To investigate effects of cytokines on rheumatoid synovial cells, proliferation and expression of cytokine and metalloproteinase genes were studied with the primary culture of rheumatoid synovial cells which was treated with TNF-alpha, GM-CSF, TGF-alpha, PDGF and IL-B. By [3H] thymidine incorporation assay, TGF-beta and PDGF increased proliferation of synovial cells by 1.5 and 2.5 folds respectively. Cytokine gene expression was assessed by RT-PCR. Rheumatoid synovial cells expressed constitutively TGF-beta and IL-B at a high level and IL-1B, GM-CSF, and MIP-1a at a relatively low level. TGF-beta, GM-CSF and PDGF increased IL-B expression. Expression of pro-inflammatory cytokines and chemokines was increased by GM-CSF and PDGF. Both GM-CSF and PDGF increased the expression of IL-1B, GM-CSF MIP-la and IL-8. In addition, GM-CSF enhanced expression of TNF-alpha. Stromelysin and collagenase are the major proteinases responsible for destruction ot joints in rheumatoid arthritis (RA). These genes were expressed constitutivefy in rheumatoid synovial cells. In summary, PDGF and GM-CSF may piay an important role by inducing or increasing expression of IL-1B, TGF-beta and PDGF by increasing proliferation of rheumatoid synovial cells.
Tumor Necrosis Factor-alpha

PURPOSE: Men with documented chronic prostatitis, with elevated serum prostate specific antigen (PSA), were investigated to assess whether treatment lowers serum PSA and thus avoids unnecessary biopsies. MATERIALS AND METHODS: The medical records of 46 men who presented with serum PSA higher than 4ng/ml, and subsequently diagnosed with chronic prostatitis, were retrospectively reviewed. After the administration of antibiotics and anti-inflammatory drugs for 4 to 8 weeks, the follow-up PSA levels were determined, and those with levels higher than 4ng/ml underwent a prostate biopsy. RESULTS: The mean PSA level decreased 61% from 11.66ng/ml before, to 3.79ng/ml after, treatment (p<0.001). In 30 patients the serum PSA level decreased to below 4ng/ml (mean 1.69), with these patients no longer having an indication for a prostate biopsy. In the remaining 16 patients the serum PSA level remained elevated above 4ng/ml, so they underwent a prostate biopsy. Pathological study revealed benign prostatic hyperplasia in 11 cases and prostate cancer in 5. The PSA level in patients associated with benign prostatic hyperplasia decreased 61.9% with treatment, from 19.96 to 7.88ng/ml (p=0.006) and the PSA in those associated with prostate cancer decreased 30.6% with treatment, from 12.85 to 7.32ng/ml (p<0.05). CONCLUSIONS: This study demonstrates that chronic prostatitis can cause elevation of serum PSA levels, and when identified, antibiotics and anti-inflammatory treatment can lower these levels and an unnecessary prostate biopsy can be avoided.
Anti-Bacterial Agents ; Biopsy ; Follow-Up Studies ; Humans ; Male ; Medical Records ; Prostate* ; Prostate-Specific Antigen* ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Prostatitis* ; Retrospective Studies

PURPOSE: Dendritic cells (DC) play a crucial role in the initiation of primary immune response and are known as an excellent adjuvant for anti-cancer immunity. In this study, we tried to obtain substantial numbers of DC from peripheral blood of normal volunteers. We also investigated the anti-tumor immune response of DC pulsed by renal cell carcinoma cell line A498 in vitro. MATERIALS AND METHODS: DC were generated by culturing plastic adherent mononuclear cells from the peripheral blood in the presence of granulocyte-macrophage colony- stimulating factor and interleukin-4. Immature DC were cocultured with T-cells and pulsed by A498. MTT analysis was performed using the medium in which A498 only was cultured as control. Our experiments were analyzed by means of a commercial IL-12 p70 ELISA (Quantikine; R & D Systems, Minneapolis, MN). The capture antibodies used in both tests specifically recognize the p70 heterodimer, but not the free p40 chains. Detection limits were 30pg/ml of IL-12. RESULTS: We could obtain 1.5-2.0x106 DC with phenotype typical of mature DC (CD14-, CD80+, and CD83+) from the normal peripheral blood. On T-cell proliferation assay, the number of T-cells increased in proportion to that of DC and when DC were pulsed by A498, the same phenomenon could be observed. DC and T-cell media with A498 tumor lysate showed more production of IL-12 on IL-12 p70 ELISA than the media without A498 tumor lysate. CONCLUSIONS: We could successfully obtain mature DC from the peripheral blood. The data revealed indirectly that DC treated with tumor lysate enhance immune activity and thereby increase the anti-cancer effect of T-cells. Further investigations including in-vivo study are necessary to realize the effect of immunotherapy using DC against metastatic renal cell carcinoma.
Antibodies ; Carcinoma, Renal Cell* ; Cell Line* ; Dendritic Cells* ; Enzyme-Linked Immunosorbent Assay ; Healthy Volunteers ; Immunotherapy ; Interleukin-12 ; Interleukin-4 ; Limit of Detection ; Monocytes* ; Phenotype ; Plastics ; T-Lymphocytes

