Anti-inflammatory effects of Brazilian ginseng (Pfaffia paniculata) on TNBS-induced intestinal inflammation: Experimental evidence.

Inflammatory bowel disease (IBD) is a chronic, relapsing, idiopathic inflammation of the gastrointestinal tract. Clinical studies suggest that the initiation of IBD is multifactorial, involving genetics, the immune system and environmental factors, such as diet, drugs and stress. Pfaffia paniculata is an adaptogenic medicinal plant used in Brazilian folk medicine as an "anti-stress" agent. Thus, we hypothesised that the P. paniculata enhances the response of animals subjected to colonic inflammation. Our aim was to investigate the intestinal anti-inflammatory activity of P. paniculata in rats before or after induction of intestinal inflammation using trinitrobenzenesulfonic acid (TNBS). The animals were divided into groups that received the vehicle, prednisolone or P. paniculata extract daily starting 14 days before or 7 days after TNBS induction. At the end of the procedure, the animals were killed and their colons were assessed for the macroscopic damage score (MDS), extent of the lesion (EL) and weight/length ratio, myeloperoxidase (MPO) activity and glutathione (GSH), cytokines and C-reactive protein (CRP) levels. Histological evaluation and ultrastructural analysis of the colonic samples were performed. Treatment with the 200mg/kg dose on the curative schedule was able to reduce the MDS and the EL. In addition, MPO activity was reduced, GSH levels were maintained, and the levels of pro-inflammatory cytokines and CRP were decreased. In conclusion, the protective effect of P. paniculata was related to reduced oxidative stress and CRP colonic levels, and due to immunomodulatory activity as evidenced by reduced levels of IL-1ß, INF-γ, TNF-α and IL-6.

Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer.

BACKGROUND: The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases. METHODS: Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or ≥4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis. RESULTS: In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and ++ was 19.3% and 53.4%, respectively, and that in patients with ≥4 LN metastases who were OSNA+ and ++ was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (≥5.0 × 10(3); OSNA++) in the SLN was the most significant predictors of non-SLN metastases (P=0.003). The CK19 mRNA copy number (≥1.0 × 10(5)) in the SLN was the only independent predictor of ≥4 LN metastases (P=0.014). CONCLUSION: Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and ≥4 LN metastases.

Morphologic and pharmacological investigations in the epicatechin gastroprotective effect.

Previous studies of the gastroprotective activity of plants have highlighted the importance of the polyphenolic compound epicatechin (EC) in the treatment of gastric ulcers. This paper aimed to evaluate and characterize the gastroprotective mechanism of action of EC using male rats. The gastroprotective action of EC was analyzed in gastric ulcers induced by ethanol or indomethacin. The involvement of sulfhydryl (SH) groups, K(+) (ATP) channels, α(2) adrenoceptors, gastric antisecretory activity, and the amount of mucus in the development of gastric ulcers were investigated. The lowest effective dose of EC providing gastroprotective effects was 50 mg/kg in the ethanol-induced gastric ulcers and 25 mg/kg in the indomethacin-induced gastric ulcers. The gastroprotection seen upon treatment with EC was significantly decreased in rats pretreated with a SH compound reagent or an α(2)-receptor antagonist, but not with a K(+) (ATP) channel blocker. Furthermore, oral treatment with EC increased mucus production and decreased H(+) secretion. Immunohistochemistry demonstrated the involvement of superoxide dismutase (SOD), nitric oxide (NO), and heat shock protein-70 (HSP-70) in the gastroprotection. These results demonstrate that EC provides gastroprotection through reinforcement of the mucus barrier and neutralization of gastric juice and this protection occurs through the involvement of SH compounds, α(2)-adrenoceptors, NO, SOD, and HSP-70.

Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen.

Y-box-binding proteins are members of the human cold-shock domain protein superfamily, which includes dbpA, dbpB/YB-1, and dbpC/contrin. dbpC/contrin is a germ cell-specific Y-box-binding protein and is suggested to function as a nuclear transcription factor and RNA-binding protein in the cytoplasm. Whereas ubiquitous dbpB/YB-1 expression has been well studied in various types of human carcinomas as a prognostic or predictive marker, the dbpC/contrin expression in human tumour cells has not been reported. In this report, we provide the first evidence showing that dbpC was highly expressed in human testicular seminoma and ovarian dysgerminomas, and in carcinomas in other tissues and that its expression in normal tissues is nearly restricted to germ cells and placental trophoblasts. These results indicate that dbpC/contrin would be a potentially novel cancer/testis antigen.

