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Peripheral Circulation (peripheral + circulation)
Selected AbstractsCD146+ T lymphocytes are increased in both the peripheral circulation and in the synovial effusions of patients with various musculoskeletal diseases and display pro-inflammatory gene profiles,,CYTOMETRY, Issue 2 2010Pradeep Kumar Dagur Abstract Twenty-eight synovial effusions (SE) were obtained from 24 patients, paired samples of peripheral blood (PB) from 10 of these patients, and PB from 36 healthy individuals for analysis of CD146 on T-lymphocytes by flow cytometry. CD146+ or CD146, T-lymphocytes were sorted from three SE to study gene expression profiles and selected genes revalidated using QPCR assays. We found more CD3+CD146+ and CD4+CD146+ T-lymphocytes in PB from patients compared with PB of healthy individuals (4.71% ± 2.48% vs. 2.53% ± 1.08%, P = 0.028) and (6.29% ± 2.74% vs. 2.41% ± 0.96%, P = 0.0017), respectively, whereas CD8+CD146+ T-lymphocytes were not significantly different (2.55% ± 1.65% vs. 3.18% ± 2.59%, P = 0.5008). SE displayed CD146 staining on 16.32% ± 6.06% of CD3+ cells. This expression was skewed toward CD4+ T-lymphocytes, with CD146 present on 24.06% ± 8.20% of the CD4+ T-lymphocytes compared with 6.19% ± 5.22% of the CD8+ T-lymphocytes. CD146 on CD3+, CD4+ and CD8+ T-lymphocytes in SE was significantly higher compared with PB in patients (P < 0.0001, P < 0.0001 and P = 0.0036, respectively). Gene expression profiles of sorted CD146+CD4+CD3+ vs. CD146,CD4+CD3+ T-lymphocytes (n = 2) and CD2+CD146+ vs. CD2+CD 146, (n = 1) from SE, displayed increased CD146, LAIR2, CXCL13, CD109, IL6ST, IL6R, TNFRsf18, and TNFRsf4 genes, whereas decreased CCR7, CCL5, and cytotoxicity-associated genes including granzymes b, h, and k, perforin were found with the CD146, T-lymphocytes. By QPCR higher mRNA expression of CXCL13, CD146 and CD109 was also noted in the CD146+ subset, compared with the CD146, subset, in PB of healthy individuals and in PB and SE from patients. Our study establishes increased CD146+ T-lymphocytes in diseases with joint effusions, and demonstrates pro-inflammatory gene profiles in these cells. Published 2009 Wiley-Liss, Inc. [source] Higher arterial stiffness, greater peripheral vascular resistance and lower blood flow in lower-leg arteries are associated with long-term hyperglycaemia in type 2 diabetic patients with normal ankle-brachial indexDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2009Eiji Suzuki Abstract Background Higher arterial stiffness and greater peripheral vascular resistance reduce blood flow in lower-leg arteries and contribute to the development of ischaemic limb in diabetic patients even without peripheral artery occlusive disease. The aim of this study was to clarify whether these vascular parameters are associated with long-term hyperglycaemia in diabetic patients. Methods We examined 45 type 2 diabetic patients and 38 age-matched nondiabetic subjects without peripheral artery occlusive disease assessed by ankle-brachial index consecutively admitted to our hospital, and followed them over a 3-year period (3.7 ± 0.7 years) with no vasodilative medication. Blood flow and resistive index, a measure of peripheral vascular resistance, at the popliteal artery were evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. Brachial-ankle pulse wave velocity was measured to assess arterial stiffness. Results At baseline, consistent with our previous report, diabetic patients showed higher brachial-ankle pulse wave velocity (p < 0.0001) and resistive index (p < 0.0001) and lower flow volume (p = 0.0044) than those of nondiabetic subjects. Stepwise multiple regression analysis revealed that duration of diabetes, mean HbA1c during the study, use of renin-angiotensin system inhibitors and change per year in resistive index were identified as significant independent variables predicting change per year in blood flow (r2 = 0.733, p < 0.0001) in diabetic patients. Mean HbA1c during the study was positively correlated with changes per year in brachial-ankle pulse wave velocity (p = 0.00007) and resistive index (p = 0.0014) and was negatively correlated with that in blood flow (p < 0.0001) in diabetic patients. Conclusions Long-term hyperglycaemia is a major cause of impaired peripheral circulation in lower-leg arteries in diabetic patients without peripheral artery occlusive disease. Copyright © 2009 John Wiley & Sons, Ltd. [source] Feasibility of conducting the micronucleus test in circulating erythrocytes from different mammalian species: An anatomical perspectiveENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2006Ion Udroiu Abstract The in vivo mammalian micronucleus test can be conducted easily on peripheral blood samples since the maturation of erythrocytes involves the loss of the major nucleus. In addition, mature erythrocytes are relatively long-lived, so that the test potentially can detect genotoxic damage caused by chronic exposures. However, some species have spleens that remove micronuclei from the peripheral circulation, making such measurements problematical. This report summarises haematological and mutagenesis studies dealing with this subject and provides an anatomical interpretation of the phenomenon. Anatomical features can be used to identify those species in which micronuclei are removed by the spleen. