The role of psychological factors in the development of burning mouth syndrome.

The psychiatric profiles of 50 patients diagnosed with burning mouth syndrome (BMS) were compared to those of 50 age- and sex-matched individuals as the control group. The Symptom Checklist-90-Revised (SCL-90-R) questionnaire was used to evaluate the role of psychological factors in the development of BMS. Somatization, obsessive-compulsive, depression, anxiety, hostility, phobic anxiety, psychoticism, global severity index (GSI), positive symptom total (PST), and positive symptom distress index (PSDI) scores were significantly higher in the patients with BMS than in the control group. In a subgroup analysis according to sex, women with BMS had higher T-scores for somatization, obsessive-compulsive, paranoid ideation, GSI, PST, and PSDI than women in the control group. In contrast, only the PSDI score was significantly higher in men with BMS compared to men in the control group. There was a significant difference in the T-scores for somatization, psychoticism, and GSI between the three age subgroups (≤50, 51-65, and ≥66 years). The obsessive-compulsive and PSDI scores were significantly higher in patients with BMS who also had at least one chronic disease than in patients with BMS who had no chronic disease. In conclusion, psychological factors are correlated with BMS.

A clinical drug library screen identifies clobetasol propionate as an NRF2 inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer.

The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor. Mechanistically, CP prevented nuclear accumulation and promoted ß-TrCP-dependent degradation of NRF2 in a glucocorticoid receptor- and a glycogen synthase kinase 3 (GSK3)-dependent manner. As a result, CP induced oxidative stress and strongly suppressed the anchorage-independent growth of tumors with KEAP1 mutation, but not with the wild-type KEAP1. Further, CP alone or in combination with rapamycin strongly inhibited the in vitro and in vivo growth of tumors harboring mutations in KEAP1 or both KEAP1 and LKB1 that are frequently observed in lung cancer. Thus, CP could be a repurposed therapeutic agent for cancers with high NRF2 activity. We also proposed that the use CP and rapamycin in combination could be a potential therapeutic strategy for tumors harboring both KEAP1 and LKB1 mutations.

Synthetic lethal screening reveals FGFR as one of the combinatorial targets to overcome resistance to Met-targeted therapy.

Met is a receptor tyrosine kinase that promotes cancer progression. In addition, Met has been implicated in resistance of tumors to various targeted therapies such as epidermal growth factor receptor inhibitors in lung cancers, and has been prioritized as a key molecular target for cancer therapy. However, the underlying mechanism of resistance to Met-targeting drugs is poorly understood. Here, we describe screening of 1310 genes to search for key regulators related to drug resistance to an anti-Met therapeutic antibody (SAIT301) by using a small interfering RNA-based synthetic lethal screening method. We found that knockdown of 69 genes in Met-amplified MKN45 cells sensitized the antitumor activity of SAIT301. Pathway analysis of these 69 genes implicated fibroblast growth factor receptor (FGFR) as a key regulator for antiproliferative effects of Met-targeting drugs. Inhibition of FGFR3 increased target cell apoptosis through the suppression of Bcl-xL expression, followed by reduced cancer cell growth in the presence of Met-targeting drugs. Treatment of cells with the FGFR inhibitors substantially restored the efficacy of SAIT301 in SAIT301-resistant cells and enhanced the efficacy in SAIT301-sensitive cells. In addition to FGFR3, integrin ß3 is another potential target for combination treatment with SAIT301. Suppression of integrin ß3 decreased AKT phosphorylation in SAIT301-resistant cells and restored SAIT301 responsiveness in HCC1954 cells, which are resistant to SAIT301. Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin ß3 are resistant to crizotinib treatment, suggesting that FGFR and integrin ß3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs.

Bone marrow-derived clonal mesenchymal stem cells inhibit ovalbumin-induced atopic dermatitis.

