[Show abstract][Hide abstract] ABSTRACT: Unstable carotid atherosclerotic plaques are characterized by cap rupture, leading to thromboembolism and stroke. Matrix metalloproteinases (MMPs) have been implicated in the progression of atherosclerosis and plaque rupture. The aim of this study was to assess the relationship between the expressions of MMP-2 and MMP-9 and carotid plaque instability.
Eighty atherosclerotic plaques were collected from 74 patients undergoing carotid endarterectomy. Clinical information was obtained from each patient, and plaque morphology was examined at the macroscopic and microscopic levels. The immunohistochemical expressions of MMPs were graded using semiquantitative scales.
Macroscopic ulceration (84.6% versus 63.4%, p=0.042) and microscopic cap rupture (79.5% versus 51.2%, p=0.010) were more common in symptomatic than in asymptomatic patients. Immunoreactivities of MMP-2 and MMP-9 were increased in 40 and 36 atheromatous plaques, respectively. Macroscopic ulceration was strongly correlated with the expressions of MMP-2 (p<0.001) and MMP-9 (p=0.001). There were significant correlations between increased MMP-2 expression and cap rupture (p=0.002), intraplaque hemorrhage (p=0.039), and a thin fibrous cap (p=0.002), and between increased MMP-9 expression and cap rupture (p=0.010) and a large lipid core (p=0.013).
Plaque rupture was significantly associated with the development of vascular events in carotid atherosclerotic disease. MMP-2 and MMP-9 are strongly correlated with plaque instability.
[Show abstract][Hide abstract] ABSTRACT: Alpha1-antitrypsin (AAT) is the main inhibitor of human neutrophil elastase, and plays a role in counteracting the tissue damage caused by elastase in local inflammatory conditions. The study evaluated the involvement of AAT in nasal allergic inflammation.
Forty subjects with mono-sensitization to Dermatophagoides pteronyssinus (Dpt) were enrolled. Twenty allergic rhinitis patients frequently complained of nasal symptoms such as rhinorrhea, stuffiness, sneezing, and showed positive responses to the nasal provocation test (NPT) with Dpt (Group I). The other 20 asymptomatic patients showed sensitization to Dpt but negative NPT (Group II). The levels of AAT, eosinophil cationic protein (ECP), and Dpt-specific IgA antibodies were measured in the nasal lavage fluids (NLFs), collected at baseline, 10 minutes, 30 minutes, 3 hours, and 6 hours after the NPT. Nasal mucosa AAT expression was evaluated with immunohistochemical staining from Group I and Group II.
At baseline, only the Dpt-specific IgA level was significantly increased in the NLFs of Group I compared with Group II, while ECP and AAT levels were not significantly different between two groups. After Dpt provocation, AAT, ECP, and Dpt-specific IgA levels were significantly increased in the NLFs of Group I during the early and late responses. The protein expression level of AAT was mostly found in the infiltrating inflammatory cells of the nasal mucosa, which was significantly increased in Group I compared to Group II.
The increment of AAT showed a close relationship with the activation of eosinophils induced by allergen-specific IgA in the NLFs of patients with allergic rhinitis after allergen stimulation. These findings implicate AAT in allergen-induced nasal inflammation.
[Show abstract][Hide abstract] ABSTRACT: Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia.
[Show abstract][Hide abstract] ABSTRACT: Granulocytic sarcoma (GS) is defined as a localized tumor mass composed of myeloid blasts and/or immature myeloid cells in an extramedullary site. Usually, GS occurs concomitantly with or after acute myelogenous leukemia (AML), myeloproliferative disorder, or myelodysplastic syndrome. In rare cases, it occurs as a "preleukemic" condition and may precede the onset of AML, which occurs within several months if the patient is not treated with AML-type systemic chemotherapy. Recently, we discovered one case of nonleukemic GS in the small intestine incidentally when intussusception was suspected. The patient visited the emergency department, in October 2006, with symptoms of small-bowel obstruction. Intussusception due to a small-intestinal mass was suspected after evaluation, and small-intestine segmental resection was performed. The patient had no previous history of leukemia, and immunohistochemical staining was used to diagnose GS. Bone-marrow biopsy performed subsequently revealed no lesions that could be suspected as leukemia. The patient received three cycles of chemotherapy, applied as for AML (cytosine arabinoside and anthracycline), and is currently, as of October 29, 2007, showing no other marked indisposition; he has been disease-free for 12 months.
