Treatment with anti-TNF-α antibody infliximab reduces serum IL-15 levels in patients with rheumatoid arthritis

The aim of this study was to analyze the change of serum cytokines and pentosidine levels in patients with rheumatoid arthritis (RA) by infliximab treatment. Twenty-three patients with RA were studied for 30 weeks on the effects of infliximab treatment. Serum levels of IL-15, IL-16, IL-17, and granulocyte–macrophage colony-stimulating factor (GM-CSF) were measured with ELISA methods and pentosidine levels were determined using high-performance liquid chromatography, both at baseline and at 14 and 30 weeks after the initial treatment with infliximab. In addition, the patients also underwent physical and routine blood examinations. The higher levels of serum IL-15 in RA patients before treatment with infliximab significantly decreased at 14 and 30 weeks after the initial treatment with infliximab, but serum IL-16, IL-17, GM-CSF, and pentosidine levels did not decrease. The serum IL-17 and GM-CSF levels remained to be a limited detectable level at the pre- and posttreatment with infliximab. Infliximab treatment significantly lowered the serum levels of IL-15 in patients with RA. IL-15 is one of the crucial cytokines affected by infliximab.     

Plasmid encoding interleukin-4 in the amelioration of murine collagen-induced arthritis

OBJECTIVE: To evaluate the therapeutic effect of the administration of plasmid encoding interleukin-4 (IL-4) via gene-gun delivery and via intradermal injection on collagen-induced arthritis (CIA). METHODS: IL-4 plasmid was administered by gene-gun delivery and intradermal injection to DBA/1 mice immunized with type II collagen (CII). The therapeutic effect on the development of CIA was evaluated clinically with a visual scoring method for arthritis and serologically by enzyme-linked immunosorbent assays and polymerase chain reaction. RESULTS: Treatment with IL-4-expressing plasmid significantly reduced the incidence and severity of CIA, including a reduction in the anti-CII antibody level. In particular, gene-gun delivery had a higher immunosuppressive effect on CIA compared with intradermal injection. As shown by in vitro stimulation assay, the spleen cells from mice immunized with CII and treated with IL-4 plasmid via gene gun exhibited higher Th2 cytokine responses compared with cells treated with control plasmid after in vitro stimulation with CII. CONCLUSION: The results of this study suggest that treatment with IL-4 plasmid may constitute a new clinical use of cytokine gene therapy for rheumatoid arthritis.     

The efferent blood flow of early hepatocellular carcinoma and borderline lesions: Demonstration by color Doppler imaging

We performed waveform analysis of the efferent signal detected within early hepatocellular carcinomas and borderline lesions, in which portal flow was demonstrated. Continuity of this flow with the surrounding vessels was also analyzed. Nine nodules in 7 patients with early hepatocellular carcinomas and borderline lesions were included in this study. Tumor diameter ranged from 1.2 to 3.5 cm; average, 2.1 cm. Waveform of the efferent flow signal from within these nodules was continuous in 5 nodules and biphasic venous in 4 nodules. Outside the nodules, the waveform of the efferent flow signal was that of a biphasic venous wave. All efferent signals were confirmed to continue in the hepatic vein. These findings thus suggest that the draining vessel in early hepatocellular carcinomas and their borderline lesions is the hepatic vein.     

Methotrexate reduces the levels of pentosidine and 8-hydroxy-deoxy guanosine in patients with rheumatoid arthritis

This study was performed to investigate whether methotrexate (MTX) affects the levels of oxidative stress markers, including pentosidine one of the glycation end products (AGEs) or 8-hydroxy-deoxy guanosine (8-OHdG). These stress markers represent DNA damage; 19 rheumatoid arthritis (RA) patients underwent MTX treatment. The levels of serum total, urinary total, urinary-free pentosidine and also urinary 8-OHdG, as well as clinical parameters, including disease activity scores for 28 joints (DAS28) were measured at baseline and at 3 and 6 months after the initial treatment with MTX. After the initial treatment with MTX, serum total and urinary total pentosidine levels were reduced at 6 months, and urinary-free pentosidine levels were reduced at 3 and 6 months. Urinary 8-OHdG levels also were significantly reduced at 6 months after the initial treatment with MTX. This study demonstrated that MTX plays a role as a regulator against pentosidine formation and oxidative DNA damage in RA patients.     