A case of a clear cell carcinoma of the urinary bladder is reported. A 48-year-old female was referred to our hospital complaining of gross hematuria and terminal dysuria. She had a nodular tumor, 3x4cm in diameter, located on the bladder neck, trigone and posterior urethra. The patient underwent anterior pelvic exenteration and urinary diversion with an ileal conduit. A histopathological examination revealed a tumor composed of cells with eosinophilic cytoplasm, and partly of cells with clear cytoplasm or hobnail-shaped cells, arranged in tubular and papillary architectures. This showed the findings of a clear cell adenocarcinoma of the bladder and urethra. The patient underwent 6 courses of adjuvant chemotherapy with cisplatin and 5-FU. The patient shows no evidence of recurrence or metastasis at the 8 month postoperative follow-up.
Adenocarcinoma, Clear Cell* ; Chemotherapy, Adjuvant ; Cisplatin ; Cytoplasm ; Dysuria ; Eosinophils ; Female ; Fluorouracil ; Follow-Up Studies ; Hematuria ; Humans ; Middle Aged ; Neck ; Neoplasm Metastasis ; Pelvic Exenteration ; Recurrence ; Urethra ; Urinary Bladder* ; Urinary Diversion

PURPOSE: To compare clinical characteristics and surgical results in adolescents and adults with varicocele. MATERIALS AND METHODS: We retrospectively analyzed the characteristics of 93 patients, 34 adolescents (mean age, 14.4+/-2.1 years) and 59 adults (mean age, 30.4+/-12.4 years), who underwent surgical repair of varicocele between 2006 and 2009. Median follow-up time in all patients was 18.7 months. The most bothersome symptoms, bilaterality, grades, surgical methods, artery-sparing rates, operation times, semen analysis, success rates, and recurrence-free period were compared between the two groups. RESULTS: The overall success rate of surgical repair was 92.5%. The most bothersome symptoms were scrotal mass, pain, and hypotrophy in adolescents and pain, scrotal mass, infertility, and hypotrophy in adults (p=0.008). There were no significant between-group differences in bilaterality, grades, surgical methods, operation times, pre- or postoperative semen analyses, success rates, or recurrence-free periods. Patients who underwent artery-sparing surgery had higher recurrence rates than did those who underwent surgery that did not spare arteries. In adults, semen density increased significantly after surgery, from 35.6 million/ml to 49.6 million/ml (p=0.046). CONCLUSIONS: There were no significant differences in clinical characteristics or surgical results between adolescents and adults with varicocele, except for the most bothersome symptoms. Semen density increased after surgery in both groups.
Adolescent ; Adult ; Arteries ; Follow-Up Studies ; Humans ; Infertility ; Recurrence ; Retrospective Studies ; Semen ; Semen Analysis ; Spermatic Cord ; Treatment Outcome ; Varicocele

