Anticentromere antibody-positive primary Sjögren's syndrome: Epitope analysis of a subset of anticentromere antibody-positive patients.

OBJECTIVES: Anticentromere antibody (ACA) is generally considered to be a serological marker for systemic sclerosis (SSc). ACA-positive patients with primary Sjögren's syndrome (pSS) have also been reported. ACA often recognizes centromere proteins (CENPs): CENP-A, CENP-B, and CENP-C, and sometimes reacts to heterochromatin protein 1 (HP1)α. We compared the reactivity against six different epitopes for three ACA-positive clinical subgroups: 29 patients with pSS, 36 SSc patients with sicca symptoms, and 28 SSc patients without sicca symptoms. METHODS: We utilized enzyme-linked immunosorbent assays (ELISAs) with recombinant proteins covering six different epitope regions of ACA (the amino terminus (Nt) of CENP-A, CENP-B, and CENP-C, the carboxyl terminus (Ct) of CENP-B and CENP-C, and HP1α). RESULTS: The patients with pSS were found to have IgG-class autoantibodies against CENP-C-Nt and HP1α, and IgA-class autoantibodies against CENP-C-Ct with significantly higher frequencies than the SSc patients with or without sicca symptoms. The positive predictive value and the negative predictive value of the combination of these three autoantibodies for pSS were 73% and 82%, respectively, for pSS. CONCLUSIONS: Based on the result that reactivities against CENP-C and HP1α in patients with pSS differ from those in patients with SSc, we propose ACA-positive pSS as a clinical subset of SS that is independent of SSc.

G-Induced Loss of Consciousness Prediction Using a Support Vector Machine.

INTRODUCTION: Gravity-induced loss of consciousness (G-LOC) is a major threat to fighter pilots and may result in fatal accidents. The brain has a period of 5-6 s from the onset of high +Gz exposure, called the functional buffer period, during which transient ischemia is tolerated without loss of consciousness. We tried to establish a method for predicting G-LOC within the functional buffer period by using machine learning. We used a support vector machine (SVM), which is a popular classification algorithm in machine learning.METHODS: The subjects were 124 flight course students. We used a linear soft-margin SVM, a nonlinear SVM Gaussian kernel function (GSVM), and a polynomial kernel function, for each of which 10 classifiers were built every 0.5 s from the onset of high +Gz exposure (Classifiers 0.5-5.0) to predict G-LOC. Explanatory variables used for each SVM were age, height, weight, with/without anti-G suit, +Gz level, cerebral oxyhemoglobin concentration, and deoxyhemoglobin concentration.RESULTS: The performance of GSVM was better than that of other SVMs. The accuracy of each classifier of GSVM was as follows: Classifier 0.5, 58.1%; 1.0, 54.8%; 1.5, 57.3%; 2.0, 58.1%; 2.5, 64.5%; 3.0, 63.7%; 3.5, 65.3%; 4.0, 64.5%; 4.5, 64.5%; and 5.0, 64.5%.CONCLUSION: We could predict G-LOC with an accuracy rate of approximately 65% from 2.5 s after the onset of high +Gz exposure by using GSVM. Analysis of a larger number of cases and factors to enhance accuracy may be needed to apply those classifiers in centrifuge training and actual flight.Ohrui N, Iino Y, Kuramoto K, Kikukawa A, Okano K, Takada K, Tsujimoto T. G-induced loss of consciousness prediction using a support vector machine. Aerosp Med Hum Perform. 2024; 95(1):29-36.

A case of multicentric Castleman's disease having lung lesion successfully treated with humanized anti-interleukin-6 receptor antibody, tocilizumab.

This report presents the case of a patient demonstrating multicentric Castleman's disease (MCD) with a lung lesion that was successfully treated with an anti-interleukin-6 receptor antibody, tocilizumab in combination with corticosteroid and tacrolimus. A 43-yr-old female with abnormal shadows on a chest X-ray was referred to the hospital for further examination. She was diagnosed as having MCD based on the characteristic pathology of inguinal lymph node, lung lesions, laboratory data, and undifferentiated arthritis. Corticosteroid and rituximab therapy did not fully ameliorate the symptoms; thus, the therapeutic regimen was changed to include tocilizumab, oral corticosteroid and tacrolimus. This regimen resulted in clinical remission and the dose of tocilizumab and corticosteroid could be tapered. Tocilizumab in combination with corticosteroid and tacrolimus may therefore be a beneficial treatment regimen for lung lesions associated with MCD.

Ultra-high-purity iron is a novel and very compatible biomaterial.