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source] BNP and N-terminal proBNP are both extracted in the normal kidneyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2006J. P. Goetze Abstract Background, Increased plasma concentrations of cardiac-derived B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (proBNP) are both associated with left ventricular dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We therefore examined the renal and peripheral extraction of N-terminal proBNP and BNP. Materials and methods, The study comprised 18 patients with essential arterial hypertension, 51 with cirrhosis, and 18 control patients without kidney or liver disease. All patients underwent a haemodynamic investigation with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N-terminal proBNP and BNP. Results, Neither the peripheral N-terminal proBNP (13, 11, 19 pmol L,1, NS) nor the BNP plasma concentrations (4, 12, 9 pmol L,1, NS) differed between the patient groups. In addition, similar renal extractions were observed in the groups. The renal extraction of N-terminal proBNP (0·16) was not different from that of BNP (0·16). In contrast, the N-terminal proBNP extraction in the lower extremity was markedly lower compared with BNP (0·00 vs. 0·125, P = 0·007). Conclusions, A comparable renal elimination of N-terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may explain the higher N-terminal proBNP compared with BNP concentrations in normal plasma. [source] Interleukin-8 fails to induce human immunodeficiency virus-1 expression in chronically infected promonocytic U1 cells but differentially modulates induction by proinflammatory cytokinesIMMUNOLOGY, Issue 1 2000C. T. Tiemessen Summary This study addresses the role of interleukin (IL)-8, a CXC-chemokine, the level of which is reported to be raised in the peripheral circulation of human immunodeficiency virus-1 (HIV-1)-infected individuals, during the induction of HIV-1 expression from latency and during cytokine-mediated HIV-1 up-regulation. IL-8 at the higher concentrations tested (, 100 ng/ml) was unable to induce HIV-1 expression in the chronically infected promonocytic U1 cell line, as measured by p24 antigen enzyme-linked immunosorbent assay (ELISA), whereas at lower concentrations of 1 and 10 ng/ml, constitutive HIV-1 expression was only marginally reduced. HIV-1 replication in acutely infected U937 cells was also significantly reduced by IL-8. The potent up-regulation of HIV-1 expression in U1 cells by tumour necrosis factor-, (TNF-,) remained unaffected by the addition of IL-8. HIV-1 induction by IL-1,, IL-6 and TNF-,, cytokines grouped here as intermediate HIV-1 inducers, was suppressed by IL-8 at concentrations of 1 and 10 ng/ml. However, IL-8 at 100 ng/ml did not significantly alter the effect of IL-1,, synergized with IL-6 in enhancing, and marginally suppressed TNF-,-induced HIV-1 expression. IL-8 suppressed granulocyte,macrophage colony-stimulating factor (GM-CSF) and enhanced interferon-, (IFN-,)-induced HIV-1 expression in a dose-dependent manner. Pretreatment of U1 cells with IL-8 did not alter the IL-8-mediated effects on cytokine-induced HIV-1 expression, suggesting that this chemokine exerts its effect at the time of HIV-1 induction or at a postinduction stage. Furthermore, IL-8 was itself induced by cytokines that up-regulate HIV-1 expression in U1 cells and the levels produced correlated directly with the levels of p24 antigen produced, suggesting common pathways for cytokine induction of both HIV-1 and IL-8. These results show that IL-8, typically a non-inducer, can differentially modulate HIV-1 expression in U1 cells and that this is dependent on the inducing cytokine and on the concentration of IL-8. [source] Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged miceAGING CELL, Issue 2 2010Robert S. Weinstein Summary Aging or glucocorticoid excess decrease bone strength more than bone mass in humans and mice, but an explanation for this mismatch remains elusive. We report that aging in C57BL/6 mice was associated with an increase in adrenal production