Ten-year survival of immediate-loading implants in fully edentulous mandibles in the Japanese population: a multilevel analysis.

PURPOSE: To evaluate the long-term clinical results of and risk factors for immediate-loading implant treatment of completely edentulous mandibles. METHODS: We retrospectively studied 220 implants in 52 patients who received immediate-loading implants in fully edentulous mandibles. Kaplan-Meier survival analyses, log-rank tests, and multilevel mixed-effects parametric survival analysis was used for statistical analyses. RESULTS: Thirteen of implants in seven patients failed, and the 10-year cumulative implant survival rate was 93.9 % and significantly (p=0.049) higher in women than in men. None of the predictor variables were significantly associated with implant survival, although sex tended to be associated with implant survival. CONCLUSIONS: Immediate-loading implant treatment for completely edentulous mandibles had acceptable clinical results in the long term. Although we could not identify significant risk factors, we established a multilevel mixed-effects parametric survival analysis with the immediate-loading implant survival data.

Cell-SELEX based selection and characterization of DNA aptamer recognizing human hepatocarcinoma.

Single-stranded DNA aptamers recognizing human hepatocarcinoma were isolated by means of a systematic evolution of ligands by exponential enrichment using whole cells as targets (cell-SELEX). After 11 rounds of cell-SELEX procedure using human hepatoma HepG2 cells as targets and human normal hepatocyte cells as counterparts, 12 independent DNA aptamer candidate sequences were obtained. The specific interaction between selected DNA aptamers and targeted cell was confirmed. Dissociation constants of the 12 sequences obtained were also estimated in the range of 19-450nM. Moreover, the consensus secondary structure was found in the isolated aptamers, which was responsible to the recognition of HepG2 cells.

Isolated angiitis in the hypothalamus mimicking brain tumor.

A 64-year-old female presented with exaggerating somnolence without contributory medical and lifestyle histories. She was not aware of any preceding infection or headache. Cerebral magnetic resonance imaging demonstrated an isolated enhanced mass in the hypothalamus without meningeal enhancement. Blood and cerebrospinal fluid examinations showed no significant findings except for hypernatremia and hyperprolactinemia. She underwent an open biopsy via the interhemispheric route. Histological examination revealed marked perivascular lymphocytic aggregation with polyclonal immunostaining both for B and T lymphocytes. No findings suggestive of underlying malignancy were recognized. Extensive work-up aiming at systemic vasculitis and lymphoma revealed no signs of extracranial lesion, so the most probable diagnosis was isolated angiitis in the hypothalamus. Angiitis may originate from the hypothalamus and should be considered in the differential diagnosis of hypothalamic lesion mimicking brain tumor on neuroimaging.

Detection of serum IgE class anti-SSA antibodies in mothers with foetal loss.

We previously reported a close relationship between serum immunoglobulin (Ig)E and anti-SSA antibody levels in mothers with foetal loss. Here, we investigated the existence of IgE class anti-SSA antibodies (IgE anti-SSA antibody) and the relationship of such antibodies with foetal loss. Serum samples from 24 women who were positive for IgG class anti-SSA antibody (IgG anti-SSA antibody) were examined for IgE anti-SSA antibody by enzyme-linked immunosorbent assay (ELISA). Then, a retrospective analysis of the relationship between the IgE anti-SSA antibody positivity and the frequency of foetal loss was performed. Using our ELISA system, IgE anti-SSA antibodies were detected in the serum samples, and the frequency of foetal loss was increased among the mothers with higher IgE anti-SSA antibody titers. Our results indicate that IgE anti-SSA antibodies may be a useful marker for the risk of foetal loss in mothers with anti-SSA antibodies.

Two cases of refractory Wegener's granulomatosis successfully treated with rituximab.

Conventional therapy for Wegener's granulomatosis, steroid and cyclophosphamide, fails to control disease activity in some refractory patients and has treatment-related toxicity. B cell depletion therapy using rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for certain autoimmune diseases including antineutrophil cytoplasmic antibody (ANCA) -associated systemic vasculitis. We report two refractory cases of Wegener's granulomatosis: one with bronchial and pulmonary involvement and retroorbital granuloma, the other with retroorbital granuloma and hypertrophic pachymeningitis causing severe headache. Rituximab was effective in both cases, with diminished granuloma and reduced ANCA titers, allowing steroids to be tapered. No adverse effects were detected.

Reactive arthritis after influenza vaccination: report of a case.

We describe a patient with reactive arthritis (ReA) induced by influenza vaccination. A healthy 79-year-old Japanese man began suffering from migrating polyarthritis 2 days after receiving influenza vaccine. He proved negative for rheumatoid factor, showing no evidence for microbial infections such as Streptoccocci, Chlamydia, or Parbovirus B19. Human leukocyte antigen (HLA) typing analysis revealed positive results for HLA-B54 (22), which is one of the cross-reactive antigens to HLA-B27. His arthritis improved with administration of nonsteroidal anti-inflammatory drugs, and recovery was attained within 6 weeks. Reactive arthritis is a rare adverse effect induced by influenza vaccination; however, it is important that it is recognized by all physicians.

Autoimmune response to proteins of proliferating cell nuclear antigen multiprotein complexes in patients with connective tissue diseases.