Metals and alloys are used widely in bone prosthetic materials, stents and dental tissue reconstructions. The most common materials are stainless steels and cobalt-chromium-nickel and titanium alloys. These alloys can be easily deformed but are hard to break. However, their affinity for cells and tissues is very low. In addition, they can sometimes provoke unexpected metal allergies. Iron is an abundant trace element essential for humans. However, excess amounts in particular of Fe2+ ions are toxic. We previously succeeded in obtaining 99.9996% ultra-high-purity iron (ABIKO iron). The chemical properties of ABIKO iron are completely different from that of conventional pure iron. For example, the reaction rate in hydrochloric acid is very slow and there is barely any corrosion. Here, we found that, in the absence of any type of coating, mammalian cells could easily attach to, and normally proliferate and differentiate on, ABIKO iron. On the other hand, cell densities and proliferation rate of the surfaces of plates made from Co-Cr-Mo or Ti-6Al-4V were significantly reduced. In addition, several stress and iron response genes, HSP70, SOD1, ATM and IRP2 did not change in the cells on ABIKO iron, while these genes were induced with exogenous application of FeSO4. Cells also secreted and fastened some organics on ABIKO iron. In vitro collagen binding assay showed that ABIKO iron binds higher amount of collagens. These findings highlight ABIKO iron as a novel biocompatible prosthetic material.

Successful coil embolization of a ruptured hepatic aneurysm in a patient with polyarteritis nodosa accompanied by angioimmunoblastic T cell lymphoma.

Polyarteritis nodosa (PN) occasionally develops in association with malignant disorders. A 71-year-old man suddenly suffered from bleeding due to the rupture of a hepatic artery aneurysm. The ruptured lesion was embolized endovascularly by coiling, and the bleeding was stopped. A biopsy of the right inguinal lymph node demonstrated angioimmunoblastic T cell lymphoma (AITL). He received immunosuppressive treatment with transient response, although he relapsed 4 months later. To our knowledge, this is the first case of which PN was associated with AITL.

Detection of up-regulated genes in thrombin-stimulated human umbilical vein endothelial cells.

INTRODUCTION: Thrombin, a serine protease, plays an important role in such actions as coagulation, cell proliferation and inflammation. It has been sporadically reported that endothelial cells, when stimulated by thrombin via protease-activated receptors (PAR), express various mediators and proteins including cytokines, chemokines, growth factors, and adhesion molecules. However, the pleiotropic effect of thrombin on endothelial cells has not yet been fully elucidated. MATERIALS AND METHODS: We newly searched for the up-regulated genes in the thrombin-stimulated endothelial cells by thorough screening using a microarray chip, printed with 22,575 human genes, followed by verification using real-time PCR (n=3). RESULTS AND CONCLUSIONS: Twelve genes, which were 4.8 times or more up-regulated in a microarray analysis, were selected and further analyzed. In real-time PCR, ICAM-1, IL-8, BIRC3, COL3A1, CXCL3, and CXCL1 were significantly up-regulated in the thrombin-stimulated cells: 16.0-, 8.81-, 5.92-, 3.74-, 1.74-, and 1.66-fold, respectively. VCAM-1, CXCL2, CCL20, CSF2, CD69, and CCL2 were up-regulated in the thrombin-stimulated cells: 12.2-, 2.44-, 1.90-, 1.82-, 1.62-, and 1.06-fold, respectively, without attaining statistical significance. We demonstrated, for the first time, that BIRC3 (anti-apoptotic protein), COL3A1 (matrix protein synthesis), and CXCL3 (chemokine) were up-regulated in the thrombin-stimulated HUVECs.

Complex regional pain syndrome type I induced by pacemaker implantation, with a good response to steroids and neurotropin.

An 84-year-old woman was referred to our hospital because of aches and pain in her left hand and foot. Three months before her symptoms occurred, a pacemaker had been implanted for the treatment of a 2:1 atrioventricular block with bradycardia. In an X-ray examination, prominently decreased bone density was noted in her left fingers and toes. She was diagnosed to have CRPS-I, which was considered to have been induced by the pacemaker implantation. After treatment with methylprednisolone and Neurotropin, her symptoms dramatically improved.

Polyarteritis associated with hypopharyngeal carcinoma.

