BACKGROUND: T cell immunoglobulin and mucin domain containing 3 protein (Tim-3) expressed on terminally differentiated Th1 cells plays a suppressive role in Th1-mediated immune responses. Recently, it has been shown that N-glycosylation affects the binding activity of the Tim-3-Ig fusion protein to its ligand, galectin-9, but the binding properties of non-glycosylated Tim-3 on CD4+CD25+ T cells has not been fully examined. In this study, we produced recombinant Tim-3-Ig fusion proteins in different cellular sources and its N-glycosylation mutant forms to evaluate their binding activities to CD4+CD25+ T cells. METHODS: We isolated and cloned Tim-3 cDNA from BALB/C mouse splenocytes. Then, we constructed a mammalian expression vector and a prokaryotic expression vector for the Tim-3-Ig fusion protein. Using a site directed mutagenesis method, plasmid vectors for Tim-3-Ig N-glycosylation mutant expression were produced. The recombinant protein was purified by protein A sepharose column chromatography. The binding activity of Tim-3-Ig fusion protein to CD4+CD25+ T cells was analyzed using flow cytometry. RESULTS: We found that the nonglycosylated Tim-3-Ig fusion proteins expressed in bacteria bound to CD4+CD25+ T cells similarly to the glycosylated Tim-3-Ig protein produced in CHO cells. Further, three N-glycosylation mutant forms (N53Q, N100Q, N53/100Q) of Tim-3-Ig showed similar binding activities to those of wild type glycosylated Tim-3-Ig. CONCLUSION: Our results suggest that N-glycosylation of Tim-3 may not affect its binding activity to ligands expressed on CD4+CD25+ T cells.
Animals ; Bacteria ; CHO Cells ; Chromatography ; Clone Cells ; Cricetinae ; DNA, Complementary ; Flow Cytometry ; Immunoglobulins ; Ligands ; Mice ; Mucins ; Mutagenesis, Site-Directed ; Plasmids ; Proteins ; Sepharose ; Staphylococcal Protein A ; T-Lymphocytes ; Th1 Cells

We would like to correct the phrases.

During Toxoplasma gondii infection, macrophages, dendritic cells, and neutrophils are important sources of pro-inflammatory cytokines from the host. To counteract the pro-inflammatory activities, T. gondii is known to have several mechanisms inducing down-regulation of the host immunity. In the present study, we analyzed the production of proand anti-inflammatory cytokines from a human myelomonocytic cell line, THP-1 cells, in response to treatment with T. gondii lysate or lipopolysaccharide (LPS). Treatment of THP-1 cells with LPS induced production of IL-12, TNF-alpha, IL-8, and IL-10. Co-treatment of THP-1 cells with T. gondii lysate inhibited the LPS-induced IL-12, IL-8 and TNF-alpha expression, but increased the level of IL-10 synergistically. IL-12 and IL-10 production was down-regulated by anti-human toll-like receptor (TLR)-2 and TLR4 antibodies. T. gondii lysate triggered nuclear factor (NF)-kappaB-dependent IL-8 expression in HEK293 cells transfected with TLR2. It is suggested that immunosuppression induced by T. gondii lysate treatment might occur via TLR2-mediated NF-kappaB activation.
Animals ; Cell Line ; Cytokines/*biosynthesis ; Humans ; Inflammation/metabolism ; Lipopolysaccharides/*pharmacology ; Macrophages/*drug effects/*metabolism ; Toxoplasma

PURPOSE: The major aim of this study is to evaluate the patterns of recurrence of the stomach cancer after curative resection. MATERIALS AND METHODS: Patterns of the fimt failure and survival after relapse of 136 female gastric cancer patients who had received curative resection were evaluated. Factors influencing survival after relapse were analyzed using Cox proportional hazard model. RESULTS: Peritoneal relapse was the most common pattern of the first failure, with 3-year estimate of overall peritoneal relapse being 13.0%. The 3-year estimates of overall local- regional relapse, liver metastasis, and extraabdominal relapse were 11.2%, 4.8%, and 3.8%, respectively. Patients younger than 45 years developed peritoneal relapse at a significantly higher rate than patients aged 45-65 years (p 0.037). The most significant factor affecting the survival of relapsed patients was whether resection was performed for recurrent disease without remaining gross residual disease. Patterns of relapse did not significantly affect survival, but patients whose recurrences were limited to local-regional area tended to survive longer than those with extraaMominal component (p=0.067). CONCLUSION: Peritoneal relapse was the most common pattem and significantly associated with younger age after curative resection af gastric cancer of Korean female patients.
Female* ; Humans ; Liver ; Neoplasm Metastasis ; Proportional Hazards Models ; Recurrence ; Stomach Neoplasms*