of glucocorticoids as well as bone expression of 11,-hydroxysteroid dehydrogenase (11,-HSD) type 1, the enzyme that activates glucocorticoids. Aging also decreased the volume of the bone vasculature and solute transport from the peripheral circulation to the lacunar-canalicular system. The same changes were reproduced by pharmacologic hyperglucocorticoidism. Furthermore, mice in which osteoblasts and osteocytes were shielded from glucocorticoids via cell-specific transgenic expression of 11,-HSD type 2, the enzyme that inactivates glucocorticoids, were protected from the adverse effects of aging on osteoblast and osteocyte apoptosis, bone formation rate and microarchitecture, crystallinity, vasculature volume, interstitial fluid, and strength. In addition, glucocorticoids suppressed angiogenesis in fetal metatarsals and hypoxia inducible factor-1, transcription and vascular endothelial growth factor production in osteoblasts and osteocytes. These results, together with the evidence that dehydration of bone decreases strength, reveal that endogenous glucocorticoids increase skeletal fragility in old age as a result of cell autonomous effects on osteoblasts and osteocytes leading to interconnected decrements in bone angiogenesis, vasculature volume, and osteocyte-lacunar-canalicular fluid. [source] Low expression of XIAP-associated factor 1 in human colorectal cancersJOURNAL OF DIGESTIVE DISEASES, Issue 1 2005Tian Le MA OBJECTIVE: Eight cellular homologs of the inhibitors-of-apoptosis proteins (IAP) have been identified in humans and of them, the X-linked IAP (XIAP) is the most potent. XIAP-associated factor 1 (XAF1) is a newly discovered XIAP-binding protein that negatively regulates the caspase-inhibiting activity of XIAP. It is either not expressed or present at extremely low levels in many cancer cell lines. The aims of the present study were: (i) to investigate the expression of XAF1 in human colorectal cancers (CRC) both in vitro and in vivo, and (ii) to evaluate the possibility of XAF1 as a new tumor marker. METHODS: The expression of XAF1 in four human colon cancer cell lines (Colo205, Colo320, SW1116, LoVo) and in samples from 70 patients with CRC was analyzed by reverse transcriptase-polymerase chain reaction. XAF1 concentrations were also detected in the peripheral circulation of the 70 patients, as well as three traditional circulating cancer-associated antigens. RESULTS: A low concentration of XAF1 mRNA was detectable in the three colon cancer cell lines other than Colo205, which showed the strongest expression of XAF1. The expression of XAF1 in tissue was relatively lower in primary CRC compared with a relatively higher level in benign colorectal tumors (P < 0.01). Although the XAF1 expression in circulation of those with CRC was also lower than in those with benign tumors, there was no statistical significance (P > 0.05). CONCLUSIONS: The present results suggest that the low expression of XAF1 in tumor tissue coincides with a similar level in the peripheral circulation, which contributes at least part to the malignant behavior of CRC. Integrating the XAF1 relative expression value with the other three traditional tumor biomarkers created a four-parameter assay that significantly improved the rate of diagnosis of CRC. [source] Haematology and leucocyte morphology of wild caught Thunnus maccoyiiJOURNAL OF FISH BIOLOGY, Issue 6 2005K. M. Rough The haematology of wild southern bluefin tuna Thunnus maccoyii was described using blood samples collected from fish immediately after they were caught. Cytology and cytochemistry revealed that the blood in peripheral circulation is comprised of erythrocytes, reticulocytes, ghost cells, lymphocytes, thrombocytes, eosinophilic granulocytes, neutrophilic granulocytes and monocytes. Reference ranges established were 41·09,55·50% for haematocrit, 0·62,3·00% for leucocrit, 13·25,17·92 g dl,1 for haemoglobin and 2·1,2·9 million erythrocytes ,l,1 for erythrocyte count. Differential cell counts showed 94·58 ± 2·15% erythrocytes, 3·99 ± 1·44% leucocytes and 1·43 ± 1·03% thrombocytes (mean ± s.d.). Normal ranges for differential leucocyte counts were 0·00,5·45% for neutrophils, 0·69,12·06% for eosinophils, 0·00,5·03% for monocytes, 46·97,74·32% for lymphocytes and 14·47,43·92% for thrombocytes. Erythrocyte indices, leucocyte types and cytochemistry were comparable to other species of scombrids. Packed cell volume was sensitive to the physiological state of the fish and to sample handling technique. [source] Peripheral Atherectomy: A Critical ReviewJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 6 2007TROY A. BUNTING M.D. Atherectomy is experiencing increased interest from endovascular specialists as a therapeutic treatment