A variety of benzylidenethiazole analogs have been demonstrated to inhibit 5-lipoxygenase (5-LOX). Here we report the anti-atherogenic potential of 5-(4-hydroxy-2,3,5-trimethylbenzylidene) thiazolidin-2,4-dione (HMB-TZD), a benzylidenethiazole analog, and its potential mechanism of action in LDL receptor-deficient (Ldlr-/-) mice. HMB-TZD Treatment reduced leukotriene B4 (LTB4) production significantly in RAW264.7 macrophages and SVEC4-10 endothelial cells. Macrophages or endothelial cells pre-incubated with HMB-TZD for 2 h and then stimulated with lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha) displayed reduced cytokine production. Also, HMB-TZD reduced cell migration and adhesion in accordance with decreased proinflammatory molecule production in vitro and ex vivo. HMB-TZD treatment of 8-week-old male Ldlr-/- mice resulted in significantly reduced atherosclerotic lesions without a change to plasma lipid profiles. Moreover, aortic expression of pro-atherogenic molecules involved in the recruitment of monocytes to the aortic wall, including TNF-alpha , MCP-1, and VCAM-1, was downregulated. HMB-TZD also reduced macrophage infiltration into atherosclerotic lesions. In conclusion, HMB-TZD ameliorates atherosclerotic lesion formation possibly by reducing the expression of proinflammatory molecules and monocyte/macrophage recruitment to the lesion. These results suggest that HMB-TZD, and benzylidenethiazole analogs in general, may have therapeutic potential as treatments for atherosclerosis.
Animals ; Atherosclerosis/*drug therapy ; Cell Adhesion/drug effects ; Cell Line ; Cell Movement/drug effects ; Chemokine CCL2/metabolism ; Dinoprostone/metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Leukotriene B4/metabolism ; Macrophages/cytology/drug effects ; Male ; Mice ; Monocytes/cytology/*drug effects ; Random Allocation ; Receptors, LDL/deficiency/genetics ; Thiazolidinediones/*therapeutic use ; Tumor Necrosis Factor-alpha/pharmacology

Synaptotagmin is a Ca2+ sensing protein, which triggers a fusion of synaptic vesicles in neuronal transmission. Little is known regarding the expression of Ca2+ - dependent synaptotagmin isoforms and their contribution to the release of secretory vesicles in mouse and rat parotid acinar cells. We investigated a type of Ca2+ - dependent synaptotagmin and Ca2+ signaling in both rat and mouse parotid acinar cells using RT-PCR, microfluorometry, and amylase assay. Mouse parotid acinar cells exhibited much more sensitive amylase release in response to muscarinic stimulation than did rat parotid acinar cells. However, transient [Ca2+]i increases and Ca2+ influx in response to muscarinic stimulation in both cells were identical, suggesting that the expression or activity of the Ca2+ sensing proteins is different. Seven Ca2+ - dependent synaptotagmins, from 1 to 7, were expressed in the mouse parotid acinar cells. However, in the rat parotid acinar cells, only synaptotagmins 1, 3, 4 and 7 were expressed. These results indicate that the expression of Ca2+ - dependent synaptotagmins may contribute to the release of secretory vesicles in parotid acinar cells.
Synaptotagmins/*metabolism ; Signal Transduction ; Rats ; Protein Isoforms/metabolism ; Parotid Gland/cytology/*metabolism ; Muscarinic Agonists/pharmacology ; Mice ; Exocytosis/drug effects/physiology ; Carbachol/pharmacology ; Calcium/metabolism/*physiology ; Animals ; Amylases/secretion

BACKGROUND: Constipation occurs frequently in diabetes mellitus (DM). However, there are few reports that investigated the characteristics of constipation associated with DM. The purpose of this study was to evaluate the clinical features of constipation associated with DM. METHODS: Among constipated patients who visited Asan Medical Center from January 2000 to December 2004, 45 patients with DM (DM group) and 104 patients without DM (non-DM group) were included in this study. We reviewed the clinical presentation, results of anorectal manometry, colon transit time study, and defecogram. We also analyzed the response to biofeedback therapy. RESULTS: The severity of constipation symptoms before treatment was not different between DM and non-DM group. Patients with colon transit time over 56 hours were more frequent in DM group than in non-DM group (21/45, 46.7% vs. 31/104, 29.8% ; p=0.047). Among DM group, colon transit time and the duration of DM showed positive correlation (r=0.431, p=0.003). The resting anal sphincter pressure was significantly lower in DM group than in non-DM group (43.5+/-21.5 mmHg vs. 51.7+/-22.6 mmHg ; p=0.048). The results of defecography were similar between DM and non-DM group. Successful responses to biofeedback therapy were not different between DM and non-DM group (19/34, 55.9% vs. 43/79, 54.4% ; p=0.887). CONCLUSIONS: Slow transit constipation was more frequent in DM group than in non-DM group. The successful responses to biofeedback therapy appear to be similar between DM and non-DM group.
Anal Canal ; Biofeedback, Psychology ; Chungcheongnam-do ; Colon ; Constipation* ; Defecography ; Diabetes Mellitus* ; Humans ; Manometry ; Time and Motion Studies

