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Biomedical subjects

V Marin

Publications and source records attributed to V Marin.

At least 19 recordsLinked to original sources
PubMed2006

T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet optimal functional requirements for adoptive T-cell therapy.

Adoptive T-cell immunotherapy may provide complementary therapy for childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In this study, we have analyzed the functional characteristics of anti-BCP-ALL effector T cells generated by co-culturing T lymphocytes and dendritic cells (DC) from allogeneic human stem cell transplantation (HSCT) donors. After 21-day co-culture with DC pulsed with CD40L+ apoptotic BCP-ALL blasts, T cells presented with both effector and central memory phenotype, and showed high and specific cytotoxic activity against leukemic cells (average lysis = 77%), mostly mediated by CD8+ T cells. Noticeably, growth of CD4 T cells was maintained (45% of total cells), which actively produced Th1 cytokines (IFN-gamma, TNF-alpha, IL-2), but not IL-4, IL-5 and IL-10. Anti-BCP-ALL T cells expressed CD49d and CXCR4 (implicated in the recruitment to bone marrow), and CD62L and CCR7 (involved in the migration to lymphoid organs). In accordance with this profile, T cells significantly migrated in response to the chemokines CXCL12 and CCL19. In conclusion, stimulation of T cells with CD40L+BCP-ALL cells-loaded DC not only elicited the generation of potent and specific anti-leukemic cytotoxic effectors, but also the differentiation of specific and functional Th-1 CD4 lymphocytes. These effectors are fully equipped to reach leukemia-infiltrated tissues and have characteristics to support and orchestrate the anti-tumor immune-response.

Adoptive Transfer↗
PubMed2005

Kt/V and nPNA in pediatric peritoneal dialysis: a clinical or a mathematical association?

The relationship between dialysis dose and nutrition is a field of particular interest in chronic pediatric dialysis (PD), and a positive correlation between ureaKt/V and nPNA has been published, suggesting a better nutritional status is associated with higher dialysis doses. However, this relationship has also been criticized as being the result of a mathematical coupling resulting from the same variables. The objective of the study was to establish the relationship between dialysis dose (Kt/V) and nutritional variables: daily protein intake (DPI), protein catabolic rate (PCR), protein equivalent of total nitrogen appearance (PNA) and nitrogen balance (NB) in dialyzed children. A cohort, prospective, observational study was carried out, for which 223 biochemical measurements were performed in 20 patients, ages 1 month to 14.3 years old (13 males), under PD for a 12-month period of follow-up. Monthly residual and total ureaKt/V, DPI, PCR, nPNA and NB were calculated, and the correlation between Kt/V and the nutritional parameters was evaluated. The Borah equation was used to calculate the nPNA. The data are reported as the mean plus or minus the standard error. All statistical comparisons were done with a paired t test, and two-way ANOVA for repeated measures was used to calculate correlations. A P <0.05 was considered significant. Mean total and residual Kt/V was 3.4+/-1.3 and 1.69+/-1.27, respectively; nPNA and PCR were 1.38+/-0.44 and 1.39+/-0.43 g/kg/day, daily protein intake (DPI) was 3.25+/-1.27 g/kg/day, and NB showed a value of 1.86+/-1.25 g/kg/day. A significant positive correlation was found between Kt/V and DPI, PCR, DPC and nPNA (all values P <0.0001), but no correlation was found between total and residual Kt/V vs. nitrogen balance ( P:ns). Total Kt/V showed a significant positive correlation with nPNA, but it did not show any correlation with nitrogen balance, suggesting that the relationship with nPNA is the result of a mathematical association calculated from the same variables.

Adolescent↗
PubMed2004

Effect of LNA modifications on small molecule binding to nucleic acids.

Locked nucleic acid (LNA) is a conformationally constrained DNA analogue that exhibits exceptionally high affinity for complementary DNA and RNA strands. The deoxyribose sugar is modified by a 2'-O, 4'-C oxymethylene bridge, which projects into the minor groove. In addition to changing the distribution of functional groups in the groove and the overall helical geometry relative to unmodified DNA, the bridge likely alters the hydration of the groove. Each of these factors will impact the ability of small molecules, proteins and other nucleic acids to recognize LNA-containing hybrids. This report describes the ability of several DNA-intercalating ligands and one minor groove binder to recognize LNA-DNA and LNA-RNA hybrid duplexes. Using UV-vis, fluorescence and circular dichroism spectroscopies, we find that the minor groove binder as well as the intercalators exhibit significantly lower affinity for LNA-containing duplexes. The lone exception is the alkaloid ellipticine, which intercalates into LNA-DNA and LNA-RNA duplexes with affinities comparable to unmodified DNA-DNA and RNA-DNA duplexes.