A rare case of polyarteritis associated with a solid tumor is presented. A 66-year-old man was referred to our hospital, because of gangrene in the bilateral fingers and toes, right pleural effusion, and an abnormal sensation in the throat. A diagnosis of polyarteritis was made based on pleuritis, digital gangrene and the arteriography findings. He also had a hypopharyngeal carcinoma. After being treated with intermittent intravenous cyclophosphamide, oral corticosteroid, alprostadil and aspirin, the pleural effusion rapidly disappeared, while the digital gangrene gradually improved. For the treatment of hypopharyngeal carcinoma, radiation therapy was initiated and resulted in complete disappearance.

The relationships between titers of anti-Ro or anti-La as measured by ELISA and salivary production rate with age correction.

The objective of this work was to clarify the clinical significance of titers of anti-Ro and anti-La, the relationships between titers of either anti-Ro or anti-La, and salivary production rate (SPR). These autoantibodies were titrated using enzyme-linked immunosorbent assay. The Saxon test was performed to measure SPR. Fifty-one females who had anti-Ro but not anticentromere antibodies or anti-U1RNP were enrolled. SPR decreased significantly with age. In order to exclude the effect of aging on SPR, we calculated the "SPR with age correction." According to the results of a multiple regression analysis, only the anti-La titer was significantly associated with SPR with age correction. The distribution pattern of the anti-La titers consisted of two subgroups (with a titer index cutoff of 100.0): a negative anti-La titer (anti-La<25.0) and low anti-La titer (25.0or=100.0). The concentration of serum IgG and the frequency of Sjögren's syndrome in the high anti-La titer group were significantly higher than those in the negative anti-La and low anti-La titer group. Several new aspects of the clinical significance of titrating anti-Ro and anti-La in comparison with SPR have been revealed.

Negative correlation of anti-U1RNP antibody titers and the amount of salivary secretion with age correction.

OBJECTIVE: The aim of this study was to reveal whether or not the presence of anti-U1RNP antibodies is associated with a low amount of salivary secretion (ASS). SUBJECTS AND METHODS: Twenty females (mean age 49+/-12 years) who had anti-U1RNP but not ACA, anti-Ro, or anti-La antibodies (anti-U1RNP-positive group), and 65 control females (mean age 50+/-12 years) were included in this study. The saxon test was performed to measure the ASS. RESULTS: After a correction for age by ANCOVA, ASS in the anti-U1RNP-positive group was significantly lower than ASS in the control group (p <0.001). In the control group, ASS was not significantly decreased with advanced age (r=-0.140, p=0.211). In the anti-U1RNP-positive group, ASS was decreased with age, without a significant difference (r=-0.379, p=0.100). In the next analysis, we introduced 'ASS with age correction', assuming that all subjects in the anti-U1RNP-positive group were 49 years of age. A negative correlation between the titers of anti-U1RNP antibodies and the ASS with the age correction in the anti-U1RNP-positive group was noted (r=-0.520, p=0.019). The log of the antinuclear antibodies titers, or titers of rheumatoid factor was significantly correlated with the titers of anti-U1RNP antibodies, respectively (r=0.466, p=0.038 and r=0.595, p=0.006; respectively). The pathological findings of minor salivary gland biopsy in 2 subjects were compatible with Sjögren's syndrome; one subject showed moderate lymphocytic infiltration. CONCLUSION: The presence of anti-U1RNP antibodies is associated with reduced ASS.

Investigation for analytical procedure for determination of trace metallic ions in simulated body fluids by inductively coupled plasma atomic emission spectrometry (ICP-AES).

Influences of matrix elements and high viscosity in three kind of simulated body fluids (SBFs) on determination of trace metallic elements (Co, Cr, Ni, Al and V) by inductively coupled plasma atomic emission spectrometry (ICP-AES) were investigated. In addition, decreases of these effects were attempted by H(2)SO(4) fume treatment. Calibration lines of the elements were constructed by the standard solutions made of elemental solutions and HCl or the SBFs. Gradients of calibration lines constructed by the each standard solution were different. Therefore, for accurate determination, calibration curve must be constructed by the elemental standard solution and the analytical solution. Limit of detection (LOD) of each element in the solutions was measured by a blank test. Although LODs of microg [Symbol: see text] L(-1) (ppb) order were nominal instrumental data, because of influences of the matrix elements and the high viscosity, the measured LODs of the elements in the SBFs were higher than those. However, the LODs were lowered by employing the H(2)SO(4)-fume treatment and approached to the nominal instrumental data. Therefore, H(2)SO(4)-fume treatment is extremely effective treatment in order to reduce the influences.

Primary biliary cirrhosis in female subjects with sicca-associated antibodies.

