A transmembrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion

Stromal cells in lymphoid tissues provide microenvironmental fields required for the triggering of efficient immune responses. Fibroblastic reticular cells (FRCs) are one of the integral constituents of such stromal fields; they construct the reticular network and are considered to regulate immune cells' behavior. However, the factors that mediate the interaction between lymphocytes and FRCs are poorly understood. Here we show that a mouse lymph node (LN)-derived FRC cell line, BLS4, expresses a transmembrane chemokine, CXC chemokine ligand (CXCL) 16, in response to tumor necrosis factor alpha (TNFalpha) and IFNgamma. TNFalpha-induced expression of CXCL16 depends on NFkappaB, p38 MAPK and PKA. Matrix metalloproteinase activity is required for producing soluble CXCL16 in the culture supernatant, likely via shedding at the juxtamembrane region of the extracellular domain. IL-12 enhances the expression of CXCR6 in anti-CD3/CD28-stimulated CD8+ T cells and their adhesion to the BLS4 cell surface in a TNFalpha-dependent fashion. The adherence is significantly inhibited in the presence of both anti-CXCL16 and anti-vascular cell adhesion molecule 1 (VCAM-1) antibodies. CXCL16 expression is also detected in the FRCs in LN sections and in gp38+VCAM-1+ FRCs isolated from LNs. Taken together, these findings suggest that CXCL16 is an important mediator of lymphocyte-stromal interaction within lymphoid tissues.     

Significant induction of apoptosis in renal cell carcinoma cells transfected with cationic multilamellar liposomes containing the human interferon-β gene through activation of the intracellular type 1 interferon signal pathway

We previously reported that cationic multilamellar liposome containing the human interferon-β (huIFN-β) gene (IAB-1) demonstrated significant cytotoxic effect in the NC65 human renal cell carcinoma (RCC) cell line. In this study, we investigated the molecular mechanisms of IAB-1-induced apoptosis and cytotoxicity in RCC cells. Remarkable in vitro cytotoxic and apoptosis-inducing effects of IAB-1 against NC65 cells were observed by a colorimetric method and TUNEL staining, respectively. In contrast, treatment of NC65 cells with exogenously added huIFN-β protein induced low-level cytotoxicity without apoptosis. Neutralizing antibodies against huIFN-β significantly suppressed the cytotoxic effect of huIFN-β protein, but they were unable to block the effect of IAB-1. Cytotoxicity assays using transwell plates revealed that NC65 cells treated with IAB-1 did not secrete cytotoxic soluble factors other than IFN-β. Substantial enhancement of interferon-stimulated response element (ISRE) activity of NC65 cells by IAB-1 was demonstrated by promoter reporter assays. In addition, immunofluorescence using confocal microscopy revealed the intracellular expression of IFN-β and its receptor induced by IAB-1. The induction of c-Myc by IAB-1 was suggested by a cDNA macroarray and was confirmed by western blot analysis. These findings indicate that IAB-1 induces significant cytotoxicity and apoptosis in NC65 cells, possibly through enhanced ISRE activity, that is associated with increased intracellular localization of huIFN-β and IFN-receptor. Our data support the potential clinical application of IAB-1 gene therapy for RCC resistant to IFN.     

Complication of topoisomerase II inhibitor-related acute promyelocytic leukemia with t(1;10) (q21;q26) in a patient with Sézary syndrome

A 74-year-old man was diagnosed as having Sézary syndrome in 1999. Treatment with combination chemotherapy could not completely control both the erythroderma and Sézary cells. However, treatment with oral administration of etoposide was able to maintain the patient in a good condition for about 4 years. In June 2004, he developed topoisomerase II inhibitor-related acute promyelocytic leukemia. Chromosomal analysis demonstrated abnormalities of t(1;10) (q21;q26) and t(15;17) (q22;q12) in 17 of 20 cells. Despite treatment with ATRA and combination chemotherapy, the patient died of brain hemorrhage.     

Accuracy of histologic grading of synovial inflammation in temporomandibular joints with internal derangement using Gynther's system.

PURPOSE: The purpose of this study was to evaluate the accuracy of the system by Gynther et al (J Oral Maxillofac Surg 56:1281, 1998) for histologic grading of synovial inflammation in the temporomandibular joint (TMJ) in arthroscopically obtained synovial biopsy specimens. PATIENT AND METHODS: Thirty-three human TMJ synovial biopsy specimens from patients with internal derangement of the TMJ were evaluated using the system of Gynther et al. The results were compared statistically with the intensity of synovitis seen arthroscopically using Spearman ranked correlation coefficient. RESULTS: In 2 of the 3 parameters tested, a statistically significant correlation was found between the histologic findings by the system of Gynther et al and arthroscopic findings using the scale of Murakami et al (J Oral Maxillofac Surg 49:1159, 1991) CONCLUSION: These results suggest that histologic grading of synovial inflammation by the system of Gynther et al has considerable accuracy. However, more investigations are necessary to confirm the results.     