Bisbenzimidazole↗
PubMed2002

Increased soluble p55 and p75 tumour necrosis factor-alpha receptors in patients with hepatitis C-associated mixed cryoglobulinaemia.

To investigate whether tumour necrosis factor alpha (TNFalpha) plays a role in the pathogenesis of hepatitis C virus-associated mixed cryoglobulinaemia (HCV-MC), we measured soluble TNFalpha and its soluble p55 (sTNFR1) and p75 (sTNFR2) receptors in the serum of patients with HCV-MC. TNFalpha, sTNFR1 and sTNFR2 were measured in the serum of 32 patients with HCV-MC, 18 patients with hepatitis C without MC (HCV) and 18 healthy volunteers, using specific immunoassays. Correlations between clinical and biological parameters and the concentrations of TNFalpha and sTNFRs were established by studying detailed clinical records of the 32 HCV-MC patients. Although higher, TNFalpha levels were not significantly different in HCV-MC patients compared with healthy or HCV controls. sTNFR1 and sTNFR2, however, were significantly higher in HCV-MC compared with controls or with HCV patients, and higher concentrations of sTNFR1 and sTNFR2 were observed in patients with severe visceral vasculitis, compared with patients with limited purpura. sTNFR1 concentrations positively correlated with fibrinogen levels but TNFalpha, sTNFR1 and sTNFR2 did not correlate with other biological parameters such as rheumatoid factor concentrations, CH50 or C4 values. These data suggest a role for TNFalpha in the pathogenesis of the immune complex-mediated vasculitis associated with HCV-MC.

Aged↗
PubMed2001

The IL-6-soluble IL-6Ralpha autocrine loop of endothelial activation as an intermediate between acute and chronic inflammation: an experimental model involving thrombin.

Thrombin is a procoagulant and proinflammatory molecule in vivo. In vitro, thrombin has been shown to induce endothelial activation, notably IL-8 secretion and adhesion molecule expression. In this study, we showed that thrombin may induce a new cascade leading from acute to chronic inflammation. Thrombin was able to induce the production of both IL-6 and monocyte chemotactic protein-1 (MCP-1) by HUVEC independently of IL-1alphabeta and TNF-alpha. Addition of physiological concentrations of exogenous soluble IL-6Ralpha (sIL-6Ralpha) to thrombin-activated HUVEC was sufficient to increase the amounts of MCP-1 produced, but not those of IL-8. These effects could be blocked by anti-IL-6 or anti-sIL-6Ralpha blocking mAb, demonstrating the existence of an autocrine loop of MCP-1 secretion, involving the IL-6/IL-6Ralpha/gp130 complex on HUVEC. In addition, we identified IL-8-activated neutrophils as a potential source of sIL-6Ralpha because IL-8 induced IL-6Ralpha shedding from the neutrophil membranes and increased in parallel sIL-6Ralpha concentrations in neutrophil supernatants. Furthermore, addition of neutrophils to thrombin-activated HUVEC significantly increased MCP-1 secretion, which could be decreased by blocking IL-6. Thus, thrombin-activated endothelium may induce a cascade of events characterized by IL-8 secretion, neutrophil local infiltration, and the release of IL-6Ralpha from neutrophil membranes. sIL-6Ralpha may then complex with IL-6 and increase the amount of MCP-1 produced by thrombin-activated endothelium, favoring monocyte infiltration, and the transformation of acute into chronic inflammation.

Acute Disease↗
PubMed2001

Endothelial cell culture: protocol to obtain and cultivate human umbilical endothelial cells.

Endothelial cells play a key role in prominent immunological and pathological processes such as leukocyte trafficking, inflammation, atheroma or cancer cell metastasis. Umbilical veins are probably the most widely used source for human endothelial cells, since they are more easily available than many other vessels, they are free from any pathological process and they are physiologically more relevant than many established cell lines. Here, we describe a standard protocol for preparation, maintenance and quality control of these cells.

