveira Porfírio, Carina Elisei de Oliveira, Samanta Cristina das Chagas Xavier, Heitor Miraglia Herrera, Ana Maria Jansen

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#33078845   2020/10/20 To Up

FcγRI plays a critical role in patients with ulcerative colitis relapse.

Ulcerative colitis (UC) is a disease that frequently relapses and affects more than 0.1% general population; the underlying mechanism is poorly understood. Published data show that polymorphonuclear neutrophils (PMN) contribute to the pathogenesis of UC. This study aims to identify antigen (Ag)-specific PMNs and investigate their role in UC relapse. In this study, the correlation between PMN activities and UC relapse was assessed in a group of UC patients. A UC mouse model was developed to expand the findings of UC patient study. The results showed that a positive correlation was detected between the high PMN activities and the food Ag-specific IgG (sIgG) amounts in colon biopsies of UC patients. UC patient-derived Ag-specific PMNs could be activated upon exposure to food specific Ag (sAg). The Ag/FcγRI complexes were detected on the surface of PMNs in UC patients. Re-exposure of sensitized PMNs to sAg triggered PMN activation and induced UC-like inflammation in the mouse colon. We conclude that FcγRI play a critical role in UC relapse. Inhibition of FcγRI can efficiently inhibits experimental UC. This article is protected by copyright. All rights reserved.
Yan Li, Yuan-Yi Zhang, Li-Teng Yang, Jiang-Qi Liu, Chuan Zhou, Zhi-Qiang Liu, Gui Yang, Li-Hua Mo, Zhi-Gang Liu, Bai-Sui Feng, Ping-Chang Yang

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#33078702   2020/10/19 To Up

Delayed Time to Cryptosporidiosis in Bangladeshi Children is Associated with Greater Fecal IgA against Two Sporozoite-Expressed Antigens.

Cryptosporidiosis is common in early childhood, and both diarrheal and subclinical infections are associated with adverse developmental outcomes. Improved therapeutic medications may help reduce the burden of cryptosporidial diarrhea; however, an effective vaccine would be better able to prevent the detrimental impact of both diarrheal and subclinical disease. A more complete understanding of naturally occurring immunity may further inform strategies to develop an effective vaccine. In this prospective cohort study of Bangladeshi children, greater fecal IgA at 12 months, but not plasma IgG, directed against two sporozoite-expressed, immunodominant and vaccine candidate antigens was associated with delayed time to subsequent cryptosporidiosis to 3 years of life. These findings extend prior work and further support the role of mucosal antibody responses in naturally developing protective immunity to .
Kevin L Steiner, Mamun Kabir, Biplob Hossain, Carol A Gilchrist, Jennie Z Ma, Tahmeed Ahmed, Abu S G Faruque, Rashidul Haque, William A Petri

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#33078290   2020/10/19 To Up

MOG expressing teratoma followed by MOG-IgG-positive optic neuritis.


Brigitte Wildemann, Sven Jarius, Jonas Franz, Klemens Ruprecht, Markus Reindl, Christine Stadelmann

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