Ultrasonographic evaluation of synovial effusion and synovial proliferation pattern in the knee joints of patients with rheumatoid arthritis.

Abstract In the present study, 49 knee joints of 26 patients with rheumatoid arthritis and 17 knee joints of 17 healthy subjects were ultrasonographically examined. Lateral, superior, and medial aspects of the patella were scanned using an ultrasonograph with a 7.5-MHz annular array transducer to evaluate the thickness of synovial effusion and the synovial proliferation pattern. The overall mean thickness of synovial effusion (mean of all three sites) in the knee joints was 4.9 ± 3.4 mm for rheumatoid arthritis patients and 1.4 ± 0.5 mm for healthy subjects. In rheumatoid arthritis patients, the mean thickness of synovial effusion at the superior aspect of the patella (6.5 ± 4.1 mm) was significantly greater than that at the lateral aspect (4.5 ± 4.8 mm) (P < 0.05) and the medial aspect (4.0 ± 3.1 mm) (P < 0.01). Patients with the villonodular pattern of synovial proliferation had a shorter duration of disease than those with uniform thickening or an overlapping pattern.

Ultrasonographic evaluation of knee joint synovitis in two patients with palindromic rheumatism.

Abstract The aim was to evaluate synovial proliferation ultrasonographically in order to identify the period of conversion from palindromic rheumatism to the early-stage of rheumatoid arthritis. Two patients, a 35-year-old man and a 44-year-old man, had been suffering from episodic attacks and remission of oligoarthralgia for 15 years and 6 years, respectively. Both patients were negative for rheumatoid factors, and exhibited slightly elevated levels of C-reactive protein and erythrocyte sedimentation rate at the times of the attacks. Radiograms of the affected joints showed no erosion of the bones in either patient. Ultrasonographic examination revealed both synovial effusion and synovial proliferation in the 35-year-old patient, suggesting conversion from palindromic rheumatism to rheumatoid arthritis, whereas only synovial effusion was found in the 44-year-old patient, suggesting the persistence of palindromic rheumatism. Ultrasonographic evaluations of synovial proliferation in the knee joints provide data that can be used to identify the period of conversion from palindromic rheumatism to the early-stage of rheumatoid arthritis.

A patient with Wegener's granulomatosis with initial clinical presentations of Henoch-Schönlein purpura.

The initial presentation of a patient with Wegener's granulomatosis was indistinguishable from that of Henoch-Schönlein purpura. The patient presented with skin purpura and pulmonary hemorrhage followed by purpura in the colon. The diagnosis of this patient at that time was Henoch-Schönlein purpura. With time, massive lesions in the sinus and those with cavities in the lung became apparent, and a specimen obtained from the sinus massive lesion was disclosed to be granulomatous inflammation. Retrospectively, the proteinase 3 antineutrophil cytoplasmic antibody turned out to be strongly positive in her stored serum from the time of the initial presentation.

An ancient lectin-dependent complement system in an ascidian: novel lectin isolated from the plasma of the solitary ascidian, Halocynthia roretzi.

Mannose-binding lectin (MBL) is a C-type lectin involved in the first line of host defense against pathogens and it requires MBL-associated serine protease (MASP) for activation of the complement lectin pathway. To elucidate the origin and evolution of MBL, MBL-like lectin was isolated from the plasma of a urochordate, the solitary ascidian Halocynthia roretzi, using affinity chromatography on a yeast mannan-Sepharose. SDS-PAGE of the eluted proteins revealed a major band of approximately 36 kDa (p36). p36 cDNA was cloned from an ascidian hepatopancreas cDNA library. Sequence analysis revealed that the carboxy-terminal half of the ascidian lectin contains a carbohydrate recognition domain (CRD) that is homologous to C-type lectin, but it lacks a collagen-like domain that is present in mammalian MBLs. Purified p36 binds specifically to glucose but not to mannose or N-acetylglucosamine, and it was designated glucose-binding lectin (GBL). The two ascidian MASPs associated with GBL activate ascidian C3, which had been reported to act as an opsonin. The removal of GBL-MASPs complex from ascidian plasma using Ab against GBL inhibits C3-dependent phagocytosis. These observations strongly suggest that GBL acts as a recognition molecule and that the primitive complement system, consisting of the lectin-proteases complex and C3, played a major role in innate immunity before the evolution of an adaptive immune system in vertebrates.

