Ju Hie Lee's scientific contributions

Publications (21)

Publications citing this author (312)

    • This diagnosis can be made if there is diffuse wall thickening or polyp or mass-like lesion with relevant histological changes [4]. According to this, we found several cases of gastric IgG4-RD, reported in literature [3,[6][7][8][9][10][11][12][13]. A summary of them is described in Table 1.
    [Show abstract] [Hide abstract] ABSTRACT: Background IgG4-related disease (IgG4-RD) is a newly recognized disorder, characterized by massive IgG4+ lymphocyte and plasma cell infiltration, storiform fibrosis, causing enlargement, nodules or thickening of the various organs, simultaneously or metachronously. Involvement of the gastrointestinal tract is very rare and can be presented as a diffuse wall thickening or polyp or mass-like lesion. Up to now, there have been reported only a few cases of isolated gastric IgG4-RD. Case presentation We present an unusual case of IgG4-RD of the stomach with involvement of the regional lymph nodes, clinically manifested as a gastric cancer with related pyloric stenosis. The patient underwent distal gastrectomy, omentectomy and lymph node dissection. The postoperative serum IgG4 level was increased. The diagnosis was confirmed by immunohistochemical study. Conclusions In the most of the reported cases there was not sufficient data about the regional lymph nodal status, although the majority of the patients had been operated with presumptive diagnosis of gastric neoplasm. Our case is rare and valuable because it presents a gastric IgG4-related lesion larger than all previously reported in literature, and IgG4-related lymphadenopathy, confirmed histologically, which contributes to better knowledge of the disease.
    Full-text · Article · Dec 2016
    • The most common findings on endoscopy includes esophagitis, colitis, gastritis, gastric erosions, duodenitis , proctitis, and polyps [7]. Myeloid sarcoma involving the gastrointestinal tract is very rare and can present with abdominal pain, bleeding, perforation, obstruction, intussusception , liver infarction, pancreatitis, appendicitis, bile duct obstruction, and portal hypertension891011. CT imaging might show focal bowel wall thickening, a single mass, polyps, multiple masses obstructing the gut lumen, or exophytic lesions involving the peritoneum [12].
    [Show abstract] [Hide abstract] ABSTRACT: Myeloid Sarcoma is a rare tumor composed of myeloblasts occurring at an extramedullary site like bones, or various soft tissues. Myeloid sarcoma may involve the gastrointestinal tract very rarely either solitarily, or occurring simultaneously with acute myeloid leukemia. Its diagnosis is challenging and needs biopsy and immunohistochemical staining. We are describing a case of myeloid sarcoma which presented as a painful anal ulcer mimicking an atypical fissure. Its appearance resembled crohn's disease on sigmoidoscopy. A biopsy of the ulcer along with histochemical staining led to the diagnosis of myeloid sarcoma. Our case demonstrates the need for aggressive evaluation of any common gastrointestinal complaint with an atypical presentation.
    Full-text · Article · May 2012
    • The primary location of EBVMCU is the oropharynx (52 %), with skin (29 %) and GI tract (19 %) occurring less frequently. The recurrent localization of EBVMCU to the oral cavity and GI tract likely reflects the initial site of EBV inoculation in the oropharynx and persistence of latent EBV within lymphocytes of Waldeyer's ring [44] and gut-associated lymphoid tissue [54] . EBV also has tropism for epithelial cells [55, 56], and 60 % of skin-localized EBVMCU occur on the face at sites overlying the oropharynx.
