Histological examination of the cellular reactions around schistosomula of Schistosoma mansoni in the lungs of sublethally irradiated and unirradiated, immune and control rats

Parasitology ◽  
1989 ◽  
Vol 98 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Dario A. A. Vignali ◽  
S. N. Klaus ◽  
Q. D. Bickle ◽  
M. G. Taylor
Keyword(s):  
Schistosoma Mansoni ◽  
Mononuclear Cells ◽  
Significant Proportion ◽  
Immune Serum ◽  
Immune Recognition ◽  
Cellular Infiltration ◽  
Cellular Composition ◽  
Immune Mediated ◽  
Immune Attack ◽  
And Control

SummaryHistopathological data on the cellular reactions (foci) around Schistosoma mansoni schistosomula in the lungs of both irradiated (750 rad) and unirradiated, passively immunized and normal rats were consistent with the idea that a significant proportion of immune-mediated attrition in passively immunized rats occurs in the lungs. In unirradiated rats, immune serum elicited an enhanced (i.e. larger) and accelerated (i.e. more rapidly developing) inflammatory cellular infiltration around lung-stage parasites when administered 5 days post-infection, when the parasites were already in the lungs. This demonstrated the antigenicity of lung-stage schistosomula and their potential as targets for immune attack. In irradiated rats, innate immunity was decreased as judged by an increase in the number of worms recovered by portal perfusion, and was accompanied by an overall decreased percentage of trapped parasites compared with unirradiated controls, suggesting that trapping in the lungs is involved in innate, as well as acquired immunity. In contrast to the results in unirradiated rats, passive transfer of immune serum into irradiated recipients did not result in larger lung foci than in the NRS-recipients. However, there was evidence of an accelerated response resulting in an essentially similar ratio of trapped parasites (VRS- compared with NRS-recipients) in irradiated rats, as compared with unirradiated rats, reflecting the similar levels of resistance manifested in both groups of rats. This also lent credence to the notion that it was the speed of immune recognition of the migrating schistosomula and the establishment of trapping foci that were of greater importance rather than the size of the enveloping granulomata. Investigations into the cellular composition of the foci surrounding trapped parasites in unirradiated rats revealed a predominance of mononuclear cells, with equal proportions of lymphocytes and macrophages. Eosinophils represented less than 3% of the cellular composition of the foci and were typically distant from the parasites themselves, arguing against their role in specific immunity in this model. Irradiation of recipient rats resulted in a corresponding increase in the percentage of macrophages in lung foci.

scholarly journals 727 Resistance to enzalutamide and abiraterone drives tumor phenotypic plasticity and resistance to immune-mediated cytotoxicity

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A757-A757
Author(s):  
Madeline Dahut ◽  
Kristen Fousek ◽  
Lucas Horn ◽  
Haiyan Qin ◽  
Jeffrey Schlom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phenotypic Plasticity ◽  
Nk Cell ◽  
Significant Proportion ◽  
Xenograft Model ◽  
Lncap Cells ◽  
Mesenchymal Transition ◽  
Immune Mediated ◽  
Healthy Donors ◽  
Immune Attack