Mycoplasma pneumoniae (M. pneumoniae) infection causes a wide variety of clinical manifestations in children and young adults, the main one being pneumonia. M. pneumoniae is transmitted from person to person by infected respiratory droplets. Symptoms caused by M. pneumoniae infection can be divided into those involving the respiratory tract, and those caused by extrapulmonary disease. M. pneumoniae infections may cause central nervous system (CNS) complications-with encephalitis being the most frequent-and stroke being a rare complication. The pathogenesis of the CNS disease is unclear; possibilities include direct infection and an immune-mediated reaction. We present two cases of CNS complications subsequent to infection with M. pneumoniae; both cases had convincing evidence of preceding M. pneumoniae respiratory disease with no evidence of viable M. pneumoniae in the cerebrospinal fluid. We report cases of encephalitis and stroke following a recent M. pneumoniae infection.
Central Nervous System ; Central Nervous System Diseases ; Child ; Encephalitis ; Humans ; Mycoplasma ; Mycoplasma pneumoniae ; Pneumonia ; Pneumonia, Mycoplasma ; Respiratory System ; Stroke ; Young Adult

BACKGROUND: Increased low density lipoprotein cholesterol (LDL-C) level and the presence of metabolic syndrome (MetS) are important risk factors for cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Recent studies demonstrated apolipoprotein B (apoB), a protein mainly located in LDL-C, was an independent predictor of the development of CVD especially in patients with T2DM. The aim of this study was to investigate the relationship between apoB and MetS in T2DM patients. METHODS: We analyzed 912 patients with T2DM. Fasting blood samples were taken for glycated hemoglobin, high-sensitivity C-reactive protein, total cholesterol, triglyceride (TG), high density lipoprotein cholesterol, LDL-C, and apoB. MetS was defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria. We performed a hierarchical regression analysis with apoB as the dependent variable. Age, sex, the number of components of MetS and LDL-C were entered at model 1, the use of lipid-lowering medications at model 2, and the individual components of MetS were added at model 3. RESULTS: Seventy percent of total subjects had MetS. ApoB level was higher in subjects with than those without MetS (104.5+/-53.3 mg/dL vs. 87.7+/-33.7 mg/dL, P<0.01) even after adjusting for LDL-C. ApoB and LDL-C were positively correlated to the number of MetS components. The hierarchical regression analysis showed that the increasing number of MetS components was associated with higher level of apoB at step 1 and step 2 (beta=0.120, P<0.001 and beta=0.110, P<0.001, respectively). At step 3, TG (beta=0.116, P<0.001) and systolic blood pressure (beta=0.099, P<0.05) were found to significantly contribute to apoB. CONCLUSION: In patients with T2DM, apoB is significantly related to MetS independently of LDL-C level. Of the components of MetS, TG, and systolic blood pressure appeared to be determinants of apoB.
Adult ; Apolipoproteins B ; Apolipoproteins* ; Blood Pressure ; C-Reactive Protein ; Cardiovascular Diseases ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL* ; Diabetes Mellitus, Type 2 ; Education ; Fasting ; Hemoglobin A, Glycosylated ; Humans ; Risk Factors ; Triglycerides

PURPOSE: A phase II study of vinorelbine and ifosfamide combination chemotherapy in patients with advanced or recurrent non-small cell lung cancer (NSCLC) was conducted to assess response rate, response duration, and toxicites. MATERIALS AND METHODS: Patients with advanced NSCLC who had no prior systemic chemotherapy were eligible. They have no central nervous system metastasis and recurrent or progressive disease after surgery or radiotherapy. Each cycle consisted of vinorelbine 25 mg/m' i.v. days 1 & 8, and ifosfamide 2 g/m i.v. days 1, 2 & 3 with Mesna and treatments were repeated every 21 days. RESULTS: Forty patients with advanced or recurrent NSCLC were treated at multi center between March, 1997 and March, 1998. Six patients were not evaluable because five patients refused therapy after the first course and one patient was protocol violation. Of 34 evaluable patients, objective responses were seen in 11 (32.4%) patients (CR 0%, PR 32.4%). The median duration of response was 16.4 weeks. The median overall survival was 9.5 months. The toicities of this regimen were acceptable without treatment related toxic death. CONCLUSION: We concluded that combination regimen of vinorelbine and ifosfamide was effective and tolerable in the treatment of advanced non-small cell lung cancer.
Carcinoma, Non-Small-Cell Lung ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Ifosfamide* ; Mesna ; Neoplasm Metastasis ; Radiotherapy ; Small Cell Lung Carcinoma*

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.

PURPOSE: Chemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage. METHODS: DOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated. RESULTS: DOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise. CONCLUSIONS Apoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.