The effect of endostatin evaluated in an experimental animal model of collagen-induced arthritis.

OBJECTIVE: To investigate the arthritis-inhibiting effect of endostatin, a potent angiogenesis inhibitor, on type II collagen-induced arthritis (CIA). METHODS: In an experimental system of prophylactic administration, endostatin was administered once daily at 1 mg/kg/day or 10 mg/kg/day for 2 weeks from before the onset of arthritis. In the experimental system of therapeutic administration, mice with an arthritis score of 1 to 3 were administered endostatin once daily at 10 mg/kg. In the experimental system of continuous administration, endostatin was administered using an osmotic pump capable of continuously administering a calculated dose of 1 mg/kg/day for 2 weeks. RESULTS: Arthritis scores were lower in a dose-dependent manner in the prophylactic administration group than in the control group. Arthritis scores were lower in the therapeutic administration group than in the control group. Compared with the once-daily dosage regimen, the administration of endostatin by an osmotic pump achieved a similar arthritis-inhibiting effect at one-tenth of the dose. CONCLUSION: Both prophylactic and therapeutic administration of endostatin inhibited type II CIA in mice. The administration method using an osmotic pump is useful.

Inhibition of arthritis by systemic administration of endostatin in passive murine collagen induced arthritis.

OBJECTIVE: To investigate the arthritis inhibiting effect of endostatin, known to have potent antiangiogenic activity, systemically given to animal models of rheumatoid arthritis (RA). METHODS: Four kinds of monoclonal anti-type II collagen antibody followed by lipopolysaccharide (LPS) three days later were given to 6 week old, female Balb/c mice to induce arthritis. Three groups of mice received 0.2 mg/kg/day, 2 mg/kg/day, and 10 mg/kg/day of endostatin, respectively, whereas a control group received phosphate buffered saline (PBS). Endostatin or PBS was given for 13 days, starting before the development of arthritis. Arthritis was evaluated by arthritis scores and hind paw thicknesses. Mice were killed for histological examination on the 22nd day after the administration of monoclonal anti-type II collagen antibody. RESULTS: Arthritis developed within three days after LPS administration in both the control and endostatin treatment groups. No difference in the development rate of arthritis was noted between the control and endostatin treatment groups. Arthritis scores remained significantly lower in the endostatin 10 mg/kg/day group than in the control group. Hind paw thicknesses also remained significantly smaller in the endostatin 10 mg/kg/day group than in the control group. Histopathological examination showed that synovial thickening and subchondral bone erosion improved more in the endostatin treatment groups than in the control group. CONCLUSION: The systemic administration of endostatin had an arthritis inhibiting effect in RA animal models. Endostatin inhibited, in particular, pannus formation and bone destruction.

[A case of systemic lupus erythematosus associated with superior vena cava syndrome].

We report on a case of systemic lupus erythematosus associated with superior vena cava syndrome. A 46-year-old woman developed polyarthralgia in December 1994. She was treated with nonsteroidal anti-inflammatory drugs. In February 1995, she was admitted to our hospital with systemic convulsion and disturbance of consciousness (III-300/Japan coma scale). Severe facial edema was also present. Laboratory studies revealed the presence of anti-nuclear antibody, anti-DNA antibody, anti-Sm antibody, and proteinuria. An X-ray film of the chest showed pericardial effusion and bilateral pleural effusions. Computed tomography of the chest showed a severe swelling of mediastinal lymph nodes. A diagnosis of systemic lupus erythematosus was made according to the American Rheumatism Association criteria. Initial treatment with intravenous dexamethasone improved the level of consciousness and decreased the facial edema, mediastinal lymphadenopathy, and the effusions on computed tomography of the chest. We believe that the most likely explanation for the facial edema is superior vena cava syndrome due to severe mediastinal lymphadenopathy.

Common antigenicity between Japanese cedar (Cryptomeria japonica) pollen and Japanese cypress (Chamaecyparis obtusa) pollen, I. H-2 complex affects cross responsiveness to Cry j 1 and Cha o 1 at the T- and B-cell level in mice.

Common antigenicity among two purified Japanese cedar pollen allergens (Cry j 1 and Cry j 2) and one Japanese cypress pollen allergen (Cha o 1) was explored at the T-cell and B-cell level in mice of different H-2 haplotypes. Cry j 2 did not show any common antigenicity with Cry j 1 or Cha o 1. B10.S (H-2S) mice immunized with Cry j 1 or Cha o 1 generated T cells and antibodies reactive to both antigens, indicating the common antigenicity of these antigens. C57BL/6 (H-2b) mice were non-responders to Cry j 1. BALB/c (H-2d) mice immunized with Cry j 1 or Cha o 1 and C57BL/6 mice immunized with Cha o 1 generated T cells that were only reactive with the respective immunogen, but produced antibody reactive to both Cry j 1 and Cha o 1, indicating that Cry j 1 and Cha o 1 share their B-cell epitope but not their T-cell epitope. This finding may provide a clue for the clarification of the T-cell and B-cell epitopes of Cry j 1 and Cha o 1, even though the data are influenced by H-2 complex restriction in mice. Considering that H-2 complex restriction affects cross responsiveness to Cry j 1 and Cha o 1 at the T- and B-cell level in mice, we assessed the possible situation in humans exposed sequentially to Japanese cedar pollen and Japanese cypress pollen.

[A case of systemic lupus erythematosus associated with thrombotic thrombocytopenic purpura manifestating homonymous hemianopsia].

We report on a 35-year-old Japanese woman with systemic lupus erythematosus (SLE) in whom homonymous hemianopsia developed. In August 1987, SLE was diagnosed. In November 1987, the patient was admitted to our hospital because of severe thrombotic thrombocytopenic purpura; however, clinical symptoms improved after treatment with vincristine. In 1992, severe lupus nephritis developed but improved after steroid therapy. In February 1994, diplopia developed owing to inflammatory invasion of the orbit by acute maxillary sinusitis. Humphrey Field Analyzer perimetry revealed a homonymous quadrantic hemianopic scotoma in the lower left side. Magnetic resonance imaging of the brain revealed a small infarct lesion in the posterior pole of the upper calcarine cortex. This lesion was thought to be responsible for homonymous hemianopsia. However, the lesion was not visualized with computed tomography. Our experience in the present case suggests that magnetic resonance imaging is more useful than computed tomography for identifying lesion causing visual field disorders in SLE.

Cell electrophoretic mobility and glycerol lysis of human erythrocytes in various diseases.

Using an automated cell electrophoresis system equipped with an image processor, we studied electrophoretic mobilities of erythrocytes of healthy donors and of patients suffering from systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), hypergammaglobulinemia and diabetes mellitus (DM). On average, erythrocytes from SLE patients showed mean electrophoretic mobilities (EPM) which were significantly lower (p < 0.005) than the EPM of red blood cells of normal donors. Evaluation of mean EPM and standard deviations revealed that three groups of SLE patients could be distinguished regarding the electrophoretic behavior of their erythrocytes. Some patients had red blood cells with normal EPM, others had erythrocytes with significantly reduced EPM, and a third group appeared to have both kinds of erythrocytes. In addition, erythrocytes of various SLE patients showed enhanced resistance to lysis by glycerol and their membranes contained less quantities of band 3 proteins.