A number of novel autoantibodies have been recently described in rheumatoid arthritis (RA), and their clinical significance and possible pathogenic roles have been discussed. In particular, new autoantibodies to citrullinated proteins such as filaggrin and its circular form (cyclic citrullinated peptide: CCP) are especially noteworthy because of their high sensitivity and high specificity. There are many studies that anti-CCP antibodies may serve as a powerful serologic marker for early diagnosis of RA and prognostic prediction of joint destruction. Anti-citrullinated protein antibodies are locally produced in RA joints, and citrullinated proteins (most are fibrins) are localized in RA synovial tissue. This finding strongly suggests a possibility that local citrullination of intraarticular proteins might be the initial event leading to autoantibody production in RA. Genetic factors such as a gene polymorphism of the citrullinating enzyme, PADI, might be associated with the breakage of self-tolerance and induction of autoimmunity against citrullinated proteins.

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Objective The aim of the present study was to determine the effects of glucose intolerance on oxidative stress in patients with coronary artery disease (CAD).
Methods The patients were divided into 3 groups, diabetes mellitus (DM), IGT or normal glucose tolerance (NGT) according to the criteria of the American Diabetes Association.
Patients The present study consisted of 178 consecutive patients who underwent diagnostic coronary arteriography and a 75-g glucose tolerance test.
Results The level of plasma thioredoxin, a marker of oxidative stress was measured in every patient during the fasting state. The levels of plasma thioredoxin were significantly higher in the DM and IGT groups than the NGT group. Furthermore, we found that there was a positive association between thioredoxin levels and glycosylated hemoglobin (σ=0.225, p=0.018). In multivariate logistic regression analysis, glucose intolerance (DM or IGT) was only independently associated with the high levels of thioredoxin. The levels of plasma thioredoxin were significantly higher in the CAD group compared to the non-CAD group. In multivariate logistic regression analysis, high levels of thioredoxin, male, age and hypertension were independently associated with the presence of CAD.
Conclusion Glucose intolerance was associated with the high levels of thioredoxin. High levels of thioredoxin were related to the presence of CAD. The measurement of thioredoxin as the marker of oxidative stress may be useful for monitoring the development of the cardiovascular diseases.

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Objective To determine the cause of outbreak mimicking food poisoning, we studied the toxic polyamine contents of the food and analyzed the clinical characteristics of the affected eight patients.
Patients and Methods Eight cases of histamine poisoning which occurred in tuberculous patients after dinner in our hospital were analyzed by clinical and biochemical methods. We examined the contents of four representative toxic polyamines, histamine, putrescine, cadaverine and tyramine, of the each food of the dinner and their serum concentrations of the monoamine oxidase (MAO), one of histaminases, using radioimmunoassay.
Results The allergy-like symptoms such as flushing, headache, palpitation, itching, wheezing, dyspnea and diarrhea appeared from 20 minutes to two hours after ingestion in those eight patients taking isoniazid (INH), although the other 378 inpatients had no symptom. The histamine content of the ground saury paste was increased to 32 mg/100 g of food, however, the toxic level of food poisoning is less than 50 mg/100 g of food. All eight patients were taking INH, and their serum concentrations of MAO were decreased.
Conclusion We concluded that this accident was the histamine fish poisoning. We speculated that those allergy-like symptoms were due to both the increased histamine in the food made with the saury under poor storage conditions and the patients’ reduced histaminase activities due to INH. We should perceive possible adverse effects depending on the interactions between certain drugs and food.

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Objective Apoptosis may be involved in the pathophysiology of cachexia in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study is to assess the potential role of the Fas-Fas ligand (FasL) system in cachexic patients with COPD.
Patients and Methods We measured the circulating levels of soluble FasL (sFasL), with a newly developed, highly sensitive enzyme-linked immunosorbent assay system in seventy patients with COPD and forty-seven control subjects.
Results The levels of sFasL in the COPD patients were significantly lower than those in the control subjects (46±29 vs. 55±28 pg/ml; p<0.05), whereas the levels of soluble Fas (sFas) remained unchanged between the two groups. The significant correlation between the levels of sFasL and sFas, observed in the control subjects (r=0.304; p<0.05), was absent in the COPD patients. Cachexic COPD patients with a relatively lower BMI (BMI <20 kg/m², n=45) and %fat (%fat <20%, n=34), showed significantly increased levels of sFasL compared to non-cachexic COPD patients with a relatively higher BMI (BMI ≥20 kg/m², n=25) and %fat (%fat ≥20%, n=36) (BMI; 51±33 vs. 36±15 pg/ml; p<0.05. %fat; 55±33 vs. 37±21 pg/ml; p<0.01), due to the inverse relationships between the body composition measurements and the levels of sFasL observed exclusively in the patients (BMI; r=-0.307; p<0.05. %fat; r=-0.283; p<0.05).
Conclusion These results may suggest that the Fas-FasL system does not play a significant role in the potential triggers of enhanced apoptosis leading to skeletal muscle wasting and adipose tissue depletion in cachexic patients with COPD.