in the peripheral arteries. Long studied in the coronary vasculature, atherectomy has several theoretical advantages that make it uniquely suited for the peripheral circulation. In particular, infra-inguinal peripheral arterial disease experiences physiologic stresses and forces that have made traditional percutaneous coronary treatments such as angioplasty and stenting not as successful. Restenosis has been a major problem for angioplasty and stenting alone. The SilverHawk atherectomy device has favorable short-term data but important longer-term data are limited and need further study. Laser atherectomy also has favorable applications in niche patients but the number of studies is limited. Unfortunately, athero-ablative technologies for peripheral arterial disease require more definitive objective data regarding 12-month and longer-term outcomes in order to obtain widespread scientific acceptance. [source] The behaviour of doramectin in the gastrointestinal tract, its secretion in bile and pharmacokinetic disposition in the peripheral circulation after oral and intravenous administration to sheepJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2000D. R. HENNESSY Sheep were ,compartmentalized' by surgically implanting cannulae in the rumen, abomasum and terminal ileum with a re-entrant cannula inserted between the cystic duct and the duodenum to monitor bile secretion. Doramectin, containing a trace of [3H]-doramectin, was administered both intravenously (i.v.) and intraruminally (i.r.) at a dosage of 150 ,g/kg. The pharmacokinetic behaviour of [3H]-labelled products was determined in these pools, and also in peripheral plasma, urine and faeces. Parent doramectin was also determined in plasma, abomasal digesta fluid and bile. Following i.r. administration, [3H] compounds were almost entirely associated with particulate digesta. A 14.5-h half-life in the rumen prolonged the presence of [3H] in the abomasum. Doramectin appeared to be degraded in abomasal digesta because only 24% of abomasal [3H] was attributed to the parent drug. Absorption of doramectin resulted in a systemic availability of 35%, of which 1.6 and 23.6% of the dose was contained in urine and biliary secretions, respectively. Following i.v. administration, almost negligible quantities of [3H] were secreted into the rumen or abomasum and only 2.7% of the dose was excreted in urine, whereas 132% was secreted in bile. This indicated that approximately one-third of biliary metabolites were enterohepatically recycled with biliary metabolites, elevating the proportion of [3H] in fluid digesta in the small intestine. Passage of the IR-administered drug through the gastrointestinal tract (GIT) resulted in virtually complete faecal excretion of [3H] within 5 days, whereas the continued secretion of i.v.-administered [3H] in bile prolonged the presence of [3H] in the GIT, with faecal clearance not being complete for at least 10 days. This multi-compartmental study has provided more information on the behaviour of doramectin than can be obtained from examining drug disposition in the peripheral circulation alone. With this knowledge, it is anticipated that opportunities for improving drug performance will be identified. [source] Marvels, Mysteries, and Misconceptions of Vascular Compensation to Peripheral Artery OcclusionMICROCIRCULATION, Issue 1 2010MATTHEW A. ZIEGLER Microcirculation (2010) 17, 3,20. doi: 10.1111/j.1549-8719.2010.00008.x Abstract Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation. [source] ENDOTHELIAL FUNCTION OF CONDUIT AND RESISTANCE ARTERIES IN NEPHROTIC RANGE PROTEINURIANEPHROLOGY, Issue 3 2000G. Dogra OBJECTIVE: To test the hypothesis that endothelial dysfunction occurs in nephrotic range proteinuria primarily as a consequence of dyslipidaemia. METHODS: Brachial artery and forearm microcirculatory endothelial function was compared among patients with nephrotic range proteinuria (NRP, n = 14 ), primary hyperlipidaemia (HL, n = 15) and normal controls (NC, n = 16). Endothelial function was studied by measuring post-ischaemic flow-mediated dilatation (FMD) of the brachial artery using high resolution ultrasonography. Endothelium-independent, glyceryl trinitrate (GTN) mediated brachial artery vasodilatation was also measured. Basal and post-ischaemic blood flow of the forearm microcirculation was measured using venous-occlusion strain gauge plethysmography. RESULTS: Serum creatinine was similar among groups. The proteinuric group had a mean albumin of 27.6g/L(1.8) and 24-hour urinary protein excretion of 6.3g(1.3). Plasma lipids and lipoproteins were not statistically different between the NRP and HL groups. Brachial artery FMD was significantly lower in the NRP and HL groups