scholarly journals Protective Effect Against Toxoplasmosis in BALB/c Mice Vaccinated With Recombinant Toxoplasma gondii MIF, CDPK3, and 14-3-3 Protein Cocktail Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Fang Liu ◽  
Minmin Wu ◽  
Jie Wang ◽  
Hongyang Wen ◽  
Ran An ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Survival Time ◽  
The Other ◽  
Cell Mediated Immunity ◽  
Protective Effects ◽  
Protein Vaccine ◽  
Igg Antibody ◽  
Strong Immune Response ◽  
Life Threatening ◽  
Almost All

Toxoplasma gondii can infect almost all endotherm organisms including humans and cause life-threatening toxoplasmosis in immunocompromised individuals, which leads to serious public health problems. Developing an excellent vaccine against this disease is impending. In present study, we formulated a cocktail protein vaccine including the TgMIF, TgCDPK3, and Tg14-3-3 proteins, which play critical roles in T. gondii infection. The recombinant protein vaccines were constructed and assessed by vaccination in BALB/c mice. We organized the mice in various protein combination groups of vaccines, and all mice were immunized with corresponding proteins at 0, 2, and 4 weeks. The specific protective effects of the vaccines on mice against T. gondii were analyzed by the mensuration of cytokines, serum antibodies, splenocyte proliferation assay, survival time, and parasite cyst burden of mice after the challenge. The study indicated that mice immunized with all three multicomponent proteins vaccine triggered a strong immune response with highest levels of IFN-γ production and IgG antibody compared with the other two protein combinations and controls. Moreover, there was an increase in IL-4 production and antigen-specific lymphocyte proliferation. The parasite cysts were significantly reduced (resulting in an 82.7% reduction), and survival time was longer in immunized mice with three multicomponent proteins compared with the other groups of mice. The enhanced humoral and cell-mediated immunity indicated that the protein cocktail vaccine containing three antigens provided effective protection for mice. These results indicated that recombinant TgMIF, TgCDPK3, and Tg14-3-3 multicomponent proteins were potential candidates for vaccine against toxoplasmosis.

scholarly journals Interleukin-18 (IL-18) Enhances Innate IL-12-Mediated Resistance to Toxoplasma gondii

2000 ◽  
Vol 68 (12) ◽  
pp. 6932-6938 ◽  
Author(s):  
Guifang Cai ◽  
Robert Kastelein ◽  
Christopher A. Hunter
Keyword(s):  
Toxoplasma Gondii ◽  
Nk Cells ◽  
Nk Cell ◽  
Parasite Burden ◽  
Scid Mice ◽  
Interleukin 12 ◽  
Cell Mediated Immunity ◽  
Protective Effects ◽  
Innate Resistance ◽  
Ifn Γ

ABSTRACT Innate resistance to Toxoplasma gondii is dependent on the ability of interleukin-12 (IL-12) to stimulate natural killer (NK) cell production of gamma interferon (IFN-γ). Since IL-18 is a potent enhancer of IL-12-induced production of IFN-γ by NK cells, SCID mice (which lack an adaptive immune response) were used to assess the role of IL-18 in innate resistance to T. gondii. Administration of anti-IL-18 to SCID mice infected with T. gondii resulted in an early reduction in serum levels of IFN-γ but did not significantly decrease resistance to this infection. In contrast, administration of exogenous IL-18 to infected SCID mice resulted in increased production of IFN-γ, reduced parasite burden, and a delay in time to death. The protective effects of IL-18 treatment correlated with increased NK cell numbers and cytotoxic activity at the local site of administration and with elevated levels of inducible nitrous oxide synthose in the spleens of treated mice. In addition, in vivo depletion studies demonstrated that the ability of exogenous IL-18 to enhance resistance to T. gondii was dependent on IL-12, IFN-γ, and NK cells. Together, these studies demonstrate that although endogenous IL-18 appears to have a limited role in innate resistance to T. gondii, treatment with IL-18 can augment NK cell-mediated immunity to this pathogen.

scholarly journals Vaccine prophylaxis of abattoir-associated Q fever: eight years' experience in Australian abattoirs