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Objective The aim of this study was to evaluate the efficacy of cyclosporin A (CsA) in patients with interstitial pneumonia (IP).
Design Retrospective comparative study.
Patients We reviewed 33 patients (23 males and 10 females with a mean age of 62.5 years) with histologically-proven progressive IP who were treated with CsA. All patients had corticosteroid-resistant IP or developed acute exacerbation of IP in their courses.
Results The underlying systemic diseases were: idiopathic interstitial pneumonias (IIPs) in 19 patients, and collagen vascular diseases (CVDs) in 14. The histopathological patterns and underlying diseases of IP were classified as usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) in 10 patients, cellular-nonspecific interstitial pneumonia (NSIP)/IIPs in 3, fibrotic-NSIP/IIPs in 5, organizing pneumonia (OP)/IIP in 1, UIP/CVDs in 4, cellular-NSIP/CVDs in 7, fibrotic-NSIP/CVDs in 2, and diffuse alveolar damage (DAD)/CVD in 1, respectively. They received a low dosage of CsA combined with corticosteroids. The prognoses after treatment with CsA were well correlated with histopathological patterns. Cellular-NSIP and OP showed better prognoses than fibrotic-NSIP, UIP or DAD. In addition, CVDs had better prognoses than IIPs, when compared on the basis of the same histopathological patterns. Furthermore, the prognoses in the CsA-treated group were significantly better than in those without CsA treatment in regard to acute exacerbation of UIP/IPF.
Conclusions CsA combined with corticosteroids may be an efficacious treatment for corticosteroid-resistant IP and for acute exacerbation of IPF.

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Object We summarize 10 years of experience with liver transplantation for FAP patients in Japan and review the current opinions regarding this treatment for FAP.
Methods and Patients All basic report data on patients at the time of transplantation were registered with the Japanese Liver Transplantation Society (JLTS). Based on the JLST report data, more detailed information on FAP patients was requested from each center.
Results Living donor liver transplantation (LDLT) for FAP patients was first performed in Japan in 1993. LDLT has since been performed in 41 FAP patients, including nine cases of temporary auxiliary partial orthotopic liver transplantation (APOLT). Orthotopic liver transplantation (OLT) from cadaveric donors for FAP patients began in 1999, but only one FAP patient has subsequently undergone this procedure. Of these total of 43 FAP patients, 36 are currently alive: the one-year survival rate of patients after transplantation was 93%, and the five-year survival rate of these cases was 77%. Preoperative clinical severity and the nutritional status of patients are correlated with their outcome after liver transplantation. Domino (sequential) liver transplantation has been carried out in 20 domino recipients with end-stage liver diseases. Of the 20 domino recipients, 12 are currently alive.
Conclusion For FAP patients, these outcomes after the operation were very similar to those of OLT from cadaveric donors reported in other countries. Therefore, we concluded that for the treatment of FAP, LDLT from a living donor is equally effective as OLT from a cadaveric donor.

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Objective Bacteremia is one of the most serious health problems associated with high morbidity and mortality. The aim of this study was to identify risk factors for bacteremia in daily medical care to facilitate rapid and accurate clinical decisions about treatment.
Patients and Methods We studied 306 inpatients retrospectively. Age, peripheral neutrophil count, C-reactive protein (CRP), platelets, serum total cholesterol, total protein, albumin and cholinesterase were compared in patients with positive- and negative-blood cultures. The associations between blood culture positivity and glucose tolerance, bedridden state, presence of a central venous catheter (CVC) or urinary catheter were examined. On October 14, 2002, strategies for prevention of catheter-related infection were altered in our hospital. We studied the impact of these changes on the risk of bacteremia.
Results Sixty-seven patients had positive and 239 had negative blood cultures. Age, neutrophil, platelets, total protein, albumin, and cholinesterase were significantly different between the culture-positive patients and the culture-negative patients. Multivariate analysis showed albumin and platelets as independent predictors. The bedridden state and catheter-inserted states (central venous or urinary) conferred significantly higher positive blood culture rates. Multivariate analysis showed using urinary catheters and indwelling femoral CVCs as independent risk factors. There was no significant difference in the blood culture-positive rate before and after the change in prevention strategies; before the change, 6 of 9 catheter-inserted blood culture-positive cases yielded MRSA, while 4 of 12 cultures yielded Staphylococcus epidermidis after the change.
Conclusion Our study highlights the risk factors of bacteremia in vulnerable patients.

