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PubMed2001

Impaired transendothelial migration of B-CLL lymphocytes: a defect linked to low L-selectin expression.

The emigration of lymphocytes from blood into lymph nodes is regulated by the expression of the adhesion molecule, L-selectin on the lymphocyte surface which arrests the rolling of the cell on the vessel wall and allows firmer adhesive interactions to develop. The expression of L-selectin on B-CLL lymphocytes is less than half that on normal lymphocytes and this difference correlates with an impaired capacity of B-CLL lymphocytes to migrate beneath a monolayer of human umbilical vein endothelial cells. Both the B-cell and T-cell lymphocytes from normal subjects and B-CLL patients show down-regulation of L-selectin and CD23 after transendothelial migration. The reduced expression of L-selectin on B-CLL lymphocytes leads to a relative "trapping" of these cells in the vascular space and is one factor contributing to the elevation of peripheral lymphocyte count.

B-Lymphocytes↗
PubMed2000

Effects of exposure to flax dust in Polish farmers: work-related symptoms and immunologic response to microbial antigens associated with dust.

Medical examinations were performed in a group of 51 Polish farmers heavily exposed to flax dust during harvesting and scutching (threshing) and in a group of 50 healthy urban dwellers not exposed to organic dusts (controls). The examinations included: interview concerning the occurrence of respiratory disorders and work-related symptoms, physical examination, X-ray examination of chest, lung function tests, oxymetric examinations, determination of the concentration of cytokines (IL-1alpha IL-6, TNFalpha) in blood serum and allergological tests with microbial antigens associated with organic dust, comprising: skin prick test with 4 antigens, agar-gel precipitation test with 12 antigens and test for specific inhibition of leukocyte migration with 4 antigens. As many as 32 farmers (62.7%) reported the occurrence of work-related symptoms during harvesting, transporting and scutching of flax. The most common complaint was general weakness reported by 15 farmers (29.4%), followed by headache reported by 14 (27.5%), blocking of the nose - by 11 (21.6%), dry cough, shivering, and eyes itching - each by 10 (19.8%), chest tightness and hoarseness - each by 9 (17.6%). No control subjects reported these work-related symptoms. The mean spirometric values in the examined group of farmers were within a normal range and did not show a significant post-shift decline. In contrast, a significant post-shift decline of oxymetric values was found among flax farmers. The farmers showed a frequency of the positive early skin reactions to environmental allergens in the range of 0-19.6%, a frequency of positive precipitin reactions in a range of 0-56.9%, and frequency of positive reactions of leukocyte migration inhibition in a range of 7.8-21.6%. The members of the control group responded to the majority of allergens with a significantly lower frequency of positive results compared to the farmers. Elevated concentrations of IL-1alpha and IL-6, but not TNFalpha, were found in blood sera of flax farmers. In conclusion, farmers engaged in harvesting and scutching of flax represent a group of elevated professional risk because of high incidence of work-related symptoms and high frequency of allergic reactions to bacteria and fungi associated with organic dust.

Adult↗
PubMed2001

Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis.

OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) level in plasma is described as a marker for joint inflammation in rheumatoid arthritis (RA). METHODS: MCP-1 in plasma and synovial fluid (SF) was quantified by ELISA in 36 RA patients with synovitis of the knee at Day 1 and 30. Disease activity was assessed by the swollen joint count, Ritchie Articular Index (RAI), global assessment, pain on visual analog scale, Health Assessment Questionnaire, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: By linear regression analysis plasma MCP-1 levels correlated significantly with the swollen joint count (Day 1: R = 0.47, p = 0.005; Day 30: R = 0.53, p < 0.001) and the RAI (Day 1: R = 0.37, p = 0.03; Day 30: R = 0.41, p = 0.01). The correlations of swollen joint count and RAI with ESR and CRP were significant only on Day 30 for the ESR (R = 0.40, p = 0.02). No association was found between plasma MCP-1 levels and the ESR/CRP levels. MCP-1 levels in plasma in RA patients were elevated compared to controls (p < 0.001) and MCP-I levels in SF were higher than in plasma (p < 0.001). No correlation was found between SF MCP-1 levels and in vitro migration of mononuclear cells towards SF. MCP-1 appears to participate in the disease process in RA, and plasma MCP-1 may be useful in monitoring joint inflammation.