    [Show abstract] [Hide abstract] ABSTRACT: Background Epstein–Barr virus-positive mucocutaneous ulcer (EBVMCU) is a recently recognized B cell lymphoproliferative disorder that is driven by latent EBV infection and causes discrete ulcerations in the oropharynx, gastrointestinal tract, and skin. Local attenuation of immunosurveillance associated with iatrogenic immunosuppressant use, primary immunodeficiency, or age-associated immunosenescence has been implicated as a predisposing factor. This disorder is likely under reported, as it was only first defined in 2010 and shares histological features with other B-cell proliferative neoplasms. The first case series that described EBVMCU suggested that EBVMCU is generally self-limited and is likely to resolve without treatment. Since that publication, additional cases have been reported that describe a more heterogeneous clinical course, often requiring aggressive therapy. We now systematically review all published cases of EBVMCU and detail a case of aggressive and progressive EBVMCU, including diagnostic and management challenges, as well as successful treatment with radiation therapy. Case presentation A forty-nine year old woman presented with painful and debilitating multifocal oral EBVMCU that initially responded to four weekly doses of rituximab. Her disease relapsed within 3 months and continued to progress and cause significant morbidity. She was successfully treated with local external beam radiation therapy of 30 Gy in 15 fractions, with duration of response of at least 6 months. Conclusions We suggest that although many patients with EBVMCU experience a self-limited course, for others EBVMCU can be a debilitating, persistent disorder that requires aggressive therapy to prevent disease progression. CD20- and CD30-directed antibody therapy, local radiation therapy, local surgical excision, systemic chemotherapy, and a combination of these therapies have all been successfully used to treat EBVMCU with high rates of durable clinical remission. As EBVMCU is not currently included in the 2008 WHO classification of lymphoproliferative disorders and no evidence-based guidelines or expert opinions have been proposed to guide therapy, this case report and systematic review provides a foundation on which to guide therapeutic decisions.
    Full-text · Article · Apr 2016
    • Schematic overview of thrombin's effects upon miR-181c and MLL1 in human microglia. Thrombin (via PAR4) induces TNF-α secretion from human microglia[21]. Thrombin-induced TNF-α (via TNFR) suppresses miR-181c levels.
    [Show abstract] [Hide abstract] ABSTRACT: Background Controlling thrombin-driven microglial activation may serve as a therapeutic target for intracerebral hemorrhage (ICH). Here, we investigated microRNA (miRNA)-based regulation of thrombin-driven microglial activation using an in vitro thrombin toxicity model applied to primary human microglia. Methods A miRNA array identified 22 differential miRNA candidates. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) identified miR-181c as the most significantly downregulated miRNA. TargetScan analysis identified mixed lineage leukemia-1 (MLL1) as a putative gene target for miR-181c. qRT-PCR was applied to assess tumor necrosis factor-alpha (TNF-α), miR-181c, and MLL1 levels following thrombin or proteinase-activated receptor-4-specific activating peptide (PAR4AP) exposure. Anti-TNF-α antibodies and tumor necrosis factor receptor (TNFR) silencing were employed to test TNF-α/TNFR dependence. A dual-luciferase reporter system and miR-181c mimic transfection assessed whether mir-181c directly binds to and negatively regulates MLL1. Nuclear factor kappa-B (NF-κB)-dependent luciferase reporter assays and NF-κB target gene expression were assessed in wild-type (MLL1+) and MLL1-silenced cells. Results Thrombin or PAR4AP-induced miR-181c downregulation (p < 0.05) and MLL1 upregulation (p < 0.05) that were dependent upon TNF-α/TNFR. miR-181c decreased wild-type MLL1 3′-UTR luciferase reporter activity (p < 0.05), and a miR-181c mimic suppressed MLL1 expression (p < 0.05). Thrombin treatment increased, while miR-181c reduced, NF-κB activity and NF-κB target gene expression in both wild-type (MLL1+) and MLL1-silenced cells (p < 0.05). Conclusions Thrombin-induced, TNF-α/TNFR-dependent miR-181c downregulation promotes MLL1 expression, increases NF-κB activity, and upregulates NF-κB target gene expression. As miR-181c opposes thrombin’s stimulation of pro-inflammatory NF-κB activity, miR-181c mimic therapy may show promise in controlling thrombin-driven microglial activation following ICH. Electronic supplementary material The online version of this article (doi:10.1186/s12974-017-0887-5) contains supplementary material, which is available to authorized users.