15-deoxy-delta12,14-PGJ2(15d-PGJ2) is a natural ligand that activates the peroxisome proliferators-activated receptor (PPAR) gamma, a member of nuclear receptor family implicated in regulation of lipid metabolism and adipocyte differentiation. Recent studies have shown that 15d-PGJ2 is the potent anti-inflammatory agent functioning via PPARgamma-dependent and -independent mechanisms. Most postulated mechanisms for anti-inflammatory action of PPARgamma agonists are involved in inhibiting NF-kappaB signaling pathway. We examined the possibility that IL-6 signaling via the Jak-Stat pathway is modulated by 15d-PGJ2 in lymphocytes and also examined whether the inhibition of IL-6 signaling is dependent of PPARgamma. 15d-PGJ2 blocked IL-6 induced Stat1 and Stat3 activation in primary human lymphocytes, Jurkat cells and immortalized rheumatoid arthritis B cells. Inhibition of IL-6 signaling was induced rapidly within 15 min after treatment of 15d-PGJ2. Other PPARgamma-agonists, such as troglitazone and ciglitazone, did not inhibit IL-6 signaling, indicating that 15d-PGJ2 affect the IL-6-induced Jak-Stat signaling pathway via PPARgamma-independent mechanism. Although cycloheximide reversed 15d-PGJ2-mediated inhibition of Stat3 activation, actinomycin D had no effect on 15d-PGJ2-mediated inhibition of IL-6 signaling, indicating that inhibition of IL-6 signaling occur independent of de novo gene expression. These results show that 15d-PGJ2 specifically inhibit Jak-Stat signaling pathway in lymphocytes, and suggest that 15d-PGJ2 may regulate inflammatory reactions through the modulation of different signaling pathway other than NF-kappaB in lymphocytes.
Arthritis, Rheumatoid/metabolism/pathology ; Chromans/pharmacology ; Cycloheximide/pharmacology ; DNA-Binding Proteins/*metabolism ; Dactinomycin/pharmacology ; Gene Expression Regulation ; Humans ; Hypoglycemic Agents/pharmacology ; Interleukin-6/*pharmacology ; Jurkat Cells/metabolism/pathology ; Lymphocytes/cytology/*drug effects/*metabolism ; NF-kappa B/metabolism ; PPAR gamma/metabolism ; Phosphorylation ; Prostaglandin D2/*analogs & derivatives/pharmacology ; Protein Synthesis Inhibitors/pharmacology ; Research Support, Non-U.S. Gov't ; *Signal Transduction ; Thiazolidinediones/pharmacology ; Trans-Activators/*metabolism

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a prototypic halogenated aromatic hydrocarbon (HAH), is known as one of the most potent toxicants. At least a part of its toxic effects appears to be derived from its ability to induce TNF-alpha production. However, the signaling pathway of TCDD that leads to TNF-alpha expression has not been elucidated. In this study, we investigated the signaling mechanism of TCDD-induced TNF-alpha expression in PMA-differentiated THP-1 macrophages. TCDD induced both mRNA and protein expression of TNF-alpha in a dose- and time-dependent manner. Alpha-Naphthoflavone (NF), an aryl hydrocarbon receptor (AhR) inhibitor, prevented the TCDD-induced expression of TNF-alpha at both mRNA and protein levels. Genistein, a protein tyrosine kinase (PTK) inhibitor, and PD153035, an EGFR inhibitor, also blocked the increase of TNF-alpha expression by TCDD, indicating the role of EGFR in TCDD-induced TNF-alpha expression. On the other hand, PP2, a c-Src specific inhibitor, did not affect TCDD-induced TNF-alpha expression. EGFR phosphorylation was detected as early as 5 min after TCDD treatment. TCDD-induced EGFR activation was AhR-dependent since co-treatment with alpha-NF prevented it. ERK was found to be a downstream effector of EGFR activation in the signaling pathway leading to TNF-alpha production after TCDD stimulation. Activation of ERK was observed from 30 min after TCDD treatment. PD98059, an inhibitor of the MEK-ERK pathway, completely prevented the TNF-alpha mRNA and protein expression induced by TCDD, whereas inhibitors of JNK and p38 MAPK had no effect. PD153035, an EGFR inhibitor, as well as alpha-NF significantly reduced ERK phosphorylation, suggesting that ERK activation by TCDD was mediated by both EGFR and AhR. These results indicate that TNF-alpha production by TCDD in differentiated THP-1 macrophages is AhR-dependent and involves activation of EGFR and ERK, but not c-Src, JNK, nor p38 MAPK. A signaling pathway is proposed where TCDD induces sequential activation of AhR, EGFR and ERK, leading to the increased expression of TNF-alpha.
Animals ; Benzoflavones/pharmacology ; Cell Differentiation ; Cell Line, Tumor ; Enzyme Activation ; Genistein/pharmacology ; Hazardous Substances/*toxicity ; Humans ; MAP Kinase Signaling System/drug effects/physiology ; Macrophages/*metabolism ; Mice ; Phosphorylation ; Pyrimidines/pharmacology ; Quinazolines/pharmacology ; RNA, Messenger/metabolism ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/metabolism ; Receptors, Aryl Hydrocarbon/antagonists & inhibitors ; Signal Transduction ; Tetrachlorodibenzodioxin/*toxicity ; Tumor Necrosis Factor-alpha/*biosynthesis ; src-Family Kinases/antagonists & inhibitors/metabolism