compared with the controls (NRP 4.7%(1.3)*, HL 4.9%(0.7)* and NC 8.3%(0.6), *p = 0.012 vs. NC); GTN mediated dilatation and basal and post-ischaemic forearm blood flow were not statistically different among the three groups. CONCLUSION: Patients with nephrotic range proteinuria have endothelial dysfunction of conduit arteries in the peripheral circulation, similar to that observed in patients with primary hyperlipidaemia. This suggests dyslipoproteinaemia is the principal cause of endothelial dysfunction of conduit arteries in nephrotic range proteinuria. Confirmation of this should be sought with an intervention trial of lipid-regulating therapy. [source] Vasculogenesis of the embryonic heart: Origin of blood island-like structuresTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2006Anna Ratajska Abstract The earliest vascular structures (blood island-like) in the embryonic heart are clusters of angioblasts and nucleated red blood cells (NRBCs), which differentiate into endothelial cells and erythrocytes, respectively. Our purpose was to define the area and chronology of NRBC appearance in the mouse embryonic heart at the stages before a patency between coronary vessels and peripheral circulation is established (10.5,13.5 dpc). Before and at the onset of vascularization, NBCs were not present within the proepicardium; however, Ter/119+ differentiating erythroblasts and single scattered CD45+ were found in the heart beginning from 10.5 dpc. The Ter/119+ cells were in close apposition to angioblasts (PECAM1+) and were recognized as components of blood island-like structures or vascular vesicles in transmission electron microscope and were located mostly in the subepicardium. Some of the NRBCs were not accompanied by angioblasts and located close to the endocardial endothelium or at the border of the endocardial endothelium or in the subepicardium. These erythroblasts were beginning to assemble with angioblasts. CD34+ NBCs as well as progenitor cells of erythroid lineage were not detected in the heart at these stages of development. The state of differentiation of NRBCs of blood islands was similar/the same as the morphology of circulating blood cells at the respective stages of embryo development. The presence of mature NRBCs in the subendocardial area and lack of progenitor cells of erythroid lineage within the heart indicate that erythroid commitment occurs outside the heart. We suggest that NRBCs enter the heart from the blood stream at 10.5,12 dpc independently from angioblasts. © 2006 Wiley-Liss, Inc. [source] Correction of mucopolysaccharidosis type IIIA somatic and central nervous system pathology by lentiviral-mediated gene transferTHE JOURNAL OF GENE MEDICINE, Issue 9 2010Chantelle McIntyre Abstract Background The hallmark of lysosomal storage disorders (LSDs) is microscopically demonstrable lysosomal distension. In mucopolysaccharidosis type IIIA (MPS IIIA), this occurs as a result of an inherited deficiency of the lysosomal hydrolase sulphamidase. Consequently, heparan sulphate, a highly sulphated glycosaminoglycan, accumulates primarily within the cells of the reticulo-endothelial and monocyte-macrophage systems and, most importantly, neurones. Children affected by MPS IIIA experience a severe, progressive neuropathology that ultimately leads to death at around 15 years of age. Methods MPS IIIA pathology was addressed in a mouse model using two separate methods of therapeutic gene delivery. A lentiviral vector expressing murine sulphamidase was delivered to 6-week-old MPS IIIA affected mice either by intravenous injection, or by intraventricular infusion. Therapeutic outcomes were assessed 7 months after gene transfer. Results After intravenous gene delivery, liver sulphamidase was restored to approximately 30% of wild-type levels. The resultant widespread delivery of enzyme secreted from transduced cells to somatic tissues via the peripheral circulation corrected most somatic pathology. However, unlike an earlier study, central nervous system (CNS) pathology remained unchanged. Conversely, intraventricular gene delivery resulted in widespread sulphamidase gene delivery in (and reduced lysosomal storage throughout) the brain. Improvements in behaviour were observed in these mice, and interestingly, pathological urinary retention was prevented. Conclusions The CNS remains the last major barrier to effective therapy for children affected by LSDs. The blood,brain barrier (BBB) limits the uptake of lysosomal enzymes from the peripheral circulation into the CNS, making direct gene delivery to the brain a reasonable, albeit more challenging, therapeutic option. Future work will further assess the relative advantages of directly targeting the brain with somatic