Mesenchymal stem cells (MSCs) possess immunomodulatory activities, including suppression of T- and B-cell activation. However, their effects on atopic dermatitis (AD) have not yet been studied. Using an ovalbumin-induced AD mouse model, we investigated whether MSCs can be used as therapeutics in AD. We isolated both allogeneic and syngeneic clonal MSCs (cMSCs) from mouse bone marrow according to the subfractionation culturing method. Our cMSCs suppressed both T- and B-cell activation. T-cell proliferation and cytokine production, including interferon (IFN)-γ and interleukin (IL)-4, were suppressed by inhibition of transcription factors, such as T-bet, GATA-3, and c-Maf. Those transcription factors were nitric oxide dependent. Immunoglobulin E (IgE) suppression occurred through downregulation of AID and BLIMP-1, important regulators for isotype class switch and B-cell differentiation. The cMSCs were injected intravenously into ovalbumin-induced AD mouse model, and the therapeutic effects were analyzed. Injection of both allogeneic and syngeneic cMSCs in an AD mouse model inhibited cell infiltration in skin lesions and decreased the serum level of IgE. IL-4 expression was also suppressed by cMSCs in both the lymph node and skin. The cMSCs migrated to skin lesions and draining lymph nodes. Taken together, these data demonstrated that cMSCs, which suppressed T- and B-cell functions, can be used for the treatment of AD in mice.

Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G(2) /M phase arrest.

OBJECTIVES: Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti-cancer treatment have been sought from natural resources. Here, we have investigated anti-proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the de novo sphingolipid pathway, and its mechanism in B16F10 melanoma cells. MATERIAL AND METHODS: We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine-1-phosphate levels were analysed by HPLC. RESULTS: Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G(2) /M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21(waf1/cip1) was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine-1-phosphate in myriocin-treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells. CONCLUSIONS: Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21(waf1/cip1) , followed by inhibition of cyclin B1 and cdc2, resulting in G(2) /M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism-based therapy for this type of skin cancer.

Prognostic indicators of gastric carcinoma confined to the muscularis propria.

AIMS: Gastric carcinoma confined to the muscularis propria (MPGC) is considered an intermediate-stage carcinoma. A method of discriminating between more favourable and less favourable prognostic groups of this entity is critically needed in dealing with this heterogeneous disease. The aim of this study was to examine the correlation between survival of patients with MPGC and its various clinicopathological parameters. METHODS AND RESULTS: Various clinicopathological parameters were studied in 171 tissue samples including: macroscopic appearance, size, age, sex, stage, invasion depth, Lauren and Ming classifications, extent, lymphatic emboli and nodal metastasis. Tumours macroscopically resembling early gastric cancers, younger patient age, absence of lymphatic tumour emboli and lower stage were significantly associated with better prognosis of MPGC by univariate analysis. Tumours macroscopically resembling early gastric cancers, younger patient age and Lauren's diffuse type were significantly associated with a better prognosis of MPGC by multivariate analysis. CONCLUSIONS: These indicators are practical parameters for predicting patient prognosis in clinical practice. The description of these parameters should be carefully noted in the final report and pathologists should evaluate the macroscopic appearance of MPGC.

Quantitative analysis of interleukin-6 expression in porcine spleen cells and alveolar macrophages using real-time PCR.

Interleukin-6 (IL-6), a multifocal cytokine produced by lymphoid and non-lymphoid cells, regulates immune responses, acute-phase reactions against bacterial infections, and haematopoiesis. After cloning and sequencing of porcine IL-6, the expression pattern of porcine IL-6 mRNA was evaluated through real-time RT-PCR using porcine immune cells (spleen cells and alveolar macrophages) following stimulation with LPS. The sequence has been reported to GenBank with Accession no. AF 518322. The nucleotide sequence was different at the 89th and 205th positions in comparison with M80258, but only at the 205th with M86722. Comparison of porcine IL-6, Accession no. AF 518322, with IL-6 of human, canine, ovine, and mouse showed homologies of 78%, 81%, 82% and 73% in nucleotide sequence and 42%, 69%, 61% and 42% in amino acids. Expression of IL-6 mRNA was induced by stimulation with LPS. IL-6 mRNA expression in alveolar macrophages peaked at 2 h and decreased sharply to control levels at 4 h, whereas it peaked at 14 h and decreased at 24 h in spleen cells after stimulation with LPS (1 microg/ml). These results suggest that IL-6 mRNA expression in porcine immune cells is cell-type specific and the results of this study could be used as the basis for research on the porcine immune system.