The aim of this study is to clarify the time course of primary biliary cirrhosis (PBC) in subjects possessing anticentromere antibodies (ACA), anti-Ro, and/or anti-La antibodies, and who used alkaline phosphatase (ALP) as a serological marker for PBC. Female subjects (n = 165), who had at least one of ACA, anti-Ro, and/or anti-La, were enrolled in this study. Groups A (ACA alone, n = 44), B (anti-Ro alone, n = 54), E (anti-Ro and anti-La, n = 52), and DFG (ACA with anti-Ro and/or anti-La, n = 14) were analyzed. Healthy females (n = 65) were used as a control. The frequencies of the PBC in groups A (13.6%) and DFG (14.3%) were higher than those in groups B (1.9%) and E (0.0%). The ALP levels increased with age in groups A and DFG and slightly increased with age in groups B and C, and the control group. After correcting for age by analysis of covariance, a comparison of ALP levels among the groups not having anti-M(2) was as follows: group A falling dots group DFG > group B falling dots group E falling dots the control group. The subjects with ACA might thus have PBC more frequently than either those with anti-Ro and/or anti-La, or the control subjects.

Intermittent intravenous cyclophosphamide pulse therapy for the treatment of active interstitial lung disease associated with collagen vascular diseases.

The availability of intravenous cyclophosphamide (CYC) pulse therapy for collagen vascular diseases (CVD)-associated interstitial lung disease (ILD) has been indicated. However, the standard protocol concerning the dosage and the interval of CYC infusion has not yet been established. The aim of this study is to elucidate the efficacy and the safety of our "divided administration" protocol of CYC for the treatment of CVD-ILD. The treatment protocol consists of two steps: step 1, CYC 400-500 mg at 10-day intervals for at least 30 days, and step 2, CYC 500 mg at 14-day intervals for at least 4 weeks. The ILD activities were monitored by respiratory symptoms, serum levels of KL-6 (a serological marker of IP), chest computed tomography (CT), and pulmonary function tests. Seventeen patients [nonspecific interstitial pneumonia (NSIP), 12 patients; usual interstitial pneumonia (UIP), 4; lymphocytic interstitial pneumonia (LIP), 1] accomplished the study protocol. The sessions of CYC infusion ranged from 5 to 20 (mean, 8.3). In all patients, respiratory symptoms were improved and the serum levels of KL-6 were decreased (from 1572 +/- 904 to 978 +/- 392 U/ml; P < 0.01). Chest CT findings were improved in 4 patients (23.5%): they were all classified as NSIP; not deteriorated, 13 patients (76.5%). An improvement in the vital capacity percentage (%VC) was recognized in 10 patients (78.6%) and in diffusing capacity of carbon monoxide (%DLco) in 8 patients (61.5%). Nevertheless, mean %VC and mean %DLco did not change significantly. No major adverse event(s) occurred. The efficacy and safety of our "divided administration" protocol of CYC for CVD-ILD was demonstrated.

Effect of cevimeline on salivary components in patients with Sjögren syndrome.

The aim of this study is to clarify the effects of cevimeline on various components in human saliva, such as immunoglobulin A (IgA), lysozyme, alpha-amylase and squamous cell carcinoma (SCC) antigen. Twelve female patients with Sjögren syndrome (SS) and 14 healthy women were enrolled. After the first saliva collection, one capsule (30 mg) of cevimeline was administered to each subject. Saliva was collected again after 90 min. The salivary flow rate and concentration of each component were measured. In both groups the salivary flow rate and amylase concentration were significantly increased by cevimeline. The lysozyme and IgA concentrations did not change significantly in both groups. The SCC antigen concentration did not change significantly in the SS group, but it decreased significantly in the control group. The secretion rates of amylase and IgA showed significant increases in both groups. The secretion rate of lysozyme significantly increased only in the control group, while the secretion rate of SCC significantly increased only in the SS group. Cevimeline augments not only the salivary flow rate but also the secretion rate of some digestive and/or defense factors from infections. It may be beneficial for SS patients to continue taking cevimeline to prevent oral infections, and other serious sequelae.

Regulation of proteinase-activated receptor 1 by inflammatory mediators in human vascular endothelial cells.