Etanercept reduces the serum levels of interleukin-23 and macrophage inflammatory protein-3 alpha in patients with rheumatoid arthritis

The purpose of this study was to analyze the effect of the soluble TNF-α receptor etanercept on the serum levels of IL-16, IL-17, IL-23, and macrophage inflammatory protein-3α (MIP-3α) in rheumatoid arthritis (RA) patients. Twenty-two patients with RA were administered etanercept once or twice a week for more than 6 months, and we evaluated clinical and laboratory parameters and serum levels of IL-16, IL-17, IL-23, and MIP-3α at the baseline and at 3 and 6 months. Additionally, the production of IL-23 and MIP-3α of cultured synovial cells stimulated with TNF-α from RA patients was determined by ELISA. We also used ELISA kits to determine synovial fluid (SF) levels of IL-17, IL-23, and MIP-3α in patients with RA, osteoarthritis (OA), pseudogouty arthritis (PGA), and gouty arthritis (GA). A significant decrease in serum levels of IL-23 and MIP-3α was observed at 3 and 6 months after initial treatment of etanercept. TNF-α induced MIP-3α but not IL-23 production in cultured synovial cells from RA patients. SF levels of IL-17, IL-23, and MIP-3α in RA patients showed significantly higher levels than those of OA, PGA, and GA patients. This study demonstrated that the reduction of IL-23 and MIP-3α production in RA patients was a newly determined function of etanercept     

Diagnosis of advanced hepatocellular carcinoma using contrast-enhanced harmonic gray-scale imaging with enhancement agents (Levovist): Correlation with helical CT and US angiography

We compared contrast-enhanced harmonic gray-scale imaging with helical CT and US angiography to evaluate vascularity in advanced hepatocellular carcinoma (HCC). Contrast-enhanced harmonic gray-scale imaging using Levovist (Nihon Schering, Tanabe) as the contrast agent and enhanced helical CT were performed on 38 patients with 45 lesions (29 men and 9 women aged 41 to 83 years; mean age, 66 years; mean maximum tumor diameter, 30.5±23.0 mm), and angiography was performed to evaluate 37 lesions from 32 of these 38 patients (24 men and 8 women, aged 41 to 79 years; mean age, 65 years; mean maximum tumor diameter, 27.9±17.9 mm). Contrast-enhanced harmonic gray-scale imaging showed hypervascular enhancement in 41 of the 45 lesions; the other 4 lesions were not visualized as hypervascular because 3 of the them could not be detected with non-enhanced US and the remaining lesion was situated deep in the liver and more than 11 cm from the surface of the body. Helical CT showed areas of high attenuation in 40 of the 45 lesions, leaving the other 5 lesions equivocal, while US angiography achieved positive enhancement in 36 of 37 lesions. Intratumoral vessels were visualized with contrast-enhanced harmonic gray-scale imaging in 25 of the 45 lesions; however; intratumoral vessels were seen in only 4 of the 45 lesions examined with helical CT. In evaluating vascularity in advanced HCC, contrast-enhanced harmonic gray-scale imaging with Levovist was as effective as US angiography and more effective than helical CT. Motion artifacts produced by the heart make it difficult to evaluate vascularity in advanced HCC located in the left lobe of the liver with Doppler sonography. Contrast-enhanced harmonic gray-scale imaging can show intratumoral vessels and hypervascular enhancement of the tumor without motion artifacts, however, even when the tumor is located near the heart or large vessels. Contrast-enhanced harmonic gray-scale imaging is useful for evaluating vascularity in advanced HCC when the tumor can be visualized with non-enhanced US.     