International Journal of Clinical Oncology 11/2008; 13(5):467-70. DOI:10.1007/s10147-008-0774-2 · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis. Kainic acid (KA), a prototype excitotoxin is known to induce brain-derived neurotrophic factor (BDNF) in brain. In this study, we examined the role of AMPK in KA-induced BDNF expression in C6 glioma cells. We showed that KA and KA receptor agonist induced activation of AMPK and KA-induced AMPK activation was blocked by inhibition of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) beta. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPKalpha1 blocked KA-induced BDNF mRNA and protein expression. Inhibition of AMPK blocked KA-induced phosphorylation of CaMKII and I kappaB kinase (IKK) in C6 cells. Finally, we showed that inhibition of AMPK reduced DNA binding and transcriptional activation of nuclear factor-kappaB (NF-kappaB) in KA-treated cells. These results suggest that AMPK mediates KA-induced BDNF expression by regulating NF-kappaB activation.
Biochemical and Biophysical Research Communications 08/2008; 371(3):495-500. DOI:10.1016/j.bbrc.2008.04.102 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis and its activation during T cell receptor stimulation has recently been reported. In this study, we examined the role of AMPK in interleukin (IL)-2 production in T cells. Inhibition of AMPK by compound C, a specific inhibitor of AMPK or small interfering RNA of AMPKalpha1 suppressed IL-2 production in Jurkat T cells and peripheral blood lymphocytes stimulated with PMA plus ionomycin (PMA/Io) or with monoclonal anti-CD3 plus anti-CD28. We then showed that AMPK inhibition reduced PMA/Io-induced IL-2 mRNA expression and IL-2 promoter activation. Moreover, inhibition of AMPK suppressed transcriptional activation of NF-AT and AP-1, but not NF-kappaB, in PMA/Io-activated Jurkat cells. Finally, we found that compound C inhibited PMA/Io-induced phosphorylation of p38, JNK, and GSK-3beta but not of ERK. These results suggest that AMPK mediates IL-2 production by regulating NF-AT and AP-1activation during T cell stimulation.
Biochemical and Biophysical Research Communications 01/2007; 351(4):986-92. DOI:10.1016/j.bbrc.2006.10.138 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adenosine is an endogenous nucleoside that regulates many processes, including inflammatory responses, through activation of its receptors. Adenosine receptors have been reported to be expressed in microglia, which are major immune cells of brain, yet little is known about the role of adenosine receptors in microglial cytokine production. Thus, we investigated the effect of adenosine and adenosine A3 receptor ligands on LPS-induced tumor necrosis factor (TNF-alpha) production and its molecular mechanism in mouse BV2 microglial cells. Adenosine and Cl-IB-MECA, a specific adenosine A3 receptor agonist, suppressed LPS-induced TNF-alpha protein and mRNA levels. Moreover, MRS1523, a selective A3 receptor antagonist, blocked suppressive effects of both adenosine and Cl-IB-MECA on TNF-alpha. We further examined the effect of adenosine on signaling molecules, such as PI 3-kinase, Akt, p38, ERK1/2, and NF-kappaB, which are involved in the regulation of inflammatory responses. Adenosine inhibited LPS-induced phosphatidylinositol (PI) 3-kinase activation and Akt phosphorylation, whereas it had no effect on the phosphorylation of p38 and ERK1/2. We also found that adenosine as well as Cl-IB-MECA inhibited LPS-induced NF-kappaB DNA binding and luciferase reporter activity. Taken together, these results suggest that adenosine A3 receptor activation suppresses TNF-alpha production by inhibiting PI 3-kinase/Akt and NF-kappaB activation in LPS-treated BV2 microglial cells.