Prostate cancer mediates osteoclastogenesis through two different pathways

The present study was undertaken to test the effects of prostate cancer cell lines (LNCaP, DU145, PC3, and MDA PCa 2b) on osteoclastogenesis. Crude conditioned medium (CM) from all four prostate cancer cell lines enhanced expression of the mRNA for receptor activator of NF-kappaB ligand (RANKL) in a mouse osteoblast cell line, MC3T3-E1; however, CM had no effect on expression of osteoprotegerin (OPG) mRNA. Coculture of MC3T3-E1 with prostate cancer cells yielded similar results. The number of mature osteoclasts induced by soluble RANKL increased significantly when osteoclast precursor cells were cultured with CM from LNCaP and DU145 cells. CM from LNCaP and DU145 cells also induced maturation from precursor in the absence of soluble RANKL, and this effect was not blocked by OPG. Addition of CM from DU145 cells increased expression of MMP-9 mRNA by osteoclast precursors. Our findings indicate that prostate cancer mediates osteoclastogenesis through induction of RANKL expression by osteoblasts and through direct actions on osteoclast precursors mediated by some factors other than RANKL.     

Relation between erectile dysfunction and urinary incontinence after nerve-sparing and non-nerve-sparing radical prostatectomy

INTRODUCTION: We investigated the status of erectile function and urinary continence after radical prostatectomy to investigate a possible relation between them and then determined whether the status of postoperative urinary continence affected erectile function. PATIENTS AND METHODS: Seventy-six patients who had no symptoms of erectile dysfunction or urinary incontinence preoperatively were included in this study. The postoperative status of erectile function and urinary continence was investigated using a self-reported patient questionnaire. RESULTS: Thirteen of 27 patients (48.1%) who underwent nerve-sparing procedures maintained erectile function, while 7 of 49 patients (14.2%) who underwent non-nerve-sparing procedures maintained it postoperatively. None of the 27 patients in the nerve-sparing procedure group reported incontinence, whereas 3 of the 49 patients (6.1%) who underwent non-nerve-sparing procedures reported moderate incontinence. However, no significant correlation between the International Index of Erectile Function-5 score and the Incontinence Impact Questionnaire score was seen. CONCLUSION: No relation between the status of urinary continence and erectile function was shown, regardless of the nerve-sparing nature of the prostatectomy.     

Importance of proinflammatory cytokines in synovial fluid from 121 joints with temporomandibular disorders

The concentrations of cytokines were measured by an ELISA in the synovial fluid from 117 patients with temporomandibular disorders (TMD) and correlated with degenerative changes of the condyle and clinical symptoms.Fifty-seven patients had degenerative changes of the condyle. The fluid from seven healthy volunteers was used as controls. The concentrations of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly higher in the synovial fluid of patients than controls (P<0.05). The concentration of IL-6 was significantly higher in the patients with degenerative changes than in other patients (P<0.05). The detection of IL-8 correlated with the concentrations of IL-6 and TNF-alpha. However, there was no correlation between the concentrations of any cytokines and symptoms.In conclusion, the cytokines in the synovial fluid may participate in the pathogenesis of TMD. In particular, IL-6 is important and may be associated with the development of osteoarthritis.     

Hormonal chemotherapy for hormone-refractory prostate cancer

To our knowledge, no standard chemotherapy for patients with hormone-refractory prostate cancer (HRPC) has been established. Since most patients with HRPC are elderly and have bone metastasis, cytotoxic chemotherapy causes them to be at high risk for myelosuppression. Therefore, chemotherapeutic agents with low toxicity and good compliance should be elected. We conducted three regimens for HRPC on an outpatient basis. Eligibility criteria were defined as serial rising PSA values on 3 or more occasions at least 2 weeks apart or radiological new or extensive lesions under hormonal therapy. The first regimen is comprised of cyclophosphamide (CPM), 100 mg/day, UFT, 400 mg/day, and estramustine phosphate (EMP), 560 mg/day in two daily fractions. The second regimen is comprised of an oral administration of dexamethasone (DEX) (0.5-2 mg/day). The third regimen is comprised of DEX, 1 mg/day, cyclophosphamide, 100 mg/day and UFT, 400 mg/day in two daily fractions. Post-therapy prostate-specific antigen (PSA) level in serum, objective response on bone scan or measurable disease, and symptomatic response on bone pain were assessed. All regimens showed clinical efficacy with mild toxicity. Indications and limitations of these regimens are discussed. Further, the combination trials of taxane and EMP in patients with HRPC are reviewed.     

PERIPHERAL T-CELL LYMPHOMA WITH HELPER T-CELL PHENOTYPE (LEU 3a+ LEU 8−)

Eleven cases of Leu 3a⁺ Leu 8⁻ peripheral T-cell lymphoma (PTCL), excluding adult T-cell leukemia/lymphoma, were studied by Immunostalning with monoclonal antibodies and enzyme histochemistry in order to clarify the histogenesis of PTCL. Seven of the eleven cases had varying degrees of polyclonal hypergammaglobulinemia. All cases were histologically characterized by neoplastic proliferation of clear cells and some cases showed a histologic background similar to IBL or AILD lesions with proliferation of 1m-munoblasts or plasmacytoid cells and vascular proliferation. Immunohis-tologic analysis of PLP-flxed frozen tissues revealed that neoplastic clear cells expressed a Leu 3a⁺ Leu 8⁻ phenotype (helper T-cell subset). The distribution of Leu 3a⁺ Leu 8'neoplastic cells corresponded closely to that of DRC-1⁺ cells, which are localized in the lymphatic follicles, but hardly at all with that of β-glucuronidase⁺ vessels, termed PCV or HEV, which are usually present in T-cell areas. One case only progressed from Leu 3a⁺ Leu 8⁻ IBL-like T-cell lymphoma (IBL-T), with proliferation of immunoblasts or plasmacytoid cells and vascular proliferation, to diffuse lymphoma of the large cell type showing none of these lesions. From these observations it is suggested that IBL-T might progress to T-cell-type monomorphous diffuse lymphoma.