Adult↗
PubMed2002

Role of ether-linked lysophosphatidic acids in ovarian cancer cells.

Naturally occurring alkyl- and alkenyl-lysophosphatidic acids (al-LPAs) are detected and elevated in ovarian cancer ascites compared with ascites from non-malignant diseases. Here we describe the biological functions and signaling properties of these ether-linked LPAs in ovarian cancer cells. They are elevated and stable in ovarian cancer ascites, which represents an in vivo environment for ovarian cancer cells. They stimulated DNA synthesis and proliferation of ovarian cancer cells. In addition, they induced cell migration and the secretion of a pro-angiogenic factor, interleukin-8 (IL-8), in ovarian cancer cells. The latter two processes are potentially related to tumor metastasis and angiogenesis, respectively. Al-LPAs induced diverse signaling pathways in ovarian cancer cells. Their mitogenic activity depended on the activation of the G(i/o) protein, phosphatidylinositol-3 kinase (PI3K), and mitogen-activated protein (MAP) kinase kinase (MEK), but not p38 mitogen activated protein kinase (MAP kinase). S473 phosphorylation of protein kinase B (Akt) by these lipids required activation of the G(i/o) protein, PI3K, MEK, p38 MAP kinase, and Rho. However, T308 phosphorylation of Akt stimulated by al-LPAs did not require activation of p38 MAP kinase. On the other hand, cell migration induced by al-LPAs depended on activities of the G(i/o) protein, PI3K, and Rho, but not MEK. These data suggest that ether-linked LPAs may play an important role in ovarian cancer development.

Ascites↗
PubMed1991

MHC class II expression by Langerhans' cells and lymph node dendritic cells: possible evidence for maturation of Langerhans' cells following contact sensitization.

Following exposure of mice to contact sensitizing chemicals, dendritic cells (DC) rapidly accumulate in the draining lymph nodes. A proportion, at least, of the DC which arrive in the nodes bear significant amounts of antigen and are derived from epidermal Langerhans' cells (LC). It is of interest that although LC are relatively inefficient antigen-presenting cells, the antigen-bearing DC found within draining nodes are potent accessory cells and induce immune responses both in vitro and in vivo. Previous in vitro studies have shown that during culture in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF), LC are subject to a functional and phenotypic maturation characterized by the development of effective accessory cell function and elevated membrane Ia antigen expression. We have hypothesized previously that LC may undergo a similar maturation in vivo as they move to the draining lymph nodes following receipt of the stimulus to migrate. As maturation in vitro is accompanied by increased Ia, we have examined the expression of this molecule on epidermal LC and lymph node DC during the induction phase of contact sensitization. The data reported provide evidence that peripheral lymph node DC, irrespective of whether they are derived from draining or resting nodes, and irrespective of whether or not they bear antigen, express comparable high levels of Ia antigen. In contrast, compared with DC, freshly isolated LC have considerably less (on average five times less) Ia antigen. These results indicate that during migration from the skin to lymphoid tissue LC are subject to a phenotypic maturation, comparable with that observed in vitro, and consistent with the acquisition of active antigen-presenting cell function.

Animals↗
PubMed1981

Cellular immune defects to Epstein-Barr virus-determined antigens in young males.

Three males with the X-linked lymphoproliferative syndrome (XLP) with hypo- or agammaglobulinemia following Epstein-Barr virus (EBV) infection and two males with the chronic mononucleosis syndrome were investigated for immune responses to EBV-determined antigens. Males with XLP showed profound cellular immune defects. Markedly diminished responses of natural killer cell and interferon-activated killer cell activities and impaired leukocyte migration inhibition responses to phytohemagglutinin were determined in patients with XLP. The two patients with chronic mononucleosis showed less severe defects. All patients showed partial or complete impairment of their EBV-specific immune responses as measured by leukocyte migration inhibition. EBV-specific antibodies were markedly diminished against EBV-associated nuclear antigen, early antigen, and viral capsid antigen in males with XLP. In contrast, patients with chronic mononucleosis had elevated antibodies to most EBV-specific antigens. Individuals with life-threatening EBV-induced lymphoproliferative disorders may exhibit multiple defective immune mechanisms against the virus.

