Activated leucocytes express and secrete macrophage inflammatory protein-1alpha upon interaction with synovial fibroblasts of rheumatoid arthritis via a beta2-integrin/ICAM-1 mechanism.

OBJECTIVE: To examine the expression and regulation of chemotactic factor, macrophage inflammatory protein-1alpha (MIP-1alpha) by fibroblast-like synoviocytes (FLS), monocytes and polymorphonuclear neutrophils (PMN) isolated from the synovial fluid (SF) of rheumatoid arthritis (RA) patients. METHODS: Monocytes or PMN obtained from RA SF were co-cultured with unstimulated semiconfluent RA FLS. Culture supernatants were assayed for MIP-1alpha by enzyme-linked immunosorbent assay. The expression of MIP-1alpha mRNA and protein was also determined by Northern blot analyss and immunohistochemistry respectively. RESULTS: Interaction of activated leucocytes with FLS synergistically increased MIP-1alpha expression and secretion via a mechanism mediated by beta2-integrin/ intercellular adhesion molecule 1. CONCLUSION: MIP-1alpha expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leucocytes and FLS, and plays a crucial role in the progression and maintenance of RA synovitis.

Relationship between psychological factors and arthralgia in patients with rheumatoid arthritis.

Abstract Various factors were assessed in terms of their contribution to arthralgia in a rheumatoid arthritis patient. Eighty-two outpatients (62 women and 20 men) with rheumatoid arthritis (RA) were examined with respect to the subjective degree of arthralgia, age, disease duration, dysfunction, steroid dose, steroid period, depression, anxiety, extroversion, neurotic disorder, and number of caretakers. The results were explained on the basis of stepwise regression analysis and psychological and clinical data. We analyzed results of a correlation coefficient test on the mutual relationship between variables. Stepwise regression analysis was performed to assess factors of arthralgia in terms of "depression," "mean activity," "morning stiffness," and "steroid dose." Depression is a factor of arthralgia as shown in this study, but it is clear that other factors are also involved. Anxiety was a factor distinct from the activity of RA. The factor contributing most to arthralgia was found to be depression, whereas anxiety had no effect.

Vascular endothelial growth factor expression by activated synovial leukocytes in rheumatoid arthritis: critical involvement of the interaction with synovial fibroblasts.

OBJECTIVE: To examine the expression and regulation of the angiogenic factor, vascular endothelial growth factor (VEGF), by fibroblast-like synoviocytes (FLS), monocytes, and polymorphonuclear neutrophils (PMNs) isolated from the synovial fluid (SF) of rheumatoid arthritis (RA) patients. METHODS: Monocytes or PMNs obtained from RA SF were cocultured with unstimulated, semiconfluent RA FLS. Culture supernatants were assayed for the proliferation and in vitro tube formation of endothelial cells, and for the production of VEGF, by enzyme-linked immunosorbent assay. The expression of VEGF messenger RNA and protein was also determined by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: We found that the interaction of inflammatory, activated leukocytes with FLS resulted in synergistic increases in VEGF expression and secretion, which contributed to the proliferation of endothelial cells and to in vitro endothelial tube formation. The induction of VEGF was mediated via specific adhesion molecules, as indicated by the finding that anti-integrin antibodies significantly inhibited VEGF. Furthermore, the levels of VEGF secretion correlated with the expression of cell surface integrin (CD11b and CD18) on both monocytes and PMNs in the SF. CONCLUSION: VEGF expression within inflamed joints thus appears to be regulated not only by inflammatory cytokines, but also by the physical interaction of activated leukocytes and FLS. Once expressed, VEGF likely plays a crucial role in the neovascularization of the pannus and the progressive joint destruction associated with the synovial inflammation of RA.

Vascular endothelial growth factor expression and regulation of murine collagen-induced arthritis.

We have examined the expression and function of the angiogenic factor, vascular endothelial growth factor (VEGF) during the evolution of type II collagen-induced arthritis (CIA). Biologically active VEGF was expressed along a time course that paralleled the expression of two specific VEGF receptors, Flk-1 and Flt-1, and the progression of joint disease. Moreover, levels of VEGF expression correlated with the degree of neovascularization, as defined by vWF levels, and arthritis severity. Macrophage- and fibroblast-like cells, which infiltrated inflamed sites and were then activated by other inflammatory mediators, are probably important sources of VEGF and may thus regulate angiogenesis during the development of CIA. Administration of anti-VEGF antiserum to CIA mice before the onset of arthritis delayed the onset, reduced the severity, and diminished the vWF content of arthritic joints. By contrast, administration of anti-VEGF antiserum after the onset of the disease had no effect on the progression or ultimate severity of the arthritis. These data suggest that VEGF plays a crucial role during an early stage of arthritis development, affecting both neovascularization and the progression of experimentally induced synovitis.

[Feasibility of limited surgery for small peripheral lung cancer].

We investigated the pathologic factors of small (< or = 20 mm in diameter) peripheral non-small-cell lung cancer lesions and postoperative course of the patients with these lesions to evaluate feasibility of limited surgery for small peripheral lung cancer. From 1982 to 1997, 114 patients underwent resection for small (< or = 20 mm in diameter) peripheral non-small-cell lung cancer. The histologic type was adenocarcinoma in 92 and squamous cell carcinoma in 22. Lobectomy was performed in 111, pneumonectomy in two and segmentectomy in one patient. The systematic mediastinal dissection was carried out in all patients. In 33 patients with tumors 12 mm in diameter or smaller, there were no one with lymph-node metastasis or pulmonary metastasis. Likewise, all patients were survived without relapse. In conclusion, curative resection may be possible without mediastinal dissection or with lesser lung resection (segmentectomy or partial resection), when the tumor diameter is less than 10 mm, for small peripheral non-small-cell lung cancer.

[Effects of bilateral lung volume reduction surgery in a patient with severe pulmonary emphysema].

A 61-year-old man suffering from severe pulmonary emphysema underwent lung volume reduction surgery on both upper lobes. By one year after surgery functional residual capacity had decreased by 2.5 L and FEV1 had increased by a factor of 2.4. Diaphragm excursion, as assessed by dynamic magnetic resonance imaging, had increased and ventilation and pulmonary gas exchange had improved. Performance on a 6-minute-walk test and exercise tolerance measured on a bicycle ergometer improved, and both peak VE and VO2 increased. Before surgery, pulmonary artery pressure Ppa and pulmonary capillary wedge pressure Pewp during exercise were abnormally high, but 6 months after the operation the increases in Ppa and Pcwp during exercise were markedly reduced.

[Thoracic duct cyst--a case report].

A case of thoracic duct cyst was reported. The patient, 72 year old man, was admitted with chief complaint of dysphagia. Chest X-ray film demonstrated an ovoid mass at the right upper mediastinum and the esophagus pressed by the tumor to the right. CT scan showed a round tumor with obscure margin located at the right upper mediastinum. Other laboratory data were almost within normal limits. Thoracotomy was performed on March 26, 1987 under diagnosis of leiomyoma of the esophagus. A fluid containing cyst covered with pleura was found at the upper mediastinum. The tumor was connected to the thoracic duct at its upper and lower portion. The cyst was isolated by sharp and blunt dissection without difficulties and removed. The cyst measured 7.5 X 4.5 X 4.5 cm and contained chyle. Pathological examination revealed no evidence of malignancy. Postoperative course of this patient was uneventful, and dysphagia was disappeared.