PURPOSE: To determine the impact of noise on heart rate variability (HRV) in men, with a focus on the noise type rather than on noise intensity. MATERIALS AND METHODS: Forty college-going male volunteers were enrolled in this study and were randomly divided into four groups according to the type of noise they were exposed to: background, traffic, speech, or mixed (traffic and speech) noise. All groups except the background group (35 dB) were exposed to 45 dB sound pressure levels. We collected data on age, smoking status, alcohol consumption, and disease status from responses to self-reported questionnaires and medical examinations. We also measured HRV parameters and blood pressure levels before and after exposure to noise. The HRV parameters were evaluated while patients remained seated for 5 minutes, and frequency and time domain analyses were then performed. RESULTS: After noise exposure, only the speech noise group showed a reduced low frequency (LF) value, reflecting the activity of both the sympathetic and parasympathetic nervous systems. The low-to-high frequency (LF/HF) ratio, which reflected the activity of the autonomic nervous system (ANS), became more stable, decreasing from 5.21 to 1.37; however, this change was not statistically significant. CONCLUSION: These results indicate that 45 dB(A) of noise, 10 dB(A) higher than background noise, affects the ANS. Additionally, the impact on HRV activity might differ according to the noise quality. Further studies will be required to ascertain the role of noise type.
Adaptation, Psychological ; Confounding Factors (Epidemiology) ; Environment ; Heart Rate/*physiology ; Humans ; Male ; *Noise ; Questionnaires ; Stress, Psychological/physiopathology ; Young Adult

The hemodynamic effects of thyroid hormones which is well established, affect myocardial contractility, heart rate, and myocardial oxygen consumption. The alterations in thyroid function test are frequently seen in patients with nonthyroidal illness and often correlate with the severity of the illness and the prognosis. In this study, thyroid hormone changes were investigated in 20 patients who received cardiopulmonary bypass(CPB). All patients showed a state of biochemical euthyroidism preoperatively. The results were as follows : 1. Serum triiodothyronine(T3) reached to its nadir(30.05+/-17.5ng/dl, p<0.001) at 10 minutes after the start of CPB and remained low(p<0.05) throughout the study period. 2. Serum thyroxine(T4) concentration slightly decreased after CPB, but maintained within normal range. 3. Serum free thyroxine(fT4) concentration slightly increased after CPB, but maintained within normal range. 4. Serum thyroid stimulating hormone(TSH) concentration increased 10 minute after CPB, reached to its nadir(3.37+/-0.81uIU/ml, p<0.001) at 2 hours after CPB. After then, serum TSH concentration decreased and reached its normal levels at 24 hours after CPB. 5. The patients whose postoperative recovery was uneventful(Group 1) had higher serum T3 levels than those who had postoperative complications(Group 2)(p<0.05). Group 1 showed elevating patterns of serum T3 in the fourth day after operation, whereas group 2 did not show such an elevating pattern. These findings are similar to the euthyroid sick syndrome seen in severely ill patients and indicate that patients undergoing open heart surgery have suppression of the pituitary-thyroid axis.
Axis, Cervical Vertebra ; Euthyroid Sick Syndromes ; Heart* ; Hemodynamics ; Humans ; Myocardial Contraction ; Oxygen Consumption ; Prognosis ; Reference Values ; Thoracic Surgery* ; Thyroid Function Tests ; Thyroid Gland* ; Thyroid Hormones

A 16-year-old girl presented with proteinuria and microscopic hematuria detected through mass urinary screening and was diagnosed as having suspected postinfectious glomerulonephritis by renal biopsy. However, heavy proteinuria did not respond to angiotensin converting enzyme inhibitor therapy. After 6 months, cervical lymphadenitis developed and a neck node biopsy showed subacute necrotizing lymphadenitis. After an additional 2 months, she developed facial erythema and thrombocytopenia. A repeat renal biopsy demonstrated lupus nephritis class IV. She was treated with pulse methylprednisolone(500 mg/day intravenously for 3 consecutive days) followed by oral deflazacort and monthly intravenous cyclophosphamide pulse(1 g/m2) for 6 months. We report a case diagnosed as systemic lupus erythematosus(SLE) during medical follow-up after urinary screening.
Adolescent ; Biopsy ; Cyclophosphamide ; Erythema ; Follow-Up Studies ; Glomerulonephritis ; Hematuria ; Humans ; Lupus Erythematosus, Systemic ; Lupus Nephritis ; Lymphadenitis ; Mass Screening ; Neck ; Peptidyl-Dipeptidase A ; Pregnenediones ; Proteinuria ; Thrombocytopenia