Adolescent↗
PubMed1982

Acute experimental silicosis. Lung morphology, histology, and macrophage chemotaxin secretion.

The acute inflammatory reaction in the lungs of guinea pigs produced by the intratracheal injection of silica was assessed by histologic studies and whole-lung lavage 1, 2, 4, 7, and 14 days after the intratracheal instillation of quartz particles or saline. In addition, lavaged macrophages were cultured in vitro, and the media were assayed for chemotactic factors. This exposure to silica produced a neutrophilic inflammatory response around terminal bronchioles that was well developed within 1 day after injection. Four days after injection, neutrophils were replaced by mononuclear cells; and by 7 days, loosely organized granulomas and collagen deposition were detected in the interstitium. The number of neutrophils (PMNs) recovered by lavage from experimental animals was greatest 1 day after injection and was significantly greater (P less than 0.01) than that for controls at all time points. In contrast, the number of macrophages recovered by lavage did not exceed control levels until 7 days after injection and remained elevated thereafter. Thus, the cells recovered by lavage tended to mirror the changes seen in the inflamed lung. In experiments utilizing blind-well chemotactic chambers, both peritoneal exudate neutrophils and macrophages migrated toward supernatants from cultures of alveolar macrophages lavaged from silica-exposed animals in greater numbers (P less than 0.02) than toward supernatant from control animal macrophage cultures at each time point. Migration of normal alveolar macrophages toward supernatants from all cultures was minimal. Thus, exposure to silica in vivo appears to be a potent stimulus for the release of neutrophil and monocyte chemotactic factors by alveolar macrophages in vitro. The correlation between the types of inflammatory cells identified in the lung both microscopically and by lavage and the chemotactic factors released in vitro by alveolar macrophages from these lungs suggests that alveolar macrophages play a role in mediating pulmonary inflammation in this form of experimental silicosis.

Acute Disease↗
PubMed1981

Protocol for a study of nutritional factors and the low risk of colon cancer in Southern retirement areas.

Colon cancer shows a distinct geographic pattern in the United States, with mortality rates in the Northeast exceeding those in the South by about 50%. The North-South gradient remains even after adjustment for differences in urbanization and socioeconomic status. Those counties in the South that attract large numbers of retirees from the North retain the low colon mortality rates characteristic of the South, even at older ages. This observation implies either that certain life-style changes associated with migration at retirement rapidly reduce the risk of colon cancer or that individuals migrate selectively, based on some correlate of health. A specific hypothesis related to the former possibility is that consumption of fruits and vegetables, and the associated vitamin C, carotene, and fiber, is elevated in the South and related to the reduced risk of colon cancer. A protocol is presented for a case-control interview study in Southern retirement areas to assess these possible explanations. A detailed residential history, as well as information on frequency of consumption of specific foods, food groups, and micronutrients, will be collected by interview and will be complemented by selected serum micronutrient determinations and fecal mutagenicity assays.

Adult↗
PubMed1993

[Elevation of serum apo E-rich HDL concentration in a patient with cholestatic liver disease].

A remarkable elevation of serum HDL cholesterol concentration (165mg/dl) was found in a 42-year-old Japanese male with chronic pancreatitis who had been cholestatic for several years. An abnormal slow alpha-migrating lipoprotein, larger in particle size and more enriched with cholesteryl ester and apo E than normal HDL, was found in the patient's plasma. Quantitative determination of apo E-rich HDL revealed a striking increase of this lipoprotein in plasma. After choledocho-jejunostomy, a prompt and remarkable decrease of plasma apo E-rich HDL was observed, indicating a direct contribution of cholestasis to the accumulation of apo E-rich HDL in plasma in this patient.

Adult↗
PubMedDate not supplied

Determination of TNF alpha, interferon alpha, interleukin 2 and reactivity in the leucocyte migration inhibition test in breast cancer patients.