The cerebrovascular response to traditional acupuncture after stroke.

Acupuncture is useful in treating the nausea and vomiting related to chemotherapy, adult postoperative surgery pain and postoperative dental pain. We obtained single-photon emission computed tomography (SPECT) brain perfusion images of six patients with middle cerebral artery occlusion obtained before and after acupuncture and compared the changes in regional cerebral blood flow (rCBF) to those in normal control. Images were obtained before and after acupuncture at six traditional acupoints (LI 4, 10, 11, 15 and 16 and TE5) in the affected arm. The baseline image was subtracted from the postacupuncture image, to produce a subtraction image displaying only voxels with values >2 SD from the mean and those voxels were coregistered to the baseline SPECT or T2-weighted MRI. Similar images were obtained before and after acupuncture of eight normal volunteers. Statistical parametric mapping with a threshold of P =0.001 and a corrected P of 0.05 was performed for group comparison between postacupuncture and baseline SPECT. Focally increased CBF was seen in all patients especially in the hypoperfused zone surrounding the ischaemic lesion, the ipsilateral or contralateral sensorimotor area, or both. Normal subjects showed increased rCBF mainly in the parahippocampal gyrus, premotor area, frontal and temporal areas bilaterally and ipsilateral globus pallidus. Acupuncture stimulation after stroke patients appears to activate perilesional or use-dependent reorganised sites and might be a way of looking at brain reorganisation.

Gallbladder lymphangioma: MR findings.

Intraabdominal lymphangiomas are rare lesions that can be difficult to diagnose. We report ultrasonographic (US), computed tomographic (CT), magnetic resonance (MR) imaging, and pathologic findings in a patient with cavernous lymphangioma originating in the gallbladder. US and CT showed a multiseptated cystic mass in the gallbladder fossa. T2-weighted MR images and MR cholangiopancreatography depicted the lumen of the gallbladder and thin septations of the cystic mass, which originated in the gallbladder. Endoscopic retrograde cholangiopancreatography showed no apparent communication between the cyst and the gallbladder. Histologic findings obtained during the operation were consistent with cavernous lymphangioma. Its characteristic histology was observed in the subserosal layer of the gallbladder. This case is a rare instance of cavernous lymphangioma originating in the gallbladder preoperatively diagnosed by MR and MR cholangiopancreatography.

Pleckstrin homology domain interacts with Rkp1/Cpc2, a RACK1 homolog, to modulate Pck2-mediated signaling process in Schizosaccharomyces pombe.

Rkp1/Cpc2, a fission yeast RACK1 homolog, interacts with Pck2, a PKC homolog, and is involved in the regulation of pck2-mediated signaling process. The N-terminal region of split pleckstrin homology domain (nPH) in human PLC-gamma1 bound to Rkp1/Cpc2 concomitantly with Pck2. nPH inhibited kinase activity of GST-Pck2 purified from Schizosaccharomyces pombe in vitro. The lethality induced by pck2(+) overexpression was suppressed by coexpression of either rkp1(+) or nPH domain. This result suggests that Rkp1/Cpc2 interacts with PH domain-containing protein and regulates the Pck2-mediated signaling process in S. pombe.

Antiplatelet activity of green tea catechins is mediated by inhibition of cytoplasmic calcium increase.