1990 ◽  
Vol 104 (2) ◽  
pp. 275-287 ◽  
Author(s):  
B. P. Marmion ◽  
R. A. Ormsbee ◽  
M. Kyrkou ◽  
J. Wright ◽  
D. A. Worswick ◽  
...  
Keyword(s):  
Q Fever ◽  
Protective Efficacy ◽  
Phase 1 ◽  
South Australia ◽  
Risk Groups ◽  
The Other ◽  
Cell Mediated Immunity ◽  
Igg Antibody ◽  
Inoculation Site ◽  
Other Hand

SUMMARYDuring the period 1981–8 a clinical trial of a Q fever vaccine (Q-vax; Commonwealth Serum Laboratories, Melbourne) has been conducted in abattoir workers and other at-risk groups in South Australia. Volunteers in four abattoirs and visitors to the abattoirs were given one subcutaneous dose of 30 μg of a formalin-inactivated, highly-purifiedCoxiella burnetiicells, Henzerling strain, Phase 1 antigenic state, in a volume of 0·5 ml.During the period, over 4000 subjects have been vaccinated and the programme continues in the abattoirs and related groups. ‘Common’ reactions to the vaccine comprised tenderness and erythema, rarely oedema at the inoculation site and sometimes transient headache. Two more serious ‘uncommon’ reactions, immune abscess at the inoculation site, were observed in two subjects, and two others developed small subcutaneous lumps which gradually dispersed without intervention.Protective efficacy of the vaccine appeared to be absolute and to last for 5 years at least. Eight Q fever cases were observed in vaccinees, but all were in persons vaccinated during the incubation period of a natural attack of Q fever before vaccine-induced immunity had had time (≥ 13 days after vaccination) to develop. On the other hand, 97 Q fever cases were detected in persons working in, or visiting the same abattoir environments.Assays for antibody and cellular immunity showed an 80–82% seroconversion after vaccination, mostly IgM antibody to Phase 2 antigen, in the 3 months after vaccination. This fell to about 60%, mostly IgG antibody to Phase 1 antigen, after 20 months. On the other hand, 85–95% of vaccinees developed markers of cell mediated immunity as judged by lymphoproliferative responses withC. burnetiiantigens; these rates remained elevated for at least 5 years.The Q fever vaccine, unlike other killed rickettsial vaccines, has the property of stimulating long-lasting T lymphocyte memory and this may account for its unusual protective efficacy as a killed vaccine.

Starość w nauczaniu św. Bazylego Wielkiego

Vox Patrum ◽  
2011 ◽  
Vol 56 ◽  
pp. 339-348
Author(s):  
Bogdan Czyżewski
Keyword(s):  
Old Age ◽  
Spiritual Maturity ◽  
The Other ◽  
Interesting Aspect ◽  
Other Hand ◽  
Physical Suffering ◽  
Way Of Thinking ◽  
Almost All

Although St. Basil did not live 50 years, the topic of the old age appears in his works quite often. On the other hand, it is clear that Basil does not discuss this issue in one par­ticular work or in the longer argumentation. The fragmentary statements about old age can be found in almost all his works, but most of them can be found in the correspondence of Basil. In this paper we present the most important ad the most interesting aspect of teach­ing of Basil the Great. As these certificates show that the bishop of Caesarea looked at the old age maturely, rationally estimated passage of time, which very often makes a man different. He experienced it, for example as a spiritual and physical suffering, which often were connected with his person. He saw a lot of aspect of the old age, especially its advan­tages – spiritual maturity and wisdom. What is more, he pointed also to passage of time, which leads a man to eternity, which should be prepared to, regardless how old he is. In his opinion fear is not seen opinions of St. Basil present really Christian way of thinking, well-balanced and calm.

HCA587 protein vaccine induces specific antitumor immunity mediated by CD4+ T-cells expressing granzyme B in a mouse model of melanoma

2020 ◽  
Vol 20 ◽  
Author(s):  
Weiming Yang ◽  
Weiheng Zhang ◽  
Xiaozhong Wang ◽  
Liming Tan ◽  
Hua Li ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Antitumor Effect ◽  
Granzyme B ◽  
Cell Subset ◽  
Cell Mediated Immunity ◽  
Protein Vaccine ◽  
Tumor Tissues ◽  
Wide Range ◽  
Ifn Γ