Autoantibodies of sera from patients with primary biliary cirrhosis recognize the alpha subunit of the decarboxylase component of human branched-chain 2-oxo acid dehydrogenase complex.

BACKGROUND/AIMS: The major antigens for anti-mitochondrial autoantibodies in primary biliary cirrhosis (PBC) are the lipoyl-containing components of 2-oxo acid dehydrogenase complexes. Autoantibodies against the E1alpha subunit of the pyruvate dehydrogenase complex (PDH) also have been found, but those against the E1alpha subunit of branched-chain 2-oxo acid dehydrogenase complex (BCKADH) have not been detected. We investigated the occurrence of BCKADH-E1alpha-specific autoantibodies by employing the purified human antigen. METHODS: The reactivities of PBC sera against purified antigens were assessed by ELISA and by immunoblotting analysis. The specificity of immunoreactivity was confirmed by absorption tests and affinity-purified antibodies. RESULTS: Fourteen out of 27 PBC sera reacted with BCKADH-E1alpha, and these same sera also reacted with BCKADH-E2. No PBC sera reacted with BCKADH-E1beta. The reactivity of PBC sera with BCKADH-E1alpha was removed only when the sera were pre-absorbed with this antigen. However, reactivities to BCKADH-E2 and PDH-E1alpha were retained. Affinity-purified antibodies to BCKADH-E1alpha reacted with BCKADH-E1alpha, but not PDH-E1alpha. Thus, it was confirmed that anti-BCKADH-Elalpha did not cross-react with either BCKADH-E2 or PDH-E1alpha. CONCLUSIONS: BCKADH-E1alpha-specific autoantibodies were found in the sera of PBC patients. The antibodies seem to occur subsequent to the anti-BCKADH-E2 antibody production, supporting the concept of intermolecular determinant spreading.

CpG-DNA derived from sera in systemic lupus erythematosus enhances ICAM-1 expression on endothelial cells.

OBJECTIVE: To examine the effect of transfection of oligodeoxynucleotides (ODNs) containing a CpG motif (CpG-ODN), of which the sequence was derived from circulating DNA in the sera of patients with systemic lupus erythematosus (SLE), on the expression of intercellular adhesion molecule-1 (ICAM-1) and synthesis of mRNA for proinflammatory cytokines and ICAM-1 in human umbilical vein endothelial cells (EC). METHODS: A CpG-ODN or a control analogue, GpC-ODN, was transfected into EC. ICAM-1 expression was examined by flow cytometry, and expression of mRNA in EC encoding interleukin 1 (IL1), IL6, IL8, tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), and ICAM-1 was examined by semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: The CpG-ODN augmented the expression of ICAM-1 on EC determined by flow cytometry and increased mRNA levels of IL6, IL8, TNFalpha, IFNgamma, and ICAM-1, but the GpC-ODN did not. CONCLUSION: Synthesised DNA, with a sequence corresponding to that of the fragment containing the CpG motif, in sera of patients with SLE was found to enhance ICAM-1 expression on EC, suggesting the participation of circulating DNA fragments in the pathogenesis of vasculitis in SLE.

Protein-losing enteropathy exacerbated with the appearance of symptoms of systemic lupus erythematosus.