We have previously reported that green tea catechins (GTC) display a potent antithrombotic activity, which might be due to antiplatelet rather than anticoagulation effects. In the current study, we investigated the antiplatelet mechanism of GTC. We tested the effects of GTC on the aggregation of human platelets and on the binding of fluorescein isothiocyanate-conjugated fibrinogen to human platelet glycoprotein (GP) IIb/IIIa. GTC inhibited the collagen-, thrombin-, adenosine diphosphate (ADP)-, and calcium ionophore A23187-induced aggregation of washed human platelets, with 50% inhibitory concentration values of 0.64, 0.52, 0.63, and 0.45 mg/ml, respectively. GTC significantly inhibited fibrinogen binding to human platelet surface GPIIb/IIIa complex but failed to inhibit binding to purified GPIIb/IIIa complex. These results indicate that the antiplatelet activity of GTC may be due to inhibition of an intracellular pathway preceding GPIIb/IIIa complex exposure. We also investigated the effects of GTC on intracellular calcium levels, which are critical in determining the activation status of platelets and on induction of platelet aggregation by thapsigargin, which is a selective inhibitor of the Ca(2+)-ATPase pump. Pretreatment of human platelets with GTC significantly inhibited the rise in intracellular Ca(2+) concentration induced by thrombin treatment, and GTC significantly inhibited the thapsigargin-induced platelet aggregation. We also examined the effect of GTC on the second messenger, inositol 1,4,5-triphosphate (IP(3)). GTC significantly inhibited the phosphoinositide breakdown induced by thrombin. Taken together, these observations suggest that the antiplatelet activity of GTC is be mediated by inhibition of cytoplasmic calcium increase, which leads to the inhibition of fibrinogen-GPIIb/IIIa binding via the activation of Ca(2+)-ATPase and inhibition of IP(3) formation.

Recurrent pyogenic cholangitis: comparison between MR cholangiography and direct cholangiography.

PURPOSE: To compare the accuracy of magnetic resonance (MR) cholangiography with that of direct cholangiography for the evaluation of recurrent pyogenic cholangitis. MATERIALS AND METHODS: Twenty-four patients with recurrent pyogenic cholangitis underwent MR cholangiography before surgery, and 18 of these 24 also underwent direct cholangiography. Two reviewers evaluated MR cholangiograms and direct cholangiograms and focused on identifying intrahepatic ductal dilatation, stricture, and calculi, as well as coexistent parenchymal abnormalities, on the basis of the classification of the internal lobes and segments of the liver. These observations were compared with surgical findings. RESULTS: According to examination results in the surgical specimens, 24 patients had 46 segmental abnormalities. MR cholangiography depicted all 46 (100%) segments with ductal dilatation, 22 (96%) of 23 segments with focal ductal stricture, and 43 (98%) of 44 segments with ductal calculi. Eighteen patients who underwent direct cholangiography had 32 segmental abnormalities according to examination results in the surgical specimens. Direct cholangiography depicted 15 (47%) of 32 segments with ductal dilatation, eight (44%) of 18 segments with focal ductal stricture, and 14 (45%) of 31 segments with ductal calculi. CONCLUSION: MR cholangiography is superior to direct cholangiography for accurate topographic evaluation of recurrent pyogenic cholangitis because it is able to depict all of the biliary tree, despite obstruction or stenosis.

Isolation of a novel gene from Schizosaccharomyces pombe: stm1+ encoding a seven-transmembrane loop protein that may couple with the heterotrimeric Galpha 2 protein, Gpa2.

