• Title/Summary/Keyword: pathobiology

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RUNX1 Mutations in the Leukemic Progression of Severe Congenital Neutropenia

  • Olofsen, Patricia A.;Touw, Ivo P.
    • Molecules and Cells
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    • v.43 no.2
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    • pp.139-144
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    • 2020
  • Somatic RUNX1 mutations are found in approximately 10% of patients with de novo acute myeloid leukemia (AML), but are more common in secondary forms of myelodysplastic syndrome (MDS) or AML. Particularly, this applies to MDS/AML developing from certain types of leukemia-prone inherited bone marrow failure syndromes. How these RUNX1 mutations contribute to the pathobiology of secondary MDS/AML is still unknown. This mini-review focusses on the role of RUNX1 mutations as the most common secondary leukemogenic hit in MDS/AML evolving from severe congenital neutropenia (SCN).

Interleukin-4, Oxidative Stress, Vascular Inflammation and Atherosclerosis

  • Lee, Yong-Woo;Kim, Paul H.;Lee, Won-Hee;Hirani, Anjali A.
    • Biomolecules & Therapeutics
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    • v.18 no.2
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    • pp.135-144
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    • 2010
  • The pro-oxidative and pro-inflammatory pathways in vascular endothelium have been implicated in the initiation and progression of atherosclerosis. In fact, inflammatory responses in vascular endothelium are primarily regulated through oxidative stress-mediated signaling pathways leading to overexpression of pro-inflammatory mediators. Enhanced expression of cytokines, chemokines and adhesion molecules in endothelial cells and their close interactions facilitate recruiting and adhering blood leukocytes to vessel wall, and subsequently stimulate transendothelial migration, which are thought to be critical early pathologic events in atherogenesis. Although interleukin-4 (IL-4) was traditionally considered as an anti-inflammatory cytokine, recent in vitro and in vivo studies have provided robust evidence that IL-4 exerts pro-inflammatory effects on vascular endothelium and may play a critical role in the development of atherosclerosis. The cellular and molecular mechanisms responsible for IL-4-induced atherosclerosis, however, remain largely unknown. The present review focuses on the distinct sources of IL-4-mediated reactive oxygen species (ROS) generation as well as the pivotal role of ROS in IL-4-induced vascular inflammation. These studies will provide novel insights into a clear delineation of the oxidative mechanisms of IL-4-mediated stimulation of vascular inflammation and subsequent development of atherosclerosis. It will also contribute to novel therapeutic approaches for atherosclerosis specifically targeted against pro-oxidative and pro-inflammatory pathways in vascular endothelium.

Pregnancy outcomes following the administration of high doses of dexamethasone in early pregnancy

  • Ahmadabad, Hasan Namdar;Jafari, Sabah Kayvan;Firizi, Maryam Nezafat;Abbaspour, Ali Reza;Gharib, Fahime Ghafoori;Ghobadi, Yusef;Gholizadeh, Samira
    • Clinical and Experimental Reproductive Medicine
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    • v.43 no.1
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    • pp.15-25
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    • 2016
  • Objective: In the present study, we aimed to evaluate the effects of high doses of dexamethasone (DEX) in early pregnancy on pregnancy outcomes. Methods: Pregnant BALB/c mice were treated with high-dose DEX in the experimental group or saline in the control group on gestational days (GDs) 0.5 to 4.5. Pregnant mice were sacrificed on GDs 7.5, 13.5, or 18.5 and their peripheral blood, placentas, fetuses, and uterine tissue were collected. Decidual and placenta cell supernatants were examined to evaluate the effect of DEX on the proliferation of mononuclear cells, the quantity of uterine macrophages and uterine natural killer (uNK) cells, and levels of progesterone and $17{\beta}-estradiol$, as determined by an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We also were measured fetal and placental growth parameters on GD 18.5. Results: We found that high doses of DEX were associated with an increased abortion rate, enhancement of the immunosuppressive effect of the decidua, alterations in placental growth parameters, decreased progesterone and $17{\beta}-estradiol$ levels, and a reduced frequency of macrophages and uNK cells. Conclusion: Our data suggest that the high-dose administration of DEX during early pregnancy negatively affected pregnancy outcomes.

Characterization of a Toxocara canis species-specific excretory-secretory antigen(TcES-57) and development of a double sandwich ELISA for diagnosis of visceral larva migrans

  • Iddawela, R.D.;Rajapakse, R.P.V.J.;Perera, N.A.N.D.;Agatsuma, Takeshi
    • Parasites, Hosts and Diseases
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    • v.45 no.1 s.141
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    • pp.19-26
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    • 2007
  • This study describes the isolation of a Toxocara canis species-specific excretory-secretory(ES) antigen and the development of an enzyme-linked immunosorbent assay(ELISA) based on this antigen. Analysis of the ES antigens of T. canis, Toxocara vitulorum, Ascaris lumbricoides and Necator americanus larval antigen was performed by SDS-PAGE followed by western blotting. A 57 kDa T. canis-specific antibody fraction(TcES-57) was identified by western blotting and labelling with anti-Toxocara antibodies(from experimental rabbits and human patients) and tracing with anti-human or anti-rabbit peroxidase conjugate. No protein fraction of 57 kDa was detected in ES or larval antigens collected from T. canis, T. vitulorum, A. lumbricoides and N. americanus. Using TcES-57, a specific anti-serum was produced in rabbits and a double sandwich ELISA was developed. This test was validated using known seropositive sera from toxocariasis patients, sera from A. lumbricoides or N. americanus patients, and 50 serum samples from cats. These tests revealed that TcES-57 antigen is specific to T. canis infection and does not cross react with sera of other related infections. Thus, ELISA based on TcES-57 antigen was proven to be an effective tool in the diagnosis of toxocariasis and studies on the role of T. canis in the epidemiology of human toxocariasis.

Survey for zoonotic liver and intestinal trematode metacercariae in cultured and wild fish in An Giang Province, Vietnam

  • Thu Nguyen Diem;Dalsgaard Anders;Loan Ly Thi Thanh;Murrell K. Darwin
    • Parasites, Hosts and Diseases
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    • v.45 no.1 s.141
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    • pp.45-54
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    • 2007
  • Although Vietnam has a high risk of fish borne zoonotic trematode(FZT) infections for humans, little information exists on the epidemiology of these infections in the country's fish. Because of the importance of cultured cat-fish and snakehead production in An Giang province, a major production area in the Mekong Delta of Vietnam, a survey for FZTs was carried out in randomly selected fish farms between June 2005 and March 2006. For comparison, wild fish from the same area were also surveyed. A total of 852 cultured fish from 4 districts were collected and examined by pepsin digestion to determine their FZT infection status. In Tra catfish, the prevalence of all types of metacercariae was 2.6%, of which the prevalence of Haplorchis pumilio was 0.7%. The overall prevalence of metacercariae in wild fish was 30.6%, of which 10.3% harbored zoonotic species: H. pumilio(2.8%) and Procerovum sp.(5.6%). The prevalence of Opisthorchis metacercariae, which were diagnosed as O. viverrini, was 1.9%. No metacercariae were found in cultured snake head fish, although wild-caught snakehead fish had a FZT prevalence of 10.3%: 5.1% were O. viverrini; 2.6% H. pumilio; and 2.6% were Procerovum sp. These are the first reports of H. pumilio, Procerovum sp., and O. viverrini metacercariae in Vietnamese fish. These results indicate that consumption of improperly prepared fish represents a significant risk of acquiring FZTs in this south Vietnam region.