Cell Culture Techniques↗
PubMed2001

The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment.

Thrombin, the terminal serine protease in the coagulation cascade, is a proinflammatory molecule in vivo and induces endothelial activation in vitro. The cellular signaling mechanisms involved in this function are unknown. The role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in thrombin-induced chemokine production was studied. Phosphorylation of both p38 MAPK and its substrate, ATF-2, was observed in human umbilical vein endothelial cells (HUVECs) stimulated with thrombin, with a maximum after 5 minutes of stimulation. Using the selective p38 MAPK inhibitor SB203580, there was a significant decrease in thrombin-induced interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) protein production and messenger RNA steady-state levels. In addition, SB203580 decreased IL-8 and MCP-1 production induced by the thrombin receptor-1 agonist peptide (TRAP), suggesting functional links between the thrombin G protein-coupled receptor and the p38 MAPK pathway. Furthermore, endothelial activation in the presence of SB203580 decreased the chemotactic activity of thrombin-stimulated HUVEC supernatant on neutrophils and monocytic cells. In contrast, the p42/p44 MAPK pathway did not appear to be involved in thrombin- or TRAP-induced endothelial chemokine production, because there was no reduction in the presence of the p42/p44-specific inhibitor PD98059. These results demonstrate that the p38 rather than p42/44 MAPK signaling pathway plays an important role in thrombin-induced endothelial proinflammatory activation and suggest that inhibition of p38 MAPK may be an interesting target for anti-inflammatory strategies in vascular diseases combining thrombosis and inflammation. (Blood. 2001;98:667-673)

Cells, Cultured↗
PubMed2001

Venom immunotherapy induces monocyte activation.

BACKGROUND: Venom immunotherapy (VIT) is an efficient treatment of hymenoptera venom allergy. The mechanism of VIT is based on the induction of tolerance of allergen-specific Th2 cells. The mechanisms of this T cell modulation are unknown, and could depend on cytokines produced by other cell types such as interleukin (IL)-12, tumour necrosis factor (TNF)-alpha and IL-10 by monocytes. OBJECTIVE: To assess if VIT modifies the monocyte production of IL-12, TNF-alpha and IL-10 during the 45 first days of treatment. METHODS: Fourteen patients and seven controls were included. Blood samples were taken once in controls and at day (D)1, D30 and D45 of VIT in patients. Monocytes were isolated, cultured with and without lipopolysaccharide (LPS), and the culture supernatant was harvested. IL-10, IL-12 and TNF-alpha were assayed in supernatants by ELISA. RESULTS: Baseline cytokine levels were not statistically different between patients and controls. During treatment, an increase of spontaneous monocyte production of IL-12 and TNF-alpha was observed at D15 and D45. The production of IL-10 increased at D15 and D45 but not significantly. After LPS-stimulation, IL-12, TNF-alpha and IL-10 monocyte production was not modified by VIT. CONCLUSION: VIT induces a monocyte activation characterized by a delayed overproduction of IL-12 and TNF-alpha. These cytokines could be relevant to the inhibition of Th2 cells during VIT. Therefore, VIT-induced tolerance could depend not only on the specific action of venom antigens on T cells, but also on a secondary non-specific action of monocytes.

Adult↗
PubMed2001

Cranial reossification with absorbable plates.

The purpose of this study was to examine the effect of Lactosorb absorbable plates on bone healing across cranial bone defects in the rabbit skull. Two 10-mm diameter parietal skull defects were created in each of 20 rabbits, with one defect being placed on either side of the sagittal suture. In 10 rabbits, an absorbable plate was placed across both the inner and outer cortices of the left defect, and in the other 10 rabbits, an absorbable plate was placed across the outer cortex only of the left defect. The right defect always served as the control side, with no plate being placed across it. Rabbits were killed an average of 25 weeks postoperatively. Areas of reossification in the experimental and control defects of each rabbit were then measured, examined histologically, and compared. Growth across defects spanned by one plate was also compared with growth across defects spanned by two plates. Histologic and statistical analyses revealed no significant differences in reossification between the control and experimental defects in each animal and between the defects spanned by one versus two plates. This study suggests that these copolymer absorbable plates neither inhibit nor facilitate reossification across 10-mm diameter rabbit cranial defects.