A putative seven transmembrane protein gene, stm1(+), which is required for proper recognition of nitrogen starvation signals, was isolated as a multicopy suppressor of a ras1 synthetic lethal mutant in Schizosaccharomyces pombe. Under nitrogen-deficient conditions, transcription of the stm1 gene was induced; deletion of stm1 was associated with early entry into G(1) arrest. Under nutritionally sufficient conditions, overexpression of Stm1 inhibited vegetative cell growth, resulted in decreased intracellular cAMP levels, increased the expression of the meiosis-specific genes ste11, mei2, and mam2, and facilitated sexual development in homothallic cells. However inhibition of vegetative cell growth and reduction of cAMP levels were not observed in a deletion mutant of the heterotrimeric G protein Galpha2 gene, gpa2, that is responsible for regulating intracellular cAMP levels, a key factor in determining the sexual development in S. pombe. Stm1 protein was shown to interact with Gpa2 through its C-terminal transmembrane domains 5-7. Mutation at Lys(199) in the C-terminal domain (stm1(K199A)) abolished the Stm1 overexpression effect on lowering cAMP levels. Induction of ste11, a meiosis-specific gene transcription factor, by Stm1 overexpression was enhanced in gpa2-deleted cells but was absent in a deletion mutant of sty1, a key protein kinase that links mitotic control with environmental signals and induces stress-responsive genes. Moreover, deletion of both stm1 and ras1 caused delayed entry into G(1) arrest in S. pombe when the cells were grown in a nitrogen-deficient medium. Thus we consider that the stm1 gene can function through Gpa2-dependent and/or -independent pathways and may play a role in providing the prerequisite state for entering the pheromone-dependent differentiation cycle in which heterotrimeric Galpha1 protein, Gpa1, and Ras1 play major roles. Stm1 could function as a sentinel molecule sensing the nutritional state of the cells, stopping the proliferative cell cycle, and preparing the cell to enter meiosis under nutritionally deficient conditions.

Sphingolipid metabolic changes during chiral C2-ceramides induced apoptosis in human leukemia cells.

N-acetylsphingosine (C2-ceramide) is a synthetic water-soluble ceramide mimicking the activity of natural ceramides. By fixing chiral conformation on carbon numbers 2 and 3 in the ceramide structure, four chiral C2-ceramides naming d-erythro-, l-erythro-, d-threo- and l-threo C2-ceramide were synthesized. We have investigated the chiral effects of these C2-ceramides on the sphingolipid metabolism, particularly on both the sphingolipid biosynthetic pathway and on the degradation pathway. In both HL-60 and U937 cells, the chiral C2-ceramide (10 microM) showed sphingosine accumulation monitored fluoromatrically by a high performance liquid chromatographic separation of the sphingoid bases. Most importantly, in HL-60 cells, l-erythro C2-ceramide induced a 50 fold increase in sphingosine as compared to the control, while l-threo C2-ceramide exhibited a minimal 7-fold increase. In contrast, sphinganine, another sphingoid base, showed less accumulation by any chiral C2-ceramide tested under the same conditions. These results suggested that chiral C2-ceramide primarily acts on the sphingolipid degradation pathway rather than on the sphingolipid biosynthetic route. The strong G0/G1 phase arrest in the cell cycle by treatment of l-erythro C2-ceramide indicates that the blockade of the sphingolipid degradation pathway might be concomitantly involved in the dysfunction of the cell cycle. On the other hand, the fact that all chiral C2-ceramides tested failed to inhibit the activity of sphingosine kinase acting on the removal of sphingosine by producing sphingosine-l-phosphate demonstrates that chiral C2- ceramides may increase sphingosine by activating various ceramidases by which natural ceramides are divided into sphingosine and free fatty acids. However, the precise steps involved in this interaction are still unknown.

Differential effects of fumonisin B1 on cell death in cultured cells: the significance of the elevated sphinganine.