Flash effect of contrast microbubbles by ultrasound exposure

Background Microbubbles used in contrast echo examination are destroyed by exposure to ultrasound but develop a new ultrasound wave on destruction; the so-called flash effect. Factors influencing the magnitude of the new wave have yet to be elucidated. Here we investigate the method of assessing this effect and attempt to clarify the relevant differences between contrast agents. Methods Three contrast agents were used: Albunex, Optison (FS 069), and Levovist. We used fundamental mode (3.75 MHz) and harmonic mode (2.5 to 5.0 MHz) ultrasound produced by a prototype echocardiograph (Toshiba) and measured the video intensity (VI) (256 gray scale) of each contrast agent contained in a thin rubber sack while changing acoustic power from a minimum level to high levels of +10.5 dB +16.5 dB, and +22.5 dB. Results VI was not changed by low acoustic power; however, it increased rapidly for a short time and then decreased rapidly when exposed to high acoustic power. The increase in VI varied with acoustic power: 30 to 60 at +10.5 dB and 70 to 115 at +22.5 dB. The increase in VI was larger in harmonic mode than in fundamental mode. The degree of decrease in VI after the flash effect correlated with the extent of increase in VI produced by the flash effect. Conclusions The flash effect occurred with each of the contrast agents, and its magnitude varied with acoustic power and contrast agent.     

Tissue harmonic imaging in the diagnosis of small hepatocellular carcinoma: Usefulness for detecting posterior acoustic enhancement

We attempted to evaluate the usefulness of ultrasonic tissue harmonic imaging (HI) in the diagnosis of small hepatocellular carcinoma (HCC) and compare its effectiveness with that of conventional fundamental imaging (FI) prospectively. Nine patients with 16 nodules of HCC measuring less than 20 mm in diameter were evaluated with both FI and HI. The boundaries of 14 nodules were more clearly visualized on HI than on FI. Posterior acoustic enhancement, which is diagnostic of HCC, was not detected on FI, although it was detected in 5 nodules on HI (p<0.05); however, one nodule located in a section of the liver that was 8 cm below the abdominal wall was visualized only by FI. We conclude that HI is more useful than FI in the diagnosis of small HCC nodules, although HI has minor limitations of the applicable location.     

Use of ultrasonography to measure liver size in children

We used a real-time, ultrasound scanner to establish a reference interval of liver size in children based on their height and age. The study group comprised 476 children ranging in age from 1 month to 15 years. Maximal craniocaudal length (L1) and anteroposterior width (L2) determined in the longitudinal plane passing through the aorta were used as parameters for size of the anatomical left lobe; for the anatomical right lobe the shortest distance between the anterior, surface of the liver and the midpoint of the horizontal portion of the portal vein (R1) and the distance between the midpoint of the horizontal portion of the portal vein and the deepest phrenic surface (R2) determined by the right subcostal approach were used. The strongest correlation obtained was between height and the sums L1+L2 and R1+R2. Because the liver naturally enlarges as children grow, this reference should prove useful in evaluating hepatic size in children of all ages.     

Chemopreventive effect of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase

Sulfur-containing substances derived from garlic and onion havebeen shown to prevent experimental carcinogenesis. One of thehypotheses explaining the mechanisms of the chemopreventiveactivity of these substances is that they activate detoxificationsystems such as glutathione S-trans-ferase (GST). In this studythe effects of S-allylcysteine (SAC), a water-soluble organosulfurcompound derived from garlic, on GST activities in the liver,small intestine and colon were investigated. Additionally, weexamined SAC for chemopreventive effects on aberrant crypt foci,which are the most likely precursors of colon cancers. In therat colonic aberrant crypt assay administration of SAC duringthe initiation period decreased the number of aberrant cryptfoci by 33 and 54% in groups given 40 or 80% maximum tolerateddose (MTD) of SAC respectively. The number of aberrant cryptfoci, however, was not changed when SAC was given during thepromotion period. GST activity in the liver was increased significantlyby 41% 12 h after a single oral administration of 3.5 mmol/kgSAC and this elevated GST level was maintained over a 72 h period.GST levels were increased significantly by the administrationof SAC (1.8 mmol/kg/ day for 3 days) not only in the liver butalso in the proximal and middle small bowel. Isozyme levelsof GST after administration of SAC were also determined usingWestern blotting. Hepatic GST-