Background: The antigen HCA587 (also known as MAGE-C2), which is considered a cancer-testis antigen, exhibits upregulated expression in a wide range of malignant tumors with unique immunological properties, and may thus serve as a promising target for tumor immunotherapy. Objective: To explore the antitumor effect of the HCA587 protein vaccine and the response of humoral and cell-mediated immunity. Methods: The HCA587 protein vaccine was formulated with adjuvants CpG and and ISCOM. B16 melanoma cells were subcutaneously inoculated to C57BL/6 mice, followed by treatment with HCA587 protein vaccine subcutaneously. Mouse survival was monitored daily, and tumor volume was measured every 2 to 3 days. The tumor sizes, survival time and immune cells in tumor tissues were detected. And the vital immune cell subset and effector molecules were explored. Results: After treatment with HCA587 protein vaccine, the vaccination generated elicited significant immune responses, which delayed tumor growth and improved animal survival. The vaccination increased the proportion of CD4+ T cells expressing IFN-γ and granzyme B in tumor tissues. Depletion of CD4+T cells resulted in an almost complete abrogation of the antitumor effect of the vaccination, suggesting that the antitumor efficacy was mediated by CD4+ T cells. In addition, knockout of IFN-γ resulted in a decrease in granzyme B levels which were secreted by CD4+ T cells, and the antitumor effect was also significantly attenuated. Conclusion: The HCA587 protein vaccine may increase the levels of granzyme B expressed by CD4+ T cells, and this increase is dependent on IFN-γ, and the vaccine resulted in a specific tumor immune response and subsequent eradication of the tumor.

scholarly journals The Diverse Calpain Family in Trypanosomatidae: Functional Proteins Devoid of Proteolytic Activity?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 299
Author(s):  
Vítor Ennes-Vidal ◽  
Marta Helena Branquinha ◽  
André Luis Souza dos Santos ◽  
Claudia Masini d’Avila-Levy
Keyword(s):  
Proteolytic Activity ◽  
Current Knowledge ◽  
Current Therapy ◽  
Calcium Dependent ◽  
Administration Routes ◽  
Life Threatening ◽  
Living Organisms ◽  
Almost All ◽  
Open Question ◽  
Calpain Inhibitors

Calpains are calcium-dependent cysteine peptidases that were originally described in mammals and, thereafter, their homologues were identified in almost all known living organisms. The deregulated activity of these peptidases is associated with several pathologies and, consequently, huge efforts have been made to identify selective inhibitors. Trypanosomatids, responsible for life-threatening human diseases, possess a large and diverse family of calpain sequences in their genomes. Considering that the current therapy to treat trypanosomatid diseases is limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures, a repurposed approach with calpain inhibitors could be a shortcut to successful chemotherapy. However, there is a general lack of knowledge about calpain functions in these parasites and, currently, the proteolytic activity of these proteins is still an open question. Here, we highlight the current research and perspectives on trypanosomatid calpains, overview calpain description in these organisms, and explore the potential of targeting the calpain system as a therapeutic strategy. This review gathers the current knowledge about this fascinating family of peptidases as well as insights into the puzzle: are we unable to measure calpain activity in trypanosomatids, or are the functions of these proteins devoid of proteolytic activity in these parasites?

scholarly journals ML-23 The outcome of malignant lymphoma of the central nervous system in a single institution

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii18-ii18
Author(s):  
Kiyonori Kuwahara ◽  
Shigeo Ohba ◽  
Kazuyasu Matsumura ◽  
Saeko Higashiguchi ◽  
Daijiro Kojima ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adverse Events ◽  
Malignant Lymphoma ◽  
Survival Time ◽  
Progression Free Survival ◽  
Treatment Method ◽  
The Other ◽  
High Dose ◽  
Other Hand