[Show abstract][Hide abstract] ABSTRACT: Malignant insulinomas are very rare endocrine tumours with a variable clinical course. Here, a case of a malignant insulinoma, resected from the tail of the pancreas 10 years previously, which was found to have hepatic metastasis, is reported. A pancreatic mass, without evidence of metastasis, has been found using an abdominal CT scan and intra-operative ultrasonography 10 years previously. Recently, the patient has suffered from dizziness, sweating and an altered mentality. Hyperinsulinemia was diagnosed from the biochemical laboratory finding. An abdominal CT scan and intra-operative abdominal sonography showed multiple hepatic metastasis, without local recurrence in pancreas. Therefore, a partial hepatic segmentectomy was performed. Immunohistochemical staining of the postoperative specimen was strongly positive for insulin. The postoperative biochemical response was normalized, and the patient experienced no further hypoglycemic symptom.
Journal of Korean Endocrine Society 01/2006; 21(1). DOI:10.3803/jkes.2006.21.1.68
[Show abstract][Hide abstract] ABSTRACT: Cryptococcus albidus, a non-neoformans species of the genus Cryptococcus, is generally regarded as a rare cause of disease. There have been only 14 previously reported cases in which this organism has been isolated as a pathogen, none of which occurred in a renal transplant recipient. A 23-year-old renal transplant recipient taking medication consisting of cyclosporine and prednisolone was admitted with a 10-day history of dry cough, fever and progressive dyspnea. The next day, his respiratory status deteriorated dramatically, and he developed acute respiratory distress syndrome (ARDS) and fulminant septic shock. On the eighth hospital day, tender macules on both his shins coalesced to form erythematous patches. Cryptococcus albidus was isolated by skin biopsy and tissue culture. We report here the first case of disseminated cryptococcosis caused by C. albidus in a renal transplant recipient who had been successfully treated with fluconazole monotherapy.
The Korean Journal of Internal Medicine 04/2004; 19(1):53-7. DOI:10.3904/kjim.2004.19.1.53 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have suggested a probable association between Epstein-Barr virus (EBV) and nasal/nasopharyngeal T cell lymphomas but the role of oncogenes or tumor suppressor genes is poorly understood. We have studied the frequency of p53 expression and its relation to the EBV infection in 33 Korean patients with head and neck (H&N) lymphomas. All cases (23 B cell & 10 T cell) were immunostained for p53 protein using the mAb D07 (Novocastra) and the avidin biotin peroxidase method. EBER in situ hybridization was performed using a fluorescein conjugated EBV oligonucleotide probe (Dako). Among 33 lymphomas, 16 cases stained positively for p53 protein. P53 expression was frequent both in higher grade lymphomas and in advanced stage. Nine cases were EBER positive, EBER was more commonly found in T cell lymphomas than in B cell lymphomas (70% vs 8.7%). EBER positive lymphomas showed a higher frequency of p53 positivity than EBER negative lymphomas (78% vs 38%), although the difference was not statistically significant (p = 0.095). These findings indicate altered expression of p53 protein occurs in H&N lymphomas, especially in late event lymphoma progression and appears to play a role in the development of EBER positive T cell lymphomas.
Journal of Korean Medical Science 12/1995; 10(6):399-405. DOI:10.3346/jkms.1922.214.171.1249 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We retrospectively studied 156 patients with non-Hodgkin's; ymphoma (NHL) in order to evaluate the incidence of bone marrow (BM) involvement at the time of diagnosis. The incidence of marrow involvement in NHL was 35% (55 patients). The most common histologic type of lymphoma was diffuse large cell lymphoma with 30% of the cases having bone marrow involvement. The highest incidence of marrow involvement was seen in immunoblastic lymphoma & the lowest incidence in diffuse mixed cell lymphoma. Bone marrow lymphoma was present in 50% of low-, 34% of intermediate-, and 55% of high-grade lymphomas. B-cell vs T-cell lymphoma in cases of marrow involvement was 56% to 42%. The most frequent pattern of marrow involvement was interstitial & diffuse (56% & 31%). The paratrabecular pattern was rare (4%). Most lymphomas (42%) extensively involved marrow space greater than 76% of the total marrow space. Discordant histology between lymph node and BM was seen in 10 cases (18%). Biopsy was the best method compared to smear & clot section (sensitivity 82% vs 72% vs 69%). In conclusion, our study revealed that the most common histologic type of marrow lymphoma was diffuse large cell type with frequent interstitial and diffuse pattern and extensive involvement of the marrow space. No predilection for a trabecular pattern was found. This result was in contrast to that in the Western literature.
