Quantum kinetic equation in the closed-time-path formalism

A systematic derivation of the quantum kinetic equation is presented in the framework of a closed-time-path formalism. Introducing a probe, the expectation value of the number operator is calculated as a functional of the probing source. Then, solving for the source by inverting the relation, the removal of the source leads to the quantum kinetic equation as the equation of motion for the number, which gives a generalization of the Boltzmann equation including memory. The inversion formula is used in the course of the derivation. The calculation is presented up to third order in interaction, and the effect of initial correlations is also considered.

[A case with rheumatoid arthritis complicated with ANCA-associated vasculitis].

A 50-year-old woman with rheumatoid arthritis (RA) developed constitutive symptoms such as fever and weight loss, mononeuritis multiplex and rapidly progressive glomerulonephritis (RPGN). The renal biopsy revealed crescentic glomerulonephritis (CrGN) with few immune deposits such as IgG and C 3 and necrotizing vasculitis, which led to the pathological diagnosis of microscopic polyangiitis (MPA). Moreover the high serum level of anti-myeloperoxidase (MPO) antibody, one of the anti-neutrophil cytoplasmic antibody (ANCA), suggested that she had ANCA-associated vasculitis. The renal prognosis of the ANCA-associated vasculitis is said to be poor unless patients were treated in the early phase of the disease. As we started to treat the patient when her serum creatinine level (sCr) was 1.7 mg/dl and creatinine clearance (CCr) was 27 ml/min, her renal function returned to the almost normal level (sCr = 0.6, CCr = 91). It is well known that patients with RA may develop various kinds of extraarticular manifestations which are usually related to immune-complex mediated vasculitis, what we call malignant RA. We emphasize that ANCA-associated vasculitis is another important complication of RA. When we see a RA patient with constitutional symptom, abnormal urinary sediments and other clinical signs of vasculitis such as mononeuritis multiplex, ANCA-associated vasculitis should be considered. Since the early diagnosis and treatment of ANCA-associated vasculitis is a key to prevent renal failure, it is encouraged to measure the serum ANCA titer for not only the diagnosis of such patients but the evaluation of their clinical course.

Diagnosis of measles viral pneumonia in a patient with Hodgkin's disease by reverse transcription-polymerase chain reaction of serum.

We report a case of fatal measles viral pneumonia in a patient with Hodgkin's disease who had no rash. The measles viral cDNA was detected in autopsy tissue from the lung by reverse transcription-polymerase chain reaction. This method was then applied successfully to stored serum. The diagnosis of measles viral pneumonia may be improved by the application of RT-PCR using peripheral blood. Sequence analysis of amplified cDNA suggested the virus infecting this patient was a recent strain, predominantly isolated after 1980. The fatal outcome may have been due to a lack of immune response to the newer strain.

Granulomatous amoebic encephalitis caused by Acanthamoeba in a patient with systemic lupus erythematosus.

A 25-year-old chronically immunosuppressed woman with systemic lupus erythematosus (SLE) died after developing subacute granulomatous encephalitis caused by Acanthamoeba. Amoebic trophozoites were also found in the lung, suggesting a primary pulmonary focus of infection. The infectious encephalitis was difficult to differentiate from a flare-up of central nervous system lupus. This case illustrates that Acanthamoeba can cause fatal encephalitis in lupus patients, as well as in patients with acquired immunodeficiency syndrome as previously reported. To our knowledge, this is the first reported case of granulomatous amoebic encephalitis due to Acanthamoeba in a patient with SLE.

TCR zeta chain lacking exon 7 in two patients with systemic lupus erythematosus.

To address the molecular mechanism underlying the functional defects of peripheral T cells in systemic lupus erythematosus (SLE), we focused on early signaling events. We demonstrated that protein expression of the TCR zeta chain was significantly decreased in peripheral T cells from patients with SLE compared to normal controls and patients with systemic sclerosis (SSc). Among those patients showing decreased TCR zeta chain expression, we found two patients with pronounced TCR zeta chain abnormalities, including an aberrant 14 kDa form in one and only trace expression in the other. RT-PCR, SSCP and subsequent cloning of the transcripts revealed that bases 468503, corresponding to exon 7, were deleted in both patients. Since exon 7 spans the GTP/GDP binding site and N-terminal tyrosine in the third ITAM domain of TCR zeta chain, the transcript lacking exon 7 may be responsible for altered signal transduction via TCR in these SLE patients.

Up-regulation of alphaEbeta7, a novel integrin adhesion molecule, on T cells from systemic lupus erythematosus patients with specific epithelial involvement.