BACKGROUND: Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anemias, with the majority of patients responding to immunosuppressive therapy. Fas, a member of the tumor necrosis factor (TNF) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon gamma (IFN-gamma) and TNF-alpha can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. METHODS: In order to investigate the involvement of apoptosis in the pathogenesis of aplastic anemia (AA), we measured the expression of Fas antigen and caspase-3 on bone marrow (BM) mononuclear cells (MNCs) of AA in the presence or absence of IFN-gamma, TNF-alpha, or macrophage inflammatory protein 1-alpha (MIP-1alpha). RESULTS: We confirmed that AA BM MNCs were more apoptotic and highly expressed Fas antigen than normal donors. Stimulation by IFN-gamma, TNF-alpha, or MIP-1alpha increased Fas antigen and caspase-3 expression in AA BM MNCs than BM MNCs of normal donors. Anti-Fas monoclonal antibody enhanced IFN-gamma, TNF-alpha, or MIP-1alpha mediated caspase-3 expression in BM MNCs of normal donors. Among these three cytokines, IFN-gamma enhanced apoptosis most strongly via Fas-caspase-3 pathway. CONCLUSION: These results suggest that Fas signal pathway may play a role in the pathophysiology of aplastic anemia and negative hematopoietic regulators like IFN-gamma can induce apoptosis of bone marrow progenitors in part by Fas induction.
Anemia, Aplastic* ; Antigens, CD95* ; Apoptosis* ; Bone Marrow Cells* ; Bone Marrow* ; Caspase 3 ; Chemokine CCL3 ; Cytokines ; Hematopoietic Stem Cells ; Humans ; Immunity, Cellular ; Interferons ; Signal Transduction ; Tissue Donors ; Tumor Necrosis Factor-alpha

Skeletal muscle is one of the most unusual metastatic sites for any malignancy. Duodenal cancer is extremely rare, and no cases of skeletal muscle metastasis from duodenal cancer have been reported. We report here in a case of metastasis to the skeletal muscle of the left thigh from duodenal cancer. Our patient was a 47-year-old man, exhibiting a painful mass in the posterior aspect of his left thigh over a 4 month period. An imaging study, and a biopsy, revealed a duodenal adenocarcinoma metastasize to the skeletal muscle. The patient refused chemotherapy and has followed up for 4 months.
Adenocarcinoma* ; Biopsy ; Drug Therapy ; Duodenal Neoplasms ; Duodenum* ; Humans ; Middle Aged ; Muscle, Skeletal* ; Neoplasm Metastasis* ; Thigh*

Citrullinemia is a rare inborn error of metabolism of the urea cycle, and was first reported by McMurray, et al. in 1962. It is inherited as an autosomal recessive trait. The normal synthesis of argininosuccinic acid is blocked in this disease due to a deficiency of argininosuccinic acid synthetase(AS), which has been demonstrated in liver cells and fibroblasts. The clinical symptoms are vomiting, lethargy or irritability, convulsion and mental retardation. The diagnosis is made by the finding of an increased plasma citrulline level. Every effort should be made to reduce the blood ammonia level as rapidly as possible before irreversible brain damage occurs. This report describes a case of citrullinemia that was diagnosed through organic acid analysis and amino acid analysis, and reviews the related literatures.
Ammonia ; Argininosuccinic Acid ; Brain ; Citrulline ; Citrullinemia* ; Diagnosis ; Fibroblasts ; Intellectual Disability ; Lethargy ; Liver ; Metabolism ; Plasma ; Seizures ; Urea ; Vomiting

PURPOSE: High dose chemotherapy (HDC) is increasingly being used for ovarian cancer. Although early studies of autotransplantation for advanced ovarian cancer have been encouraging, most reported series were small, and no randomized trials have been reported. HDC and autologous hematopoietic stem cell transplantation were rarely performed in patients with ovarian cancer in Korea, and no results have been reported with the exception of one case report. MATERIALS AND METHODS: We retrospectively analyzed 10 patients with refractory or relapsed ovarian cancer having received HDC and autologous peripheral blood stem cell transplantation (APBSCT), between January 1996 and September 1998, at the Soon Chun Hyang and Ajou University Hospitals. RESULTS: Ten patients were treated with HDC and APBSCT. Six patients achieved complete response (CR) and 1 a partial response (PR), with a response rate of 70%. Three patients did not respond following mobilization chemotherapy, and failed to respond after HDC. The median duration of progression free survival (PFS) and overall survival (OS) were 6 (4~46) and 13 (3~50+) months, respectively. The median duration of OS of the responders following mobilization chemotherapy was 23 (8~50+) compared with 12 (3~18) months of the non- responders. With regard to the treatment related toxicity, 8 patients had neutropenic fevers, and bacteremia was documented in 4. The non-hematological toxicities were never life threatening, and there were no treatment related deaths. CONCLUSION: HDC, followed by APBSCT, is well-tolerated patients with refractory or relapsed ovarian cancer, and following mobilization chemotherapy the responders survived longer than the non-responders.
Autografts ; Bacteremia ; Disease-Free Survival ; Drug Therapy* ; Fever ; Hematopoietic Stem Cell Transplantation ; Hospitals, University ; Humans ; Korea ; Ovarian Neoplasms* ; Peripheral Blood Stem Cell Transplantation* ; Retrospective Studies ; Stem Cell Transplantation