Transactivation of human cdc2 promoter by adenovirus E1A.

Expression of the adenovirus oncoprotein E1A 12S induces the heterotrimeric transcription factor, NF-Y. NF-Y binds to the two CCAAT motifs upstream of the transcriptional start site of the human cdc2 promoter and is required for activation of the promoter by E1A 12S in cycling cells. The observations that a number of eukaryotic cell cycle regulatory genes also contain the CCAAT motifs and NF-Y binds to them support the notion that E1A 12S could play an important role in deregulated expression of these genes through activation of NF-Y gene in cycling cells.

Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a member of the scavenger receptor family, and is known to be expressed in monocytes/macrophages. We investigated the effect of histamine on the expression of LOX-1 in cells of the human monocytic leukemia cell line THP-1. Histamine as well as forskolin and dibutyryl cyclic AMP (Bt2-cAMP) stimulated the THP-1 monocytes to express the LOX-1 gene at the transcription level. This histamine effect on LOX-1 gene expression, via the histamine H2 receptor-mediated cAMP signal transduction pathway, was reduced after differentiation of the cells into macrophages, even though forskolin and Bt2-cAMP still enhanced the gene expression. The alteration of the responsiveness of LOX-1 expression to histamine was related to suppressed expression of the H2 receptor in THP-1 macrophages. The switch of the predominant class of histamine receptors between H1 and H2 would modulate the effects of histamine on LOX-1 gene expression in monocytes and macrophages, and therefore, would play a certain role in the inflammatory aspects of atherogenesis.

Cardiovascular response to epinephrine-containing local anesthesia in patients with cardiovascular disease.

OBJECTIVE: The purpose of the present study was to examine the safety of epinephrine-containing local anesthesia for use on patients with cardiovascular disease. STUDY DESIGN: Twenty-seven patients with cardiovascular disease were studied. The cardiac functional capacity of 9 patients was New York Heart Association class I; 11, class II; and 7, class III. Hemodynamic responses to intraoral injection of 1.8 mL of 2% lidocaine with 1:80,000 epinephrine were measured with impedance cardiography. RESULTS: Systolic blood pressure and heart rate increased by 4.1% and 5.1%, respectively, immediately after the lidocaine-epinephrine injection. Consequently, rate pressure product increased by 10.0%. Cardiac index increased by 14.2%, and total peripheral resistance decreased by approximately 10%. No patient complained of cardiac symptoms. There were no significant differences in hemodynamic responses related to the extent of the cardiac functional capacity. CONCLUSION: We concluded that lidocaine-epinephrine was safe and had few, if any, hemodynamic consequences in patients with cardiovascular disease.

[Effective clinical information system closely connected with clinical laboratory data for infectious diseases].

Nowadays, information on clinical laboratory tests for infectious disease is almost supported by information on such as clinical, identical and susceptible microbiological tests. However, information support necessary for clinical diagnosis and therapy with clinically valuable data remains unsatisfactory. To offer more useful microbiological information to support clinics from clinical laboratory division, exchange of clinical information between clinical divisions, integrated systems of clinical information in the district and establishment of domestic and international information network et al are required. Establishment of these advanced total information network systems for clinical microbiological tests for infectious diseases may exceedingly contribute to earlier diagnosis, control and prevention of various infectious diseases.

Comparison of gadobenate dimeglumine with gadopentetate dimeglumine for magnetic resonance imaging of liver tumors.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (Gd-BOPTA) with gadopentetate dimeglumine (Gd-DTPA) for magnetic resonance imaging of the liver. METHODS: The contrast agent Gd-BOPTA or Gd-DTPA was administered at a dose of 0.1 mmol/kg to 257 patients suspected of having malignant liver tumors. Dynamic phase images, spin-echo images obtained within 10 minutes of injection, and delayed images obtained 40 to 120 minutes after injection were acquired. All postcontrast images were compared with unenhanced T1-weighted and T2-weighted images obtained immediately before injection. A full safety assessment was performed. RESULTS: The contrast efficacy for dynamic phase imaging was moderately or markedly improved in 90.9% (110/121) and 87.9% (109/124) of patients for Gd-BOPTA and Gd-DTPA, respectively. At 40 to 120 minutes after injection, the cor- responding improvements were 21.7% (26/120) and 11.6% (14/121) for spin-echo sequences and 44.5% (53/119) and 19.0% (23/121) for breath-hold gradient-echo sequences, respectively. The differences at 40 to 120 minutes after injection were statistically significant (P < 0.02). Increased information at 40 to 120 minutes after injection compared with information acquired within 10 minutes of injection was available for 24.0% (29/121) of patients with Gd-BOPTA and for 14.5% (18/124) of patients with Gd-DTPA (P < 0.03). Adverse events were seen in 4.7% (6/128) and 1.6% (2/127) of patients receiving Gd-BOPTA and Gd-DTPA, respectively. The difference was not statistically significant. CONCLUSIONS: The efficacy of Gd-BOPTA is equivalent to that of Gd-DTPA for liver imaging during the dynamic phase and superior during the delayed (40-120 minutes) phase of contrast enhancement. Both agents are safe for use in magnetic resonance imaging of the liver.