    Full-text · Article · Jun 2017
    • Another important signalling protein that is linked to BDNF is phosphorylated AMP-activated protein kinase (pAMPK). Studies have demonstrated that pAMPK activation increases BDNF expression in the brain (Gomez-Pinilla et al., 2008; Yoon et al., 2008; Zhao et al., 2008), suggesting that its activation plays a crucial role in promoting synaptic plasticity. Furthermore, it has been reported that a HF diet reduces the phosphorylation of AMPK in the hippocampus in rats (Wu et al., 2006).
    [Show abstract] [Hide abstract] ABSTRACT: High fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6 J male mice were fed a lab chow (LC) (5% of energy as fat), HF (40% of energy as fat), or HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via western blotting and N-methyl-D-aspartate (NMDA) receptor binding. BM treatment prevented HF diet induced impairment in recognition memory (p < 0.001). In HF diet fed mice, BM administration attenuated alterations in NMDA receptor binding density in the PFC (p < 0.05), however, no changes were seen in the hippocampus (p > 0.05). In the PFC and hippocampus of HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p < 0.05). BM administration also prevented the HF diet induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus.
    Full-text · Article · Jan 2015
    • Other pathogens have also been detected in dust storm particles. According to a current outline of the current state of affairs in the Middle East, many of the opportunistic dust-borne pathogens can play an important role in human health [25,888990919293. Microbial products including lipopolysaccharide (LPS) that is a glycolipid of gram-negative bacteria cell wall, and β-glucan that is the major constituent of fungi wall are also found in sand dust particles.
    [Show abstract] [Hide abstract] ABSTRACT: Incidences of sand storms have increased in recent years and there is evidence that these dusts can move across long distances. Sand dusts have different adverse effects on health, but one of the most important of them is pulmonary disease. After inhalation of dust, many dust particles are moved to the airways. Dust particles can be sensed by airways epithelial cells, activate macrophages, dendritic cells and innate immune cells and then initiate responses in various populations of specific immune cells such as T helper cells subsets (Th1, Th2, Th17), T cytotoxic cells and B cells. Initiation of inflammatory immune responses, activation of immune cells and releases of many cytokines, chemokines and other inflammatory molecules, have variable pathologic affects on lung in different respiratory diseases. Unfortunately control of desert dusts is more difficult than control of air pollution. For prevention and treatment of respiratory diseases that are caused by desert dusts, researchers need well-designed epidemiological studies, combined with analysis of the precise composition of sand dusts, and the precise mechanisms of the immune responses. Recognizing the exact cellular and molecular immune mechanisms would be very useful to find new approaches for treatment of desert dust associated pulmonary diseases.
    Full-text · Article · Mar 2014
    • Of these, at least, oleoamide and palmitic acid has been reported to show some pharmacological activities related to the antinociceptive activity of PEMM. Oleamide, for example, has been reported to exert anti-inflammatory activity when assessed using the lipopolysaccharide (LPS)-induced BV2 micro- glial [68] . The inhibition of inflammation occurs via inhibition of NO and PGE 2 production.