A 38-year-old woman visited our hospital with edema on her face and conjunctivae. The underlying disease was not clarified, and she did not visit the hospital afterwards. She suffered from diarrhea, polyarthralgia, Raynaud's phenomenon, malar rash and hair loss in the subsequent two years, and was hospitalized because of hypoproteinemia. Her urine, liver and heart test results did not account for her hypoproteinemia. She was diagnosed as having protein-losing enteropathy (PLE) associated with SLE based on the 99mtechnetium-labeled human serum albumin scintigraphy findings, clinical findings and laboratory results of antinuclear and anti-Sm antibodies. This case report demonstrates a strong association between PLE and SLE because PLE was aggravated along with the appearance of SLE symptoms and PLE subsided with prednisolone treatment along with improvement of SLE.

[Advances in immunoserology tests in clinical medicine: autoantibodies, immune complexes and DNA analysis].

I reviewed first the history of detection for autoantibodies and the methods to detect the circulating immune complexes. Then I presented several unusual tests for detecting autoantibodies which I had experienced. They are agglutination tests in agarose gel using the particulate antigens of human tissues or lipid antigens and the mixed agglutination test using the cultured cells. The characteristics of rheumatoid factor(RF) were analyzed by the following methods: 1) solid-phase radioimmunoassay for IgG-RF using the formalinized sheep RBC, 2) mixed agglutination test for IgG-RF on the slide glass smeared with the sensitized sheep RBC, 3) hemolysis in agarose gel for competitive reaction of RF with complement to the IgG hemolysin and 4) ELISA for detecting the complement-fixation of the monoclonal IgM-RF. The IgG-Fc and C3b receptors on the tissue sections of the mammalian aorta were detected by an adhesion of the IgG-sensitized or C3b-bound RBC. DNA-analysis studies using the molecular biology techniques which were done in the Department of Internal Medicine II, Fukushima Medical University were presented. 1) Nucleic acid sequences of the cloned DNA polypeptide fragments in the serum of patients with systemic lupus erythematosus. 2) SSCP analysis for clonality of Vb repertoires in T cell receptors in the patients with rheumatoid arthritis, primary biliary cirrhosis or CREST syndrome. 3) Detection of mRNA of TNFa and Fas ligand in the mononuclear cells(FICL-PCR) in the synovial fluids of RA patients.

Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study.

Active ulcerative colitis (UC) is characterized by activation and infiltration of granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated leukocytes can cause mucosal damage by releasing degradative proteases, reactive oxygen derivatives, and proinflammatory cytokines. The aim of this trial (conducted in 14 specialist centers) was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active UC most of whom were refractory to conventional drug therapy. We used a new adsorptive type extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in combination with 24.4 +/- 3.60 mg prednisolone (mean +/- SE per patient per day, baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of patients had remission or improved, the dose of prednisolone was reduced to 14.2 +/- 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non-severe side effects (in 5 patients) were reported. Based on our results, we believe that in patients with active severe UC, patients who are refractory to conventional drugs, granulocyte and monocyte adsorption apheresis is a useful adjunct to conventional therapy. This procedure should have the potential to allow tapering the dose of corticosteroids, shorten the time to remission and delay relapse.

Effect of a serotonin receptor antagonist on interleukin-6-induced pulmonary hypertension in rats.