BackgroundBackground: Treatment of patients with castration-resistant prostate cancer (CRPC) includes the use of next-generation hormonal therapies such as abiraterone or enzalutamide. Although these agents extend survival, a significant proportion of patients exhibit primary or acquired resistance to treatment. In recent years, immune checkpoint blockade has led to remarkable responses in patients with several tumor types, however, CRPC has remained resistant to immunotherapy. Previous studies have demonstrated that different tumor variants could emerge along the progression of prostate cancer, including tumors undergoing phenotypic plasticity in the context of an epithelial-mesenchymal transition. Our laboratory and others have shown that phenotypic plasticity is a driver of resistance to immunotherapy. Based on this knowledge, we investigated whether changes in tumor phenotype could affect the response of CRPC to immune-based therapies, and ways this can be mitigated.MethodsThe androgen sensitive LNCAP prostate cancer cell line was used to derive LNCAP cells resistant to enzalutamide (LNCAP-EnzaR) or abiraterone (LNCAP-AbiR). Resistant cell lines and parental LNCAP cells were comparatively evaluated for features of EMT and neuroendocrine phenotype via RT-PCR, ELISA, western blot, immunofluorescence, and RNAseq. Changes in the susceptibility to NK-cell mediated cytotoxicity were evaluated with NK cells isolated from peripheral blood from healthy donors. LNCAP-EnzaR cells were also grown in vivo in NSG MHC-deficient mice, and tumors were characterized for phenotypic markers and potential therapeutic targets.ResultsAcquisition of resistance to both enzalutamide and abiraterone was associated with a significant increase in mesenchymal tumor features, including high levels of vimentin and fibronectin, and the loss of epithelial features and cell-to-cell attachments. LNCAP-Enza-R and LNCAP-AbiR cells showed a significant reduction (up to 90%) in susceptibility to NK-cell mediated cytotoxicity and antibody-dependent cell cytotoxicity (ADCC), compared with parental cells. These results prompted us to investigate approaches to improve immune-mediated lysis, including inhibition of estrogen receptor 1 (ESR1), which was identified as highly upregulated in LNCAP-EnzaR cells via RNAseq analysis. In a xenograft model of LNCAP-EnzaR cells, we corroborated the maintenance of tumor phenotypic plasticity and the expression of actionable targets.ConclusionsOur data indicates that acquisition of resistance to androgen receptor inhibition is associated with marked reduction of susceptibility to immune attack, and the acquisition of tumor phenotypic plasticity. Future studies will investigate approaches that revert tumor plasticity, including blockade of ESR1, TGF-beta or IL-8, for potential improvement of tumor susceptibility to immune attack in CRPC.Ethics ApprovalPBMCs were obtained from healthy donors at the NIH Clinical Center Blood Bank (NCT00001846). All animal studies were approved and conducted in accordance with an IACUC-approved animal protocol (LTIB-57) with the approval the NIH/NCI Institutional Animal Care and Use Committee.

scholarly journals Mealtime Environment and Control of Food Intake in Healthy Children and in Children with Gastrointestinal Diseases

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 77
Author(s):  
Katerina Sdravou ◽  
Elpida Emmanouilidou-Fotoulaki ◽  
Athanasia Printza ◽  
Elias Andreoulakis ◽  
Athanasios Evangeliou ◽  
...  
Keyword(s):  
Food Intake ◽  
Gastrointestinal Disease ◽  
Significant Proportion ◽  
Gastrointestinal Diseases ◽  
Healthy Children ◽  
Cross Sectional ◽  
Frequent Use ◽  
Child Autonomy ◽  
And Control ◽  
Mealtime Environment

Parental feeding practices and mealtime routine significantly influence a child’s eating behavior. The aim of this study was to investigate the mealtime environment in healthy children and children with gastrointestinal diseases. We conducted a cross-sectional case–control study among 787 healthy, typically developing children and 141 children with gastrointestinal diseases, aged two to seven years. Parents were asked to provide data on demographics and describe their mealtime environment by answering to 24 closed-ended questions. It was found that the majority of the children had the same number of meals every day and at the same hour. Parents of both groups exerted considerable control on the child’s food intake by deciding both when and what their child eats. Almost one third of the parents also decided how much their child eats. The two groups differed significantly in nine of the 24 questions. The study showed that both groups provided structured and consistent mealtime environments. However, a significant proportion of children did not control how much they eat which might impede their ability to self-regulate eating. The presence of a gastrointestinal disease was found to be associated with reduced child autonomy, hampered hunger cues and frequent use of distractions during meals.

scholarly journals Evaluation of the phagocytic activity of peripheral blood monocytes of patients with Jorge Lobo's disease

2004 ◽  
Vol 37 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Fátima Regina Vilani-Moreno ◽  
Luciana Moreira Silva ◽  
Diltor Vladimir Araújo Opromolla
Keyword(s):  
Incubation Time ◽  
Peripheral Blood ◽  
Phagocytic Activity ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Significant Difference ◽  
Host Parasite ◽  
And Control