To date, the results concerning the prognostic importance of parameters of cell-mediated immunity in breast cancer patients are very contradictory; moreover, in most of them the results are hardly comparable due to methodological differences and heterogeneous groups of patients. In 123 patients with nonmetastatic breast carcinoma TNF alpha, INF alpha, IL 2 and reactivity in the leucocyte migration inhibition test (LMI-Test) against autologous tumor tissue were determined and the results correlated with the clinical course of the disease up to a maximum of 108 months. In breast cancer patients TNF alpha-serum levels were significantly (p less than 0.05) elevated compared to healthy controls. We also found that patients with progressive disease had higher levels than patients without recurrences. There were no differences concerning the IL-2 and IFN alpha serum levels between cancer patients and controls, nor did we find a correlation with the clinical course of the disease. In 38% of all breast cancer patients examined, a MIF production against tumor tissue could be demonstrated in the LMI-test. There was no difference concerning the LMI-reactivity between the groups of lymph-node negative and positive patients, but the observation that those patients with an unfavourable clinical course respond more frequently with an enhanced macrophage migration and rarely with migration inhibition was considered of notable prognostic significance. According to these results, it is possible that determination of TNF alpha and delayed type hypersensitivity reaction against tumor tissue in the LMI-test is of clinical value for the determination of risk groups.

Biomarkers, Tumor↗
PubMed2006

Intralymphatic dendritic cell vaccination induces tumor antigen-specific, skin-homing T lymphocytes.

PURPOSE: The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen-specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo. EXPERIMENTAL DESIGN: In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100. RESULTS: Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen-specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash. CONCLUSIONS: The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are "imprinted" in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease.

Adult↗
PubMed1975

Cell-mediated immunity to hepatitis B surface antigen in blood donors with persistent antigenaemia.

Cellular immunity to the hepatitis B surface antigen (HBsAg) and a liver-specific lipoprotein was studied, using the leucocyte migration test, in 38 asymptomatic blood donors found to have HBsAg in the serum. Sensitization to HBsAg was found in 26% and was related to the presence of liver damage, being detected in 47% of those with elevated serum aspartate aminotransferase but in only 13% with normal enzyme levels. The frequency of sensitization to this antigen in those with chronic persistent or chronic aggressive hepatitis on biopsy was also higher than in those with unrelated or minimal changes. The findings using the liver-specific lipoprotein as antigen were similar and there was a correlation between the results obtained with this and the hapatitis B surface antigen. This study supports the hypothesis that a T-lymphocyte response to hepatitis B virus antigen can initiate an autoimmune reaction to antigens such as liver-specific lipoprotein on the hepatocyte surface, and that this reaction may be of importance in the production of chronic liver damage. In the absence of the T-cell response, the autoimmune reaction cannot occur and the virus is able to establish a harmless symbiotic union with the host.

Aspartate Aminotransferases↗
PubMed2001

Control of vascular cell proliferation and migration by PPAR-gamma: a new approach to the macrovascular complications of diabetes.

Compared with nondiabetic subjects, type 2 diabetic individuals are at an increased risk for coronary artery disease and coronary restenosis after angioplasty or stenting. Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. Therefore, pharmaceutical interventions targeting proteins that regulate VSMC growth or movement are a promising new approach to treat diabetes-associated cardiovascular disease. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor superfamily that, when activated by thiazolidinedione (TZD) insulin sensitizers, regulates a host of target genes. All of the major cells in the vasculature express PPAR-gamma, including endothelial cells, VSMCs, and monocytes/macrophages. PPAR-gamma is present in intimal macrophages and VSMCs in early human atheromas. In an animal model of vascular injury; PPAR-gamma levels are substantially elevated in the neointima that forms after mechanical injury of the endothelium. Recent experimental studies provide evidence that PPAR-gamma may function to protect the vasculature from injury. Cell culture studies have shown that TZD PPAR-gamma ligands inhibit both the proliferation and migration of VSMCs. These antiatherogenic activities of PPAR-gamma may also occur in vivo, because TZDs inhibit lesion formation in several animal models. PPAR-gamma ligands may also protect the vasculature indirectly by normalizing metabolic abnormalities of the diabetic milieu that increase cardiovascular risk. Activation of PPAR-gamma, newly defined in vascular cells, may be a useful approach to protect the vasculature in diabetes.

Blood Vessels↗
PubMed1996

Forskolin Stimulates Aggrecan Gene Expression in Cultured Bovine Chondrocytes.