[Liver-specific MR contrast agents: current status and prospects].

Liver-specific MR contrast agents include superparamagnetic iron oxide (SPIO) particles and hepatobiliary paramagnetic agents. SPIO particles are phagocytosed by reticuloendothelial cells in the liver, resulting in negative enhancement of the liver parenchyma on T2- or T2*-weighted images. Ferumoxides and related iron oxide formulations have been tested clinically throughout the world, and have been demonstrated to improve the detection and characterization of hepatic neoplasms. Hepatobiliary paramagnetic agents are partially taken up by hepatocytes, yielding positive, sustained enhancement of the liver parenchyma on T1-weighted images. These agents are referred to as "value-added" versions of extracellular gadolinium compounds because they increase tumor-liver contrast in both the perfusion phase and hepatobiliary phase. Although only ferumoxides are currently available for clinical use, many agents are in the pipeline. The possibility of "one-stop shopping" diagnosis by liver-specific MR contrast agents is an attractive alternative to the existing multistep diagnosis in liver imaging. Further studies to analyze the cost-benefit ratio will follow, to determine whether liver-specific MR contrast agents lead to change in patient treatment and whether such a decision would be reliable.

Immunohistochemical study of the ontogeny of prochymosin--and pepsinogen-producing cells in the abomasum of sheep.

The appearance and development of prochymosin- and pepsinogen-producing cells were investigated in the ovine abomasum from fetus to adult using immunohistochemistry. Prochymosin immunoreactivity appeared first in the proper gastric glands of the 100-day-old fetus. The intensity and distribution of prochymosin-immunoreactive cells increased gradually with the progress of gestation, and their most intense immunoreactivities and widest distribution were observed in 3-day-old lambs. They were subsequently reduced throughout postnatal growth. A few prochymosin-immunoreactive cells were scattered in the glands of adult sheep. Pepsinogen immunoreactivity appeared at first in a small number of cells in the base of some proper gastric glands of 120-day-old fetuses. After 130 days, pepsinogen-immunoreactive cells increased their staining intensities and distribution. They reached a peak in area at 21 days, which is comparable to adult sheep. In the pyloric glands, prochymosin- and pepsinogen-immunoreactive cells appeared from 100 and 130 days, respectively. Numbers were reduced in comparison to gastric glands and their occurrence was capricious. The results demonstrated that the ontogeny of prochymosin- and pepsinogen-immunoreactive cells in the abomasum of sheep is more similar to that in cattle than to that in the goat. The present data will contribute to the overall understanding of the development of ruminant gastric proteases.

Effects of histamine and interleukin-4 synthesized in arterial intima on phagocytosis by monocytes/macrophages in relation to atherosclerosis.

We investigated the localization of histidine decarboxylase (HDC), which is the rate-limiting enzyme that generates histamine from histidine, in human aorta/coronary artery. RT-PCR and immunohistochemical staining revealed that the HDC gene was expressed in monocytes/macrophages and T cells in the arterial intima but not in smooth muscle cells in either the arterial intima or the media. A luciferase promoter assay with U937 and Jurkat cells demonstrated that interleukin-4 (IL-4) inhibited the expression of the HDC gene. In contrast, among a scavenger receptor family, IL-4 as well as histamine up-regulated U937 cells to express the LOX-1 gene but not the SR-A gene, which genes encode receptors that scavenge oxidized lipids. These findings suggest that histamine synthesized in the arterial wall participates in the initiation and progression of atherosclerosis and that IL-4 can act as an important inhibitory and/or stimulatory factor in the function of monocytes/macrophages modulated by histamine in relation to the process of atherosclerosis.