Studies on host-parasite interaction in Jorge Lobo's disease are scarce, with no report in the literature on the phagocytosis of Lacazia loboi by phagocytic mononuclear cells. Thus, the objective of the present study was to assess the phagocytic activity of blood monocytes in the presence of L. loboi in patients with the disease and in healthy subjects (controls) over 3 and 24 hours of incubation. Statistical analyses of the results showed no significant difference in percent phagocytosis of the fungus between patient and control monocytes. With respect to incubation time, however, there was a significant difference, in that percent phagocytosis was higher at 3 hours than at 24 hours (p <0.01). These results suggest that monocytes from patients with the mycosis are able to phagocyte the fungus, as also observed in control individuals.

scholarly journals 30USE OF ADULT STEM/PROGENITOR CELLS AS NUCLEAR DONORS TO PRODUCE CLONED PORCINE EMBRYOS

2004 ◽  
Vol 16 (2) ◽  
pp. 137
Author(s):  
P. Bosch ◽  
S.L. Pratt ◽  
E. Sherrer ◽  
C.A. Hodges ◽  
E. Ivy Hill ◽  
...  
Keyword(s):  
Alcian Blue ◽  
Mononuclear Cells ◽  
Electric Pulse ◽  
Adipogenic Differentiation ◽  
Blastocyst Stage ◽  
Calcium Deposition ◽  
Nuclear Reprogramming ◽  
Live Animal ◽  
And Control ◽  
Oil Red O

Incomplete or defective nuclear reprogramming may be responsible for low cloning efficiencies. Less differentiated stem cells are thought to be more easily reprogrammed, resulting in improved survival of cloned mice (Rideout WM III et al., 2000 Nat. Genet. 24, 109–110). Our objective was to establish porcine mesenchymal stem cell (MSC) cultures and use these as donor cells in nuclear transfer (NT). A bone marrow (BM) aspirate was collected from an anesthetized gilt. BM mononuclear cells were isolated by centrifugation over a density gradient (Histopaque-1077; Sigma, St. Louis, MO, USA), resuspended in low glucose DMEM (Gibco) plus 10% FBS and plated on flasks; fibroblast-like MSCs were later passaged. Ear skin fibroblast (SF) cultures from the same BM donor gilt were established. Cultures of MSC and SF were exposed to lipogenic, osteogenic or chondrogenic differentiation media (Pittenger MF et al., 1999 Science 284, 143–147) for 14 days. Cells cultured in DMEM with 10% FBS served as controls. Differentiation was assessed by histochemical methods. Calcium deposits and alkaline phosphatase (AP) activity (Vector Red AP Substrate Kit, Vector Labs) were indicative of osteogenic differentiation. MSCs cultured under osteogenic conditions were positive for AP activity and developed a black color after von Kossa staining, indicative of calcium deposition. Oil red O stain identified cellular lipid accumulation. When exposed to adipogenic differentiation media, 10–15% of MSCs developed an adipocyte phenotype with lipid droplet accumulation and oil red O staining. Lipogenic differentiation was not observed in SF and control cultures. Presence of acidic mucopolysaccharides associated with cartilage formation was determined by alcian blue stain. MSCs exposed to chondrogenic conditions were alcian blue-positive, and SF and control cultures were alcian blue negative. For NT, confluent (passage 2) MSC and SF cultures were exposed to roscovitine (15μM; Sigma) for 24h. In vitro-matured oocytes were enucleated and a single cell (MSC or SF) was transferred into the periviteline space. Cell-oocyte couplets were fused in Zimmerman’s medium with a single electric pulse (250V/mm for 20μs) delivered through a needle-type electrode. NT units were electrically activated (2 pulses of 100V/mm for 60μs separated by 5s) in a chamber 1h after fusion and transferred to NCSU-23 medium. Embryos were examined for cleavage and blastocyst formation at 2 and 7 days after NT, respectively. Cleavage rates were 53.3% (40/75) for MSC and 59.7% (46/77) for SF NT embryos. Development to blastocyst stage was 6.6% (5/75) in the MSC group and 1.2% (1/77) in SF group. In conclusion, we established an adult MSC line from a live animal using a minimally invasive BM aspiration technique. Additionally, MSC donor-derived NTs developed to the blastocyst stage. Further experiments will determine nuclear reprogramming in MSC-derived NT embryos.

