Human skin is exposed to high amount of solar ultraviolet (UV) radiation, as well as to other environmental oxidants. Photoaging refers to the effect of long-term UV exposure and sun damage superimposed on intrinsically aged skin. The clinical photoaging features are dyspigmentation, laxity, wrinkles, and cutaneous malignancies. Most conspicuous photoaging change in dermis, which is caused by elastin materials accumulation, is termed “solar elastosis”. Reactive oxygen species are known to be generated by UV radiation, and play an important role of photoaging. Although the pathogenesis of systemic sclerosis (SSc) remains unknown, oxidative stress has been suggested to contribute to clinical manifestations associated with SSc, such as vascular damage including Raynaud's phenomenon. This review focuses on recent data including our data which have demonstrated the critical role of oxidative stress in photoaging and the pathogenesis of SSc.

View full abstract

  The homeostasis of the immune system is maintained by the recirculation of naive lymphocytes through the secondary lymphoid tissues, such as the lymph nodes, Peyer's patches and spleen. Upon antigen encounter in the secondary lymphoid tissues, lymphocytes become activated and undergo a reprogramming of their trafficking properties. Most antigen-experienced lymphocytes traffic through the secondary lymphoid organs, but they can also migrate to extralymphoid tissues, where they exert effector functions. Dendritic cells in the secondary lymphoid tissues are crucial for the reprogramming of trafficking properties of activated T-lymphocytes. The exquisite specificity of such lymphocyte trafficking is determined by tissue-specific guidance signals expressed by the vascular endothelial cells, combined with counter receptors expressed by circulating lymphocytes. The high endothelial venules can selectively recruit naive lymphocytes into the lymph nodes and Peyer's patches by expressing a unique combination of vascular addressins and chemoattractants. The inflamed postcapillary venules in extralymphoid tissues also use a distinct array of endothelial adhesion molecules and tissue selective chemokines to support the recruitment of effector and memory lymphocytes that express appropriate trafficking receptors. Exit of lymphocytes from lymphoid and extralymphoid tissues into circulation is actively regulated by signals through specific receptors for sphingosine-1-phosphate and a certain chemokine(s), respectively. This review summarizes the present understandings of the mechanisms regulating homeostatic recirculation of naive lymphocytes through the secondary lymphoid tissues and tissue-specific trafficking of antigen-experienced lymphocytes.

View full abstract

  In order to know the comlement activation, the changes of compliment were evaluated in recurrent abortion and pregnancy loss patients with antiphospholipid antibody (APA) positive. Serum samples were taken from 82 patients with more than 2 recurrent abortion patients and/or pregnancy loss. Fifty eight cases of 82 patients were APA and antinuclear antibody negative without autoimmune disease. Anticardiolipin antibody (ACA), anti CL/β2-GPI antibody (CL/β2-GPI) were measured using ELISA. Lupus anticoagulant (LAC) was measured using diluted RVVT. CH50 and C3 and C4 were measured as complements. The number of positive cases of ACA, CL/β2-GPI, LAC was 23, 9 and 5 cases, respectively.
  Results: The levels (mean±SD) of CH50, C3 and C4 in ACA positive and negative cases were 38.8±8.3 U/ml, 82.7±20.1 mg/dl, 18.5±5.7 mg/dl and 42.4±6.9 U/ml, 93.5±17.6 mg/dl, 21.1±4.6 mg/dl, respectively. The levels of CH50, C3 and C4 in positive cases were significantly lower than negatives. The levels of CH50, C3 and C4 in CL/β2-GPI and LAC positive cases were also significantly lower than negatives.
  Conclusion: The comlement activation was demonstrated in recurrent abortion and pregnancy loss with antiphospholipid antibody positive.

View full abstract

  The patient was a 7-year-old girl. At the age of 6, deposits of pigment had appeared on the skin of her face and limbs, the skin had become sclerosed, and she had developed dyspnea on exertion. Her previous physician had hospitalized her. She was diagnosed as systemic scleroderma that accompanied pulmonary hypertension by her symptoms and laboratory findings. She was referred to our hospital at 7 years of age, and she was hospitalized. At that time, the entire skin showed deposition of brown pigment, the skin of the limbs was sclerotic. And the face was mask-like, flexion of the joints of the fingers and knees was limited, and the fingertips were ulcerated. Raynaud's phenomenon was present. She was positive for antinuclear antibodies, and negative for other autoantibodies. Echocardiography revealed pulmonary hypertension. After admission, steroid pulse therapy and cyclophosphamide (CY) pulse therapy were initiated, and for aftercare, 15 mg/day of prednisolone (PSL) and mizolibin (MZB) were administered orally. After several months, the sclerosis of the skin improved and the restriction of limb flexion was almost eliminated. The pulmonary hypertension advanced temporarily (maximum: 70 mmHg), but after oral administration of a PGI2 preparation and low-flow supplemental oxygen therapy and the initiation of anticoagulant therapy, the systolic pressure of the pulmonary artery improved to 34 mmHg. The CY pulse therapy was terminated after two years, and internal use of PSL and MZB was continued. The patient's condition is now stable.
  This case was treated from an early stage with steroid pulse therapy and CY pulse therapy, accompanied with oral administration of a PGI2 preparation for the pulmonary hypertension. The dermal symptoms improved, and it was possible to maintain a state of remission.

View full abstract

  The case: A 44-year-old female. Developed polyarthralgia in August 2002. The patient was diagnosed with systemic lupus erythematosus (SLE) in November, due to polyarthralgia, leukopenia, anti ds-DNA antibody positive, antinuclear antibody positive, and false positive serologic test for syphilis. Hypocomplementemia continued even after the steroid treatment was conducted with insufficient control. In November 2003, ran fever and observed polyarthralgia. In December, gross hematuria and purpura appeared. The patient was hospitalized on December 25. Thrombotic thrombocytopenic purpura (TTP) was suspected from the emergence of fragmented red cells, hemolysis, thrombocytopenic purpura, headache, renal dysfunction and fever. As hemophagocytic syndrome (HPS) was suspected from hyper-ferritinemia, bone marrow aspiration was conducted. Macrophage confirmed hemophagocytic image and the patient was diagnosed with HPS complication. Methylprednisolone pulse therapy was conducted for three days, followed by the administration of prednisolone 60 mg. Plasma exchange therapy was also conducted from the first day of hospitalization. Recurrence of TTP after plasma exchange therapy, but it improved by additional plasma exchange. Low vWF-CP (ADAMTS-13) activity was observed in this case, and anti-vWF-CP antibody was positive. TTP and HPS are both critical intractable complications of SLE. Bearing in mind the possibility of simultaneous complication of both symptoms, prompt diagnosis is crucial for life-saving.

View full abstract