OBJECTIVE: To analyze the autoimmune response to the proliferating cell nuclear antigen (PCNA) multiprotein complex in patients with connective tissue diseases (CTD). METHODS: The PCNA complex was purified by affinity chromatography using anti-PCNA monoclonal antibodies. Then 196 serum samples from patients with systemic lupus erythematosus (SLE) and 82 from patients with other CTD were tested for reactivity with the complex by immunoblotting. RESULTS: Of 196 SLE sera, 61 (31%) reacted with at least one component of the PCNA complex, and most reactive sera contained autoantibodies to several components of the complex. Autoantibodies to PCNA complex were less common in patients with other CTD, and most of their sera reacted only with one or a few proteins in the complex. Two out of 20 scleroderma sera reactive with 100, 85, and 70 kDa proteins in the PCNA complex also had autoantibodies to topoisomerase I (topo I) antibodies, which is an element of the complex. These findings suggest that the autoimmune response to the PCNA complex was specific for SLE. Anti-PCNA complex antibodies were associated with an increased serum level of PCNA detected by ELISA. The spreading of the autoimmune response to the elements of the complex was observed in parallel with the increased serum PCNA level when a series of sera from a lupus patient were tested longitudinally. In addition, anti-PCNA complex antibodies were significantly correlated with lupus erythematosus cells. CONCLUSION: The "antigen-drive" system may play a crucial role in inducing the autoimmune response to the PCNA complex in patients with SLE.

Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients.

Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.

Anticyclic citrullinated peptide antibodies in patients with mixed connective tissue disease.

The clinical significance of anticyclic citrullinated peptide (CCP) antibodies in patients with mixed connective tissue disease (MCTD) was assessed. Altogether, 86 sera from MCTD patients, 96 from rheumatoid arthritis (RA) patients, 42 from systemic lupus erythematosus (SLE) patients, 23 from systemic sclerosis (SSc) patients, 21 from polymyositis/dermatomyositis (PM/DM) patients, and 17 from those with Sjögren's syndrome (SjS) were tested for anti-CCP antibodies using an enzyme-lined immunosorbent assay. Among the 96 RA patients, anti-CCP antibodies were detected in 85%, with the frequency being significantly higher than in MCTD, SLE, SSc, PM/DM, and SjS patients (9%, 14%, 13%, 14%, and 18%, respectively; P < 0.001). Among eight MCTD patients who fulfilled the diagnostic criteria for RA, only 50% had anti-CCP antibodies, and the prevalence was significantly lower than for all RA patients (p < 0.01). All eight patients who fulfilled the criteria for RA had overlap of SLE and SSc, except one patient, whereas the four anti-CCP-positive patients who did not fulfill the criteria for RA had SjS without overlapping features of SLE and SSc; moreover, most of their antibody titers were low. These results suggested that anti-CCP antibodies are associated with RA in MCTD patients, but careful diagnosis of RA is required if patients with low titers of anti-CCP antibodies lack overlapping SLE and SSc.

Churg-Strauss syndrome (CSS) in a patient receiving pranlukast.

Pranlukast is a cysteinyl leukotriene receptor I antagonist (LTRAs) approved for treatment of asthma in Japan since 1995. Compared to other LTRAs, such as zafilukast and montelukast, only few cases with Churg-Strauss syndrome (CSS) have been reported in association with treatment with pranlukast. We describe a 17-year-old Japanese male patient who developed CSS with a 13 month history of mild asthma receiving pranlukast for 11 months without systemic and/or inhaled corticosteroid administration prior to development of CSS. From the aspect of temporal relationship between treatment with pranlukast and development of CSS, a direct induction of CSS by pranlukast is suggested in our case.

A case of aplastic anemia in a patient with systemic lupus erythematosus.

Abstract A case of aplastic anemia with a 16-year history of systemic lupus erythematosus (SLE) is described. The diagnosis of aplastic anemia was established by bone marrow biopsy. Aplastic anemia is an extremely rare complication of SLE. The pathogenesis of aplastic anemia associated with SLE remains to be clarified.

Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus.

OBJECTIVE: To analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation. METHODS: PCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK-PCNA) were purified using anti-PCNA serum AK. The reactions to these antigens of 10 anti-PCNA-positive and 40 anti-PCNA-negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme-linked immunosorbent assays (ELISAs). RESULTS: With one exception (serum OK), anti-PCNA-positive sera reacted exclusively with only the 34-kd polypeptide. In contrast, 14 of 40 anti-PCNA-negative sera reacted with multiple proteins within PCNA complexes. Most anti-PCNA-positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK-PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58-kd polypeptide and the 34-kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes. CONCLUSION: Intermolecular-intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.

Anti-TS1-RNA: characterization of novel antibodies against sequence-specific RNA by random RNA selection in patients with Sjögren's syndrome.

OBJECTIVE: To define a novel RNA epitope recognized by serum from a patient with Sjögren's syndrome (SS) from a randomized RNA epitope library and investigate the epitope reactivity of the anti-RNA antibodies in patients with various connective tissue diseases. METHODS: Serum from a patient with SS was used to select ligands from a library of RNA oligomers with a central region of 25 degenerate nucleotides. Bound RNA was recovered by reverse transcription, PCR amplification, and subcloning. The relationship between the antibodies to the selected RNA and disease specificity was studied using immunoprecipitation. RESULTS: From the random RNA library, several unique RNA sequences were obtained. Sera from 32 of 61 patients with SS (52.5%) precipitated with one of the selected RNA (TS1-RNA), whereas sera from 8 of 41 patients with systemic lupus erythematosus (19.5%) and 3 of 25 patients with rheumatoid arthritis (12.0%) precipitated. Although the frequency of reactivity to the TS1-RNA was higher in anti-SSA/Ro positive sera, the presence of either native or recombinant SSA/Ro antigen showed no detectable competition, and no apparent sequence homology was found between the TS1-RNA and hY RNA. CONCLUSION: These data suggest that anti-TS1-RNA is a novel antibody against sequence-specific RNA in many patients with SS.