gene delivery with sulphamidase modified to increase the efficiency of transport across the BBB. Copyright © 2010 John Wiley & Sons, Ltd. [source] ORIGINAL ARTICLE: Preterm Labor: CD55 in Maternal Blood LeukocytesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009Stella Nowicki Problem, Intrauterine inflammation is a frequent and significant factor associated with the pathogenesis of preterm labor/birth (PTL/PTB). However, it remains unclear whether the intrauterine inflammatory responses activate the maternal peripheral circulation. We explored the association between PTL/PTB and the ,activation' of the peripheral circulatory system by determining whether CD55 mRNA expression within peripheral WBCs differed between PTL and control patients not in labor. Method of Study, RNA was purified from white blood cells collected from pregnant women with preterm labor (n = 45), and from pregnant (n = 30) control women. CD55 gene expression was evaluated by quantitative PCR. Results, The mean CD55 mRNA level within the PTL group (0.77 ± 0.03) was 1.48-fold higher than that observed (0.52 ± 0.02) within the control group (P < 0.0001); 71% of PTL patients and only 6.7% of control subjects expressed elevated CD55 mRNA. The receiver operating characteristics (with 95% CI) of CD55 as a marker for PTL were as follows: Sensitivity, 69% (53,82%); Specificity, 93% (78,99%); Positive Predictive Value, 94% (80,99%); and Negative Predictive Value, 67% (51,80%). In the patient population that delivered prematurely (before 37 weeks), 81% expressed elevated CD55 mRNA levels with a mean of 0.78 ± 0.03 and 95% CI of 0.71,0.84. The receiver operating characteristics were as follows: Sensitivity, 73% (54,88%); Specificity, 86% (71,95%); Positive Predictive Value, 81.5% (62,94%); and Negative Predictive Value, 80% (64,91%). Conclusion, Here we report for the first time that CD55 mRNA expression was elevated in the peripheral WBCs of subjects with preterm labor compared with control gestationally-matched pregnant woman and that elevated leukocyte CD55 may be a useful predictor of subsequent PTB. [source] 1141420984 Placental exosome suppression of T cell activation and differential target of T cell subsetsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006DD Taylor Problem:, One immunoregulatory pathway that has received little attention is placental exosome release. In normal pregnancy, as factors linked with early immunomodulation decline, placental exosomes become key in modulating T-cell activation, maintaining the absence of effector T-cells by enhancing T cell apoptosis and loss of CD3-z. Method of Study:, Placental exosomes were isolated from the maternal peripheral circulation by a chromatographic/MACS procedure developed to specifically purify exosomes of placental origin. Exosomal FasL was identified by immunoelectron microscopy (IEM) and quantified by ELISA. Exosomal suppression of T cell signaling molecules and induction of apoptosis was determined by flow cytometry and DNA fragmentation, respectively. The role of FasL in these events was defined by use of FasL blocking antibody. The differential effect of exosomes on CD3-z on T subsets was analyzed by western immunoblot (WB). Results:, When T cells were co-incubated with placental exosomes, CD3-z was down-regulated, with placental exosomes treated cells expressing 18,900 ± 7,000 MESF units of zeta, while control fraction-treated cells expressed 49,000 ± 4,800 MESF units of zeta (P < 0.001). This down-regulation of CD3-z was partially reversed by pre-incubating T cells with ZB4 antibody, suggesting a role for FasL. IEM revealed FasL-antibody complexes located on the exterior of placental exosomes; however, only 20/27 preparations were FasL+. When placental exosomes were added to T cells, the level of CD3-z expression on CD8+ cells was 7.1%, (8.7% vs 59.7%) inhibited 1.43-fold more than in CD4+ cells (85.5 P < 0.01). On CD4+CD25+ cells, CD3-z was not significantly inhibited. (P < 0.05). Conclusions:, While all term placental exosome preparations tested induced apoptosis, exosomes obtained from 7/27 patients were negative for FasL but were able to induce DNA degradation. These results indicate that, while exosomal FasL is apoptogenic, additional exosome components are capable of inducing apoptosis, but these factors exhibit differential effect on T subsets. [source] Analysis of the CD4 Protein on Human Vaginal T LymphocytesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2001PAUL L. FIDEL PROBLEM: Although T lymphocytes at the human vaginal mucosa have been partially characterized, there remains a paucity of information regarding cell-mediated immune mechanisms at this mucosal site. In mice and humans, there are several