STUDY OBJECTIVES: To determine the significance of serotonin in the pathogenesis of interleukin (IL) 6-induced pulmonary hypertension (IL-6-PH) in rats, the plasma serotonin concentrations, and the effects of a specific antagonist of the serotonin (5-hydroxytryptamine [5-HT]) receptor, 1-[o-(m-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propyl hydrogen succinate hydrochloride (MCI) on the degree of pulmonary hypertension (PH) were investigated in MCI-treated IL-6-PH (IL-6-MCI-PH) rats. MEASUREMENTS: The thickness of the media of small pulmonary arteries and the ratio of the weight of the right ventricle free wall (RV) to that of the left ventricle with the septum (LV + S) were measured as indexes of the degree of PH. Serotonin concentrations in plasma and in supernatants of cultured vascular smooth muscle cells (VSMCs) stimulated by IL-6 were measured by high-performance liquid chromatography. The amplification of DNA encoding the 5-HT receptor in the lung specimen and VSMCs was performed by polymerase chain reaction. RESULTS: The degree of PH, as determined by the medial thickness of small pulmonary arteries, was significantly increased in IL-6-PH rats as compared with normal control rats (p<0.05), and that in IL-6-MCI-PH rats was not significantly different from that in normal control rats. The RV/LV + S weight ratio in the IL-6-PH rats was significantly higher than that in normal control rats (p < 0.01). The RV/LV + S weight ratio in IL-6-MCI-PH rats was significantly lower than that in IL-6-PH rats (p < 0.01) and was not significantly different from that in normal control rats. The serotonin concentration was significantly higher in IL-6-PH rats than in normal control rats (p < 0.02), and the serotonin concentration in IL-6-MCI-PH rats was not significantly different from that in the normal control rats. The expression levels of the 5-HT receptor messenger RNA in the lung tissue tended to increase in IL-6-PH rats but was suppressed in IL-6-MCI-PH rats. IL-6 significantly increased the amount of serotonin released from VSMCs (p < 0.02). The expression of the 5-HT receptor messenger RNA was observed with IL-6 stimulation as was observed with serotonin stimulation in VSMCs. CONCLUSIONS: Serotonin receptor antagonists could be considered as potentially useful agents for the treatment of chronic thromboembolic PH, as well as for that of primary PH and PH associated with collagen vascular diseases.

Endoscopic recurrence of esophageal varices is associated with the specific EUS abnormalities: severe periesophageal collateral veins and large perforating veins.

BACKGROUND: Endoscopic ultrasonography (EUS) with a 20 MHz ultrasound (US) catheter probe can clearly demonstrate esophageal collateral veins. The presence of large periesophageal collateral veins has been correlated with large esophageal varices in patients with portal hypertension. The correlation between the size of esophageal collateral veins and endoscopic recurrence of esophageal varices in patients with portal hypertension who had undergone endoscopic injection sclerotherapy was investigated. Furthermore, whether EUS findings could predict the variceal recurrence was retrospectively studied. METHODS: Thirty-eight patients who had undergone endoscopic injection sclerotherapy were examined every 3 to 4 months with endoscopy and US catheter probe for a period of 2 years. Recurrence of esophageal varices was determined by endoscopic findings of either new varix formation or appearance of red color sign. Esophageal collateral veins were identified by US catheter probe as peri-esophageal collateral veins (adjacent to the esophageal wall) and para-esophageal collateral veins (separated from the esophageal wall) along with perforating veins; and they were graded as severe and mild type by US catheter probe. RESULT: Ten of the 38 patients (26.3%) had endoscopic recurrence at a mean of 10.9 months after endoscopic injection sclerotherapy. In patients with endoscopic recurrences, EUS findings included a significantly (p < 0.001) higher incidence of severe type peri-esophageal collateral veins, a significantly larger number of perforating veins (p < 0.001) and a significantly larger diameter of perforating veins (p < 0.001) compared with patients without recurrence (8 of 10, 80% vs. 2 of 28, 7.1%; 1.30 vs. 0.21; 2.00 vs. 0.32 mm, respectively). The presence of veins at the esophagogastric junction did not correlate with recurrence. CONCLUSION: Severe type peri-esophageal collateral veins and large perforating veins of the esophagus detected by EUS in patients treated by endoscopic injection sclerotherapy signify recurrence of esophageal varices and predict endoscopic recurrence of varices in subsequent months.

Lipo prostaglandin E1 reduces the production of CXC chemokines in endotoxin-induced rat liver injury.