Thrombin plays a critical role in haemostasis, inflammation, and cell proliferation, mediated by proteinase-activated receptor 1 (PAR-1; thrombin receptor). The physiological and pathological regulation of PAR-1 by inflammatory mediators has not yet been fully elucidated. The aim of this study is to investigate the effects of inflammatory mediators on mRNA and protein expression of PAR-1 in early passage human vascular endothelial cells. Endothelial cells were activated by inflammatory mediators, such as tumour necrosis factor alpha (TNFalpha), interferon gamma (IFN gamma), and bacterial substance lipopolysaccharide (LPS), and the PAR-1 expression was verified by flow cytometry or RT-PCR. By stimulating endothelial cells with TNFalpha, IFN gamma, and LPS, the PAR-1 expression on the cell surface remained almost unchanged for 48 h. After stimulation with 20-300 U/ml TNFalpha, the total cellular PAR-1 expression (both on cell surface and in the cytoplasm) significantly decreased at 24h and thereafter recovered to the basal level at 48 h. The stimulation with 100 U/ml TNFalpha transiently down-regulated the PAR-1 mRNA expression to approximately 0.3-fold of the basal level at 30 min, but it rebounded 3-fold above the basal level at 6h, and again decreased to 0.5-fold of the basal level at 12h, and finally returned to the basal level at 24h. In contrast, IFN gamma or LPS did not affect the PAR-1 mRNA expression.

Panniculitis in a patient with mixed connective tissue disease.

A 51-year-old woman who had been suffering from mixed connective tissue disease (MCTD) for 8 years developed an erythematous rash with pain and tenderness on her left leg. A skin biopsy revealed septal panniculitis with multiple lymphangiectasis. No vasculitis was observed. An increase in her prednisolone dose from 5 mg to 20 mg/day led to an improvement in these lesions. Panniculitis is very rare in MCTD. The clinical significance of panniculitis in MCTD is also discussed.

A case of rheumatoid arthritis that developed autoimmune hepatitis associated with anti-Golgi complex antibody.

Abstract A 50-year-old woman, who had been diagnosed as having rheumatoid arthritis (RA) 7 months earlier, was admitted to our hospital because of liver dysfunction. Her laboratory data and histological findings satisfied the criteria for autoimmune hepatitis (AIH) as revised by the International AIH Group. Laboratory examinations (indirect immunofluorescence and immunoblotting analyses) revealed that anti-Golgi complex antibodies (AGA) were positive in her serum. AGA are thought to be closely associated with AIH and/or liver dysfunction according to several reports.

A patient with a Mycobacterium avium complex infection complicated by systemic lupus erythematosus.

A 41-year-old woman was admitted to our hospital because of fever and polyarthralgia. A diagnosis of systemic lupus erythematosus (SLE) was made based on the findings of polyarthritis, leukocytopenia, lymphocytopenia, proteinuria, and positive reactions for antinuclear antibody (ANA) and anti-double strand (ds)DNA antibody. She had also been suffering from a pulmonary Mycobacterium avium complex (MAC) infection with such symptoms as cough and sputum for the past 3 years. Antimicrobial drugs for MAC infection were administered first, and later she was given cyclophosphamide pulse therapy, consisting of methylprednisolone (8 mg/day) and mizoribine (100 mg/day). Owing to these therapeutic regimens, SLE was successfully treated without an exacerbation of the MAC infection. The risk factors for MAC infection and SLE are also discussed.

The effects of affinity-purified anti-DNA antibodies from patients with systemic lupus erythematosus on the fluorescent antinuclear antibody assay using HEp-2 cells.

The aim of this study was to clarify the effects of anti-dsDNA antibodies on the titer and the nuclear staining pattern(s) in a fluorescent antinuclear antibody (FANA) assay using HEp-2 cells. Anti-dsDNA derived from 14 patients with systemic lupus erythematosus (SLE) was individually affinity-purified. The anti-dsDNA titer of the purified anti-dsDNA solution was measured by radioimmunoassay (RIA) or by enzyme-linked immunosorbent assay (ELISA). In the FANA assay, the anti-dsDNA solution was diluted in a stepwise manner and its titer was expressed by the endpoint dilution. The nuclear staining pattern in the anti-dsDNA solution was examined at the 1:5 and 1:20 dilutions and at the endpoint dilution. The anti-dsDNA titers of the affinity-purified anti-dsDNA solution were high enough (13 to 126 IU/ml) to be measured by RIA. However, the antinuclear antibody (ANA) titers of this solution were relatively low: 1:20 to 1:320. In the study of nuclear staining the peripheral pattern was observed in nine of the 14 cases at a 1:5 dilution. However, at the endpoint dilution, all cases exhibited the homogeneous pattern. These findings indicate that in the FANA assay using HEp-2 cells, 1) although serum samples show high anti-dsDNA titers by RIA or by ELISA, the antibodies' direct contribution to ANA titers is limited, and 2) when samples reveal a homogeneous staining pattern at the endpoint dilution, this suggests the presence of anti-dsDNA.