Journal of Korean Medical Science 11/1994; 9(5):402-8. DOI:10.3346/jkms.19126.96.36.1992 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A high incidence of a T cell phenotype of sinonasal lymphomas in other Asian countries has been associated with a high incidence of Epstein Barr virus (EBV) infection. We analyzed 13 sinonasal and 18 Waldeyer's ring lymphomas for the prevalence of EBV encoded RNA (EBER) using a sensitive and specific in situ hybridization. In addition, we examined the relationship of histologic findings and immunophenotype as well as the location of the lymphomas to the presence of EBV. The EBER was detected in each of 12 sinonasal lymphomas with a T cell immunophenotype. One B cell sinonasal lymphoma was EBER negative. Four of 18 Waldeyer's ring lymphomas were positive for EBER, including two T cell lymphomas. Two of 16 B cell Waldeyer's ring lymphomas were EBER positive. Morphologically, 11 of 20 diffuse large cell lymphomas, 2 diffuse mixed small and large cell lymphomas, 2 of 4 immunoblastic lymphomas and 1 lymphoplasmacytic lymphoma were EBER positive. Four follicular large cell lymphomas were EBER negative. A characteristic angiocentric or angiodestructive pattern was found in most T cell lymphomas and EBER positive cases. These findings indicate that EBV infection is more strongly associated with the T cell immunophenotype, angiocentric pattern and sinonasal location of the lymphoma.
Journal of Korean Medical Science 09/1994; 9(4):281-8. DOI:10.3346/jkms.19188.8.131.521 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to compare the prognoses of patients with diffuse malignant lymphomas on the basis of histology and immunophenotypes, we retrospectively studied 62 cases of diffuse lymphoma arising in lymph nodes. We also evaluated the reactivity patterns of monoclonal antibodies (MoAb) LN1, LN2 and LN3 to determine the criteria for making a differential diagnosis in B cell lymphomas. The immunologic phenotypes were determined by the avidin biotin peroxidase complex method, using frozen or paraffin fixed tissues. The majority (66.3%) were B cell with the remaining 20.9% being T cell and 12.9% were non-B, non-T cell lineage. Immunological heterogeneity was found especially in the mixed small and large cell and the immunoblastic lymphomas. There was no significant difference between B- and T-cell lymphomas with respect to survival and death (P > 0.05). Histologically 79% (49/62) of the lymphoma was large cell and 21% (13/62), small cell lymphoma. There was a difference in prognosis between low, intermediate and high-grade of lymphomas. However there were no significant differences among the subtypes of the diffuse aggressive lymphomas. Factors associated with poor prognosis were advanced stages (P < 0.025) and histology of the malignant lymphomas. MoAb LN1, LN2 and LN3 gave positive staining in 83.3%, 91.7% and 60% of B cell lymphomas, respectively. The most common phenotypic pattern in B cell lymphomas was LN1+, LN2+, LN3+/-, suggestive of follicular center cell origin. As a panel, phenotypic patterns of MoAb LN1, LN2 and LN3 may be useful in differentiation of follicular center cell lymphoma from others.
Journal of Korean Medical Science 10/1992; 7(3):204-13. DOI:10.3346/jkms.19184.108.40.206 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe two cases of multiple lymphomatous polyposis in the gastrointestinal tract from the esophagus to the rectum. Clinical findings, histopathologic and immunohistochemical findings in paraffin embedded tissue are discussed. It is important to recognize this rare form of gastrointestinal lymphoma because of the prognostic and therapeutic implications.
Journal of Korean Medical Science 07/1992; 7(2):173-8. DOI:10.3346/jkms.19220.127.116.11 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case of rare intranasal hemangiopericytoma in a 68-year-old male was reported with typical histological and ultrastructural findings. The lesion clinically resembled a nasal polyp. The experience in the present case raised the need for differential diagnoses of vascularised spindle cell tumors and of traditional hemangiopericytoma in soft tissue.
Journal of Korean Medical Science 10/1990; 5(3):173-8. DOI:10.3346/jkms.1918.104.22.168 · 1.27 Impact Factor