All-trans retinoic acid (ATRA) therapy induces complete remission in acute promyelocytic leukemia (APL) via differentiation of the APL cells. Recent clinical trials in China and United states showed that arsenic trioxide (ATO) is an effective and relatively safe drug in the treatment of APL. The patient was 29-year-old woman with APL who had been treated heavily with allogeneic bone marrow transplantation (BMT) in 4 years ago and reinduction chemotherapy plus donor lymphocyte infusion (DLI) after relapse in 2 years ago. After diagnosis for relapse, she had been treated with ATRA, but unfortunately failed. She was treated with ATO at the dose of 10 mg/day intravenously for 6 weeks. Complete remission was achieved at 3 weeks and the cumulative dose of ATO during induction was 420mg. She had complete remission without severe adverse effects except mild impairment of liver function and is following up for 6 months. We report a case of remission induction by ATO in ATRA refractory APL patient who experienced multiple relapse after allogeneic BMT, chemotherapy and DLI.
Adult ; Arsenic* ; Bone Marrow Transplantation* ; Bone Marrow* ; China ; Diagnosis ; Drug Therapy ; Female ; Humans ; Leukemia, Promyelocytic, Acute* ; Liver ; Lymphocytes ; Recurrence ; Remission Induction* ; Tissue Donors ; Tretinoin ; United States

We report a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. The patient demonstrated a round mass in the right occipital area for 12 months and the lesion grew rapidly to assume 8x6.5x4cm in diameter, with areas of superficial erosion and crusting within the recent 3 months. The entire lesion was removed with a wide surgical excision. It recurred on the neck area 4 months after excision and the lesion was removed with surgical resection again. There was evidence of multiple metastases on CNS and mediastinal lymph nodes after 6 months. The patient was treated with cisplatin and etoposide combination chemotherapy and a partial response was achieved.
Adult ; Antineoplastic Agents, Combined/administration & dosage ; Biopsy, Needle ; Brain Neoplasms/therapy ; Brain Neoplasms/secondary* ; Brain Neoplasms/pathology ; Case Report ; Combined Modality Therapy ; Follow-Up Studies ; Head and Neck Neoplasms/therapy ; Head and Neck Neoplasms/surgery ; Head and Neck Neoplasms/pathology* ; Human ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Neoplasms, Basal Cell/therapy ; Neoplasms, Basal Cell/secondary* ; Neurosurgical Procedures/methods ; Reoperation ; Scalp* ; Skin Neoplasms/therapy ; Skin Neoplasms/surgery ; Skin Neoplasms/pathology* ; Tomography, X-Ray Computed

BACKGROUND: The aim of this study was to evaluate the effect of 4-aminopyridine (4-AP) combined with anticholiesterase (antiChE) in antagonizing MgSO4-rocuronium-induced neuromuscualr blockade using a rat hemidiaphragm. METHODS: A hemidiaphragm with phrenic nerve was dissected and was mounted in a bath containing oxygenated Krebs solution. The phrenic nerve was stimulated supramaximally and the twitch response (0.1 Hz) was stabilized for at least 30 minutes. After maximal twitch inhibition by IC95 (concentration of 95% twitch inhibition) of rocuronium and MgSO4 20 mg was achieved, antagonistic effects of 1.6, 16 microgram/ml of edrophonium, 0.1, 1.0 microgram/ml of neostigmine, 0.5, 5.0 microgram/ml of pyridostigmine, and 0.8 microgram/ml of 4-AP combined with each of the above mentioned antiChEs were investigated. RESULTS: Whereas antiChE alone at low concentration partially recovered only the twitch response, 4-AP combined with antiChE recovered both the twitch and train-of-four responses significantly. CONCLUSIONS: 4-AP enhances antagonism of a magnesium-rocuronium induced neuromuscular blockade by edrophonium, neostigmine or pyridostigmine in vitro.
4-Aminopyridine* ; Animals ; Baths ; Cholinesterase Inhibitors* ; Edrophonium ; Neostigmine ; Neuromuscular Blockade* ; Oxygen ; Phrenic Nerve ; Pyridostigmine Bromide ; Rats