phenotypic distinctions between vaginal T lymphocytes and those in the peripheral circulation. Recently, we observed as well that the N-terminus of the CD4 protein on murine vaginal T lymphocytes is atypically expressed compared to its systemic counterpart, and that the atypical expression extends to the mRNA level. METHOD OF STUDY: The purpose of this study was to evaluate the CD4 protein on human vaginal T lymphocytes by flow cytometry and RT-PCR. RESULTS: Results showed that, in contrast to mice, the CD4 protein on human vaginal and peripheral blood T lymphocytes are similar at both the molecular and protein levels. CONCLUSIONS: These results indicate that based on several differences between human and mouse vaginal T cells, caution is urged when using mice as a model to study human vaginal immunity. [source] Development of the Pulsation Device for Rotary Blood Pumps,ARTIFICIAL ORGANS, Issue 11 2005Tomoyuki Yambe Abstract A rotary blood pump (RP) is desirable as a small ventricular assist device (VAD). However, an RP is nonpulsatile. We tried to develop a device that attaches a pulse to the RP. We also tried to develop a pulse-generating equipment that was not air-pressure driven. The ball screw motor was considered a candidate. The application of a small-sized shape memory alloy was also attempted. An electrohydraulic system was adopted, and actuator power was connected to the diaphragm. The diaphragm was placed on the outer side of the ventricle. Most RPs that have been developed all over the world drain blood from the ventricle. The wave of a pulse should be generated if a pulse is added by the drawn part. The output assistance from the outer side of the ventricle was attempted in animal experiments, and the device operated effectively. This device can be used during implantable operation of RP. This may serve as an effective device in patients experiencing problems in peripheral circulation and in the function of internal organs. [source] Study of peripheral circulation in non-pregnant, pregnant and pre-eclamptic women using applied potential tomographyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2004Badreldeen AHMED Abstract Background:, Profound changes are known to occur in the cardiovascular system during pregnancy, involving an increase in cardiac output and a fall in peripheral resistance. In some women these adaptations may be inappropriate and this may result in pregnancy-induced hypertension and pre-eclampsia. Aims and methods:, The aims of the study were to evaluate the relatively new, non-invasive technique of applied potential tomography (APT) in measurements of peripheral blood flow, to study peripheral blood flow in a sample of non-pregnant, pregnant and pre-eclamptic women, and to investigate whether the adaptive changes in the peripheral circulation are different in pre-eclampsia compared with normal pregnancy. Applied potential tomography was used to assess peripheral vascular reactivity, by monitoring fluid distribution in calf muscles during postural change Results:, The APT technique was able to detect peripheral vasoconstriction in response to an increase in intramural pressure brought about by passive lowering of the leg (peripheral mechanisms). The peripheral vasoconstriction response was found to be more prominent in woman with pre-eclampsia. Conclusions:, The presence of a local reflex in the lower limb had been postulated and the effect of this reflex on the peripheral circulation could be detected using APT, regardless of how it was initiated. In normal pregnant women this reflex was diminished when compared to non-pregnant women, which might contribute to the reduction in peripheral vascular resistance seen in normal pregnancy. This reflex was defective in pre-eclampsia and this lack of adaptation may be a local reflex contributing to the raised peripheral resistance, which in turn may be a factor in high blood pressure in pre-eclampsia. [source] Non-invasive assessment of endothelial function , relation between vasodilatory responses in skin microcirculation and brachial arteryCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 6 2004Jimmy Hansell Summary Objective:, To compare different non-invasive methods for determination of human endothelial function in peripheral circulation. Design:, Observational, cross-sectional study in 39 healthy subjects (21 females, age 17,56 years). Setting:, Vascular research laboratory at university hospital. Methods:, Laser Doppler (LD) flowmetry was used to compare skin microvascular perfusion changes during postocclusive reactive hyperaemia with those induced by iontophoretic administration of acetylcholine (ACh), an endothelial-dependent vasodilator. LD measurements were compared with