Prostaglandins are autacoids that elevate intracellular 3prime prime or minute:5prime prime or minute-cyclic adenosine monophosphate (cAMP) levels in chondrocytes and other cells in culture. To facilitate intracellular cAMP accumulation, bovine chondrocytes were incubated with forskolin alone or forskolin and isobutylmethylxanthine. Both significantly increased proteoglycan synthesis, which was inhibited by the cAMP-dependent protein kinase inhibitor H89. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) on 3--16% gels revealed the presence of two large proteoglycan core proteins which migrated more slowly than the 200-kDa marker protein and two small proteoglycan core proteins which migrated slightly slower than the 46-kDa marker. Northern blot hybridization, employing (32)P-labeled cDNA probes, showed that aggrecan steady-state mRNA levels were increased by forskolin and isobutylmethylxanthine after 1 h and 5 h incubation. Decorin and type II collagen mRNA levels were not altered under these conditions. Link protein mRNA levels were slightly elevated, but only at the 5-h time point. These results indicated that stimulation of intracellular cAMP accumulation by forskolin or forskolin and isobutylmethylxanthine resulted in augmented proteoglycan synthesis via increased steady-state aggrecan mRNA levels. Suppression of proteoglycan synthesis by the cAMP-dependent protein kinase inhibitor H89 suggested that cAMP-dependent protein kinase may also play a role in regulating the synthesis and completion of newly synthesized proteoglycans.

Journal Article↗
PubMed1998

Regulation of tissue-degrading factors and in vitro invasiveness in progression of breast cancer cells.

Hormone-independent growth and invasiveness represent phenotypic properties acquired during early progression of breast cancer. We compared human mammary adenocarcinoma cells, MCF-7, which are estrogen-dependent and poorly metastatic, with the estrogen-independent and highly metastatic subline, MCF7/LCC1, with regard to expression of tissue-degrading factors of the matrix metalloproteinase (MMP)-and urokinase (uPA)-dependent degradative pathways, as well as for their in vitro invasive properties. Both cell lines showed low constitutive mRNA expression of the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was also very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher (approximately 10-fold). Furthermore, both cell lines revealed low constitutive capacity to migrate in an in vitro invasion assay. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRNAs for TIMP-1 as well as for MMP-1, MMP-9, the uPA receptor, and the uPA inhibitor PAI-1, amongst which only the responses of MMP-9 and PAI-1 were cell-specific. The mRNA levels of MMP-9 and PAI-1 were approximately 10-fold and approximately 15-fold higher in MCF7/LCC1 cells compared to MCF-7 cells. The secretion of immunoreactive PAI-1 was considerably elevated (> 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the TPA-dependent level of 92-kDa MMP-9 was only approximately 2-fold higher in MCF7/LCC1 cells than in MCF-7 cells. In both cell lines treatment with TPA was associated with an increase (approximately 10-fold) in in vitro migration, which in the MCF7/LCC1 cells was significantly attenuated by a reconstituted basement membrane extract (Matrigel). These data suggest that TPA-responsive in vitro invasive properties that are probably associated with PAI-1 expression may co-vary with progression from hormone-dependent to -independent breast cancer.

Breast Neoplasms↗
PubMed2003

Swarm-cell differentiation in Salmonella enterica serovar typhimurium results in elevated resistance to multiple antibiotics.

Although a wealth of knowledge exists about the molecular and biochemical mechanisms governing the swimming motility of Salmonella enterica serovar Typhimurium, its surface swarming behavior has not been extensively characterized. When inoculated onto a semisolid agar medium supplemented with appropriate nutrients, serovar Typhimurium undergoes a morphological differentiation whereby single cells hyperflagellate and elongate into nonseptate, multinucleate swarm cells. Swarm migration is a collective behavior of groups of cells. We have isolated a MudJ insertion mutant of serovar Typhimurium 14028 that failed to swarm under any conditions. The site of the MudJ insertion was determined to be in the pmrK locus within the pmrHFIJKLM operon, which was previously demonstrated to confer resistance to cationic antimicrobial peptides. beta-Galactosidase assays, using the pmrK::lacZ transcriptional fusion, showed increased expression of the pmr operon in swarm cells compared to that in vegetative cells. In concurrence with the expression data, swarm cells exhibited greater tolerance to polymyxin. To compare the profiles of vegetative and swarm-cell resistance to other antibiotics, E-test strips representing a wide range of antibiotic classes were used. Swarm cells exhibited elevated resistance to a variety of antibiotics, including those that target the cell envelope, protein translation, DNA replication, and transcription. These observations, in addition to the dramatic morphological changes associated with the swarming phenotype, provide an intriguing model for examining global differences between the physiological states of vegetative and swarm cells of serovar Typhimurium.