The present study attempted to assess the effect of prostaglandin E1 (PGE1) incorporated into lipid microspheres (Lipo PGE1) on chemokine production in endotoxin-induced rat liver injury. Male Wistar rats weighing 200-250 g were injected with 2 mg lipopolysaccharide (LPS) per kg intravenously. Lipo PGE1 was administered simultaneously at various concentrations (0.002, 0.02, 0.2, 2 µg/kg) in the tail vein. Blood samples and liver specimens were taken from the rats at 1, 3, 8, 12 and 24 h after injection with LPS alone or with LPS and Lipo PGE1. Serum macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) levels were measured by the enzyme-linked immunosorbant assay using the corresponding antibodies. Liver specimens were fixed, and the number of neutrophils that had infiltrated each liver section was determined under a microscope. Serum alanine aminotransferase (ALT) levels were significantly lower in the rats injected with LPS and Lipo PGE1 compared with those in the rats injected with LPS alone, and this difference was expressed in a PGE1 dose-dependent manner. Serum MIP-2 levels were significantly lower at 3 h (141.4+/-95.5 pg/ml) and 8 h (44.9+/-44.7 pg/ml) after injection with LPS and Lipo-PGE1 (2 µg/kg) than at the same times after injection with LPS alone (342.9+/-35.9 and 358.3+/-23.4 pg/ml, respectively). Similarly, serum CINC levels were significantly lower at 8 h (482.7+/-156.0 ng/ml) after injection with LPS and Lipo-PGE1 (2 µg/kg) than at the same time after injection LPS alone (723.3+/-29.0 ng/ml). No significant differences were observed at any time between serum tumor necrosis factor-alpha (TNF-alpha) levels in rats injected with LPS alone and in rats injected with LPS and Lipo-PGE1 (2 µg/kg). The number of neutrophils that had infiltrated the liver was significantly lower at 8 h after injection with LPS and Lipo PGE1 than at the same time after injection with LPS alone. This difference was expressed in a Lipo PGE1 dose-dependent manner. In conclusion, Lipo PGE1 reduces liver injury and serum levels of MIP-2 and CINC, but not TNF-alpha, in rats injected with LPS and also reduces the number of neutrophils that infiltrate in the liver.

Usefulness of endoscopic ultrasonographic analysis of variceal hemodynamics for the treatment of esophageal varices.

The correlation of between the endoscopic findings of esophageal varices and endoscopic ultrasound findings of the collaterals outside the esophageal wall in patients with portal hypertension remains unclear. We investigated the relationship between esophageal varices and the collaterals by endoscopy and endoscopic ultrasound. Moreover, we investigated the correlation between the collaterals around the esophagus and recurrence of esophageal varices in patients with portal hypertension who had undergone endoscopic injection sclerotherapy. The collaterals were divided into two groups: 1; those with peri-esophageal collateral veins (peri-ECVs) adjacent to the muscularis externa of the esophagus, and 2; those with para-esophageal collateral veins (para-ECVs) distal to the esophageal wall without contact with the muscularis externa. Peri- and para-ECVs were scored as mild or severe according to the stage of development. According to endoscopy, the varix form was significantly larger in severe peri-ECVs group than in mild peri-ECVs group. In contrast, the varix form did not differ significantly between the mild and severe para-ECVs group. The prevalence of perforating veins increased according to the varix form. With regard to variceal recurrence, in patients with variceal recurrences, EUS findings included a significantly higher incidence of severe-type peri-ECVs, a significantly larger number of perforating veins, and a significantly larger diameter of perforating veins compared with patients without recurrence. Moreover, when EUS found the abnormalities when no endoscopic recurrence was found, the results were the almost same as the findings when EUS was performed at the same time when endoscopic recurrence was found. In conclusion, the presence of severe peri-ECVs and large perforating veins in the esophageal wall strongly correlates with occurrence and recurrence of esophageal varices in patients with portal hypertension. An understanding of these EUS abnormalities on the basis of hemodynamics around the esophagus is thought to be important for management of esophageal varices in patients with portal hypertension.

Adherence of cyanoacrylate which leaked from gastric varices to the left renal vein during endoscopic injection sclerotherapy: a histopathologic study.