Fumonisins are specific inhibitors of ceramide synthase in sphingolipid metabolism. An alteration in sphingolipid metabolism as a result of fumonisin exposure is related to cell death (Yoo et al., 1992). The objective of this study was to investigate whether elevated free sphinganine levels are related to the sensitivity of cultured cells to fumonisin exposure. Fumonisin B1 elevated the intracellular free sphinganine concentraions in both LLC-PK1 and Chinese hamster ovary (CHO) cells. However, CHO cells are resistant to fumonisin cytotoxicity at 50 microM, while LLC-PK1 cells are sensitive at concentrations greater than 35 microM. The intracellular concentration of free sphinganine in LLC-PK, cells treated at 50 microM fumonisin B1 for 72 h was approximately 1450 pmol/mg protein relative to the 37 pmol observed in the control culture. Under the same conditions, the population of apoptotic cells in the 50 M fumonisin B1-treated culture was approximately 37% of the total compared to 12% in the control. The caspase III-like activity after 72 h in the 50 microM fumonisin B1-exposed culture increased to approximately 50 pmol/mg protein/hr compared to 6 pmol/mg protein/hr in the control. L-cycloserine, a serine palmitoyltransferase inhibitor, reduced the fumonisin B1-stimulated caspase III-like activity down to the control level. Under the same culture conditions, the intracellular concentration of free sphinganine after L-cycloserine plus fumonisin B1 treatment was 140 pmol/mg protein compared to 1450 pmol/mg protein in fumonisin B1 alone. The intracellular concentration of free sphinganine in CHO cells treated with 50 microM fumonisin B1 for 72 h was approximately 460 pmol/mg protein, indicating that the mass amount of elevated free sphinganine in the CHO cells was about 32% of that in LLC-PK1 cells. Adding exogenous sphinganine to the CHO cells along with 50 microM fumonisin B1 treatment for 72 h caused both necrosis and apoptosis. In conclusion, the elevated endogenous sphinganine acts as a contributing factor to the fumonisin-induced cell death.

Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA-PEG block copolymer.

Biodegradable polymeric micelles containing doxorubicin in the core region were prepared from a di-block copolymer composed of doxorubicin-conjugated poly(DL-lactic-co-glycolic acid) (PLGA) and polyethyleneglycol (PEG). The di-block copolymer of PLGA-PEG was first synthesized and the primary amino group of doxorubicin was then conjugated to the terminal hydroxyl group of PLGA, which had been pre-activated using p-nitrophenyl chloroformate. The resulting polymeric micelles in aqueous solution were characterized by measurement of size, drug loading, and critical micelle concentration. The micelles containing chemically-conjugated doxorubicin exhibited a more sustained release profile than PEG-PLGA micelles containing physically-entrapped doxorubicin. The cytotoxic activity of the micelles against HepG2 cells was greater than free doxorubicin, suggesting that the micelles containing conjugated doxorubicin were more effectively taken up cellularly, by an endocytosis mechanism rather than by passive diffusion. Confocal microscopic observation and flow cytometry analysis supported the enhanced cellular uptake of the micelles.

Immunostimulatory effects of anionic alkali mineral complex solution Barodon in porcine lymphocytes.