Adaptation, Biological↗
PubMed2005

Antimetastatic effect of a lipophilic ascorbic acid derivative with antioxidation through inhibition of tumor invasion.

PURPOSE: Ascorbic acid (AA), the natural antioxidant, has been demonstrated to exert an antimetastatic action; however, AA is quite unstable in physiological condition. The aim of the present study is to investigate the stability, the antioxidation and the antimetastatic effects of three lipophilic AA derivatives in vitro as well as in vivo. METHODS: The 95D cells were treated with ascorbic acid-2-O-phosphate-6-O-laureate (AA2P6L), ascorbic acid-2-O-phosphate-6-O-myristate (AA2P6M) and ascorbic acid-2-O-phosphate-6-O-stearate (AA2P6S). AA derivatives' stability in medium under cell culture condition, in the presence and in the absence of 95D cells, was assessed by high-performance liquid chromatography assay. Cell viability and intracellular oxidative stress were measured by MTT assay and CDCFH assay, respectively. Wound healing assay and cell adhesion assay were used to investigate the antimetastatic activities against 95D cells in vitro, and the C57BL/6 mice model was used to evaluate the antimetastatic action in vivo. RESULTS: All the three AA derivatives exhibited excellent stability, significantly different from AA. Results of MTT assay showed that IC(50) values of the cytotoxicity of those AA derivatives, namely AA2P6L, AA2P6M and AA2P6S, were 38.46, 28 and 22.97 microg/ml, while the CDCFH assay indicated that EC(50) values of antioxidant effects on 95D cells were 31.12, 33.51 and 38.31 microg/ml, respectively. Through the ratio of IC(50) vs EC(50) for AA derivatives, AA2P6L was demonstrated to be the most effective AA derivative, which retained the antioxidant ability as well as low cytotoxicity. AA2P6L dose-dependently inhibited 95D cells' migration and adhesion, by 50% at the concentration of 20 and 57 microg/ml, respectively. In the animal experiment, intraperitoneal administration of 75 mg/kg AA2P6L decreased the number of metastatic nodules by 62% and elevated the survival rate of C57BL/6 mice about onefold compared to the control group. CONCLUSION: AA2P6L, a lipophilic AA derivative with antioxidation, is shown to be a potent antimetastatic agent through the inhibition of tumor invasion. These results support future investigations on the feasibility of cancer chemotherapy with AA2P6L.

Animals↗
PubMed2002

Advances in research and clinical practice in motor disorders of the sphincter of Oddi.

Perfusion manometry of the sphincter of Oddi (SO) using a pneumohydraulic capillary infusion system records phasic wave activity superimposed on basal pressure. A triple-lumen catheter allows the recording of propagation of the phasic waves. Microtransducer manometry is an alternative that permits prolonged recording of biliary pressure without the need for infusion. A cyclic change is recognized in SO motility in coordination with the migrating motor complex (MMC) of the duodenum during fasting. SO contractions occur at maximal frequency and amplitude during phase 3 of the duodenal MMC. Using two microtransducer catheters placed by duodenoscopy, a cyclic elevation of biliary pressure can be recorded in concert with phase 3. These findings indicate that human SO contractions impede bile flow. SO dysfunction causing biliary-type pain can be diagnosed by manometry. The pressure elevation during phase 3 may contribute to the development of pain in patients with biliary dyskinesia. Gastrectomy and proximal duodenal transection were proven to affect sphincter motility, as evidenced by the paradoxical response to cholecystokinin. Choledocholithiasis and hepatolithiasis are associated with low basal pressure, presumably due to repeated injury to the sphincter by passing stones. SO and biliary manometry leads to better understanding of biliary dynamics and the pathophysiology of biliary diseases.

Biliary Dyskinesia↗