We report a case involving leakage of cyanoacrylate (CA) to the inferior vena cava (IVC) through a gastrorenal shunt and left renal vein. A 72-year-old man with liver cirrhosis was admitted to our hospital to undergo emergency treatment for massive hemorrhage of gastric varices. Endoscopic injection sclerotherapy (EIS) using CA was performed on the varices. Radiographic fluoroscopy revealed that most of the injected CA had adhered firmly to the gastric varices, but a certain portion of the CA had flowed to the IVC through the gastrorenal shunt and left renal vein. At that point, the patient did not complain of any symptoms. However, 6 months later, he died of hepatic failure and an autopsy was performed. Histopathologic examination of the wall of the IVC and renal vein, to which CA had adhered, revealed that the CA was covered with endothelial cells of the vessel and no nearby thrombus was present. Long-term anticoagulant therapy may not be indicated in cases of leakage of CA from the gastric varices to other veins, since the leaked CA may be readily covered with endothelium without thrombus formation as in our patient. It is possible for CA to flow to the IVC and have a fatal impact. Our patient was fortunate, and for safe EIS it is important that these complications are prevented.

Unmethylated oligo-DNA containing CpG motifs aggravates collagen-induced arthritis in mice.

OBJECTIVE: To investigate the effects of an intradermal injection of an unmethylated oligodeoxynucleotide (ODN) containing CpG motifs on the severity of collagen-induced arthritis (CIA). METHODS: CIA was induced in DBA/1 LacJ mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant followed 3 weeks later by immunization with CII in Freund's incomplete adjuvant (yielding CIA mice). Unmethylated ODN containing a CpG motif was injected intradermally into DBA/1 LacJ mice at a dosage of 20 microg (yielding CpG-CIA mice) 1 week prior to the first immunization with CII. Unmethylated ODN containing a GpC motif instead of a CpG motif and ODN containing a methylated CpG motif were used to produce controls (GpC-CIA mice and mCpG-CIA mice, respectively). After the second immunization with CII, arthritis scores were measured weekly up to the eighth week. At the eighth week, the mice were killed, histopathologic changes in the ankle joints were examined, and titers of interferon-gamma (IFNgamma) in the supernatants of splenocytes (1 x 10(7)) stimulated in culture by CII for 3 days were determined by enzyme-linked immunosorbent assay. RESULTS: CpG-CIA mice had significantly higher arthritis scores than CIA mice. CpG-CIA mice had more severe histopathologic changes than CIA mice and mCpG-CIA mice. Moreover, splenocytes in CpG-CIA mice produced higher IFNgamma titers in response to CII than did splenocytes in CIA mice and mCpG-CIA mice. CONCLUSION: Injection of unmethylated oligo-DNA containing CpG motifs aggravated CIA through activation of the Th1-type immune response, suggesting that microbial infection could be one of the mechanisms for aggravation or exacerbation of arthritis or, alternatively, that such infection could be an adjuvant in the induction of arthritis in rheumatoid arthritis.

Anti-cathepsin G antibodies in the sera of patients with ulcerative colitis.

The presence of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCAs) and that of antibodies against cathepsin G, a target antigen for P-ANCAs, was determined in the sera of patients with ulcerative colitis (UC), relative to the endoscopic severity and disease activity. P-ANCAs were detected by indirect immunofluorescent assay (IIF) on ethanol-fixed human neutrophils. Antibodies to cathepsin G were detected by an enzyme-linked immunosorbent assay (ELISA) and Western blotting. P-ANCAs were detected by IIF in 62.5% of 32 patients with active UC. Anti-cathepsin G antibodies were detected in 40.6% of 32 patients with active UC, and their prevalence was significantly higher in patients with severe colitis, as determined by endoscopy, than in those with mild or moderate colitis (P < 0.05). The prevalence and titers of anti-cathepsin G antibodies were significantly higher during the active than the inactive phase of the disease (P < 0.05). Measurement of titers of anti-cathepsin G antibodies by ELISA in the serum is useful for evaluating the activity of UC.