    [Show abstract] [Hide abstract] ABSTRACT: Background Melastoma malabathricum L. (family Melastomaceae) has been traditionally used as remedies against various ailments including those related to pain. The methanol extract of M. malabathricum leaves has been proven to show antinociceptive activity. Thus, the present study aimed to determine the most effective fraction among the petroleum ether- (PEMM), ethyl acetate- (EAMM) and aqueous- (AQMM) fractions obtained through successive fractionation of crude, dried methanol extract of M. malabathricum (MEMM) and to elucidate the possible mechanisms of antinociception involved. Methods The effectiveness of fractions (100, 250 and 500 mg/kg; orally) were determine using the acetic acid-induced abdominal constriction test and the most effective extract was further subjected to the hot plate- or formalin-induced paw licking-test to establish its antinociceptive profile. Further elucidation of the role of opioid and vanilloid receptors, glutamatergic system, and nitric oxide/cyclic guanosine phosphate (NO/cGMP) pathway was also performed using the appropriate nociceptive models while the phytoconstituents analyses were performed using the phytochemical screening test and, HPLC-ESI and GCMS analyses. ResultsPEMM, EAMM and AQMM significantly (p < 0.05) attenuated acetic acid-induced nociception with the recorded EC50 of 119.5, 125.9 and 352.6 mg/kg. Based on the EC50 value, PEMM was further studied and also exerted significant (p < 0.05) antinociception against the hot plate- and formalin-induced paw licking-test. With regards to the mechanisms of antinociception,: i) PEMM significantly (p < 0.05) attenuated the nociceptive action in capsaicin- and glutamate-induced paw licking test.; ii) naloxone (5 mg/kg), a non-selective opioid antagonist, failed to significantly (p < 0.05) inhibit PEMM’s antinociception iii) L-arginine (a nitric oxide precursor), but not NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase), methylene blue (MB; an inhibitor of cGMP), or their respective combination, significantly (p < 0.05) reversed the antinociception of PEMM. Phytochemical analyses revealed the presence of several antinociceptive-bearing bioactive compounds, such as triterpenes and volatile compounds like oleoamide and palmitic acid. The presence of low flavonoids, such as gallocatechin and epigallocatechin, saponins and tannins in PEMM might synergistically contribute to enhance the major compounds antinociceptive effect. ConclusionPEMM exerted a non-opioid-mediated antinociceptive activity at the central and peripheral levels via the inhibition of vanilloid receptors and glutamatergic system, and the activation of NO-mediated/cGMP-independent pathway. Triterpenes, as well as volatile oleoamide and palmitic acid, might be responsible for the observed antinociceptive activity of PEMM.
    Full-text · Article · Dec 2016
    • Bone marrow involvement in NHL varies from 20% to 40% in different Western studies, which is similar to our studies. [1,6,23] In, different Indian studies bone marrow involvement in HL is 8.33- 9.68% which is almost similar to our study. [6,7] Extranodal lymphomas (ENL) are common and accounted for 27.7% of ML cases.
    [Show abstract] [Hide abstract] ABSTRACT: Malignant lymphoma (ML) is one of the most common cancers and is most prevalent in developed countries. The distribution of different subtypes of ML varies in the different geographical locations according to World Health Organization (WHO) Classification. The study was aimed to analyze the different patterns of ML in Eastern India and to compare it with other geographical locations. Four hundred and fifty five patients of two large hospitals in Eastern India were included over a period of four years and were categorized according to WHO classification, using the morphology and immunohistochemistry. There were 347 (76.3%) non Hodgkin lymphomas (NHL), and 108 (23.7%) Hodgkin lymphomas (HL). Diffuse large B-cell lymphoma was the most common of the NHL type (35.2%) followed by the follicular lymphoma (19.3%). B-cell lymphoblastic lymphoma was the least common type of NHL (1.4%). Mixed cellularity (33.3%) and nodular sclerosis (26.9%) were the two most common type of HL. Childhood lymphoma comprised of 12.5%of all ML. T-cell NHL and HL were the common lymphomas in this age group. Incidence of follicular lymphoma is lower compared to western studies and mixed cellularity is the most common subtype of HL unlike nodular sclerosis subtype in Western world. Burkitt's type NHL though is the most common subtype of childhood ML in many studies. However, in our study, T-cell NHL is the most common type of childhood ML.
    Full-text · Article · Oct 2013
    • Moreover, the use of the Ca 2+ chelators EGTA and BAPTA-AM and the CaMKK2 inhibitor STO-609 demonstrated that the Ca 2+ /CaMKK2/AMPK pathway is an upstream signal of PKCh phosphorylation at Thr538 in PMA/Io-stimulated Jurkat cells. The authors also demonstrated that AMPK regulates transactivation of NFAT and AP-1 in PMA/Io-induced Jurkat cells, consistent with prior studies[127,128]. Because PMA/Io, PHA (phytohemagglutinin) or anti-CD3/anti-CD28 mAbs are benchmark pharmacological activators of T cells and are also used as benchmark standards in reactivating latent HIV-1 viral reservoirs, effective candidate HIV-1 latency reversal compounds must comprehensively mirror cellular pathways associated with selective activation of memory CD4 + T cells latently infected with HIV-1 without inducing global T cell activation.