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Gastrointestinal stromal tumor (GIST) is a rare neoplasm exhibiting, in most cases, mutations of c-kit. Recently it has been demonstrated that a majority of GIST patients with c-kit mutations respond to therapy with imatinib, a c-kit tyrosine kinase inhibitor. Although the response rate in patients treated with imatinib in prospective clinical studies is above 50%, complete response is rare, and the data on the use of imatinib as neoaduvant therapy facilitating radical surgery is still scanty. Here, we report on a patient with metastatic gastric GIST who underwent surgery after 6 months of imatinib therapy. No tumor cells were detected on pathological examination of resection specimen. This case report indicates that a pathological complete response could be achieved with imatinib therapy in patients with GIST, but a wider experience and longer follow-up is necessary to appreciate the prognostic significance of pathological complete response in GIST.

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We describe a case of gastric aberrant pancreas with acute pancreatitis. Barium meal examination, endoscopic examination and computed tomography of a 32-year-old man with abdominal pain revealed a submucosal tumor, about 3.5 cm in diameter, at the angulus of his stomach. Endoscopic ultrasonography revealed a hypoechoic mass with anechoic capillary areas. His serum amylase level was high at 262 IU/l. Laparoscopy-assisted local resection was carried out. The resected tumor revealed pancreatic tissue with extensive neutrophil infiltration in the gastric wall and fat necrosis in the subserosa. There are few cases of histologically proven acute pancreatitis in gastric aberrant pancreatic tissue.

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A 55-year-old man who was diagnosed as having type 1 diabetes mellitus (DM) at the age of 50 years was started on insulin therapy. At 54 years old of age, he suddenly developed complex partial seizures, which frequently occurred despite intensive anti-epileptic drug therapy. Neurological examination on admission revealed hyporeflexia in bilateral upper and lower extremities without any muscle rigidity, painful spasm or cerebellar ataxia. Laboratory examination showed poor glycemic control with increased glycated hemoglobin levels. Positive anti-thyroglobulin antibodies and anti-thyroid peroxidase (TPO) antibodies and slight elevation of TSH levels are consistent with subclinical hypothyroidism due to Hashimoto’s thyroiditis. A high titer of anti-glutamic acid decarboxylase (GAD) antibodies was detected in the patient’s serum and cerebrospinal fluid (CSF). Electroencephalography showed temporal spikes, consistent with complex partial seizure. This is a very rare case presenting with concomitant type 1 diabetes and drug-resistant epilepsy associated with high titers of circulating and CSF anti-GAD antibodies.

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Calciphylaxis may be considered a small vessel vasculopathy which is generaly associated with end-stage renal disease and hyperparathyroidism. The precise pathogenesis of the disease is not known. It needs sensitizers and challengers to occur. Steroids and immunosuppressive drugs including methotrexate are among those challenger agents. Calciphylaxis in collagen vascular diseases is rare. Only one case in rheumatoid arthritis was recently reported. Here we describe a case of calciphylaxis associated with active rheumatoid arthritis. This patient had active disease despite treatment of steroids and methotrexate for a long time. She died shortly after the diagnosis of calciphylaxis due to sepsis.

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A 23-year-old Japanese woman with a fever and generalized skin eruptions was referred to our hospital in July 1999. At admission, her temperature was 38.9°C, and she had fluctuating symptoms including erythema of the extremities, conjunctival hyperemia, strawberry tongue, and generalized skin eruptions, but lymphadenopathy was not verified. An initially elevated urine leukocyte count (more than 100 per high power field) later returned to normal range without antibiotic therapy. Adult Kawasaki disease was diagnosed on the basis of the above symptomology. Echocardiograph showed transient effusion in the pericardium. Using the Harada scoring system for treatment of Kawasaki disease, we gave the patient aspirin and did not administer intravenous immunoglobulin. The clinical course was uneventful, and on the day of discharge (day 22 after onset), the laboratory test results were nearly normal. Laboratory test results were negative for both Epstein-Barr virus and group A Streptococcus.

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A 30-year-old woman with a 10-year history of systemic lupus erythematosus was admitted to our hospital because of the onset of hypertension and renal dysfunction. Renal arteriogram revealed multiple renal infarctions, and cut-off or tapering-stenosis in the interlobular arteries. Renal biopsy showed concentric intimal thickening with narrowed lumen in some arterioles and deposition of IgG/IgM/complement 3 in the wall of arteriole without any active lesions or immune complex deposition in glomeruli. The present case indicates that this type of renal vascular lesion in lupus nephritis, lupus vasculopathy, may cause renal infarction and the loss of renal function without active glomerular lesions.

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Primary Candida pneumonia is rare, and detailed reports of Candida glabrata pneumonia have not been described. A 71-year-old woman had been treated for heart failure and developed aspiration pneumonia, which was refractory to antibacterial treatment. Antifungal treatment against C. glabrata resulted in resolution of pneumonia and candidemia. We report a probable case of C. glabrata pneumonia.

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