Abstract Background: Although high dose-methotrexate therapy has been performed for primary central nervous system malignant lymphoma (PCNSL), R-MPV (rituximab, methotrexate (MTX), procarbazine and vincristine) therapy is currently the first line therapy for (PCNSL) in our hospital. This study examines the results of R-MPV therapy comparing with past treatment. Method/Subjects: Thirty-seven patients treated at our hospital from 2009 to 2020 were included. Overall survival time, progression free survival time, and toxicities were evaluated. Results: The average age of patients was 65.7 years. Patients included 21 males and 16 females. Thirty-six patients were diagnosed DLBCL by resected brain tumor tissues, and one was diagnosed DLBCL by vitreous biopsy. As initial treatment, rituximab±HD-MTX therapy (R±MTX group) was performed in 20 cases, HD-MTX therapy plus radiation (R±MTX+RT group) was performed in 12 cases, and RMPV therapy was performed in 5 cases (R-MPV group). Median OS of all cases was 69 months and median PFS was 38 months. Median OS was 69 months in R±MTX group and could not be calculated in R±MTX+RT, and R-MPV groups. Median PFS was 16 months and 56 months in R±MTX group and R±MTX+RT, respectively, and could not be calculated in the R-MPV group. Although the R-MPV group had a short follow-up period, the results were considered to be comparable to those of the R±MTX+RT group. On the other hand, grade 3/4 adverse events occurred in 50%, 25%, and 100%, respectively. Conclusion: R-MPV therapy may delay the timing of radiation and reduce the amount of radiation. On the other hand, the frequency of adverse events is high, and more strict management of treatment is required.

scholarly journals OP0096 EXPOSURE TO DENGUE INFECTION DO NOT RAISE RISK OF RHEUMATOID ARTHRITIS: FINDINGS FROM THE MALAYSIAN EPIDEMIOLOGICAL INVESTIGATION OF RHEUMATOID ARTHRITIS (MYEIRA) CASE-CONTROL STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 53.1-53
Author(s):  
L. K. Tan ◽  
C. L. Too ◽  
A. F. Nurul-Aain ◽  
A. A. Siti-Aisyah ◽  
S. Wahinuddin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ethnic Groups ◽  
Antibody Level ◽  
Dengue Infection ◽  
The Other ◽  
Director General ◽  
Igg Antibody ◽  
Ministry Of Health ◽  
Malaysian Population ◽  
Mixed Ethnicity

Background:Dengue infection is associated with joints pain mimicking disease onset symptom of rheumatoid arthritis (RA). However, there is lack of epidemiological studies on exposure to dengue infection and risk of future RA.Objectives:We investigated the relationship between exposure to dengue infection and risk of developing different subsets of RA, defined by the presence of anti-citrullinated peptide antibody (ACPA) in the multi-ethnic Malaysian population.Methods:Serum samples from 1,235 RA cases (i.e. 516 Malay, 254 Chinese, 405 Indians and 60 others/mixed-ethnicity) and 1,624 epidemiological matched population-based controls (i.e. 1,023 Malay, 208 Chinese, 297 Indians and 96 others/mixed-ethnicity) were assayed for presence of dengue IgG antibody using World Health Organization recommended ELISA kits. Positive results of dengue IgG antibodies indicates previous exposure to dengue infection(s). We performed chi-square and Mann-Whitney U analysis to determine the association of ever-exposed dengue infection with ACPA-positive/ACPA-negative RA and to investigate the antibody frequency and levels among the studied populations.Results:We observed high occurrence of dengue IgG antibody in the overall RA cases (79.7%) and matched controls (77.3%), with no significant differences detected between the ACPA subsets of RA. Ethnicity stratification analysis revealed a decrease risk of developing ACPA-positive RA in the Indian patients with positive dengue IgG antibody (OR=0.59, 95% CI=0.37-0.94, p=0.03), and in particular patients with elevated level of dengue IgG antibody (OR=0.44, 95% CI=0.25-0.78, p<0.05). On the other hand, the significant decrease mean levels of dengue IgG antibody were observed in the ACPA-positive RA subset for all three major ethnic groups (i.e. Malay, p<0.0001, Chinese, p<0.01 and Indian<0.05) (Figure 1). No association was observed between presence of dengue IgG antibody and ACPA-negative RA subset.Figure 1.Comparison of mean dengue IgG antibody level between ever-exposed dengue infection RA cases, stratified by ACPA status. Comparison of median dengue IgG antibody level between the ever-exposed dengue infection ACPA-positive RA and normal controls in the four ethnic groups. The red line indicates the mean level of dengue IgG antibody levelConclusion:Our findings demonstrated that exposure to dengue infection do not increase the risk of developing future RA in the multi-ethnic Malaysian population. The inverse associations observed in the Indian ethnic group are in line with the other studies investigating exposure to viral infection and risk of RA.References:[1]Sherina et al (2017) Low levels of antibodies against common viruses associate with anti-citrullinated protein antibody-positive rheumatoid arthritis; implications for disease aetiology. Arthritis Research & Therapy 2017, 19:2169[2]Gissel García et. al. (2011) Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders. International Journal of Infectious Diseases 15 (2011) e38–e43Acknowledgements:The authors would like to thank the Director General of Health, Ministry of Health Malaysia for supporting this study. The authors are also indebted to participants for their kind participation. This study was financially supported by the Ministry of Health, Malaysia (JPP-IMR 17-025) and the short-term research grant by UniKL RCMP (str16037).Disclosure of Interests:None declared