The anionic alkali mineral complex solution, Barodon (Barodon-S.F. Corp., Korea), was evaluated for its effectiveness as a nonspecific immunostimulator in pigs. The effects of Barodon were determined by analysis of feed efficiency, growth rate, and phenotype of leukocyte subpopulations using monoclonal antibodies specific to porcine leukocyte differentiation antigens and flow cytometry (FC). The study was focused to investigate the change in proportion of the CD4+CD8+ double positive T lymphocyte subpopulation (dpp) which exists uniquely in pigs. In addition, the mitogen-stimulated lymphoproliferative response, tissue distribution in lymphoid organs and the adjuvant effect of Barodon on hog cholera vaccine efficiency were determined. The study has revealed the average daily gain rates and feed conversion rates were significantly (p<0.05) improved in either group of pigs fed with 0.05% Barodon-spray feed (Tx-1) or pigs fed with 3% Barodon-fermented feed (Tx-2) in comparison with group of pigs fed with feed containing no Barodon (control). The proportion of cells expressing CD4+ antigen in Barodon-treated group increased from 3 weeks posttreatment and was significantly higher (p<0.05) than that of control at 8 weeks posttreatment. Particularly, the significantly higher proportion was maintained from 8 weeks through 13 weeks posttreatment in Tx-1 group (p<0.05). The proportion of cells expressing CD8+ antigen was significantly higher at 3 weeks posttreatment in Tx-2 (p<0.01). Proportion of MHC class II-expressing cells was significantly higher in Tx-1 and Tx-2 group at 11 weeks and 8 weeks posttreatment (p<0.05), respectively. In addition, the proportion of Non T/Non B (N) cells was also significantly higher in Tx-2 at 3 weeks posttreatment (p<0.01) and maintained to 13 weeks posttreatment (p<0.1). Between Barodon-treated groups, the proportion of MHC class II-expressing cells was observed to be larger in Tx-2 than Tx-1 from 3 weeks to 8 weeks posttreatment (p<0.05). However, there were no significant difference in the proportions of CD2+ cells, B cells, monocytes and granulocytes between Barodon-treated and control group during the experiment. Dual-color FC analysis, study has revealed an increased proportion of dpp present in lymphocytes obtained from peripheral blood (PB) and mesenteric lymph node (MLN) of Barodon-treated group at 8 and 11 weeks posttreatment. The proportion of dpp in PB was 27.5% and 32.1% in Tx-1 and Tx-2, respectively, but only 2.2% in control group at 8 weeks posttreatment. In MLN, the proportion was 45.1% and 52.1% in Tx-1 and Tx-2, respectively, otherwise 16.5% in control group at 8 weeks posttreatment. The mitogen-stimulated activity was significantly higher in Tx-1 than in the control group at 11 weeks posttreatment when cells were stimulated with Con A and PHA, respectively (p<0.01). Also, Con A-, PHA and PWM-stimulated activity was significantly higher in Tx-2 than in the control group at the same time (p<0.05). The tissue distribution of CD4+, CD8+ and CD4+CD8+ dpp in MLN and spleen was significantly larger in Tx-1 and Tx-2 than in the control group (p<0.01). Also, a larger proportion of dpp was observed in Tx-2 than Tx-1 in spleen between Barodon-treated groups (p<0.01). In conclusion, the study has demonstrated that Barodon had an immunostimulatory effect on pigs through proliferation and activation of porcine immune cells, specially CD4+CD8+ dpp lymphocytes.

Nontumorous hepatic arterial-portal venous shunts: MR imaging findings.

PURPOSE: To determine the magnetic resonance (MR) imaging findings of small nontumorous hepatic arterial-portal venous (arterioportal) shunts in the liver. MATERIALS AND METHODS: MR images in 25 patients with 38 small nontumorous arterioportal shunts verified with surgery or follow-up imaging were included in this study. The causes of arterioportal shunts were iatrogenic causes in 11 patients and/or cirrhotic changes in the remaining patients. Nonenhanced T1- and T2-weighted images and multiphase contrast material-enhanced dynamic images were retrospectively reviewed and compared with conventional hepatic arteriograms to determine the MR characteristics related to the focal hemodynamic changes. RESULTS: On arterial-dominant-phase dynamic MR images, 29 (76%) of the 38 arteriographically suggested nontumorous arterioportal shunts displayed abnormal findings distinguished against the surrounding hepatic parenchyma, including wedge-shaped (n = 14), nodular (n = 9), or irregularly outlined (n = 6) areas of focal contrast enhancement. The signal intensity on nonenhanced T1- and T2-weighted images of the corresponding areas appeared unremarkable except for three wedge-shaped high-signal-intensity areas (three [8%] of 38) on T2-weighted images accompanied by prolonged contrast enhancement. Most (24 [83%] of 29) areas of abnormal signal intensity were located at the periphery of the liver parenchyma. CONCLUSION: A small nontumorous arterioportal shunt should be considered one of the causes of focal parenchymal hyperperfusion abnormalities on contrast-enhanced dynamic MR images of the liver in the absence of abnormal signal intensity on static MR images.