OBJECTIVE: To determine the possible role of a novel integrin, alphaEbeta7, in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: Expression of alphaEbeta7 was examined on peripheral blood lymphocytes (PBL) from normal subjects (n = 25) and patients with SLE (n = 31), primary Sjogren's syndrome (n = 7), or polymyositis/dermatomyositis (n = 8) by cytofluorometry and/or immunoprecipitation. Adhesion of alphaEbeta7+ T cells to HSG epithelial cells was investigated using a confocal image analyzer. RESULTS: After phytohemagglutinin stimulation, expression of alphaEbeta7 on PBL, especially on CD8+ T cells, was significantly higher in SLE patients than in normal subjects (P<0.01). Elevated alphaEbeta7 expression was associated with the presence of oral ulcers or serositis (P<0.05). Activated SLE T cells with enhanced alphaEbeta7 expression strongly adhered to HSG; this adhesion was partially blocked by anti-alphaEbeta7. CONCLUSION: Expression and adhesion of alphaEbeta7 on activated PBL was significantly increased in patients with SLE with epithelial involvement. This suggests a role of this novel integrin in tissue-specific retention of activated PBL, due to increased alphaEbeta7-E-cadherin interaction, which may contribute to epithelial inflammation.

Reduced protein tyrosine phosphatase (PTPase) activity of CD45 on peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE).

To disclose the mechanism of aberrant function of peripheral blood lymphocytes (PBL) in SLE, we focused on the catalytic function of CD45, and determined the CD45 PTPase activity in SLE patients. The sample population consisted of 32 SLE patients with different disease activity. PTPase activity of cell lysates immunoprecipitated by anti-CD45 MoAb was assayed against phosphotyrosine analogue PNPP, followed by measuring the release of para-nitro phenol at 410 nm. CD45 PTPase activity of PBL was significantly decreased in SLE patients, compared with that of normal controls and patients with systemic sclerosis (964 +/- 265, 1202 +/- 172, 1210 +/- 125, respectively; SLE versus normal, P<0.05). It was correlated with SLE Disease Activity Index (SLEDAI) score (r = 0.597, P = 0.0006), but not with the dose of prednisolone (r = 0.214, P = 0.2657), indicating that CD45 PTPase activity became reduced when the disease was active, but it was not affected by prednisolone. Moreover, it was not corrected by in vitro culture with or without stimulation. The expression of CD45 on PBL was comparable between normal and SLE, raising a possibility that it may be due to aberrant regulation of catalytic function of CD45 in SLE. Given the evidence that tyrosine phosphorylation of cellular proteins by tyrosine kinases and phosphatases is one of the key biochemical events in the signal transduction pathway, the decreased CD45 PTPase activity in SLE may account for the defective signal transduction via TCR/CD3, leading to dysregulated effector function of the lymphocytes.

Spontaneous establishment of an Epstein-Barr virus-infected fibroblast line from the synovial tissue of a rheumatoid arthritis patient.

An Epstein-Barr virus (EBV)-infected fibroblast line, designated DSEK, was spontaneously established from synovial tissue of a patient with rheumatoid arthritis (RA). DSEK cells expressed EBV nuclear antigens EBNA-1 and EBNA-2 and latent membrane protein LMP-1. Cell surface markers of DSEK cells were similar to those of EBV-negative fibroblast clones derived from synoviocytes and were negative for lymphocyte and macrophage markers. DSEK cells expressed CD44, CD58, and HLA-DR antigens and spontaneously produced interleukin-10 basic fibroblast growth factor and transforming growth factor beta1. These results indicate that rheumatoid synoviocytes can be a target for EBV infection and suggest that EBV may play a role in the pathogenesis of RA.

Systemic lupus erythematosus with necrotizing vasculitis and upregulated expression of VLA-4 antigen.

We report on a patient (S.A.), with well-defined SLE who developed a perforation of the ileum due to pathologically confirmed necrotizing vasculitis. No anti-DNA antibody was detected at the ileal perforation, and the serum complement level was normal. These findings raise the alternative possibility of a cell-mediated immune mechanism as a cause of necrotizing vasculitis. Upregulated expression and function of VLA-4 antigen on peripheral blood T cells were observed, suggesting that T cells with VLA-4 antigen may participate in the onset and/or perpetuation of vascular inflammation.

[Clinical significance of anti-cardiolipin antibody in patients with systemic lupus erythematosus (SLE)].

Anti-cardiolipin antibody (aCL) in SLE patients reacts with cardiolipin/beta 2-GP1 complex. In order to disclose clinical significance of aCL in patients with SLE, aCL was determined by newly-developed anti-CL.beta 2-GP1 kit [Yamasa] EIA in 58 patients with SLE and the relationship between clinical manifestation of SLE and the presence of aCL was examined. Anti-cardiolipin antibody was positive in 20 patients (34.5%). In 20 SLE patients with positive aCL, livedo reticularis in 7, retinal vein thrombosis in 3, thrombophlebitis in 3 and other vasculo-occlusive episodes were observed as a characteristic clinical features of positive aCL. In contrast, a SLE patient complicated by ileal perforation due to necrotizing angiitis had negative aCL. Other clinical and laboratory features associated with aCL include recurrent fetal loss and thrombocytopenia.

Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis.

Upregulation of integrin adhesive receptors has been implicated in various pathological conditions. We examined expression and function of integrin adhesive receptors on peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE), particularly those with the complication of vasculitis, and found that VLA-4 and LFA-1 expression was increased in SLE patients with vasculitis, while LFA-1 but not VLA-4 expression was increased in those without vasculitis. These results suggested a role of VLA-4 in the pathogenesis of vasculitis in SLE. Functional studies further demonstrated that adhesion to cytokine-activated human umbilical cord vein endothelial cells and to the CS-1 alternatively spliced domain of fibronectin was significantly increased in SLE patients with vasculitis. Analysis of the functional epitopes on the alpha 4 chain demonstrated that antigen densities of all the functional epitopes were increased in those with vasculitis, indicating that the increased expression of VLA-4 resulted from the increased number of VLA-4 molecules, and was not secondary to an increase in one particular functional epitope. Immunoprecipitation studies further support these results. Interestingly, high molecular weight bands associated with VLA-4 were observed in about half of the SLE patients with vasculitis. These results introduce a possibility that upregulation of integrin adhesive receptors has a potential role in the pathogenesis of vasculitis in SLE.

Integrin VLA-5 negative primary plasma cell leukemia.

We present a case of primary plasma cell leukemia with Bence Jones proteinuria. After combination chemotherapy, leukemic cells and the urinary levels Bence Jones protein were decreased. Small lytic bone lesions were detected only in the skull. Typical plasma cells were rarely seen in peripheral blood on the hyperleukocytic phase, however they were increased in the advanced stages. The most important diagnostic sign was persistent expression of CD38 antigen on leukemic cells throughout the entire course of the illness and these leukemic cells expressed very late antigen-4 (VLA-4) but not VLA-5.

[Studies on clinical remission of rheumatoid arthritis].

Clinical remission was observed in 19 out of 276 patients with rheumatoid arthritis. Remission rate was higher in male patients. In order to determine the clinical characteristics of remission cases, comparative study was performed. Although the time between initiation of treatment and clinical remission varied from case to case, the remission was related to early diagnosis and use of immunomodulating drug. No exacerbation was observed in our 19 patients with remission for the periods of 17 observation months. However, serial X-ray examination of hands disclosed that the erosive changes developed even after clinical remission.

The presence of anti-protein A antibodies in patients with rheumatoid arthritis.

Sixteen patients with rheumatoid arthritis (RA) were examined for the presence of anti-protein A antibodies. The F(ab')2 preparations from five RA patients showed significant binding to IgG-free protein A on ELISA. The protein A binding was further examined by immunoblotting. The F(ab')2 preparations of high protein A-binding protein gave a specific reaction with IgG-free protein A on nitrocellulose paper. This demonstrates the presence of anti-protein A antibodies in patients with RA. Those RA patients with anti-protein A antibodies had more active disease as judged by the Lansbury's activity index. The level of serum rheumatoid factor (RAHA) was significantly higher in patients with anti-protein A antibodies than in those without anti-protein A antibodies.

[Morphological study of cochlea in experimental chronic serum sickness].

Relationship of circulating immune complexes to some inner ear disorders has been suggested recently. Thus, bovine serum albumin (BSA) nephritis, a model of chronic serum sickness, was made and morphological, immunological studies of cochlea were performed using light microscopy, transmission electron microscopy and immunofluorescent antibody methods. Group 1 consisted of animal sensitized with daily BSA injections for 90 days; in group 2, BSA was administered for 70 days, daily, and after a three-weeks interval, injections were continued for another 21 days; group 3 consisted of animals sensitized with daily BSA injections for 100 days followed by BSA injection into the facial nerve via the stylo-mastoid foramen. The animals (group 3) were sacrificed on day 1 and 4 following facial nerve sensitization for examination of cochlear morphological changes. No morphological changes were observed (group 1). Protrusion of marginal cells into endolymphatic space was seen, because of swelling of endoplasmic reticulum of the cells of stria vascularis's (group 2). Slight hydrops was present mainly in the basal turn (group 3). No IgG deposits were found in all groups. It appears that the changes in group 2 were caused by rather chronic nephritis than immune reaction. We conclude that damage induced in the cochlea is negligible compared to the extensive lesions observed in the kidney in chronic serum sickness.