Relaxation effects of clustered particles.

Relations between spatial distribution of superparamagnetic iron oxide (SPIO) particles and the image contrast caused by SPIO were investigated. Actual clustering pattern of particles was measured in the liver and spleen of animals using intravital laser confocal microscopy. SPIO-doped phantoms with and without Sephadex beads were made to simulate these patterns, and relaxation parameters were measured using a 1.5-T clinical scanner. Finally, these results were compared to clinical image data using SPIO particulate agent. Intravital microscopy indicated that the clustering of latex beads was more predominant in hepatic Kupffer cells than in splenic macrophages (P < 0.001). Phantoms without Sephadex beads showed an approximately linear increase of 1/T1 (R1), 1/T2 (R2) and 1/T2* (R2*) values with increasing SPIO concentration. However, with Sephadex beads, R1 and R2 showed little change with increasing SPIO concentration, while R2* showed the same linear increase with SPIO. Also, the R2* values were higher with Sephadex beads. These results were consistent with the clinical imaging data, where signal reduction was significantly smaller in the spleen (-0.4% +/- 27.4%) than in the liver (50.4% +/- 16.8%, P < 0.00001) on T2*-weighted images, but the reduction in the spleen (47.2% +/- 16.1%) was equivalent to the liver (38.8% +/- 26.0%) on T2-weighted images.

Induction of human matrix metalloproteinase-12 gene transcriptional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells.

Matrix metalloproteinase-12 (MMP-12) is critical for the migration of monocytes/macrophages into inflammatory sites through the basement membranes. We previously reported that MMP-12 expression was initially induced by granulocyte macrophage colony-stimulating factor (GM-CSF) in human peripheral blood monocytes and U937 monocytic cells. To further elucidate the molecular mechanism for the regulation of MMP-12 expression by GM-CSF in monocytes, we determined the sequence requirements for the MMP-12 gene transcriptional response of U937 monocytic cells to GM-CSF by using luciferase reporter and electrophoretic mobility shift assays. A series of 5'-deletion and site-directed mutation of the human MMP-12 promoter demonstrated that an AP-1 site spanning the -81 to -75-bp region is critical for the induction of MMP-12 promoter activity by GM-CSF. The electrophoretic mobility shift assay revealed that AP-1 binding activity was increased by GM-CSF treatment and that the AP-1 complex induced by GM-CSF consisted of multiple Jun and Fos isoforms. These results indicate that MMP-12 expression in U937 monocytes was initially induced by GM-CSF through the AP-1 binding activity.

Visualization of tumor vessels in renal tumors. Comparison between power Doppler ultrasonography and angiography.

PURPOSE: To compare the ability of power Doppler ultrasonography (PDUS) with that of renal angiography for assessment of renal tumor vessels. MATERIAL AND METHODS: We performed PDUS and angiography in 52 histologically proven renal parenchymal tumors (50 renal cell carcinomas (RCCs) and 2 oncocytomas), and compared vascularity on PDUS and angiography. The vascularity of PDUS was graded as follows: grade 0-- no recognizable tumor vessel; grade 1-- hypovascular to surrounding renal interlobar arteries; grade 2-- hyper- or isovascular to surrounding renal interlobar arteries. RESULTS: With PDUS, 41 tumors were grade 2 and 11 were grade 1. With angiography, 44 lesions had iso/hypervascular pattern, 6 hypovascular pattern, and 2 were judged to be avascular. Among 44 iso/hypervascular tumors, 41 were grade 2, and 3 were grade 1. These latter 3 were located deeper than 7 cm. Six hypovascular tumors and 2 avascular tumors were grade 1. The 2 avascular tumors were small and hypovascular. The kappa-level of agreement was 0.81. CONCLUSION: There was very good agreement between PDUS and angiography in visualizing renal tumor vessels. PDUS appears appropriate for assessing renal tumor vascularity as compared to angiography in small and hypovascular lesions, but deep location reduced the detectability of tumor vessels with PDUS.

[Fatty liver quantification with line scan echo planar spectroscopic imaging (LSEPSI)].