Absorbable Implants↗
PubMed2001

[Identification of factors influencing hospital admission delay after ischemic cerebrovascular stroke. Study of a rural population].

We studied the time of arrival of 235 consecutive patients admitted to the emergency department of a University Hospital located in a rural area after the first symptoms of ischemic stroke or TIA. Among the following factors, we determined those that might be involved in delayed admission: place of symptom onset, time and place of onset of the first symptoms, contact with a general practitioner before admission time, mode of transportation, clinical score, impairment of consciousness, presence of seizures, heart complaints or headache, age and past medical history of cerebrovascular, cardiovascular and hypertension diseases. Half of the patients arrived within 4 h 10 of symptom discovery and 55 p. cent arrived within 6 hours. The percentage of patients arriving within 3 h (p = 0.001) and 6 h (p = 0.001) was higher for those who had a stroke during the day (8 a.m.-8 p.m.) than during the evening and night. The other characteristics associated with a shorter delay included a low neurological score on the Mathew's Stroke Scale (p < 0.001 at 3 h and p = 0.001 at 6 h) and younger age (p = 0.015 at 3 h). Presence of headache delayed admission (p = 0.010). Forty-five percent of patients arrive at the hospital 6 hours after the discovery of symptoms, too late to receive optimal stroke therapy. Widespread public education on stroke is necessary to reduce the delay of admission, particularly for old patients and in case of mild to moderate deficits.

Adolescent↗
PubMed2000

Increased soluble vascular cell adhesion molecule 1 concentrations in patients with primary or systemic lupus erythematosus-related antiphospholipid syndrome: correlations with the severity of thrombosis.

OBJECTIVE: Recent studies have shown that in vitro endothelial cells are activated by antiphospholipid antibodies and may support leukocyte adhesion. We studied levels of soluble intercellular adhesion molecule 1 (sICAM-1, sCD54), soluble vascular cell adhesion molecule 1 (sVCAM-1, sCD106), and soluble E-selectin (soluble endothelial leukocyte adhesion molecule 1 [sELAM-1, sCD62E]) in sera from patients with primary antiphospholipid syndrome (primary APS), and compared them with those from patients with systemic lupus erythematosus-associated APS (SLE-APS) or pure SLE, as well as with those from 2 control groups composed of healthy volunteers and patients with thrombosis unrelated to autoimmune diseases. METHODS: Serum samples from 24 patients with primary APS, 15 patients with SLE-APS, 22 patients with pure SLE, 48 control patients with thrombosis, and 18 healthy volunteers were examined using enzyme-linked immunosorbent assays specific for sICAM-1, sVCAM-1, and sELAM-1. RESULTS: Serum levels of sVCAM-1, but not sICAM-1 or sELAM-1, were significantly increased in all patient study groups compared with thrombosis control patients and healthy volunteers, but did not differ between the groups of patients with primary APS, SLE-APS, or pure SLE. Concentrations of sVCAM-1 were significantly higher in primary APS or SLE-APS patients with severe, recurrent thrombosis and were negatively correlated with platelet counts in primary APS patients. In patients with primary APS, sVCAM-1 levels were higher if there was thrombotic kidney involvement and correlated with creatinemia. CONCLUSION: Serum sVCAM-1 concentrations are increased in patients with primary APS, especially those with repeated thrombotic events or kidney involvement. These findings suggest that endothelial/ monocyte interaction may be important in the pathogenesis of primary APS.

Adult↗
PubMed2000

Dietary soybean phosphatidylcholines lower lipidemia: mechanisms at the levels of intestine, endothelial cell, and hepato-biliary axis.

The beneficial metabolic effects of dietary soybean lecithin on lipid metabolism are now more clearly established. The intestinal absorption of cholesterol is decreased by soybean phosphatidylcholine-enriched diet and results in a cholesterol-lowering effect. There is an enhancement of the cholesterol efflux by endothelial cells incubated with soybean phosphatidylcholines, and a stimulation of the reverse cholesterol transport by high density lipoprotein-phosphatidylcholines. As a result of all these processes, phosphatidylcholines provided by the soybean lecithin metabolism appear to be key molecules controlling the biodynamic exchanges of lipids. They regulate homeostasis of cholesterol and fatty acids by decreasing their synthesis and promoting cholesterol oxidation into bile salts. Finally, the outcome is the increase in bile secretion of these lipids and/or their metabolite forms. Such findings constitute promising goals in the field of nutritional effects of soybean lecithin in the treatment or prevention of hyperlipidemia and related atherosclerosis.