scholarly journals Assessment of Expression of SOCS Genes in Acquired Immune-Mediated Polyneuropathies

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohammad Taheri ◽  
Somayeh Sangseifid ◽  
Pariya Shahani ◽  
Mohammad Mahdi Eftekharian ◽  
Shahram Arsang-Jang ◽  
...  
Keyword(s):  
Specific Pattern ◽  
Bayesian Regression ◽  
Cytokine Signaling ◽  
Control Group ◽  
Operating Characteristics ◽  
Mean Values ◽  
Immune Mediated ◽  
Male Patients ◽  
Underlying Mechanisms ◽  
And Control

Acquired immune-mediated polyneuropathies are classified to some subtypes among them are acute and chronic inflammatory demyelinating polyradiculoneuropathies (AIDP and CIDP). These two conditions share some common signs and underlying mechanisms. Based on the roles of Suppressor of cytokine signaling (SOCS) genes in the modulation of immune system reactions, these genes might be involved in the pathogenesis of these conditions. We evaluated expression of SOCS1-3 and SOCS5 genes in the leukocytes of 32 cases of CIDP, 19 cases of AIDP and 40 age- and sex-matched controls using real time PCR method. The Bayesian regression model was used to estimate differences in mean values of genes expressions between cases and control group. Expression levels of SOCS1 and SOCS2 were significantly lower in male patients compared with controls. This sex-specific pattern was also observed for SOCS3 down-regulation. Based on the area under curve values in Receiver Operating Characteristics (ROC) curve, diagnostic powers of SOCS1, SOCS2, SOCS3 and SOCS5 genes in the mentioned disorder were 0.61, 0.73, 0.68 and 0.58, respectively. Expression of none of genes was correlated with age of enrolled cases. The current study shows evidences for participation of SOCS genes in the pathophysiology of acquired immune-mediated polyneuropathies.

scholarly journals Bioimmunological responses to Schistosoma mansoni and Fasciola gigantica worm homogenates either with or without saponin

2010 ◽  
Vol 4 (05) ◽  
pp. 334-344
Author(s):  
Amany Sayed Maghraby ◽  
Manal Abdel-Aziz Hamed ◽  
Sanaa Ahmed Ali
Keyword(s):  
Free Radical ◽  
Liver Function ◽  
Schistosoma Mansoni ◽  
Subcutaneous Administration ◽  
Free Radical Scavenger ◽  
Fasciola Gigantica ◽  
Free Radical Scavengers ◽  
Radical Scavenger ◽  
Immune Mediated ◽  
Mice Liver

Background: In this study, we evaluated the biochemical, immunological, histopathological and antischistosomal activities of Schistosoma mansoni or Fasciola gigantica worm homogenates mixed either with or without saponin that was extracted from Atriplex nummularia. Methodology: The immunization schedule was based on subcutaneous administration of two doses (50 μg /100 μl PBS) of each homogenate with time intervals of 15 days. After 15 days of the last homogenate inoculation, all mice were challenged with 100 Schistosoma mansoni cercariae and sacrificed after two months. Free radical scavengers and liver function enzymes were determined in mice liver. Worm counting and the histopathological picture of the liver were also done. Results: Immunization with Schistosoma or Fasciola worm homogenates, mixed either with or without saponin, recorded an amelioration of the free radical scavenger levels, liver function enzymes and reduction in worm burden, as well as improvement of the histological feature of the liver, the number and size of granuloma, evidence of increased immune reaction manifested by a lymphocytic cuff surrounding the granuloma, diminution of its fibrotic and collagen content, and destruction of Schistosoma ova. Conclusion: Fasciola or Schistosoma worm antigens mixed with or without saponin succeeded to eliminate the product of oxidative stress and assistance in immune-mediated destruction of eggs that ameliorate the histopathological picture of the liver cells and preserve its function.