INTRODUCTION: Although fatty infiltration of liver is a benign process that generally results from chronic alcohol uptake or obesity, such lifestyle factors may lead to chronic disease. Measuring the fat concentration in liver may therefore prove useful in assessing disease status. In this study, we report the usefulness of line scan echo planar spectroscopic imaging (LSEPSI) for this problem. METHODS: Rapid successive column sampling was accomplished using orthogonal slice-selective 90 degrees and 180 degrees pulses and echo planar spectral/spatial encodings. Phantom and clinical studies of 13 patients suspected of having fatty liver were carried out with LSEPSI. Estimated fat fractions obtained with LSEPSI were compared with ultrasound findings. RESULTS: The results showed a good correlation between the actual fat content of phantoms and the estimated fat fraction obtained with LSEPSI (r = 0.95). In the clinical study, the estimated fat fraction tended to rise as the US grade of fatty liver increased. DISCUSSION: LSEPSI is largely free from T1 and T2 relaxation owing to its infinite TR and minimal T2 weighting. Thus, there is no need for relaxation analysis. In addition, the lack of phase encoding reduces motion-related ghosting artifacts. Rapid fat/water spectral quantification of liver with this technique is useful for fatty liver assessment in a clinical setting.

Teratoid carcinosarcoma of the ovary with prominent neuroectodermal differentiation.

We present what we believe to be only the second report of ovarian teratoid carcinosarcoma. The patient, a 59-year-old woman, was admitted to hospital complaining of a pelvic mass and of abdominal fullness. Advanced ovarian cancer was diagnosed, and a tumorectomy was done. The tumor occupied the pelvis, and metastasis was found in the liver and spleen. The solid tumor was composed of chondrosarcoma, squamous cell carcinoma, adenocarcinoma and malignant neuroectodermal components, which contained ganglioneuroblastoma-like and medulloepithelioma-like areas. Immunohistochemically, the neuroectodermal cells were positive for both neural and epithelial markers. This ovarian tumor consisted of frankly malignant components, with prominent neuroectodermal elements mixed with epithelial and mesenchymal elements in an organoid fashion; a quite rare tumor.

Double-phase helical CT of small renal parenchymal neoplasms: correlation with pathologic findings and tumor angiogenesis.

PURPOSE: To correlate the enhancement pattern of double-phase helical computed tomography (CT) of small renal parenchymal neoplasms with pathologic findings and tumor angiogenesis, and evaluate whether the enhancement pattern would be useful in differentiating the histomorphologic types of small renal parenchymal neoplasms. MATERIALS AND METHODS: Double-phase helical CT (5 mm slice) of the corticomedullary phase (CMP) and late nephrographic phase (NP) was performed in 40 surgically resected renal neoplasms <3.5 cm. The patterns of CT attenuation value and homogeneity were correlated with the subtypes of neoplasms, microvessel density, and the existence of intratumoral necrosis or hemorrhage. RESULTS: Clear cell renal cell carcinomas (RCC) (n = 29) showed a peak attenuation value in the CMP of >100 HU [Hounsfield units]. Chromophobe cell RCC (n = 2) showed a peak attenuation value in the CMP of <100 HU. Papillary RCC (n = 5) showed a gradual enhancement with the attenuation value in the CMP of <100 HU. However oncocytomas (n = 2) and metanephric adenomas (n = 2) also showed patterns similar to these subtypes of RCC. The degree of enhancement in the CMP correlated with microvessel density (r = 0.87). All tumors with an homogeneous enhancement pattern did not show necrosis or hemorrhage on histologic specimen. CONCLUSION: The enhancement pattern in double-phase helical CT was different among the subtypes of RCC, and correlated with microvessel density or the existence of intratumoral necrosis or hemorrhage. However it did not differentiate between RCC and other solid tumors.

MR imaging of non-CNS fetal abnormalities: a pictorial essay.

The recent popularity of prenatal magnetic resonance (MR) imaging has been associated with the development of ultrafast MR imaging techniques such as the single-shot fast spin-echo sequence. However, the majority of previous reports have concerned the fetal central nervous system (CNS) and chest disorders. MR imaging can demonstrate non-CNS fetal anatomy and pathologic conditions clearly. With its excellent tissue contrast, MR imaging provides information that supplements that provided by ultrasonography (US), especially in cases of neck, chest, and gastrointestinal lesions. Because of its large field of view, MR imaging allows evaluation of the relationship between a large lesion and adjacent structures. MR imaging should be considered if the diagnosis of a suspected non-CNS lesion is unclear at fetal US. MR imaging plays an important complementary role to US in cases of non-CNS fetal lesions and will be further accepted for fetal imaging in the future.