Journal Article↗
PubMed1998

Thrombin-activated human endothelial cells support monocyte adhesion in vitro following expression of intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106).

Thrombin, a central molecule in coagulation, is also involved in inflammation. Notably, thrombin induces endothelial neutrophil adhesion, P- and E-selectin expression, and chemokine production. We show here that thrombin induces expression of intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106) on human umbilical vein endothelial cells (HUVECs) associated with increased adhesion of monocytes. Thrombin increased mRNA steady-state levels and expression of ICAM-1 over 24 hours. Thrombin-induced VCAM-1 expression exhibited unusual kinetics, reaching maximum levels after 6 to 12 hours, but decreasing to near baseline after 24 hours. Thrombin activity on HUVECs was mediated through interaction with its specific receptor, because ICAM-1 and VCAM-1 expression were similarly induced by the 14-amino acid thrombin receptor-activating peptide. Thrombin-induced ICAM-1 and VCAM-1 expression was significantly inhibited by hirudin, but not by interleukin-1 receptor antagonist or anti-tumor necrosis factor alpha monoclonal antibody (MoAb). Thrombin-activated HUVECs significantly increased greater numbers of adhering THP-1 macrophagic cells, peripheral blood mononuclear cells, or purified monocytes than unstimulated HUVECs. This adhesion was inhibited by anti-CD18 and anti-CD49d MoAb, demonstrating that thrombin-induced ICAM-1 and VCAM-1 were functional. These results show that, in addition to selectins, thrombin directly induces a cytokine-independent expression of adhesion molecules of the Ig superfamily on HUVECs that may support firm leukocyte attachment during inflammation.

Antibodies, Monoclonal↗
PubMed1992

Iron status in low-birth-weight infants, small and appropriate for gestational age. A follow-up study.

Iron nutrition was measured in 84 low-birth-weight infants. At birth, they were assigned to three groups: preterm infants appropriate for gestational age (n = 29); preterm infants small for gestational age (n = 17); and full-term infants small for gestational age (n = 38). A sub-sample of infants was supplemented with iron 3 mg/kg from two to four months of age. At birth, preterm appropriate-for-gestational-age infants had a lower hemoglobin concentration than full-term small-for-gestational-age infants (p < 0.01) and a higher serum ferritin than preterm small-for-gestational-age infants (p < 0.05). In the non-supplemented group, full-term small-for-gestational-age infants had significantly higher hemoglobin concentrations at four months of age. At this age, iron-supplemented preterm infants appropriate or small for gestational age had significantly higher hemoglobin levels than non-supplemented subjects, while iron supplementation did not have an effect on final hemoglobin concentration in full-term small-for-gestational-age infants. We conclude that preterm infants, irrespective of their adequacy for gestational age, show evidence of iron deficiency before four months of age. Full-term infants do not develop iron deficiency up to this age.

Anemia, Hypochromic↗
PubMed1982

[Comparison of the Sensititre diagnostic system and the Bauer-Kirby test of sensitivity to chemotherapeutic agents in agar, on bacterial strains isolated from urinary infections].

The in vitro activity of nine antibiotics was tested against 50 bacterial strains isolated from urinary tract infections. The two methods showed a considerable percentage of diversity in an evaluation of their agreement. The Sensititre analytical method for the determination of minimum inhibitory concentrations is regarded as reliable and more useful to determine looked therapy. The authors suggest that the Sensititre system will be accepted in routine work.

Anti-Bacterial Agents↗
PubMed1981

Substituted 4,7-dihydroxyindoles and related quinonoid derivatives as potential antimicrobial agents.

The antimicrobial activity of some 4,7-dihydroxyindole derivatives and indole-4,7-quinones was examined by determining the MIC against selected typical microorganisms (bacteria and fungi). A few of the compounds examined showed only a feeble inhibitory effect against some Gram-positive strains. Activity seems to be correlated with the lipophilic character of the molecules; in fact, all compounds containing a strong hydrophilic group, like a carboxyl, proved completely inactive.

Anti-Bacterial Agents↗