    [Show abstract] [Hide abstract] ABSTRACT: Although the use of antiretroviral therapy (ART) has proven highly effective in controlling and suppressing HIV-1 replication, the persistence of latent but replication-competent proviruses in a small subset of CD4(+) memory T cells presents significant challenges to viral eradication from infected individuals. Attempts to eliminate latent reservoirs are epitomized by the 'shock and kill' approach, a strategy involving the combinatorial usage of compounds that influence epigenetic modulation and initiation of proviral transcription. However, efficient regulation of viral pre-mRNA splicing through manipulation of host cell splicing machinery is also indispensible for HIV-1 replication. Interestingly, aberrant alternative splicing of the LMNA gene via the usage of a cryptic splice site has been shown to be the cause of most cases of Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic condition characterized by an accelerated aging phenotype due to the accumulation of a truncated form of lamin A known as progerin. Recent evidence has shown that inhibition of the splicing factors ASF/SF2 (or SRSF1) and SRp55 (or SRSF6) leads to a reduction or an increase in progerin at both the mRNA and protein levels, respectively, thus altering the LMNA pre-mRNA splicing ratio. It is also well-established that during the latter stages of HIV-1 infection, an increase in the production and nuclear export of unspliced viral mRNA is indispensible for efficient HIV-1 replication and that the presence of ASF/SF2 leads to excessive viral pre-mRNA splicing and a reduction of unspliced mRNA, while the presence of SRp55 inhibits viral pre-mRNA splicing and aids in the generation and translation of unspliced HIV-1 mRNAs. The splicing-factor associated protein and putative mitochondrial chaperone p32 has also been shown to inhibit ASF/SF2, increase unspliced HIV-1 viral mRNA, and enhance mitochondrial DNA replication and oxidative phosphorylation. It is our hypothesis that activation of AMPK, a master regulator of cellular metabolism which has been shown to activate PKC-theta (θ) and is essential for T cell activation, may modulate the splicing activities of SRp55 as well as enhance a p32-mediated inhibition of ASF/SF2-induced alternative splicing, potentially correcting aberrant alternative splicing in the LMNA gene and reactivating latent viral HIV-1 reservoirs. Moreover, similar epigenetic modifications and cell cycle regulators also characterize the analogous stages of premature senescence in progeroid cells and latency in HIV-1 infected T cells. AMPK-activating compounds including metformin and resveratrol may thus embody a novel treatment paradigm linking the pathophysiology of HGPS with that of HIV-1 latency. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jun 2015
    • In addition, contributes to the development of myocardial injury, cardiac dysfunction and acute contractile defect by proteolitic degradation of intracellular proteins such as troponin I (Wang et al., 2002), myosin-light chain-1 (Sawicki et al., 2005) and also apha-actinin, desmin and poly-ADP-ribose polymerase (Kwan et al., 2004;Sung et al., 2007). Furthermore, increased expression of MMPs have been related with atherosclerosis (Heo et al., 2011) by degradation of collagen and smooth-muscle cell migration within a vessel, resulting in occlusion and ischemic events (Vacek et al., 2015). It has been suggested that locally produced MMP-2 is activated by thrombin and therefore increases local matrix-degrading activity in atherosclerotic plaques (Galis et al., 1997).
    [Show abstract] [Hide abstract] ABSTRACT: Matrix metalloproteinases (MMPs) are enzymes involved in cardiovascular (CV) remodeling and hypertension-mediated target organ damage (TOD). Genetic polymorphisms in matrix metalloproteinase 2 (MMP-2) gene [− 1575G/A (rs243866); − 1306C/T (rs243865); and − 735C/T (rs2285053)] are associated with several CV conditions, however the relationship between MMP-2 polymorphisms and resistant hypertension (RH) is unknown. We evaluated whether these genetic single nucleotide polymorphisms (SNPs) in MMP-2 gene are associated with 1) MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) levels in RH and mild to moderate hypertensive (HT) subjects, 2) left ventricular hypertrophy (LVH) and arterial stiffness and 3) the presence of RH.
    Full-text · Article · Apr 2017