Significance of low mRNA levels of interleukin-4 and -10 in mononuclear cells of the synovial fluid of patients with rheumatoid arthritis.

Our objective was to investigate the clinical significance of Th1 and Th2-type cytokines, such as interferon-gamma (IFNgamma) interleukin (IL)-12, IL-4 and IL-10, in the mononuclear cells (MNC) of the synovial fluid (SF) in patients with rheumatoid arthritis (RA). The cytokine production in the MNC obtained from the SF (SF-MNC) in 30 patients with RA and 10 with gout was examined by measuring the mRNA levels of IFNgamma, IL-12, IL-4 and IL-10 by semiquantitative RT-PCR. The mRNA levels of IFNgamma, IL-4 and IL-10 were significantly higher in the SF-MNC of RA patients than in those of gout patients (p<0.001, p<0.01 and p<0.001, respectively). Correlations between mRNA levels were significant for IL-12 and IL-4, IL-12 and IL-10, and IL-4 and IL-10 (p<0.05). The mRNA levels of IL-4 and IL-10 were very low compared to those of IL-12 in seven of the 30 patients with RA; all of these patients were in stage 4, and serum levels of CRP, ESR and blood platelet count which are considered as indices of the severity of inflammation, were significantly elevated in these seven patients compared to the other 23 RA patients. The markedly reduced synthesis of both IL-4 and IL-10 mRNA could be considered to be related to the progression and/or activity of RA. The results of this study therefore indicate an imbalance in the levels of Th1 and Th2 cytokines at the site of inflammation in RA, and draw attention to the possibility of treatment of progressive or intractable RA with IL-4 and/or IL-10.

Anti-tumor immunity against CT26 colon tumor in mice immunized with plasmid DNA encoding beta-galactosidase fused to an envelope protein of endogenous retrovirus.

Endogenous retroviral gene products have been recognized as being expressed in human cancerous tissues. However, these products have not been shown to be antigenic targets for T-cells, possibly due to immune tolerance. Since carcinogen-induced colon tumor CT26 expresses an envelope protein, gp70, of an endogenous ecotropic murine leukemia virus that is comparable to human tumor-associated antigens, we examined whether a DNA vaccine containing the gp70 gene induces protective immunity against CT26 cells. Injection of mice with plasmid DNA (pDNA) encoding gp70 alone failed to induce anti-gp70 antibody (Ab) or anti-CT26 cytotoxic T lymphocyte (CTL) responses. However, immunization with pDNA encoding the beta-galactosidase (beta-gal)/gp70 fusion protein induced anti-gp70 Ab and anti-CT26 CTL responses and conferred protective immunity against CT26 cells. These results indicate that beta-gal acts as an immunogenic carrier protein that helps in the induction of immune responses against the poorly immunogenic gp70. Considering these results, it is possible that potential tolerance to the endogenous retroviral gene products expressed by human tumors may be overcome by DNA vaccines that contain an endogenous retroviral gene fused to genes encoding immunogenic carrier proteins.

Primary antiphospholipid syndrome presenting with cerebral ischemia, thrombocytopenia, anemia and proteinuria successfully treated with warfarin potassium.

A 30-year-old woman with primary antiphospholipid syndrome (PAPS) presented with cerebral ischemia, thrombocytopenia, anemia and proteinuria. Administration of warfarin potassium, without concomitant corticosteroid administration, significantly improved all of these symptoms along with a decrease in the titers of antiCL-beta2-GP-I antibodies and a shortening of prolonged APTT. Therefore, the antiphospholipid antibodies in this patient could have been evoked by vitamin-K-dependent coagulation factors or plasma proteins which are assumed to undergo conformational changes exposing cryptic epitopes. This case report provides clues to the mechanisms underlying the production of antiphospholipid antibodies in patients with PAPS.