scholarly journals Screening of Highly Expressed Mycobacterial Genes Identifies Rv3615c as a Useful Differential Diagnostic Antigen for the Mycobacterium tuberculosis Complex

2008 ◽  
Vol 76 (9) ◽  
pp. 3932-3939 ◽  
Author(s):  
Ben Sidders ◽  
Chris Pirson ◽  
Philip J. Hogarth ◽  
R. Glyn Hewinson ◽  
Neil G. Stoker ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Significant Proportion ◽  
Growth Conditions ◽  
Control Measures ◽  
Human Populations ◽  
Infected Cattle ◽  
Ifn Γ ◽  
Mycobacterial Antigens ◽  
And Control ◽  
Differential Antigens

ABSTRACT Tuberculous infections caused by mycobacteria, especially tuberculosis of humans and cattle, are important both clinically and economically. Human populations can be vaccinated with Mycobacterium bovis bacille Calmette-Guérin (BCG), and control measures for cattle involving vaccination are now being actively considered. However, diagnostic tests based on tuberculin cannot distinguish between genuine infection and vaccination with BCG. Therefore, identification of differential diagnostic antigens capable of making this distinction is required, and until now sequence-based approaches have been predominant. Here we explored the link between antigenicity and mRNA expression level, as well as the possibility that we may be able to detect differential antigens by analyzing quantified global transcriptional profiles. We generated a list of 14 candidate antigens that are highly expressed in Mycobacterium tuberculosis and M. bovis under a variety of growth conditions. These candidates were screened in M. bovis-infected and naïve cattle for the ability to stimulate a gamma interferon (IFN-γ) response. We identified one antigen, Rv3615c, which stimulated IFN-γ responses in a significant proportion of M. bovis-infected cattle (11 of 30 cattle [37%] [P < 0.01]) but not in naïve or BCG-vaccinated animals. Importantly, the same antigen stimulated IFN-γ responses in a significant proportion of infected cattle that did not respond to the well-characterized mycobacterial antigens ESAT-6 and CFP-10. Therefore, use of the Rv3615c epitope in combination with previously described differential tests based on ESAT-6 and CFP-10 has the potential to significantly increase diagnostic sensitivity without reducing specificity in BCG-vaccinated populations.

scholarly journals Association of Strong Immune Responses to PPE Protein Rv1168c with Active Tuberculosis

2008 ◽  
Vol 15 (6) ◽  
pp. 974-980 ◽  
Author(s):  
Nooruddin Khan ◽  
Kaiser Alam ◽  
Shiny Nair ◽  
Vijaya Lakshmi Valluri ◽  
Kolluri J. R. Murthy ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Tuberculin Test ◽  
Interferon Response ◽  
Peripheral Blood Mononuclear ◽  
Purified Protein Derivative ◽  
Conventional Tests ◽  
Immunodominant Antigens ◽  
Smear Negative ◽  
And Control ◽  
Immunogenic Properties

ABSTRACT Accurate diagnosis of tuberculosis (TB) infection is critical for the treatment, prevention, and control of TB. Conventional diagnostic tests based on purified protein derivative (PPD) do not achieve the required diagnostic sensitivity. Therefore, in this study, we have evaluated the immunogenic properties of Rv1168c, a member of the PPE family, in comparison with PPD, which is routinely used in the tuberculin test, and Hsp60 and ESAT-6, well-known immunodominant antigens of Mycobacterium tuberculosis. In a conventional enzyme immunoassay, the recombinant Rv1168c protein displayed stronger immunoreactivity against the sera obtained from patients with clinically active TB than did PPD, Hsp60, or ESAT-6 and could distinguish TB patients from Mycobacterium bovis BCG-vaccinated controls. Interestingly, Rv1168c antigen permits diagnosis of smear-negative pulmonary TB as well as extrapulmonary TB cases, which are often difficult to diagnose by conventional tests. The immunodominant nature of Rv1168c makes it a promising candidate to use in serodiagnosis of TB. In addition, our studies also show that Rv1168c is a potent T-cell antigen which elicits a strong gamma interferon response in sensitized peripheral blood mononuclear cells obtained from TB patients.

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