ultrasonographic measurements of postocclusive flow-mediated dilatation (FMD) in the brachial artery (n = 21). Results:, Local ACh induced a larger and more sustained skin perfusion increase than reactive hyperaemia after 4 min of regional arterial occlusion (P<0·001). A significant correlation was found between the magnitude of ACh-induced vasodilatation and peak reactive hyperaemia, both in absolute (r = 0·62, P<0·001) and relative terms (r = 0·58, P<0·001). A correlation was also found between brachial artery FMD and the magnitude of ACh-induced skin perfusion increase (r = 0·43, P<0·05) but not between FMD and reactive hyperaemia. Conclusion:, Endothelial function, an early marker of cardiovascular risk, can be non-invasively assessed and graded by LD and FMD-measurements and despite inherent differences, both methods do correlate. [source] Regular or "Super-Aspirins"?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2001A Review of Thienopyridines or Aspirin to Prevent Stroke PURPOSE: To review the evidence for the effectiveness and safety of the thienopyridines (ticlopidine and clopidogrel) compared with aspirin for the prevention of vascular events among patients at high risk of vascular disease. BACKGROUND: Atherosclerosis and resultant cardiovascular disease are important causes of morbidity and mortality in older people. In particular, atherosclerosis of the cerebral arteries can lead to transient ischemic attacks (TIAs) and stroke. Stroke ranks as the third-leading cause of death in the United States and in 1997 was responsible for over 150,000 fatalities.1 In addition to the mortality associated with this disease, stroke is also a leading source of long-term disability in survivors. Nearly 4.5 million stroke survivors are alive today,1 highlighting the fact that primary, but also secondary, prevention are extremely important for minimizing the complications of this illness. DATA SOURCES: Specialized trial registers of the Cochrane Stroke Group and the Antithrombotic Trialist's Collaboration, MEDLINE, and Embase were searched. Additional unpublished information and data were sought from Sanofi, the pharmaceutical company that developed and manufactures ticlopidine and clopidogrel, as well as the principal investigators of the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial,7 the largest of the trials identified. STUDY SELECTION CRITERIA: All unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin among patients at high risk of vascular disease (those with symptoms of ischemia of the cerebral, coronary, or peripheral circulations) who were followed for at least 1 month for the recurrence of vascular events were included. DATA EXTRACTION: Data were extracted from four completed randomized trials completed in the past 20 years, which included 22,656 patients.7,10 Two authors independently extracted the data from these trials for the following information: the types of patients enrolled; the entry and exclusion criteria; the randomization method; the number of patients originally allocated to the treatment and control groups; the method and duration of follow-up; the number of patients in each group lost to follow-up; information on compliance with the treatment allocated; the definitions of outcome events; the number of outcome events in each treatment group; and any method used for blinding patients, treating clinicians, and outcome assessors to treatment allocation. MAIN RESULTS: Four completed trials involving a total of 22,656 patients were identified. Aspirin was compared with ticlopidine in three trials (3,471 patients)8,10 and with clopidogrel in one trial (19,185 patients).7 A recent TIA or ischemic stroke was the qualifying event in 9,840 patients, a recent myocardial infarction in 6,302 patients, and symptomatic peripheral arterial disease in 6,514 patients. The average age of the patients was approximately 63, with approximately two-thirds of the patients being male and white. The duration of follow-up ranged from 12 to 40 months. CONCLUSIONS: This systematic review demonstrates that, compared with aspirin, thienopyridines are only modestly more effective in preventing serious vascular events in high-risk patients. For patients who are intolerant of, or allergic to aspirin, the available safety and efficacy data suggest that clopidogrel is an appropriate, but more-expensive, alternative antiplatelet drug. It appears safer than ticlopidine and as safe as aspirin but it should not replace aspirin as the first-choice antiplatelet agent for all patients. Further studies are necessary to determine which, if any, particular types of patients would benefit most and least from clopidogrel instead of aspirin. [source] | |||||||||||||||||||||||||