NFKBIL1 confers resistance to experimental autoimmune arthritis through the regulation of dendritic cell functions.

We and others have reported that human NF-κB inhibitor-like-1 (NFKBIL1) was a putative susceptible gene for autoimmune diseases such as rheumatoid arthritis (RA). However, its precise role in the pathogenesis of RA is still largely unknown. In this study, we generated transgenic mice expressing human NFKBIL1 (NFKBIL1-Tg) and examined whether NFKBIL1 plays some role(s) in the development of autoimmune arthritis. In both a collagen-induced arthritis model and a collagen antibody-induced arthritis model, NFKBIL1-Tg mice showed resistance to arthritis compared to control mice, indicating that the gene product of NFKBIL1 was involved in the control of thusly induced arthritis. Total spleen cells of NFKBIL1-Tg mouse showed decreased proliferation to mitogenic stimuli, consistent with its resistance to arthritis. Unexpectedly, purified T cells of NFKBIL1-Tg mouse showed increased proliferation and cytokine production. This apparent discrepancy was accounted for by the impaired functions of antigen-presenting cells of NFKBIL1-Tg mouse; both T/B cell-depleted spleen cells and bone marrow-derived dendritic cells of the Tg mouse induced less prominent proliferation and IL-2 production of T cells. Furthermore, dendritic cells (DCs) derived from NFKBIL1-Tg mouse showed lower expression of co-stimulatory molecules and decreased production of inflammatory cytokines when they were activated by lipopolysaccharide. Taken together, these results indicated that NFKBIL1 affected the pathogenesis of RA at least in part through the regulation of DC functions.

[A case of unresectable pancreatic cancer successfully treated with continuous venous daily infusion of 5-FU and low-dose CDDP].

This case was a 61-year-old male diagnosed with pancreatic cancer who had a celiotomy. The tumor invasion involved the pancreas body and head. Ultrasonograph examination revealed that all the celiac artery, supramesenteric artery, and portal vein were occluded in the tumor. Because of the unresectability of the tumor, a palliative operation was carried out, and during the following 9 months he was given UFT 300 mg daily. Because abdominal ascites accompanied the tumor growth, the patient underwent combination chemotherapy of cisplatin 5 mg/day x 5/week and continuous infusion of 5-fluorouracil 250 mg/day for 4 weeks. Remarkable reduction of the abdominal ascites and decline of the tumor markers (CEA, CA19-9) was observed in the course of the chemotherapy. Bone marrow function was suppressed by the agents, but granulocyte colony stimulating factor (G-CSF) was very effective for recovery from the damage. Two months after discharge, abdominal ascites recurred. The patient received the same serial chemotherapy for 6 weeks, and now is followed as an outpatient.

Combined factor VII and protein C deficiency found in a patient with peripheral pulmonary artery stenosis accompanied by progressive pulmonary hypertension and hemoptysis.

A congenital deficiency of factor VII and protein C was found in a 21-year-old female suffering from recurrent and progressive attacks of dyspnea and hemoptysis over the last four years. She has been followed in our Department since the age of 17 under a diagnosis of peripheral pulmonary artery stenosis and pulmonary hypertension as confirmed by cardiac catheterization and angiography. Prolonged prothrombin time repeatedly examined during this time period prompted us to perform detailed coagulation studies. We found that factor VII and protein C were both half normal in activity as well as in antigen. Three other members of her immediate family were also found to be affected with this combined deficiency. Since the genes encoding factor VII and protein C are located in different chromosomes, the 13th and the second chromosomes, respectively, expression of the combined hereditary deficiency is a random and very rare association on the basis of frequencies of 1:50,000 for factor VII and 1:16,000 for protein C deficiencies.