Descriptions of the larvae of four species of Procladius from Great Slave Lake (Chironomidae:Diptera)

1978 ◽  
Vol 56 (9) ◽  
pp. 2055-2057 ◽  
Author(s):  
J. W. Moore ◽  
I. A. Moore
Keyword(s):  
Antennal Segment ◽  
The Other ◽  
Large Size ◽  
Great Slave Lake ◽  
Palpal Segment ◽  
Almost All

Descriptions of larvae of Procladius denticulatus, Procladius culiciformis, Procladius freemani, and Procladius bellus collected from Yellowknife Bay (lat., 62°25′; long., 114°20′) are given. Procladius denticulatus was separated from the other species by its large size, a character which always proved distinctive. Procladius culiciformis and P. freemani were separated from one another through several measurements including those of the basal antennal segment and the basal palpal segment. Almost all characters of the head were useful in distinguishing the much smaller P. bellus from the other species.

scholarly journals Geographical matching of volatile signals and pollinator olfactory responses in a cycad brood-site mutualism

2015 ◽  
Vol 282 (1816) ◽  
pp. 20152053 ◽  
Author(s):  
Terence N. Suinyuy ◽  
John S. Donaldson ◽  
Steven D. Johnson
Keyword(s):  
Choice Experiments ◽  
Local Region ◽  
The Other ◽  
Beetle Species ◽  
Olfactory Preference ◽  
Olfactory Responses ◽  
Volatile Emissions ◽  
Extant Species ◽  
Insect Pollinators ◽  
Almost All

Brood-site mutualisms represent extreme levels of reciprocal specialization between plants and insect pollinators, raising questions about whether these mutualisms are mediated by volatile signals and whether these signals and insect responses to them covary geographically in a manner expected from coevolution. Cycads are an ancient plant lineage in which almost all extant species are pollinated through brood-site mutualisms with insects. We investigated whether volatile emissions and insect olfactory responses are matched across the distribution range of the African cycad Encephalartos villosus . This cycad species is pollinated by the same beetle species across its distribution, but cone volatile emissions are dominated by alkenes in northern populations, and by monoterpenes and a pyrazine compound in southern populations. In reciprocal choice experiments, insects chose the scent of cones from the local region over that of cones from the other region. Antennae of beetles from northern populations responded mainly to alkenes, while those of beetles from southern populations responded mainly to pyrazine. In bioassay experiments, beetles were most strongly attracted to alkenes in northern populations and to the pyrazine compound in southern populations. Geographical matching of cone volatiles and pollinator olfactory preference is consistent with coevolution in this specialized mutualism.

Anna Karenina: The Dialectic of Prophecy

PMLA ◽  
1964 ◽  
Vol 79 (3) ◽  
pp. 266-282
Author(s):  
David H. Stewart
Keyword(s):  
Nineteenth Century ◽  
The Other ◽  
Moby Dick ◽  
Anna Karenina ◽  
Symbolic Value ◽  
Almost All ◽  
The Way

One of the most impressive features of Anna Karenina is the way in which Tolstoy draws the reader's imagination beyond the literal level of the narrative into generalizations that seem mythical in a manner difficult to articulate. With Dostoevsky or Melville, one sees immediately a propensity for exploiting the symbolic value of things. With Tolstoy, things try, as it were, to resist conversion: they strive to maintain their “thingness” as empirical entities. A character in Dostoevsky is usually only half man; the other half is Christ or Satan. Moby Dick is obviously only half whale; the other half is Evil or some principle of Nature. But Anna Karenina is emphatically Anna Karenina. Like almost all of Tolstoy's characters, she has a proficiency in the husbandry of identity; she jealously hoards her own unique reality, so that it becomes difficult to say of her that she is a “type” of nineteenth-century Russian lady or a “symbol” of modern woman or an “archetypical” Eve or Lilith.

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